PMID- 20539562 TI - Soft x-ray and extreme ultraviolet quantum detection efficiency of potassium chloride photocathode layers on microchannel plates. AB - We present measurements of the quantum detectio efficiency (QDE) of potassium chloride, applied directly to the surface of a microchannel plate (MCP), over the 44-1460-A wavelength range. The contributions of the photocathode material in the channels, and on the interchannel web, to the QDE have been determined. Two broad peaks in the QDE centered at lambda congruent with 500 A and lambda congruent with 900 A are apparent, the former with ~40% peak QDE and the latter with ~30% peak QDE. The photoelectric threshold is observed at lambda ~1400 A, and there is a narrow QDE minimum at lambda~ 670 A, which correlates with 2xthe band gap energy for KC1. The angular variation of the QDE from 0 to 35 degrees to the channel axis has also been examined. We describe a simple QDE model and show that its predictions are in accord with our QDE measurements. Assessment of the stability of KC1 shows that there was no significant degradation of the QDE at wavelengths of 40 years), (P = 0.044) and quitter status at week 2 (P = 0.001). Multivariate predictors in order of importance were Quit status at 2nd week (P = 0.002) and Age >40 years (P = 0.031). The combined predictive value of these two variables was found to be 86.3%. CONCLUSIONS: Bupropion helps in smoking cessation. This has been proved by three large multicenter randomized controlled trials. This study has also reflected the same result in the form of significantly high seven-day point prevalence abstinence at week 16 in the Bupropion group as compared to placebo. Bupropion has a beneficial effect on weight gain and withdrawal symptoms and the benign adverse effects of insomnia and dry mouth or altered taste make it a very effective and cheap treatment for nicotine addiction in smokers. PMID- 20539766 TI - Concomittant pulmonary tuberculosis and borderline leprosy with type-II lepra reaction in single patient. AB - The concommitant occurrence of both tuberculosis and leprosy in a single individual are not an uncommon clinical condition but is being reported infrequently in literature. We report a case of leprosy, diagnosed previously and also diagnosed as pulmonary tuberculosis. PMID- 20539767 TI - Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure. AB - The increased incidence of ventilator-associated complications in patients with chronic obstructive pulmonary disease (COPD) necessitates rapid weaning and extubation. The presence of secondary polycythemia in this subgroup increases the incidence of stroke and myocardial infarction due to hyperviscosity and tissue hypoxia. We present a 58-year-old male patient of COPD with secondary polycythemia (hematocrit 64%) who had possible hyperviscosity-related complications leading to cardiac arrest after a minor surgical procedure. The patient developed ventilator dependence after recovery. Phlebotomy was done to remove 10% of total blood volume. Symptomatic improvement was dramatic. Improvement in weaning indices like rapid shallow breathing index and PaO(2)/PAO(2) was observed facilitating rapid weaning and early extubation. Monitored, acute phlebotomy is safe and cost-effective. It decreases blood volume and viscosity, increases cardiac output and improves exercise tolerance in patients. PMID- 20539768 TI - A rare presentation of aspergillus infection as empyema thoracis. AB - A 57-year-old diabetic and hypertensive man presented with a short history of fever, dry cough and right side chest pain. A chest radiograph showed right pleural based homogenous shadow in middle and lower zones with obliteration of right costo-phrenic angle suggestive of right side effusion. Aspiration of pleural fluid revealed frank pus for which inter-costal tube drainage was performed. Due to persistence of empyema, the patient was subjected to thoracoscopy. Thoracoscopy showed multiloculated empyema. Thoracoscopic pleural biopsy and fluid showed septate fungal hyphae. Thoracotomy and parietal pleurectomy, with resection of part of right lower lobe, was carried out. Pleural fluid, pleural and lung tissue culture grew Aspergillus fumigatus. The patient showed good recovery with voriconazole after thoracotomy. PMID- 20539769 TI - Elongated uvula and diagnostic utility of spirometry in upper airway obstruction. AB - Elongated uvula is relatively an uncommon condition. Upper airway obstruction is often a missed complication of such a rare condition. Clinical presentations of upper airway obstruction often mimic asthma. Hence it is very easily mis diagnosed as asthma. Spirometry offers a very simple test to diagnose upper airway obstruction very early and easily. Once diagnosed, the management of elongated uvula, almost exclusively, is surgical excision leading to total cure. Here is a case report of such a rare condition. PMID- 20539770 TI - Whole lung lavage for pulmonary alveolar proteinosis. AB - A 26-year-old male presented with complaints of dry cough of six months and progressive breathlessness of three months duration. He was coughing out milky white sputum for two months and had lost 12 kg weight in two months. He had an evening rise in temperature of one month duration. Clinically, the patient was in respiratory distress and the respiratory system examination revealed bilateral velcro crackles. High resolution computed tomography chest showed bilateral diffuse reticulonodular opacities and "Crazy Paving" pattern suggestive of alveolar proteinosis. Broncho alveolar lavage showed eosinophilic granular material, which was periodic acid-Schiff positive. Open lung biopsy was done to confirm the diagnosis and the histopathologic examination revealed eosinophilic secretions with granular appearance suggestive of pulmonary alveolar proteinosis. Subsequently, patient underwent bilateral sequential whole lung lavage under general anesthesia. Patient showed marked clinical and radiological improvement after sequential whole lung lavage. PMID- 20539771 TI - Pulmonary epithelioid hemangioendothelioma: A rare pulmonary tumor in differential diagnosis of bronchogenic carcinoma. PMID- 20539772 TI - Mechanisms regulating caste differentiation in an aphid social system. AB - For evolution and maintenance of the social systems of insect colonies, caste production should be controlled in response to external cues so that caste ratio in the colony is kept at an optimal range. Recent developments using artificial diet rearing techniques have revealed an underlying mechanism for adaptive control of caste production in a social aphid, Tuberaphis styraci, which has a sterile soldier caste in the 2(nd) instar. Aphid density was the proximate cue that acts on 1(st) instar nymphs and embryos to induce soldier differentiation. The final determination of soldier differentiation occurred postnatally, probably at a late 1(st) instar stage. Direct contact stimuli from live non-soldier aphids mediated the density effect. While coexisting non-soldiers facilitated soldier differentiation in 1(st) instar nymphs, coexisting soldiers acted to suppress such differentiation. These results suggest that caste production in aphid colonies is controlled by positive and negative feedback mechanisms consisting of density-dependent induction and suppression of soldier differentiation. Here, we demonstrate the mechanisms that coordinate aphid society, and provide a striking case of clonal superorganism system where simple responses of colony members to local extrinsic stimuli are integrated into a highly organized regulation of the whole colony. PMID- 20539773 TI - Job switching in ants: Role of a kinase. AB - Reproductive division of labor is a defining characteristic of eusociality in insect societies. The task of reproduction is performed by the fertile males and queens of the colony, while the non-fertile female worker caste performs all other tasks related to colony upkeep, foraging and nest defence. Division of labor, or polyethism, within the worker caste is organized such that specific tasks are performed by discrete groups of individuals. Ordinarily, workers of one group will not participate in the tasks of other groups making the groups of workers behaviorally distinct. In some eusocial species, this has led to the evolution of a remarkable diversity of subcaste morphologies within the worker caste, and a division of labor amongst the subcastes. This caste polyethism is best represented in many species of ants where a smaller-bodied minor subcaste typically performs foraging duties while larger individuals of the major subcaste are tasked with nest defence. Recent work suggests that polyethism in the worker caste is influenced by an evolutionarily conserved, yet diversely regulated, gene called foraging (for), which encodes a cGMP-dependent protein kinase (PKG). Additionally, flexibility in the activity of this enzyme allows for workers from one task group to assist the workers of other task groups in times of need during the colony's life.In a recent article, Lucas and Sokolowski1 report that PKG mediates behavioral flexibility in the minor and major worker subcastes of the ant Pheidole pallidula. By changing the task-specific stimulus (a mealworm to induce foraging or alien intruders to induce defensive behavior) or pharmacologically manipulating PKG activity, they are able to alter the behavior of both subcastes. They also show differences in the spatial localization of the FOR protein in minor and major brains. Furthermore, manipulation of ppfor activity levels in the brain alters the behavior of both P. pallidula subcastes. The foraging gene is thus emerging as a major player in regulating the flexibility of responses to environmental change. PMID- 20539774 TI - Reliability in aposematic signaling: Thoughts on evolution and aposematic life. AB - In light of recent work, we will expand on the role and variability of aposematic signals. The focus of this review will be the concepts of reliability and honesty in aposematic signaling. We claim that reliable signaling can solve the problem of aposematic evolution, and that variability in reliability can shed light on the complexity of aposematic systems. PMID- 20539775 TI - Two-pore channels for integrative Ca signaling. AB - Two-pore channels (TPCs) are related to voltage-gated Ca(2+) and Na(+) channels. They most likely work as dimers with each of the two TPC protein subunits containing two pore-forming domains. Recent studies suggest that TPCs are expressed on the membranes of endosomes and lysosomes where they form receptors for nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing messenger inside cells. Upon activation by NAADP, Ca(2+) release from endolysosomal stores through TPCs triggers cytoplasmic Ca(2+) signals. Because of discrete localizations of these acidic vesicles and their small, albeit variable, sizes, the Ca(2+) signals from endolysosomes are local and, perhaps, represent unique elementary Ca(2+) events. These localized signals can be converted into regenerative global Ca(2+) waves by triggering Ca(2+)-induced Ca(2+) release from endoplasmic reticulum. We will discuss the implications of these findings and the significance of TPCs in integrative Ca(2+) signaling in animal cells. PMID- 20539776 TI - Apicomplexan perforin-like proteins. AB - Numerous perforin-like proteins are encoded in the genomes of apicomplexan parasites, where they are expressed in various life-cycle stages and play critical roles in pathogenesis and lifecycle progression. These ApiPLPs are characterized by the presence of a MACPF domain, responsible for pore-formation in target membranes in a number of systems, including many bacterial pathogens and effector cells of the immune response. ApiPLP MACPF domains maintain the critical structural elements but are often present in new and intriguing domain arrangements. Recent work in Toxoplasma and Plasmodium has shown that ApiPLPs are important for breaching membranes during parasite egress and cell traversal. Here we present an overview of this important protein family from a structural, functional and phylogenetic perspective across the Apicomplexa. PMID- 20539777 TI - Cryptochrome: A photoreceptor with the properties of a magnetoreceptor? AB - It was recently discovered that the photoreceptor cryptochrome is involved in mediating magnetosensitive entrainment of the internal clock of fruit flies.1 This discovery follows other recent studies implicating a role of cryptochrome in mediating magnetic sensitivity in orientation responses of fruit flies2,3 and growth responses of plants.4 Such widespread use of the same molecule for mediating magnetic sensitivity might suggest that cryptochrome is in some way optimal for detecting the magnetic field of the earth and that the magnetoreception function cannot be easily taken over by other molecules. This raises the question what properties might set cryptochromes apart from other molecules in terms of their ability to detect the geomagnetic field. Here, we will discuss possible answers to this question. We will first review the likely biophysical mechanism by which magnetic fields can be detected by a photoreceptor and discuss what constitutes an optimal photo-magneto-receptor. We will then discuss in how far cryptochrome matches the profile of an optimal molecule and what further steps are required for more conclusive answers. PMID- 20539778 TI - Root exudates mediate kin recognition in plants. AB - Though recent work has demonstrated that plants can recognize species, kin versus strangers, and self/non-self roots, no mechanism for identity recognition in plants has yet been found. Here we examined the role of soluble chemicals in signaling among roots. Utilizing Arabidopsis thaliana, we exposed young seedlings to liquid media containing exudates from siblings, strangers (non-siblings), or only their own exudates. In one experiment, root secretions were inhibited by sodium orthovanadate and root length and number of lateral roots were measured. In a second experiment, responses to siblings, strangers, and their own exudates were measured for several accessions (genotypes), and the traits of length of the longest lateral root and hypocotyl length were also measured. The exposure of plants to the root exudates of strangers induced greater lateral root formation than exposure of plants to sibling exudates. Stranger recognition was abolished upon treatment with the secretion inhibitor. In one experiment, plants exposed to sibling or stranger exudates have shorter roots than plants only exposed to their own exudates. This self/non-self recognition response was not affected by the secretion inhibitor. The results demonstrate that that kin recognition and self/non-self are two separate identity recognition systems involving soluble chemicals. Kin recognition requires active secretion by roots. PMID- 20539779 TI - A role of endocytosis in plant cytokinesis. AB - The preprophase band (PPB) of microtubules (MTs) marks the site of the future division plane irrespective of the orientation of the equatorial plane. Because the PPB MTs disappear during prometaphase, some positional information is thought to remain in the cortical cytoplasm after the disappearance of the PPB MTs. Cytoskeletal proteins are known to be excluded from the PPB site during mitosis. These depleted zones of cytoskeletal proteins are potential candidates for a "negative memory" system. However, how these depleted zones of the cytoskeletal proteins are produced remains unknown. In a recent paper, we have quantified the distribution of clathrin-coated pits and vesicles as well as of secretory structures during PPB formation using a combination of high-pressure freezing and electron tomography techniques. Our results demonstrated that the rate of endocytosis is enhanced in PPB regions. We postulate that the removal of membrane proteins by endocytosis plays a role in the creation of PPB "memory" structures. PMID- 20539780 TI - Dictyostelium centrin B localization during cell cycle progression. AB - Recently, we have reported the initial characterization of a novel centrin from Dictyostelium discoideum (DdCenB).1 Sequence and phylogenetic analyses clearly establish DdCenB as a centrin, yet further characterization revealed some interesting peculiarities about this novel centrin. Figure 1 depicts the localization of DdCenB at three points in the cell cycle: interphase, mitosis and cytokinesis. In interphase DdCenB primarily localizes to the nuclear envelope (NE). Although the NE remains intact during mitosis and cytokinesis in Dictyostelium, DdCenB disappears from the NE at these two stages of the cell cycle. In addition to localization at the NE, we also see weak localization in the nucleoplasm and cytoplasm (weakest). Although the nucleoplasmic concentration appears constant throughout the cell cycle, the very faint localization in the cytoplasm does appear to increase to the level of the nucleoplasm during mitosis and cytokinesis. Unlike most centrins characterized to date, we found no evidence of DdCenB at the centrosome at any point in the cell cycle. Here we examine the importance of DdCenB localization in cell cycle progression, as well as several other roles. PMID- 20539781 TI - Sympatric predator detection alters cutaneous respiration in Lymnaea. AB - The ability of an organism to detect a predator and then to take the appropriate vigilance actions is paramount for survival of the species. Lab-reared snails (>250 generations) maintain their ability to detect predators and alter both aerial and cutaneous respiration. However, only the scent of a sympatric predator altered aerial respiration in freshly collected 'wild' snails. Here we test the hypothesis that the detection of a sympatric predator but not an allopatric predator will alter cutaneous respiration in freshly collected 'wild' snails. We find that Alberta snails while altering their cutaneous respiration to the scent of a sympatric predator (tiger salamander) do not alter respiration to the scent of a crayfish (an allopatric predator). In Dutch snails there is a greater alteration to the scent of crayfish (sympatric predator) than to an allopatric predator (tiger salamander). PMID- 20539782 TI - Phosphorylation and dephosphorylation events allow for rapid segregation of fate determinants during Drosophila neuroblast asymmetric divisions. AB - Drosophila neuroblasts display remarkable asymmetry throughout mitosis. The most prominent asymmetry is the size difference between daughter cells at cytokinesis. The larger cell retains stem cell identity, i.e., remains a neuroblast while the smaller cell, called a ganglion mother cell (GMC), will generate differentiated neural and glial progeny. Preceding this size difference, several protein complexes localize to opposite sides of the neuroblast cortex (apical and basal in the embryo and, by analogy, referred to as such in larval neuroblasts although their asymmetry no longer correlates with such axis). The plane of division is coordinated with this molecular asymmetry such that apical and basal complexes are unequally partitioned between the two daughter cells: apical complexes are inherited by the self-renewing neuroblast while basal complexes are inherited by the GMC. This unequal segregation has been extensively shown to be functionally significant. Apical complexes contain factors required for cellular selfrenewal and basal complexes contain factors required for the differentiation of the GMC progeny. Curiously, however, some "basal" neuroblast proteins such as the scaffold protein Miranda (Mira) and its associated fate determinant Prospero (Pros), are initially apically localized prior to translocating to the opposite side of the cell cortex by the onset of mitosis. This is because mira mRNA is apically enriched, where it remains throughout the cell cycle, suggesting that Mira protein is translated within the apical environment.1,2 The transition from apical to basal enrichment of Mira and Pros takes place within minutes.2 Here, we summarize the known phosphorylation events and roles during neuroblast asymmetric divisions, as well as very recent work, including our own, identifying the first protein phosphatases implicated in this process. We then discuss models previously proposed, as well as a new model, for apical-to-basal transition of the Mira complex in light of our new results. PMID- 20539783 TI - The evolution of honest queen pheromones in insect societies. AB - Social insect workers are often capable of reproduction, but will not do so in the presence of a fertile queen. In large societies, queens are expected to produce a pheromone that honestly signals her dominance and/or fertility, to which workers respond by suppressing the development of their ovaries and by preventing other workers from reproducing (worker policing). However, what maintains the honesty of such queen pheromones is still under discussion. The explanation that an honest queen signal evolves simply because it serves the interest of all colony members does not seem to hold, since it is undermined by the fitness benefits of direct reproduction of workers at the individual level. A better explanation may be found in the idea that queen pheromones are difficult to produce for subordinate individuals, either because policing workers attack them, or because queen pheromones are intrinsically costly chemicals. Here, I discuss some of the arguments for and against these hypotheses and the evolutionary scenarios that each would lead to. PMID- 20539784 TI - Cell communication and tissue engineering. AB - Gap junction intercellular communication (GJIC) is ubiquitous in the majority of cells and is indispensable for proper development and function of most tissues. The loss of gap junction mediated cell to cell communication leads to compromised development in many tissues and organs, and also facilitates tumorigenesis and autonomous cell behavior in cancerous cells. Because cells embedded in an extracellular matrix constantly interact through gap junctions to coordinate normal tissue functions and homeostasis, our group hypothesized that increasing cell to cell communication, via genetically engineering cells to overexpress gap junction proteins, could improve cell signaling and increase differentiation in interior regions of engineered tissue equivalents. In a recent paper,1 we presented a platform to regenerate full 3D equivalents of engineered tissue, providing a strategy to overcome a barrier in regenerative medicine. These findings suggest that both targeted delivery and cell-based strategies can be used as treatments to enhance communication in 3D living tissue.2 In this addendum, we address the effects of extracellular calcium (Ca(2+) (e)) on intracellular calcium (Ca(2+) (i)), GJIC and osteogenic differentiation under conditions in which bone marrow stromal cells (BMSCs) also exhibit higher cell-to cell communication. As a key secondary messenger in many biological processes, the levels of Ca(2+) (e) and Ca(2+) (i) play a role in cell differentiation and may be a tunable signal in tissue regeneration. Higher cell-to-cell communication was achieved by both genetically engineering cells to overexpress connexin 43 (Cx43) and by a high density cell seeding technique, denoted micromass seeding (MM). The results presented in this addendum show that the intensity and duration of a second messenger, like calcium, can be augmented in a platform that enables higher cell-to-cell communication. The ability to modulate calcium signaling, combined with our previous approaches to modulate GJIC, may have an impact on tissue regeneration and therapies for communication incompetent cells, such as those associated with heart disease and certain types of cancer. PMID- 20539785 TI - Possible additional roles in mating for Ustilago maydis Rho1 and 14-3-3 homologues. AB - Both the Rho GTPases and 14-3-3 proteins each belong to ubiquitous families of proteins involved in a variety of cellular processes, including cytokinesis, cell polarity, cellular differentiation and apoptosis. In fungi, these components of signaling pathways are involved in cell cycle regulation, cytokinesis and virulence. We study cellular differentiation and pathogenesis for Ustilago maydis, the dimorphic fungal pathogen of maize. We have reported on the interactions of Pdc1, a U. maydis homologue of human 14-3-3varepsilon, with Rho1, a small GTP binding protein; these proteins participate in cell polarity and filamentation pathways that include another small G protein, Rac1, and its effector PAK kinase, Cla4. Here we describe additional experiments that explore possible relationships of Pdc1 and Rho1 with another PAK-like kinase pathway and with the a matingtype locus. PMID- 20539786 TI - Multisensory integration for odor tracking by flying Drosophila: Behavior, circuits and speculation. AB - Many see fruit flies as an annoyance, invading our homes with a nagging persistence and efficiency. Yet from a scientific perspective, these tiny animals are a wonder of multisensory integration, capable of tracking fragmented odor plumes amidst turbulent winds and constantly varying visual conditions. The peripheral olfactory, mechanosensory, and visual systems of the fruit fly, Drosophila melanogaster, have been studied in great detail;1-4 however, the mechanisms by which fly brains integrate information from multiple sensory modalities to facilitate robust odor tracking remain elusive. Our studies on olfactory orientation by flying flies reveal that these animals do not simply follow their "nose"; rather, fruit flies require mechanosensory and visual input to track odors in flight.5,6 Collectively, these results shed light on the neural circuits involved in odor localization by fruit flies in the wild and illuminate the elegant complexity underlying a behavior to which the annoyed and amazed are familiar. PMID- 20539787 TI - Myosin-1a: A motor for microvillar membrane movement and mechanics. AB - Myosin-1a is one of eight monomeric, membrane binding class I myosins expressed in vertebrates.1 As the most abundant actin-based motor protein found in the enterocyte microvillus, myosin-1a has long been known to interact with the apical membrane via a highly basic C-terminal tail domain.2 Several recent studies shed light on possible functional consequences of this protein/lipid interaction. In vitro and in vivo studies of microvillar function have revealed that myosin-1a can move apical membrane along core actin bundles, leading to the release of small vesicles from microvillar tips.3,4 Additional studies indicate that myosin 1a and other class I myosins contribute to membrane-cytoskeleton adhesion, which enables the apical membrane to resist deformation.5 These findings clearly position myosin-1a as an important player in apical membrane movement and structural stability. How this motor is able to fulfill these two seemingly distinct functions is currently unclear, but will serve as the focus of our discussion below. PMID- 20539788 TI - Adaptive molecular convergence: Molecular evolution versus molecular phylogenetics. AB - Definitive identification of convergent evolution, the acquisition of the same biological trait in unrelated lineages, provides one of the most compelling sources of evidence for natural selection. Although numerous examples of convergent morphological evolution are well known (such as the independent development of wings in birds and mammals), cases of convergent evolution at the molecular-genetic level appear to be quite rare. We recently discovered a remarkable case of convergent molecular evolution involving more than 100 parallel amino-acid changes across all 13 mitochondrially-encoded proteins of snakes and agamid lizards. Just a few of these convergent substitutions were sufficient to positively mislead the inference of phylogeny, even with thousands of sites providing latent support for the correct underlying relationships. Since this example demonstrates that molecular convergence can happen en masse in nature, affecting multiple genes, it is important to consider the threat this poses to molecular systematics, and careful genome-wide assays for convergent molecular evolution are warranted. This result implies that the protein adaptive landscape is sometimes highly constrained. PMID- 20539789 TI - Plant surfaces of vegetable crops mediate interactions between chemical footprints of true bugs and their egg parasitoids. AB - During the host location process, egg parasitoids can eavesdrop on chemical cues released from immature and adult hosts. These indirect host-related cues are highly detectable, but of low reliability because they lead egg parasitoid females to an area where oviposition is likely to occur rather then providing wasps with direct information on the presence of eggs and their location. In the host-parasitoid associations between true bugs and their scelionid egg parasitoids, female wasps perceive the chemical residues left by host adults walking on substrates as contact kairomones, displaying a characteristic arrestment posture. In this study, we demonstrated that epicuticular waxes of leaves of two vegetable crops, broad bean, Vicia faba and collard greens, Brassica oleracea, mediate the foraging behaviour of Trissolcus basalis (Wollaston) by adsorbing contact kairomones from adults of Nezara viridula (L.). Trissolcus basalis females showed no response when released on the adaxial leaf surface of broad bean or collard green plants with intact cuticular wax layers that had not been exposed to bugs, whereas wasps displayed the arrestment posture when intact leaves were contaminated by chemical residues from host females. Adaxial leaf surfaces that were dewaxed with an aqueous solution of gum arabic and afterwards contaminated by N. viridula females elicited no arrestment responses from wasp females. Similarly, leaves contaminated by host females and subsequently dewaxed did not elicit responses from female wasps. These findings reveal the important role of plant waxes in N. viridula-T. basalis semiochemical communication. PMID- 20539790 TI - Little response of cerebral metastasis from hepatocellular carcinoma to any treatments. AB - OBJECTIVE: We retrospectively evaluated the survival outcome of patients with brain metastasis from hepatocellular carcinoma (HCC). METHODS: Between 1991 and 2007, a total of 20 patients were diagnosed as having brain metastasis from HCC. The mean age of the patients was 55 +/- 13 years, and 17 (85.0%) were men. Seventeen (85.0%) patients had already extracranial metastases. The median time from diagnosis of HCC to brain metastasis was 18.5 months. Fourteen (70.0%) patients had stroke-like presentation due to intracerebral hemorrhage (ICH). Ten (50.0%) patients had single or solitary brain metastasis. Among a total of 34 brain lesions, 31 (91.2%) lesions had the hemorrhagic components. RESULTS: The median survival time was 8 weeks (95% CI, 5.08-10.92), and the actuarial survival rates were 85.0%, 45.0%, 22.5%, and 8.4% at 4, 12, 24, and 54 weeks. Age < 60 years, treatment of the primary and/or extracranial lesions, and recurrent ICH were the possible prognostic factors (p = 0.044, p < 0.001, and p = 0.111, respectively). The median progression-free survival (PFS) time was 3 months (95% CI, 0.95-5.05). CONCLUSION: The overall survival of the patients with brain metastasis from HCC was very poor with median survival time being only 8 weeks. However, the younger patients less than 60 years and/or no extracranial metastases seem to be a positive prognostic factor. PMID- 20539791 TI - Is Transradial Cerebral Angiography Feasible and Safe? A Single Center's Experience. AB - OBJECTIVE: Although a transradial angiography is accepted as the gold standard for cardiovascular procedures, cerebral angiography has been performed via transfemoral approach in most institutions. The purpose of this study is to present our experience concerning the feasibility, efficacy, and safety of a transradial approach to cerebral angiography as an alternative to a transfemoral approach. METHODS: Between February 2007 and October 2009, a total of 1,240 cerebral angiographies were performed via a transradial approach in a single center. The right radial approach was used as an initial access route. The procedure continued only after the ulnar artery was proven to provide satisfactory collateral perfusion according to two tests (a modified Allen's test and forearm angiography). RESULTS: The procedural success rate was 94.8% with a mean duration of 28 minutes. All supra-aortic vessels were successfully catheterized with a success rate of 100%. The success rates of selective catheterization to the right vertebral artery, right internal carotid artery, left internal carotid artery, and left vertebral artery were 96.1%, 98.6%, 82.6% and 52.2%, respectively. The procedure was performed more than twice in 73 patients (5.9%), including up to 4 times in 2 patients. The radial artery occlusion was found in 4 patients (5.4%) on follow-up cerebral angiography, but no ischemic symptoms were observed in any of the cases. CONCLUSION: This study suggests that cerebral angiography using a transradial approach can be performed with minimal risk of morbidity. In particular, this procedure might be useful for follow-up angiographies and place less stress on patients. PMID- 20539792 TI - Interspinous implant with unilateral laminotomy for bilateral decompression of degenerative lumbar spinal stenosis in elderly patients. AB - OBJECTIVE: This study assessed the safety and efficacy of one level unilateral laminotomy bilateral decompression (ULBD) with the placement of a device for intervertebral assisted motion (DIAM) compared with one level ULBD only in elderly patients with degenerative lumbar spinal stenosis (DLSS). METHODS: A non randomized prospective analysis was performed on 16 patients who underwent one level ULBD with DIAM (Group A) and 20 patients with one level ULBD only (Group B) between February 2007 and March 2008. Radiographic imaging, visual analog scale (VAS) and MacNab outcome scale were obtained before and after surgery at a mean interval of 21 months (range 17-27 months). RESULTS: The disc height, interpedicular distance, slip distance and segmental lordotic angle were similar between two groups. In the group A, there was no significant difference between the pre- and post-operative imaging in terms of the sagittal balance and disc height. Both groups showed significant improvement in the clinical outcomes. In addition, there was significantly less low-back pain in the group A than in the group B at the last follow up, while the clinical improvement of the leg pain and MacNab outcome scale showed no significant difference in the two groups. There were no major complications or DIAM associated complications. CONCLUSION: ULBD with DIAM is a safe and efficacious treatment for selective elderly patients with DLSS, particularly for relieving low back pain comparing to ULBD. ULBD with DIAM did not alter the disc height or sagittal alignment at the mean 21 months follow up interval. PMID- 20539793 TI - Effects of mindfulness based stress reduction program on depression, anxiety and stress in patients with aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE: In this study, the Mindfulness Based Stress Reduction (MBSR) program was applied to patients presenting with depression and anxiety after surgery from spontaneous subarachnoid hemorrhage (SAH) and the effects were assessed. METHODS: The subjects were patients admitted for cerebral aneurysm rupture and treated by means of surgery from March to December, 2007. More than 6 months had passed after surgery, without any special lesions showing up on computed tomography (CT), and the Glasgow outcome scale (GOS) was 5 points. Among patients with anxiety and depression symptoms, 11 patients completed the program. The MBSR program was conducted once a week, 2.5 hours each, for 8 weeks. The evaluation criteria were : 1) the Beck Depression Inventory (BDI): it measures the type and level of depression, 2) the State-Trait Anxiety Inventory : the anxiety state of normal adults without mental disorder, and 3) Heart Rate Variability (HRV) : the influence of the autonomous nervous system on the sinoarterial node varies continuously in response to the change of the internal/external environment. RESULTS: The BDI value was decreased from 18.5 +/- 10.9 to 9.5 +/- 7.1 (p = 0.013) : it was statistically significant, and the depression level of patients was lowered. The state anxiety was decreased from 51.3 +/- 13.9 to 42.3 +/- 15.2; the trait anxiety was reduced from 50.9 +/- 12.3 to 41.3 +/- 12.8, and a borderline significant difference was shown (p = 0.091, p = 0.056). In other words, after the treatment, although it was not statistically significant, a decreased tendency in anxiety was shown. In the HRV measurement, standard deviation normal to normal (SDNN), square root of the square root of the mean sum of squared differences between adjacent normal to normal intervals (RMSSD), and total power (TP) showed significant increase, Physical Stress Index (PSI) showed a significant reduction, and thus an improvement in the homeostatic control mechanism of the autonomic nervous system was ween. CONCLUSION: The MBSR program was applied to the patients showing anxiety and depression reaction after SAH treatment, and a reduction in depression symptoms and physiological reactions were observed. The application of the MBSR program may be considered as a new tool in improving the quality of life for patients after surgery. PMID- 20539794 TI - Anterior lumbar interbody fusion with stand-alone interbody cage in treatment of lumbar intervertebral foraminal stenosis : comparative study of two different types of cages. AB - OBJECTIVE: This retrospective study was performed to evaluate the clinical and radiological results of anterior lumbar interbody fusion (ALIF) using two different stand-alone cages in the treatment of lumbar intervertebral foraminal stenosis (IFS). METHODS: A total of 28 patients who underwent ALIF at L5-S1 using stand-alone cage were studied [Stabilis(R) (Stryker, Kalamazoo, MI, USA); 13, SynFix-LR(R) (Synthes Bettlach, Switzerland); 15]. Mean follow-up period was 27.3 +/- 4.9 months. Visual analogue pain scale (VAS) and Oswestry disability index (ODI) were assessed. Radiologically, the change of disc height, intervertebral foraminal (IVF) height and width at the operated segment were measured, and fusion status was defined. RESULTS: Final mean VAS (back and leg) and ODI scores were significantly decreased from preoperative values (5.6 +/- 2.3 --> 2.3 +/- 2.2, 6.3 +/- 3.2 --> 1.6 +/- 1.6, and 53.7 +/- 18.6 --> 28.3 +/- 13.1, respectively), which were not different between the two devices groups. In Stabilis(R) group, postoperative immediately increased disc and IVF heights (10.09 +/- 4.15 mm --> 14.99 +/- 1.73 mm, 13.00 +/- 2.44 mm --> 16.28 +/- 2.23 mm, respectively) were gradually decreased, and finally returned to preoperative value (11.29 +/- 1.67 mm, 13.59 +/- 2.01 mm, respectively). In SynFix-LR(R) group, immediately increased disc and IVF heights (9.60 +/- 2.82 mm --> 15.61 +/- 0.62 mm, 14.01 +/- 2.53 mm --> 21.27 +/- 1.93 mm, respectively) were maintained until the last follow up (13.72 +/- 1.21 mm, 17.87 +/- 2.02 mm, respectively). The changes of IVF width of each group was minimal pre- and postoperatively. Solid arthrodesis was observed in 11 patients in Stabilis group (11/13, 84.6%) and 13 in SynFix-LR(R) group (13/15, 86.7%). CONCLUSION: ALIF using stand-alone cage could assure good clinical results in the treatment of symptomatic lumbar IFS in the mid-term follow up. A degree of subsidence at the operated segment was different depending on the device type, which was higher in Stabilis(R) group. PMID- 20539795 TI - Morphometric study of the nerve roots around the lateral mass for posterior foraminotomy. AB - OBJECTIVE: Morphometric data on dorsal cervical anatomy were examined in an effort to protect the nerve root near the lateral mass during posterior foraminotomy. METHODS: Using 25 adult formalin-fixed cadaveric cervical spines, measurements were taken at the lateral mass from C3 to C7 via a total laminectomy and a medial one-half facetectomy. The morphometric relationship between the nerve roots and structures of the lateral mass was investigated. Results from both genders were compared. RESULTS: Following the total laminectomy, from C3 to C7, the mean of the vertical distance from the medial point of the facet (MPF) of the lateral mass to the axilla of the root origin was 3.2-4.7 mm. The whole length of the exposed root had a mean of 4.2-5.8 mm. Following a medial one-half facetectomy, from C3 to C7, the mean of the vertical distance to the axilla of the root origin was 2.1-3.4 mm, based on the MPF. Mean vertical distances from the MPF to the medial point of the root that crossed the inferior margin of the intervertebral disc were 1.2-2.7 mm. The mean distance of the exposed root was 8.2-9.0 mm, and the mean angle between the dura and the nerve root was significantly different between males and females, at 53.4-68.4 degrees . CONCLUSION: These data will aid in reducing root injuries during posterior cervical foraminotomy. PMID- 20539796 TI - A understanding of the temporal stem. AB - OBJECTIVE: There has been inconsistency about definition of the temporal stem despite of several descriptions demonstrating its microanatomy using fiber dissection and/or diffusion tensor tractography. This study was designed to clarify three dimensional configurations of the temporal stem. METHODS: The fronto-temporal regions of several formalin-fixed human cerebral hemispheres were dissected under an operating microscope using the fiber dissection technique. The consecutive coronal cuts of the dissected specimens were made to define the relationships of white matter tracts comprising the temporal stem and the subcortical gray matters (thalamus, caudate nucleus, amygdala) with inferior limiting (circular) sulcus of insula. RESULTS: The inferior limiting sulcus of insula, limen insulae, medial sylvian groove, and caudate nucleus/amygdala were more appropriate anatomical structures than the roof/dorso-lateral wall of the temporal horn and lateral geniculate body which were used to describe previously for delineating the temporal stem. The particular space located inside the line connecting the inferior limiting sulcus of insula, limen insulae, medial sylvian groove/amygdala, and tail of caudate nucleus could be documented. This space included the extreme capsule, uncinate fasciculus, inferior occipito-frontal fasciculus, anterior commissure, ansa peduncularis, and inferior thalamic peduncle including optic radiations, whereas the stria terminalis, cingulum, fimbria, and inferior longitudinal fiber of the temporal lobe were not passing through this space. Also, this continued posteriorly along the caudate nucleus and limiting sulcus of the insula. CONCLUSION: The temporal stem is white matter fibers passing through a particular space of the temporal lobe located inside the line connecting the inferior limiting sulcus of insula, limen insulae, medial sylvian groove/amygdala, and tail of caudate nucleus. The three dimensional configurations of the temporal stem are expected to give the very useful anatomical and surgical insights in the temporal lobe. PMID- 20539797 TI - Comparison of SpineJet XL and Conventional Instrumentation for Disk Space Preparation in Unilateral Transforaminal Lumbar Interbody Fusion. AB - OBJECTIVE: Although unilateral transforaminal lumbar interbody fusion (TLIF) is widely used because of its benefits, it does have some technical limitations. Removal of disk material and endplate cartilage is difficult, but essential, for proper fusion in unilateral surgery, leading to debate regarding the surgery's limitations in removing the disk material on the contralateral side. Therefore, authors have conducted a randomized, comparative cadaver study in order to evaluate the efficiency of the surgery when using conventional instruments in the preparation of the disk space and when using the recently developed high-pressure water jet system, SpineJet XL. METHODS: Two spine surgeons performed diskectomies and disk preparations for TLIF in 20 lumbar disks. All cadaver/surgeon/level allocations for preparation using the SpineJet XL (HydroCision Inc., Boston, MA, USA) or conventional tools were randomized. All assessments were performed by an independent spine surgeon who was unaware of the randomizations. The authors measured the areas (cm(2)) and calculated the proportion (%) of the disk surfaces. The duration of the disk preparation and number of instrument insertions and withdrawals required to complete the disk preparation were recorded for all procedures. RESULTS: The proportion of the area of removed disk tissue versus that of potentially removable disk tissue, the proportion of the area of removed endplate cartilage, and the area of removed disk tissue in the contralateral posterior portion showed 74.5 +/- 17.2%, 18.5 +/- 12.03%, and 67.55 +/- 16.10%, respectively, when the SpineJet XL was used, and 52.6 +/- 16.9%, 22.8 +/- 17.84%, and 51.64 +/- 19.63%, respectively, when conventional instrumentations were used. The results also showed that when the SpineJet XL was used, the proportion of the area of removed disk tissue versus that of potentially removable disk tissue and the area of removed disk tissue in the contralateral posterior portion were statistically significantly high (p < 0.001, p < 0.05, respectively). Also, compared to conventional instrumentations, the duration required to complete disk space preparation was shorter, and the frequency of instrument use and the numbers of insertions/withdrawals were lower when the SpineJet XL was used. CONCLUSION: The present study demonstrates that hydrosurgery using the SpineJet XL unit allows for the preparation of a greater portion of disk space and that it is less traumatic and allows for more precise endplate preparation without damage to the bony endplate. Furthermore, the SpineJet XL appears to provide tangible benefits in terms of disk space preparation for graft placement, particularly when using the unilateral TLIF approach. PMID- 20539798 TI - A case of aberrant abducens nerve in a cadaver and review of its clinical significance. AB - The abducens nerve usually travels from the brainstem to the lateral rectus muscle as a single trunk. However, it has been reported that this nerve could split into branches occasionally. We attempted to show the aberrant course of abducens nerve in a specimen with unilateral duplicated abducens nerve and review relevant literatures. The micro-dissections were performed in a head specimen injected with colored latex under the microscope. The abducens nerve was duplicated unilaterally. This nerve emerged from the pontomedullary sulcus as a single trunk and splitted into two branches in the prepontine cistern. These two separate branches were piercing the cerebral dura of the petroclival region respectively. The slender lower branch passed between the petroclinoid and petrosphenoid ligaments and the thick lower one passed under the petrosphenoid ligament. These two branches united just lateral to the ascending segment of internal carotid artery in the cavernous sinus. The fact that there are several types of aberrant abducens nerve is helpful to perform numerous neurosurgical procedures in the petroclival region and cavernous sinus without inadvertent neurovascular injuries. PMID- 20539799 TI - Clinical experience and management of cervico-thoracic epidural hematoma. AB - Spinal epidural hematoma (SEH) causing acute myelopathy is rare. The usual clinical presentation of a SEH is sudden severe neck or back pain that progresses toward paraparesis or quadriparesis, depending on the level of the lesion. Recent studies have shown that early decompressive surgery is very important for patient's recovery. We experienced five patients of cervico-thoracic epidural hematomas associated with neurologic deficits that were treated successfully with surgical intervention. PMID- 20539800 TI - Isolated recurrence of intracranial granulocytic sarcoma mimicking a falx meningioma in acute myeloblastic leukemia. AB - Intracranial granulocytic sarcomas are rare tumors, which are composed of immature granulocytic cells. Although it has been well known that these tumors are associated with acute myeloblastic leukemia (AML), they have been almost always related to bone marrow relapse. However, isolated recurrence of granulocytic sarcoma following complete remission from prior AML is extremely rare, especially in the central nervous system. A 44-year-old male presented with isolated recurrence of granulocytic sarcoma mimicking a falx meningioma two years after complete remission by allogenic peripheral blood stem cell transfusion (PBSCT) in the acute myelomonoblastic leukemia (FAB, M4). Because of depressed mental state and mass effect, total surgical resection was performed. Pathological findings were compatible with the granulocytic sarcoma. There was no evidence of leukemic relapse in the peripheral blood. We suggest that this phenomenon can be explained by the hypothesis that a certain barrier effect such as blood brain barrier might lead to the proliferation of intracranial leukemic cells which metastasized before PBSCT. PMID- 20539801 TI - Idiopathic hypereosinophilic syndrome involving thoracic spine. AB - Hypereosinophilic syndrome is a rare hematologic disorder with sustained eosinophilia. Peripheral blood eosinophilia without an underlying etiology and with organs dysfunction has been designated hypereosinophilic syndrome. We report a rare case of symptomatic spinal infiltration of eosinophils at osteolytic T5 in patient with idiopathic hypereosinophilic syndrome. PMID- 20539802 TI - Isolated, contralateral trochlear nerve palsy associated with a ruptured right posterior communicating artery aneurysm. AB - Trochlear nerve palsy associated with spontaneous subarachnoid hemorrhage (SAH) is known to be a rare malady. We report here on a patient who suffered with left trochlear nerve palsy following rupture of a right posterior communicating artery aneurysm. A 56-year-woman visited our emergency department with stuporous mental change. Her Hunt-and-Hess grade was 3 and the Fisher grade was 4. Cerebral angiography revealed a ruptured aneurysm of the right posterior communicating artery. The aneurysm was clipped via a right pterional approach on the day of admission. The patient complained of diplopia when she gazed to the left side, and the ophthalmologist found limited left inferolateral side gazing due to left superior oblique muscle palsy on day 3. Elevated intracranial pressure, intraventricular hemorrhage or a dense clot in the basal cisterns might have caused this trochlear nerve palsy. PMID- 20539803 TI - Spontaneous pneumocephalus associated with pneumosinus dilatans. AB - The majority of cases of pneumocephalus are secondary to trauma or medical intervention. Spontaneous, non-traumatic pneumocephalus is an uncommon condition. Most cases of spontaneous pneumocephalus require surgery. However, if there is no evidence of infection or cerebrospinal fluid leak, bed rest and follow-up imaging is an alternative treatment. Herein, we report a 31-year-old man with spontaneous pneumocephalus associated with pneumosinus dilatans. PMID- 20539804 TI - Percutaneous vertebroplasty for pregnancy-associated osteoporotic vertebral compression fractures. AB - Osteoporosis is a worldwide problem and it mainly affects postmenopausal women. Osteoporosis associated with pregnancy or lactation is a rare condition. The incidence and mechanism of this phenomenon has not been clarified, but it can cause one or more vertebral compression fractures with severe, prolonged back pain in the affected women. We experienced this uncommon case, treated it with percutaneous vertebroplasty. A 35-old-woman visited our hospital with complaints of severe back pain and flank pain 2 months after normal vaginal delivery. She was diagnosed with osteoporotic vertebral compression fractures on the T5, 8, 9 and 11 vertebral bodies and we performed percutaneous vertebroplasty on the T8, 9 and 11 vertebrae with a good result. We present here an unusual case of pregnancy associated compression fractures treated by percutaneous vertebroplasty. PMID- 20539805 TI - Lymphangioma in the epidural space of the thoracic spine. AB - A rare case of solitary intraspinal epidural lymphangioma is described with a review of the literature. A 16-year-old boy was admitted to our hospital with a history of two-year of progressive paraparesis. Magnetic resonance imaging study revealed a 2 x 2 x 6 cm sized epidural cystic mass in the thoracic spine. Surgical total removal and biopsy were performed. The final pathologic report on the mass indicated lymphangioma. PMID- 20539806 TI - Stent-assisted coil embolization for the proximal middle cerebral artery fusiform aneurysm. AB - Middle cerebral artery (MCA) fusiform aneurysms often have an unfavorable geometry that may limit surgical or endovascular treatment. Herein, we present a case of a fusiform aneurysm of the proximal MCA, which was successfully treated using stent-assisted coil embolization. A 42-year-old man presented with repeated headache and syncope. Five years earlier, a right MCA aneurysm had been treated by aneurismal wrapping. Magnetic resonance images (MRI) revealed a partially thrombosed proximal MCA aneurysm at the right perisylvian region. Digital subtraction angiography (DSA) revealed a multilobulated fusiform-shaped aneurysm. The patient underwent stent-assisted coil embolization under general anesthesia and symptoms resolved postoperatively. A three-month follow-up angiography revealed no recanalization of the aneurysm and indicated tolerable blood flow through the right MCA, as compared to the preoperative angiography. We suggest that in selected patients, stent-assisted coil embolization of proximal MCA fusiform aneurysms can be an effective treatment modality. PMID- 20539807 TI - Hysterectomy-a comparison of approaches. AB - BACKGROUND: The advantages and disadvantages of the various surgical techniques for hysterectomy are currently a topic of debate, with particular controversy over leaving the cervix in situ in the laparoscopic supracervical hysterectomy (LASH) procedure. METHODS: In a retrospective single-center study, medical history and clinical characteristics were compared in patients who had undergone hysterectomy for benign disease in the period 2002-2008 at the Department of Obstetrics and Gynecology, Erlangen University Hospital. Postoperative satisfaction and the frequency of secondary operations for prolapse or incontinence in women with surgery between 2002 and 2007 were surveyed by means of a questionnaire. RESULTS: The longest hospital stay was observed after abdominal hysterectomy (AH; 10 days), followed by vaginal hysterectomy (VH; 7.8 days) and laparoscopy-assisted vaginal hysterectomy (LAVH; 7.2 days). The shortest stays in hospital were seen after LASH (5.9 days) and total laparoscopic hysterectomy (TLH; 5.7 days). The shortest operating time was noted with VH (87 min) and the longest with LAVH (122 min). The lowest rates of blood loss were with LASH (1.38 g/dL) and TLH (1.51 g/dL). The highest rate of postoperative complications occurred after AH (8.9%). No differences were found in relation to postoperative satisfaction or surgery for prolapse or incontinence. CONCLUSION: No postoperative benefits were found for leaving the cervix in situ when performing LASH. However, this was not a controlled randomized study. PMID- 20539808 TI - Correspondence (letter to the editor): Pathophorias-A common cause of learning disabilities and school failure. PMID- 20539810 TI - The diagnosis of urinary tract infection: a systematic review. AB - BACKGROUND: Urinary tract infections (UTI) are among the leading reasons for treatment in adult primary care medicine, accounting for a considerable percentage of antibiotic prescriptions. Because this problem is so common and so significant in routine clinical practice, a high level of diagnostic accuracy is essential. Antibiotics should not be prescribed excessively, particularly in view of the increasing prevalence of antibiotic resistance. METHOD: Systematic review of relevant articles that were retrieved by a search of the Medline, Embase, and Cochrane Library databases. The recommendations of selected international guidelines were also taken into account, as were the German national quality standards for microbiological diagnosis. RESULTS: The diagnosis of UTI by clinical criteria alone has an error rate of approximately 33%. The use of refined diagnostic algorithms does not completely eliminate uncertainty. CONCLUSION: With the aid of a small number of additional diagnostic criteria, antibiotic treatment for UTI can be provided more specifically and thus more effectively. Differentiating UTI from asymptomatic bacteriuria, which usually requires no treatment, can lower the frequency of unnecessary antibiotic prescriptions. PMID- 20539811 TI - Contaminated food. PMID- 20539812 TI - Heroic self experiment. PMID- 20539813 TI - Immunostimulating treatment. PMID- 20539815 TI - Eradication is impossible. PMID- 20539816 TI - Decubitus ulcers: pathophysiology and primary prevention. AB - BACKGROUND: Pressure sores are a serious complication of multimorbidity and lack of mobility. Decubitus ulcers have become rarer among bed-ridden patients because of the conscientious use of pressure-reducing measures and increased mobilization. Nonetheless, not all decubitus ulcers can be considered preventable or potentially curable, because poor circulation makes some patients more susceptible to them, and because cognitive impairment can make prophylactic measures difficult to apply. METHODS: A systematic literature search was performed in 2004 and 2005 in the setting of a health technology assessment, and a selective literature search was performed in 2009 for papers on the prevention of decubitus ulcers. RESULTS: Elderly, multimorbid patients with the immobility syndrome are at high risk for the development of decubitus ulcers, as are paraplegic patients. The most beneficial way to prevent decubitus ulcers, and to treat them once they are present, is to avoid excessive pressure by encouraging movement. At the same time, the risk factors that promote the development of decubitus ulcers should be minimized as far as possible. CONCLUSIONS: Malnutrition, poor circulation (hypoperfusion), and underlying diseases that impair mobility should be recognized if present and then treated, and accompanying manifestations, such as pain, should be treated symptomatically. Over the patient's further course, the feasibility, implementation, and efficacy of ulcer-preventing measures should be repeatedly re-assessed and documented, so that any necessary changes can be made. Risk factors for the development of decubitus ulcers should be assessed at the time of the physician's first contact with an immobile patient, or as soon as the patient's condition deteriorates; this is a prerequisite for timely prevention. Once the risks have been assessed, therapeutic measures should be undertaken on the basis of the patient's individual risk profile, with an emphasis on active encouragement of movement and passive relief of pressure through frequent changes of position. PMID- 20539817 TI - Expanding HAART treatment to all currently eligible individuals under the 2008 IAS-USA Guidelines in British Columbia, Canada. AB - BACKGROUND: In 2008, the IAS-USA published the revised guidelines for the use of HAART in adults substantially increasing the number of individuals eligible for HAART. The epidemic in British Columbia (BC) is mainly among men who have sex with men and those with injection drug use. Here, we explored the potential impact of different HAART coverage scenarios, based on the new guidelines, on the HIV-related incidence, morbidity and mortality in BC, Canada. METHODOLOGY: We built a mathematical transmission model to investigate different HAART coverage scenarios (50%, 60%, 75% and 100%) of those medically eligible to receive HAART under the 2008 IAS guidelines. All new scenarios were compared to the current coverage in BC under the 2006 IAS guidelines (i.e. baseline scenario). In BC, it is estimated that 25-30% of individuals are unaware of their status. Costs were drug-related and reported in Canadian dollars. HIV-related morbidity and mortality were estimated based on the disability-adjusted life years (DALY) methodology. PRINCIPAL FINDINGS: Currently, there are 4379 individuals on HAART under the IAS 2006 guidelines and 6781 individuals who qualify for treatment based on the new guidelines. Within 5 years, increasing HAART coverage decreased yearly new infections by at least 44.8%. In the 50% scenario, in 5 years, DALY decreased by 53% corresponding to 4155 averted DALYs, and in 25 years it decreased by 66% corresponding to 5837 averted DALYs. The effect was even stronger if the 75% scenario was chosen instead. Compared to the 100% expansion scenario, we observed an excess in annual direct treatment expenditures at the end of 5 years of approximately 1 million dollars in the 75% scenario, and of approximately 2 million dollars in the 50% scenario. CONCLUSIONS/SIGNIFICANCE: The individual and public health benefits of these new guidelines are immense. The results show that by increasing the number of individuals on HAART save lives, it is cost averting, and it positively impacts society by decreasing the number of new HIV infections. Thus, public health community should consider incremental gains when considering guidelines and policy. PMID- 20539818 TI - Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. AB - BACKGROUND: The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses. METHODS AND FINDINGS: We performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR induced K65R mutation in subtype C viruses. CONCLUSIONS: This study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo. PMID- 20539819 TI - Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. AB - BACKGROUND: Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per) or Cryptochrome1 and 2 (Cry) are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Mice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. CONCLUSIONS/SIGNIFICANCE: Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor. PMID- 20539820 TI - The Effects of Peer Group Network Properties on Drug Use Among Homeless Youth. AB - The authors examine how the properties of peer networks affect amphetamine, cocaine, and injection drug use over 3 months among newly homeless adolescents, aged 12 to 20 in Los Angeles (n = 217; 83% retention at 3 months) and Melbourne (n = 119; 72% retention at 3 months). Several hypotheses regarding the effects of social network properties on the peer influence process are developed. Multivariate logistic regression analyses show that higher concentrations of homeless peers in networks at recruitment were associated with increased likelihood of amphetamine and cocaine use at 3-month follow-up. Higher concentrations of injecting peers were associated with increased risk of injection drug use 3 months later. Change in network structure over time toward increased concentrations of homeless peers was associated with increased risk of cocaine use and injecting. Higher density networks at baseline were positively associated with increased likelihood of cocaine and amphetamine use at 3 months. PMID- 20539822 TI - The Effects of Schema-Broadening Instruction on Second Graders' Word-Problem Performance and Their Ability to Represent Word Problems with Algebraic Equations: A Randomized Control Study. AB - The purpose of this study was to assess the effects of schema-broadening instruction (SBI) on second graders' word-problem-solving skills and their ability to represent the structure of word problems using algebraic equations. Teachers (n = 18) were randomly assigned to conventional word-problem instruction or SBI word-problem instruction, which taught students to represent the structural, defining features of word problems with overarching equations. Intervention lasted 16 weeks. We pretested and posttested 270 students on measures of word-problem skill; analyses that accounted for the nested structure of the data indicated superior word-problem learning for SBI students. Descriptive analyses of students' word-problem work indicated that SBI helped students represent the structure of word problems with algebraic equations, suggesting that SBI promoted this aspect of students' emerging algebraic reasoning. PMID- 20539821 TI - Targeted probes for cardiovascular MRI. AB - Molecular MRI plays an important role in studying molecular and cellular processes associated with heart disease. Targeted probes that recognize important biomarkers of atherosclerosis, apoptosis, necrosis, angiogenesis, thrombosis and inflammation have been developed. This review discusses the properties of chemically different contrast agents including iron oxide nanoparticles, gadolinium-based nanoparticles or micelles, discrete peptide conjugates and activatable probes. Numerous examples of contrast agents based on these approaches have been used in preclinical MRI of cardiovascular diseases. Clinical applications are still under investigation for some selected agents with highly promising initial results. Molecular MRI shows great potential for the detection and characterization of a wide range of cardiovascular diseases, as well as for monitoring response to therapy. PMID- 20539823 TI - The Changing Racial and Ethnic Composition of the US Population: Emerging American Identities. PMID- 20539825 TI - Estimation of Rigid-Body and Respiratory Motion of the Heart From Marker-Tracking Data for SPECT Motion Correction. AB - Motion of patients undergoing cardiac SPECT perfusion imaging causes artifacts in the acquired images which may lead to difficulty in interpretation. Our work investigates a technique of obtaining patient motion estimates from retro reflective markers on stretchy bands wrapped around the chest and abdomen of patients being imaged clinically. Motion signals obtained from the markers consist of at least two components, body motion (BM) and periodic motion (PM) due to respiration. We present a method for separating these components from the motion-tracking data of each marker, and then report a method for combining the BM estimated from chest markers to estimate the 6-degree-of-freedom (6-DOF) rigid body motion (RBM) of the heart. Motion studies of volunteers and patients are used to evaluate the methods. Illustrative examples of the motion of the heart due to patient body movement and respiration (upward creep) are presented and compared to estimates of the motion of the heart obtained directly from SPECT data. Our motion-tracking method is seen to give reasonable agreement with the motion-estimates from the SPECT data while being considerably less noisy. PMID- 20539824 TI - Are CB(1) Receptor Antagonists Nootropic or Cognitive Impairing Agents? AB - For more than a decade, a considerable amount of research has examined the effects of rimonabant (SR 141716) and other CB(1) receptor antagonists in both in vivo and in vitro models of learning and memory. In addition to its utility in determining whether the effects of drugs are mediated though a CB(1) receptor mechanism of action, these antagonists are useful in providing insight into the physiological function of the endogenous cannabinoid system. Several groups have reported that CB(1) receptor antagonists enhance memory duration in a variety of spatial and operant paradigms, but not in all paradigms. Conversely, disruption of CB(1) receptor signaling also impairs extinction learning in which the animal actively suppresses a learned response when reinforcement has been withheld. These extinction deficits occur in aversively motivated tasks, such as in fear conditioning or escape behavior in the Morris water maze task, but not in appetitively motivated tasks. Similarly, in electrophysiological models, CB(1) receptor antagonists elicit a variety of effects, including enhancement of long term potentiation (LTP), while disrupting long-term depression (LTD) and interfering with transient forms of plasticity, including depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). The collective results of the in vivo and in vitro studies employing CB(1) receptor antagonists, demonstrate that these receptors play integral roles in different components of cognitive processing. Functionally, pharmacological blockade of CB(1) receptors may strengthen memory duration, but interferes with extinction of learned behaviors that are associated with traumatic or aversive memories. PMID- 20539826 TI - Binational Substance Abuse Research and Internal Review Boards: Human Subject Risks and Suggestions for Protections. AB - Drug use research that involves transnational populations in their worksite nations and in their countries of origin requires special consideration for human subjects. These populations are exposed to similar, if not greater, research related risks than other vulnerable research subjects. If they are to be protected adequately, Internal Review Boards (IRBs) need to become familiar with transnational populations and the possible risks that their members face when participating in research that targets their drug use behaviors and practices. Addressed in this article are a number of challenges that IRBs in United States universities and research institutes encounter in assuring protections against possible research risks. Specific areas of concern are: the dearth of binational IRB reviews, IRB inexperience with transnational populations, mandatory written consent, limited research ethics training for researchers, the absence of a vulnerable population research advisory board, and the need for measures in case of a breach of confidentiality. The discourse of each one of these problem areas includes a recommendation for rectifying it. The article ends with five suggested measures that IRBs should consider in protecting transnational migrants from research related risks in the United States and in their homeland. The discussion of human subject problems and of the measures introduced to alleviate them are based on the author's experiences with preparing human subjects protocols for his ethnographic substance abuse research in both the United States and Mexico. PMID- 20539827 TI - Molecular Genetic Studies of Eating Disorders: Current Status and Future Directions. AB - We review association studies that have examined the genetic basis of eating disorders. Overall, findings suggest that serotonin, brain-derived neurotrophic factor, and estrogen genes may be important for the development of the disorders. These neuronal systems influence behavioral and personality characteristics (e.g., anxiety, food intake) that are disrupted in eating disorders. Future studies would benefit from larger sample sizes and inclusion of behavioral and personality covariates in analyses. Consideration of the mechanisms of genetic effects and interactions between genes and environment is also needed to extend conceptualizations of the genetic basis of these disorders. PMID- 20539828 TI - Analytical modeling of symmetry breaking in extraordinary optoconductance. AB - Extraordinary optoconductance (EOC) devices with symmetric leads have been shown to have a symmetric positional dependence when exposed to focused illumination. While advantageous for a position sensitive detector (PSD), this symmetric positional dependence, when the device is uniformly illuminated, leads to a minimization of the output voltage. Here, with the aid of a previously employed point charge model, we address two ways to break the symmetry and recover the output signal. The first is to impose uniform illumination but only on half the sample. This method has practical limitations as the device is miniaturized to the nanoscale. The second is via asymmetric placement of the voltage probes in a four-probe measurement. Crucial to the discussion is the effect of the surface charge density. Several ways of modeling the induced surface charge density are presented. Utilizing the above described approach, optimal asymmetric lead positions are found. PMID- 20539829 TI - Treatment retention among African-Americans in the Dane County Drug Treatment Court. AB - Drug treatment courts (DTCs) provide substance abuse treatment and case management services to offenders with substance use disorders as an alternative to incarceration. Studies indicate that African-Americans less frequently complete DTC programming. The current study analyzed data from the Dane County Drug Treatment Court (n = 573). The study ascertained factors associated with failure to complete treatment among African-American DTC participants. Significant factors were unemployment (p = 0.011), previous criminal history (p = 0.013), and, possibly, the presence of a cocaine use disorder (p = 0.064). Treatment plans for DTC participants should incorporate services addressing needs specific to African-Americans, who are over-represented in the U.S. correctional system. The current results indicate that employment, prior corrections involvement, and the presence of a cocaine use disorder may be specific issues to consider. PMID- 20539830 TI - Social Self-Reappraisal Therapy for Social Phobia: Preliminary Findings. AB - The recent psychopathology literature suggests that individuals with social phobia overestimate social standards and are deficient in setting and attaining social goals, have a negative perception of themselves as social objects and show heightened self-focused attention when confronted with social threat. They further overestimate the potential cost of a social encounter, experience their anxiety as uncontrollable and visible to others, view their social skills as inadequate, rely on safety behaviors and avoidance strategies to control their anxiety, and engage in post-event rumination. Traditional cognitive-behavior therapy does not adequately address all of these features of social phobia during treatment. We discuss here an enhanced version of cognitive-behavioral treatment for social phobia, which is specifically designed to address these factors. The results of an uncontrolled pilot study suggest that this new treatment may be more effective than traditional cognitive-behavioral therapy for social phobia. PMID- 20539831 TI - TUNABLE RING LASER BASED ON A SEMICONDUCTOR OPTICAL AMPLIFIER AT 1300 NM USING A SIMPLE WAVELENGTH SELECTION FILTER. AB - A simple, compact, and low cost tunable ring laser with a commercial semiconductor optical amplifier (SOA) was demonstrated. The tunable ring laser is based on an external wavelength filter cavity that is analogous with the Littman configuration with a diffraction grating, a mirror, and a simple slit. The unique structural advantage of this new system is that the slit is displaced to select a desired wavelength instead of tilting the mirror as in the Littman configuration. This allows easy control over the selected wavelength by the translating action of the slit. The full width half maximum (FWHM) wavelength turning range is 45 nm, and the wavelength resolution is about 2 pm. The demonstrated tunable ring laser has 2 mW output power. The side mode suppression ratios is 70-73 dB. PMID- 20539833 TI - Person Perception and Personality Pathology. AB - Studies of person perception (people's impressions and beliefs about others) have developed important concepts and methods that can be used to help improve the assessment of personality disorders. They may also inspire advances in our knowledge of the nature and origins of these conditions. Information collected from peers and other types of informants is reliable and provides a perspective that often differs substantially from that obtained using questionnaires and interviews. For some purposes, this information is quite useful. Much remains to be learned about the incremental validity (and potential biases) associated with data from various kinds of informants. PMID- 20539834 TI - Driving-Related Cognitive Performance in Older Adults with Pharmacologically Treated Cardiovascular Disease. AB - The objective of this study was to determine if older drivers with pharmacologically treated hypertension and/or heart disease demonstrate impaired performance on established driving related cognitive measures. Data regarding self-reported demographic variables (i.e., age, sex, race, income, mental and physical health diagnoses, and prescription drug use) and performance on driving related measures of cognitive function (i.e., Trail Making Test B; and Useful Field of View (UFOV(r) subtest 2) were gathered from 865 licensed drivers. No group cognitive performance differences were found among the treated hypertensives and the healthy control group, thus underscoring the importance of effective hypertension management. However, older adults with pharmacologically treated heart disease demonstrated poorer performance than older adults without heart disease on Trails B and UFOV(r) subtest 2. Although it is generally agreed that assessment and early intervention with regard to heart disease risk factors (i.e., cholesterol, tobacco smoking, obesity, etc.) beneficially affect physical health, the current results also indicate that addressing such risk factors prior to the development of heart disease may benefit cognitive function, as well. PMID- 20539835 TI - An efficient and accurate new method for locating the F3 position for prefrontal TMS applications. AB - The International 10-20 system is a method for standardized placement of electroencephalogram (EEG) electrodes. The 10-20 system correlates external skull locations with the underlying cortical areas. This system accounts for variability in patient skull size by using certain percentages of the circumference and distances between four basic anatomical landmarks. This 10-20 system has recently been used in transcranial magnetic stimulation (TMS) research for locating specific cortical areas. In the treatment of depression (and some types of pain), the desired placement of the TMS coil is often above the left dorsalateral prefrontal cortex (DLPFC) which corresponds to the F3 location given by the 10-20 system. However, for an administrator with little experience with the 10-20 system, the numerous measurements and calculations can be excessively time-consuming. Additionally, with more measurements comes more opportunity for human error. For this reason we have developed a new, simpler and faster way to find the F3 position using only three skull measurements. In this paper, we describe and illustrate the application of the new F3 location system, provide the formulas used in the calculation of the F3 position, and summarize data from 10 healthy adults. After using both the International 10-20 system and this new method, it appears that the new method is sufficiently accurate; however, future investigations may be warranted to conduct more in dept analyses of the method's utility and potential limitations. This system requires less time and training to find the optimal position for prefrontal coil placement and it saves considerable time compared to the 10-20 EEG system. PMID- 20539836 TI - A few remarks on "A capture-recapture approach for screening using two diagnostic tests with availability of disease status for the test positives only" by Bohning and Patilea. PMID- 20539837 TI - Behavioral activation interventions for well-being: A meta-analysis. AB - One of the most promising ways to increase well-being is to engage in valued and enjoyable activities. Behavioral activation (BA), an intervention approach most commonly associated with the treatment of depression, is consistent with this recommendation and can easily be adapted for non-clinical populations. This study reports on a meta-analysis of randomized controlled studies to examine the effect of BA on well-being. Twenty studies with a total of 1353 participants were included. The pooled effect size (Hedges's g) indicated that the difference in well-being between BA and control conditions at posttest was 0.52. This significant effect, which is comparable to the pooled effect achieved by positive psychology interventions, was found for non-clinical participants and participants with elevated symptoms of depression. Behavioral activation would seem to provide a ready and attractive intervention for promoting the well-being of a range of populations in both clinical and non-clinical settings. PMID- 20539838 TI - Optimal use of beta-blockers in high-risk hypertension: a guide to dosing equivalence. AB - Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP) levels>130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. beta-blockers are playing an increasingly important role in the management of hypertension in high-risk patients. beta-blockers are a heterogeneous class of agents, and this review presents the differences between beta-blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by beta-blockers are only effective if patients adhere to medication treatment long term. beta-blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients. PMID- 20539839 TI - Relationship between natriuretic peptides and echocardiography parameters in patients with poorly regulated type 2 diabetes. AB - This study evaluated the relationship between natriuretic peptide levels and a wide range of echocardiography parameters in a population of thirty-three patients with poorly regulated type 2 diabetes, and no known heart failure. Natriuretic peptides brain natriuretic peptide (BNP) and N-terminal prohormone BNP (NT-proBNP) were measured. Transthoracic echocardiography was performed and cardiac volumes and ejection fraction were measured. Doppler and tissue Doppler were measured and diastolic function was stratified according to recent guidelines. Very few echocardiography parameters were correlated with BNP or NT proBNP levels. However, left atrial end-systolic volume indexed for body surface area was correlated with natural logarithm (ln) BNP and ln NT-proBNP (r=0.62 and r=0.60; P<0.05). There were significant differences in ln BNP and ln NT-proBNP levels between those with normal and those with abnormal diastolic function (1.4 vs 3.1; P<0.001 and 3.4 vs 5.8; P<0.001). This study showed that very few echocardiography parameters were correlated with BNP or NT-proBNP levels in patients with poorly regulated type 2 diabetes, which in part contradicts previous studies in other diabetic populations. The exception was left atrial end systolic volume that showed a moderate correlation with BNP or NT-proBNP levels. There were significant differences in BNP and NT-proBNP levels between the group with normal left ventricular diastolic function and the group with abnormal diastolic function. PMID- 20539840 TI - Isolated spontaneous dissection of the celiac trunk in a patient with bicuspid aortic valve. AB - Isolated spontaneous dissection of celiac trunk is a rare entity. The spontaneous dissection of the visceral artery occurs without aortic dissection. The most consistent presenting symptom is acute onset abdominal pain. Complications consist of ischemia, aneurysm formation, and rupture. We report an exceptional case of an isolated spontaneous dissection of the celiac trunk which occurred in a 49 year old male with a previously undiagnosed bicuspid aortic valve (BAV). We also describe the classical appearance in different imaging modalities with a particular emphasis on multidetector computed tomography, and discuss the clinical manifestation and its relationship to BAV. PMID- 20539841 TI - Heart rate control with adrenergic blockade: clinical outcomes in cardiovascular medicine. AB - The sympathetic nervous system is involved in regulating various cardiovascular parameters including heart rate (HR) and HR variability. Aberrant sympathetic nervous system expression may result in elevated HR or decreased HR variability, and both are independent risk factors for development of cardiovascular disease, including heart failure, myocardial infarction, and hypertension. Epidemiologic studies have established that impaired HR control is linked to increased cardiovascular morbidity and mortality. One successful way of decreasing HR and cardiovascular mortality has been by utilizing beta-blockers, because their ability to alter cell signaling at the receptor level has been shown to mitigate the pathogenic effects of sympathetic nervous system hyperactivation. Numerous clinical studies have demonstrated that beta-blocker-mediated HR control improvements are associated with decreased mortality in postinfarct and heart failure patients. Although improved HR control benefits have yet to be established in hypertension, both traditional and vasodilating beta-blockers exert positive HR control effects in this patient population. However, differences exist between traditional and vasodilating beta-blockers; the latter reduce peripheral vascular resistance and exert neutral or positive effects on important metabolic parameters. Clinical evidence suggests that attainment of HR control is an important treatment objective for patients with cardiovascular conditions, and vasodilating beta-blocker efficacy may aid in accomplishing improved outcomes. PMID- 20539842 TI - An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog. AB - Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements. PMID- 20539843 TI - Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure. AB - For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively) testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF). It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP) levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA) classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia) for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology. PMID- 20539844 TI - Novel antiplatelet agents in the prevention of cardiovascular complications- focus on ticagrelor. AB - Atherothrombosis, thrombus formation as a result of atherosclerotic plaque rupture, is a major modern health problem, often underlying coronary artery disease, stroke, and peripheral arterial disease. After the treatment of an acute thrombotic episode, long-term therapy is warranted as a secondary prophylaxis of such events and their complications. Because of the importance of platelets' involvement in the initiation and propagation of thrombosis, antiplatelet drugs have come to the forefront of atherothrombotic disease treatment. Dual antiplatelet therapy of aspirin plus clopidogrel--the current standard--has its benefits, but it also has its limitations with regard to its pharmacologic properties and adverse effects. For these reasons, within the last decade or so, the investigation of novel antiplatelet agents has prospered. Here, we review the main pathways through which platelets participate in acute thrombosis and the interruption of these pathways by using novel antiplatelet agents, including P2Y12 receptor antagonists (the recently approved prasugrel, the probable next-in line ticagrelor, and others). The need for a more individualized patient therapy is evident; although most of the aforementioned pharmaceuticals have the potential to contribute to this, their clinical utility remains to be seen. PMID- 20539845 TI - Influence of demographic and metabolic variables on forearm blood flow and vascular conductance in individuals without overt heart disease. AB - PURPOSE: Vascular reactivity is involved in the regulation of vascular function either in normal conditions or in the pathophysiology of cardiovascular diseases. We tested the hypothesis that vascular reactivity evaluated by forearm blood flow may vary according to demographic and metabolic variables in a cohort of individuals without any evidence of heart disease after clinical examination. SUBJECTS AND METHODS: We studied 186 individuals (mean age 41.4 years, standard deviation 13.1 years; 95 (51%) men and 91 (49%) women. We investigated forearm blood flow and vascular conductance with venous occlusion plethysmography at baseline, during handgrip isometric exercise and during the recovery phase. Demographic and laboratory data were collected. Statistical analysis was performed with mixed linear models appropriate for repeated measurements. RESULTS: Mean forearm blood flow values in the different study conditions ranged between 1.7+/-0.47 mL.min(-1).100 mL(-1) of tissue and 2.82+/-1.13 mL.min(-1).100 mL(-1) of tissue. Forearm blood flow was higher in men than in women (P<0.005) and increased as the heart rate increased during handgrip maneuver (P<0.0001). Serum triglyceride levels were inversely related to forearm blood flow at baseline, during isometric exercise and recovery phase (P=0.0209). Body mass index was inversely related to forearm vascular conductance at baseline, during isometric exercise and recovery phase (P=0.0223). CONCLUSION: Our findings suggest that forearm blood flow and vascular conductance as a surrogate of the vascular function may be influenced by gender, heart rate, serum triglyceride levels and body mass index in individuals without overt heart disease. PMID- 20539847 TI - Health systems financing and the path to universal coverage. PMID- 20539848 TI - Prevention of bullying-related morbidity and mortality: a call for public health policies. PMID- 20539849 TI - Thailand's new condom crusade. PMID- 20539850 TI - Climate change: a creeping catastrophe. PMID- 20539851 TI - Network of cities tackles age-old problems. PMID- 20539852 TI - Reality check for American dream. PMID- 20539854 TI - Cardiovascular risk management and its impact on hypertension control in primary care in low-resource settings: a cluster-randomized trial. AB - OBJECTIVE: To evaluate a simple cardiovascular risk management package for assessing and managing cardiovascular risk using hypertension as an entry point in primary care facilities in low-resource settings. METHODS: Two geographically distant regions in two countries (China and Nigeria) were selected and 10 pairs of primary care facilities in each region were randomly selected and matched. Regions were then randomly assigned to a control group, which received usual care, or to an intervention group, which applied the cardiovascular risk management package. Each facility enrolled 60 consecutive patients with hypertension. Intervention sites educated patients about risk factors at baseline and initiated treatment with hydrochlorothiazide at 4 months in patients at medium risk of a cardiovascular event, according to a standardized treatment algorithm. Systolic blood pressure change from baseline to 12 months was the primary outcome measure. FINDINGS: The study included 2397 patients with baseline hypertension: 1191 in 20 intervention facilities and 1206 in 20 control facilities. Systolic and diastolic blood pressure decreased more in intervention patients than in controls. However, at 12 months more than half of patients still had uncontrolled hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg). Behavioural risk factors had improved among intervention patients in Nigeria but not in China. Only about 2% of hypertensive patients required referral to the next level of care. CONCLUSION: Even in low resource settings, hypertensive patients can be effectively assessed and managed in primary care facilities. PMID- 20539855 TI - Equity in maternal and child health in Thailand. AB - OBJECTIVE: To assess equity in health outcomes and interventions for maternal and child health (MCH) services in Thailand. METHODS: Women of reproductive age in 40 000 nationally representative households responded to the Multiple Indicator Cluster Survey in 2005-2006. We used a concentration index (CI) to assess distribution of nine MCH indicator groups across the household wealth index. For each indicator we also compared the richest and poorest quintiles or deciles, urban and rural domiciles, and mothers or caregivers with or without secondary school education. FINDINGS: CHILD UNDERWEIGHT (CI: -0.2192; P < 0.01) and stunting (CI: -0.1767; P < 0.01) were least equitably distributed, being disproportionately concentrated among the poor; these were followed by teenage pregnancy (CI: -0.1073; P < 0.01), and child pneumonia (CI: -0.0896; P < 0.05) and diarrhoea (CI: -0.0531; P < 0.1). Distribution of the MCH interventions was fairly equitable, but richer women were more likely to receive prenatal care and delivery by a skilled health worker or in a health facility. The most equitably distributed interventions were child immunization and family planning. All undesirable health outcomes were more prevalent among rural residents, although the urban-rural gap in MCH services was small. Where mothers or caregivers had no formal education, all outcome indicators were worse than in the group with the highest level of education. CONCLUSION: Equity of coverage in key MCH services is high throughout Thailand. Inequitable health outcomes are largely due to socioeconomic factors, especially differences in the educational level of mothers or caregivers. PMID- 20539856 TI - Survey of children accessing HIV services in a high prevalence setting: time for adolescents to count? AB - OBJECTIVE: To establish the proportion of adolescents among children infected with human immunodeficiency virus (HIV) in Zimbabwe who receive HIV care and support, and what clinic staff perceives to be the main problems faced by HIV infected children and adolescents. METHODS: In July 2008, we sent a questionnaire to all 131 facilities providing HIV care in Zimbabwe. In it we requested an age breakdown of the children (aged 0-19 years) registered for care and asked what were the two major problems faced by younger children (0-5 years) and adolescents (10-19 years). FINDINGS: Nationally, 115 (88%) facilities responded. In 98 (75%) that provided complete data, 196 032 patients were registered and 24 958 (13%) of them were children. Of children under HIV care, 33% were aged 0-4 years; 25%, 5-9 years; 25%, 10-14 years; and 17%, 15-19 years. Staff highlighted differences in the problems most commonly faced by younger children and adolescents. For younger children, such problems were malnutrition and lack of appropriate drugs (cited by 46% and 40% of clinics, respectively); for adolescents they concerned psychosocial issues and poor drug adherence (cited by 56% and 36%, respectively). CONCLUSION: Interventions for the large cohort of adolescents who are receiving HIV care in Zimbabwe need to target the psychosocial concerns and poor drug adherence reported by staff as being the main concerns in this age group. PMID- 20539857 TI - Priorities for research into human resources for health in low- and middle-income countries. AB - OBJECTIVE: To identify the human resources for health (HRH) policy concerns and research priorities of key stakeholders in low- and middle-income countries; to assess the extent to which existing HRH research addresses these concerns and priorities; and to develop a prioritized list of core research questions requiring immediate attention to facilitate policy development and implementation. METHODS: The study involved interviews with key informants, including health policy-makers, researchers and community and civil society representatives, in 24 low- and middle-income countries in four regions, a literature search for relevant reviews of research completed to date, and the assessment of interview and literature search findings at a consultative multinational workshop, during which research questions were prioritized. FINDINGS: Twenty-one research questions emerged from the key informant interviews, many of which had received little or no attention in the reviewed literature. The questions ranked as most important at the consultative workshop were: (i) To what extent do incentives work in attracting and retaining qualified health workers in underserviced areas? (ii) What is the impact of dual practice and multiple employment? and (iii) How can incentives be used to optimize efficiency and the quality of health care? CONCLUSION: There was a clear consensus about the type of HRH policy problems faced by different countries and the nature of evidence needed to tackle them. Coordinated action to support and implement research into the highest priority questions identified here could have a major impact on health worker policies and, ultimately, on the health of the poor. PMID- 20539858 TI - Local-level mortality surveillance in resource-limited settings: a case study of Cape Town highlights disparities in health. AB - OBJECTIVE: To identify the leading causes of mortality and premature mortality in Cape Town, South Africa, and its subdistricts, and to compare levels of mortality between subdistricts. METHODS: Cape Town mortality data for the period 2001-2006 were analysed by age, cause of death and sex. Cause-of-death codes were aggregated into three main cause groups: (i) pre-transitional causes (e.g. communicable diseases, maternal causes, perinatal conditions and nutritional deficiencies), (ii) noncommunicable diseases and (iii) injuries. Premature mortality was calculated in years of life lost (YLLs). Population estimates for the Cape Town Metro district were used to calculate age-specific rates per 100,000 population, which were then age-standardized and compared across subdistricts. FINDINGS: The pattern of mortality in Cape Town reflects the quadruple burden of disease observed in the national cause-of-death profile, with HIV/AIDS, other infectious diseases, injuries and noncommunicable diseases all accounting for a significant proportion of deaths. HIV/AIDS has replaced homicide as the leading cause of death. HIV/AIDS, homicide, tuberculosis and road traffic injuries accounted for 44% of all premature mortality. Khayelitsha, the poorest subdistrict, had the highest levels of mortality for all main cause groups. CONCLUSION: Local mortality surveillance highlights the differential needs of the population of Cape Town and provides a wealth of data to inform planning and implementation of targeted interventions. Multisectoral interventions will be required to reduce the burden of disease. PMID- 20539859 TI - Scaling up syphilis testing in China: implementation beyond the clinic. AB - China is experiencing a syphilis epidemic of enormous proportions. The regions most heavily affected by syphilis correspond to regions where sexually transmitted HIV infection is also a major public health threat. Many high-risk patients in China fail to receive routine syphilis screening. This missed public health opportunity stems from both a failure of many high-risk individuals to seek clinical care and a disconnect between policy and practice. New point-of care syphilis testing enables screening in non-traditional settings such as community organizations or sex venues. This paper describes the current Chinese syphilis policies, suggests a spatiotemporal framework (based on targeting high risk times and places) to improve screening and care practices, and emphasizes a syphilis control policy extending beyond the clinical setting. PMID- 20539860 TI - Stimulating the development of national Streptococcus suis guidelines in Viet Nam through a strategic research partnership. AB - PROBLEM: Streptococcus suis is a common cause of adult bacterial meningitis in Viet Nam, and possibly other parts of Asia, yet this disabling infection has been largely neglected. Prevention, diagnosis and treatment are relatively straightforward and affordable but, in early 2007, no national diagnostic, case management or prevention guidelines existed in Viet Nam. APPROACH: Enhanced detection of S. suis infections was established in 2007 as part of a collaborative research programme between the National Hospital for Tropical Diseases, a key national hospital with very close links to the Ministry of Health, and a research group affiliated with Oxford University based in Viet Nam. The results were reported directly to policy-makers at the Ministry of Health. LOCAL SETTING: Viet Nam is a low-income country with a health-care system that has seen considerable improvements and increased autonomy. However, parts of the system remain fairly centralized the Ministry of Health. RELEVANT CHANGES: Following the improved detection and reporting of S. suis cases, the Ministry of Health issued guidance to all hospitals in Viet Nam on the clinical and laboratory diagnosis, treatment and prevention of S. suis. A public health laboratory diagnostic service was established at the National Institute of Hygiene and Epidemiology and training courses were conducted for clinicians and microbiologists. Ministry of Health guidance on surveillance and control of communicable diseases was updated to include a section on S. suis. LESSONS LEARNT: Research collaborations can efficiently inform and influence national responses if they are well positioned to reach policy-makers. PMID- 20539861 TI - Sharing health data: good intentions are not enough. AB - Epidemiologists and public health researchers are moving very slowly in the data sharing revolution, and agencies that maintain global health databases are reluctant to share data too. Once investments in infrastructure have been made, recycling and combining data provide access to maximum knowledge for minimal additional cost. By refusing to share data, researchers are slowing progress towards reducing illness and death and are denying a public good to taxpayers who support most of the research. Funders of public health research are beginning to call for change and developing data sharing policies. However they are not yet adequately addressing the obstacles that underpin the failure to share data. These include professional structures that reward publication of analysis but not of data, and funding streams and career paths that continue to undervalue critical data management work. Practical issues need to be sorted out too: how and where should data be stored for the long term, who will control access, and who will pay for those services? Existing metadata standards need to be extended to cope with health data. These obstacles have been known for some time; most can be overcome in the field of public health just as they have been overcome in other fields. However no institution has taken the lead in defining a work plan and carving up the tasks and the bill. In this round table paper, we suggest goals for data sharing and a work plan for reaching them, and challenge respondents to move beyond well intentioned but largely aspirational data sharing plans. PMID- 20539862 TI - Publishing research data on a professional basis. PMID- 20539863 TI - Sharing data for public health: where is the vision? PMID- 20539864 TI - Sharing health data: developing country perspectives. PMID- 20539865 TI - Data sharing: reaching consensus. PMID- 20539866 TI - Linking health to microfinance to reduce poverty. PMID- 20539867 TI - Is there a role for user charges? Thoughts on health system reform in Armenia. PMID- 20539868 TI - Women and children first: an appropriate first step towards universal coverage. PMID- 20539869 TI - Taskforce on Innovative International Financing for Health Systems: showing the way forward. PMID- 20539870 TI - Taskforce on Innovative International Financing for Health Systems: what next? PMID- 20539871 TI - Further research required to determine link between khat consumption and driver impairment. PMID- 20539872 TI - Dissociation of copper(II) ternary complexes containing cystine. AB - The collision-induced dissociations are reported for Cu(II) complexes containing 1,4,7-triazacyclononane (tacn) as the auxiliary ligand and a peptide containing one cystine residue. For six of the complexes examined, cleavage of the S-S bond in the peptide was the dominant fragmentation pathway. The exceptions were for complexes containing the largest peptides, (GlyCys'Gly)(2) and (GlyGlyCys')(2) (Cys' = NHCH(CH(2)S)CO, one half of the cystine residue; terminal H and OH are implicit), for which proton transfer to the auxiliary ligand was the major channel. Cleavage of the C-S bond was observed, but was a minor channel for all complexes. The radical cation (Cys')(2)(*+) was not observed although the complementary ion [Cu(I)(tacn)](+) was present in moderate abundance. Density functional calculations (at B3LYP/6-311++G(d,p)) gave low barriers to fragmentation of (Cys')(2)(*+) by homolytic fission of the C-S bond of the canonical ion (barrier 16.5 kcal mol(-1)) and of the structure at the global minimum, a captodative ion (barrier 17.2 kcal mol(-1)). Peptide radical cations (GlyCys')(2)(*+), (GlyCys'Gly)(2)(*+), (GlyGlyCys')(2)(*+) and (GlyCys'(Cys')Gly)(*+) were observed in low abundances; the first two of these ions dissociated predominantly by fragmentation of the S-S bond, while the other two preferentially cleaved at an amide bond. No cleavage of the C-S bond was observed for the peptide radical cations. Density functional calculations at B3LYP/6-31G(d) established that the cystine in [Cu(II)(tacn)(Cys')(2)](*2+) is bound as a zwitterion through the carboxylate anion with the proton on the distal amino group. The lowest energy complex containing a canonical cystine, coordinated through the carbonyl oxygen and the amino group of the same Cys', is 8.3 kcal mol(-1) higher in enthalpy. PMID- 20539874 TI - Switching off FRET by analyte-induced decomposition of squaraine energy acceptor: A concept to transform 'turn off' chemodosimeter into ratiometric sensors. AB - FRET cassette-type sensors, SN-1 and SN-2, which contain two naphthalimide donors and a squaraine acceptor, have been developed on the concept of switching off FRET through removing the spectral overlap by the analyte-induced decompositions of acceptor chromophore. SN-2 shows sensitive responses to fluoride anion and cyanide through both naked-eye detectable colour changes and ratiometric fluorescence changes. As the first example, SN-2 confirms that transformation of the common 'turn-off' chemodosimeter into ratiometric sensors can be realized conveniently based on the novel 'switching FRET off' approach. PMID- 20539875 TI - Structural similarities in C(s)(16)-C86 and C(2)(17)-C86. AB - We report an analysis of the similar structures of C(s)(16)-C(86) and C(2)(17) C(86) from a single crystal X-ray diffraction study of C(s)(16)/C(2)(17)-C(86) x (nickel octaethylporphyrin) x 2toluene. PMID- 20539873 TI - Allosteric regulation of protease activity by small molecules. AB - Proteases regulate a plethora of biological processes. Because they irreversibly cleave peptide bonds, the activity of proteases is strictly controlled. While there are many ways to regulate protease activity, an emergent mechanism is the modulation of protease function by small molecules acting at allosteric sites. This mode of regulation holds the potential to allow for the specific and temporal control of a given biological process using small molecules. These compounds also serve as useful tools for studying protein dynamics and function. This review highlights recent advances in identifying and characterizing natural and synthetic small molecule allosteric regulators of proteases and discusses their utility in studies of protease function, drug discovery and protein engineering. PMID- 20539876 TI - Intrinsic activity and poisoning rate for HCOOH oxidation on platinum stepped surfaces. AB - Pulsed voltammetry has been used to study formic acid oxidation on platinum stepped surfaces to determine the kinetics of the reaction and the role of the surface structure in the reactivity. From the current transients at different potentials, the intrinsic activity of the electrode through the active intermediate reaction path (j(theta = 0)), as well as the rate constant for the CO formation (k(ads)) have been calculated. The kinetics for formic acid oxidation through the active intermediate reaction path is strongly dependent on the surface structure of the electrode, with the highest activity found for the Pt(100) surface. The presence of steps, both on (100) and (111) terraces, does not increase the activity of these surfaces. CO formation only takes place in a narrow potential window very close to the local potential of zero total charge. The extrapolation of the results obtained with stepped surfaces with (111) terraces to zero step density indicates that CO formation should not occur on an ideal Pt(111) electrode. Additionally, the analysis of the Tafel slopes obtained for the different electrodes suggests that the oxidation of formic acid is strongly affected by the presence of adsorbed anions, hydrogen and water. PMID- 20539877 TI - Impacts of sampling design and estimation methods on nutrient leaching of intensively monitored forest plots in the Netherlands. AB - Element fluxes through forest ecosystems are generally based on measurements of concentrations in soil solution at regular time intervals at plot locations sampled in a regular grid. Here we present spatially averaged annual element leaching fluxes in three Dutch forest monitoring plots using a new sampling strategy in which both sampling locations and sampling times are selected by probability sampling. Locations were selected by stratified random sampling with compact geographical blocks of equal surface area as strata. In each sampling round, six composite soil solution samples were collected, consisting of five aliquots, one per stratum. The plot-mean concentration was estimated by linear regression, so that the bias due to one or more strata being not represented in the composite samples is eliminated. The sampling times were selected in such a way that the cumulative precipitation surplus of the time interval between two consecutive sampling times was constant, using an estimated precipitation surplus averaged over the past 30 years. The spatially averaged annual leaching flux was estimated by using the modeled daily water flux as an ancillary variable. An important advantage of the new method is that the uncertainty in the estimated annual leaching fluxes due to spatial and temporal variation and resulting sampling errors can be quantified. Results of this new method were compared with the reference approach in which daily leaching fluxes were calculated by multiplying daily interpolated element concentrations with daily water fluxes and then aggregated to a year. Results show that the annual fluxes calculated with the reference method for the period 2003-2005, including all plots, elements and depths, lies only in 53% of the cases within the range of the average +/-2 times the standard error of the new method. Despite the differences in results, both methods indicate comparable N retention and strong Al mobilization in all plots, with Al leaching being nearly equal to the leaching of SO(4) and NO(3) with fluxes expressed in mol(c) ha(-1) yr(-1). This illustrates that Al release, which is the clearest signal of soil acidification, is mainly due to the external input of SO(4) and NO(3). PMID- 20539878 TI - A novel polyoxochromium borophosphate with new 6-membered ring crown-shaped clusters. AB - A novel chromium borophosphate with anionic clusters has been synthesized using boric acid as flux. X-ray diffraction analysis on a single crystal reveals that its structure comprises of crown-shaped 6-membered ring clusters [NaCr(8)B(4)P(12)O(60)H(8)](15-), which are built from [Cr(4)O(18)] groups, [BP(2)O(10)] anions and PO(4) tetrahedra with Na(+) cations encapsulated in the clusters. Magnetic investigation showed strong antiferromagnetic interactions between Cr(3+)-Cr(3+) dimers at low temperature. PMID- 20539879 TI - Amino/guanidino-functionalized N-(pyrrolidin-2-ethyl)glycine-based pet-PNA: design, synthesis and binding with DNA/RNA. AB - The N-(pyrrolidin-2-ethyl) glycine-based PNA (pet-PNA) backbone, with 4-amino or 4-guanidino-functionalized pyrrolidine ring, confers constrained conformational flexibility on aegPNA. The oligomers bind to the target DNA and RNA sequences with increased sequence specificity and antiparallel versus parallel orientation selectivity. The easy post-synthetic guanidination gives very good access to the positively charged PNA oligomers. PMID- 20539880 TI - Structure of the O-antigen of Acinetobacter lwoffii EK30A; identification of d homoserine, a novel non-sugar component of bacterial polysaccharides. AB - We established a peculiar structure of the O-specific polysaccharide (O-antigen) of a psychrotrophic strain of Acinetobacter lwoffii, EK30A, isolated from a 1.6 1.8 million-year-old Siberian permafrost subsoil sediment sample. The polysaccharide was released by mild acid degradation of the lipopolysaccharide and studied using chemical analyses, Smith degradation, (1)H and (13)C NMR spectroscopy and mass spectrometry. It was found to contain d-homoserine, which is N-linked to 4-amino-4,6-dideoxy-d-glucose (Qui4N) and is N-acylated itself with acetyl in about half of the repeating units or (S)-3-hydroxybutanoyl group in the other half. The following is the structure of the tetrasaccharide repeating unit of the polysaccharide: -->3)-beta-d-Quip4NAcyl-(1-->6)-alpha-d Galp-(1-->4)-alpha-d-GalpNAc-(1-->3)-alpha-d-FucpNAc-(1--> where Acyl stands for either N-acetyl- or N-[(S)-3-hydroxybutanoyl]-d-homoseryl. PMID- 20539881 TI - Interchromophore orientation scaffolding by m-terphenyl oxacyclophanes. AB - Modular oxacyclophanes featuring m-terphenyl units scaffold inter-pi-system interaction in face-to-face stacked or orthogonal orientations, leading to distinct photophysical properties. PMID- 20539882 TI - Synthesis and evaluation of a fluorogenic reagent for proteomic studies: 7-fluoro N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-F). AB - Since the successful selection of fluorogenic derivatization reagent 7-chloro-N [2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl) as a component of a novel method (FD-LC-MS/MS method) for proteomics studies, a further reactive reagent has been required to obtain more species of proteins: DAABD-Cl reacts with only thiol moieties of proteins to give fluorescence at 505 nm with excitation at 395 nm. Here, we synthesized reagent 7-fluoro-N-[2 (dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide, DAABD-F, having a 7 fluorine moiety instead of the 7-chlorine moiety in DAABD-Cl, expecting it to exhibit high reactivity to amino moieties of proteins. As expected, the reaction rates of low molecular thiols with DAABD-F were 50 times higher than those with DAABD-Cl. DAABD-F was able to react with the amino moiety of a low molecular amine, beta-alanine, producing fluorescence at 554 nm with excitation at 432 nm. The reaction with DAABD-F of a typical model protein, bovine serum albumin (BSA), needed a lower amount of reagent (DAABD-F) than DAABD-Cl to produce a single fluorescent derivative (fluorescence at 495 nm with excitation at 390 nm) that was demonstrated to be solely a cysteinyl residue modified product. A derivatization reaction with DAABD-F towards a soluble extract of a normal human mammary epithelial cell (HMEC) resulted in the same fluorescent protein profiles as those with DAABD-Cl except one (AHNAK nucleoprotein isoform1) that was produced by the derivatization at a lysinyl residue (4761Lys) and was identified according to the usual procedure of isolation and tryptic digestion of the fluorescent protein peak on the chromatogram and final LC-MS/MS with a database searching algorithm. PMID- 20539883 TI - Investigation of the influence of surface defects on peptide adsorption onto carbon nanotubes. AB - The number of possible applications that interface carbon nanotubes with biological systems is rapidly growing, and with these advances comes a need for characterisation of such interfaces. Molecular simulation is one such approach, and many recent examples exist where simulation has been used to investigate the atomic-scale details of the interface between biomolecules and carbon nanotubes (CNTs). However, these studies have been confined to the realm of pristine CNTs. Here, we build on our previous work and use molecular simulation to consider the adsorption on to defective CNTs of peptide sequences known to bind to the CNT surface [Wang et al., Nat. Mater., 2003, 2, 196]. Two types of idealised chemical defects are considered, along with two different distributions of these defects on the CNT surface. We find that the densely-packed defect distribution yields relatively little engagement with the peptides. Spreading the defects out along the nanotube increases the degree of contact with the peptide, without affecting the binding strength of the peptide-CNT interface in most cases. Both types of defect tend to act more as physical barriers to peptide mobility than as a source of attractive interactions. The resulting physical confinement of the peptide did not affect all sequences in the same way; two of the four sequences were found to be more sensitive to the presence of defects. This study has implications for the practical usage of CNTs in a wide range of biological contexts, where well dispersed, functionalised nanotubes are required. PMID- 20539884 TI - Trace detection of non-uniformly distributed analytes on surfaces using mass transfer and large-area desorption electrospray ionization (DESI) mass spectrometry. AB - Ambient ionization methods such as desorption electrospray ionization (DESI) allow the analysis of chemicals adsorbed at surfaces without the need for sample (or surface) pretreatment. A limitation of current implementations of these ionization sources is the small size of the area that can be sampled. This makes examination of surfaces of large areas time-consuming because of the need to raster across the surface. This paper describes a DESI source that produces a spray plume with an effective desorption/ionization area of 3.6 cm(2), some 200 times larger than given by conventional DESI sources. Rhodamine 6G and several drugs of abuse (codeine, heroin and diazepam) were used to demonstrate the ability to use large-area DESI MS to perform rapid (a few seconds) representative sampling of areas of the order of several square centimetres without scanning the probe across the surface. The large area ion source displayed high sensitivity (limits of detection in the high nanogram range) and high reproducibility (approximately 20 to 35% relative standard deviation). The rapid analysis of even larger surfaces (hundreds of cm(2)) for traces of explosives is possible using a sorbent surface wipe followed by large-area DESI interrogation performed directly on the wipe material. The performance of this mass transfer dry wipe method was examined by determination of the limits of detection of several explosives. Surfaces with different topographies and compositions were also tested. Using this method, absolute limits of detection observed for HMX and RDX from plastic surfaces and skin were found to be as low as 10 ng cm(-2). The concentration of residue from large surface areas in this technique allowed the detection of 100 ng of explosives from surfaces with areas ranging from 1.00 x 10(3) cm(2) to 1.40 x 10(4) cm(2). PMID- 20539885 TI - Alpha,beta-D-CNA preorganization of unpaired loop moiety stabilizes DNA hairpin. AB - DNA hairpin structures can be stabilized by introduction of constraint on the sugar phosphate backbone within the unpaired loop moiety by means of dinucleotides locked with an alpha torsion angle in gauche(+) configuration. PMID- 20539886 TI - Transformation of a 1D to 3D coordination polymer mediated by low temperature lattice solvent loss. AB - The desolvation of lattice methanol from between the 1D chains in {[Cu(4,4' bipyridine)(ccnm)(2)].4MeOH} (ccnm = carbamoylcyanonitrosomethanide) under ambient conditions, a weight loss of 22.4%, results in a solid state conversion to the 3D network [Cu(4,4'-bipyridine)(ccnm)(2)]. PMID- 20539887 TI - On the conveyance of angular momentum in electronic energy transfer. AB - When electronic excitation transfer occurs, it is of considerable interest to establish whether angular momentum can also be conveyed in the process. The question is prompted by a consideration that when the participating chromophores are atoms, ions, or molecular systems having high local symmetry, the electronic excited states that are involved are generally characterized not only by energy, but by angular momentum properties. Moreover, it is known that electron spin can be communicated between quantum dot exciton states. Resolving the general issue entails an electrodynamic representation exploiting irreducible tensor methods, the analysis being illustrated by application to energy transfer associated with a variety of multipolar transitions. The results exhibit novel connections between an angular momentum content of the electromagnetic coupling and a strongly varying distance dependence. It is concluded that the communication of angular momentum does not in general map unambiguously between a donor and energy acceptor. PMID- 20539888 TI - Electronic structure changes in cobalt phthalocyanine due to nanotube encapsulation probed using resonant inelastic X-ray scattering. AB - The electronic structure of cobalt phthalocyanine (CoPc) changes upon encapsulation inside multi-walled carbon nanotubes (CoPc@MWNT), as detected in this research using Co-K-edge X-ray absorption near-edge structure spectroscopy (XANES) and Co-Kalpha(1) resonant inelastic X-ray scattering (RIXS). The CoPc molecules are no longer planar once inside the nanotubes, and the molecular symmetry is found to change upon encapsulation from D(4h) to C(4v) symmetry. This change of symmetry increases the amount of p-d orbital mixing, which is seen in the spectra as a change in peak intensity. Energy shifts are also seen between CoPc and CoPc@MWNT, showing that Co in the encapsulated species is more oxidized due to electron donation from the phthalocyanine molecule to the surrounding nanotube. Trends seen in the spectra between CoPc and CoPc@MWNT can be calculated using density functional theory (DFT), which shows the molecular orbitals involved in different spectral features. PMID- 20539889 TI - Molecular self-assembly in a model amphiphile system. AB - The physical origin of the large and negative excess entropy of mixing of alcohols and water remains controversial. In contrast to standard explanations that evoke concepts of water structuring, recent work has shown that, at ambient conditions, it can be quantitatively explained in terms of molecular scale partial demixing of the two components. Here, we estimate the negative excess entropy (DeltaS(E)) of aqueous methanol at low temperature and high pressure using experimentally-derived structural data and a recently introduced cluster model. On cooling to 190 K the cluster sizes increase, but the change in DeltaS(E), which according to this method of calculation depends on the surface area to volume ratio of the clusters, is not significant, suggesting that the topology of the clusters must change with decreased temperature. On compression the cluster sizes also increase, and DeltaS(E) is now positive, suggesting an even more pronounced change in cluster topology with increased pressure. This work suggests that it is the amphiphilic nature of a molecule that determines aggregation and self-assembly processes in aqueous solution. The results therefore give useful insight into the processes of cold and pressure denaturation of proteins. PMID- 20539890 TI - Solubility of alkanes, alkanols and their fluorinated counterparts in tetraalkylphosphonium ionic liquids. AB - We investigated the mutual solubility of mixtures of phosphonium-based ionic liquids with alkanes, alkanols, fluorinated alkanes and fluorinated alkanols. The solubilities of other solute molecules like water, formamide, 1,4-dioxane, benzene, and dimethylsulfoxide were also tested. Whenever possible, the corresponding temperature-composition (T-x) phase diagrams at atmospheric pressure were built from cloud-point temperature determinations. The influence of the size of the solute was tested with binary mixtures of trihexyl(tetradecyl)phosphonium acetate, [P(6 6 6 14)][Ac], with hexane, decane or tetradecane. The influence of the anion of the ionic liquid, namely acetate, [Ac], bis-[(trifluoromethyl)sulfonyl]imide, [Ntf(2)], trifluoromethanesulfonate, [Otf], and dicyanamide, [dca], on the solubility of the ionic liquids in hexane was also studied. For the ionic liquid [P(6 6 6 14)][Ntf(2)] the liquid-liquid phase diagrams were determined with different solutes-alkanes, perfluoroalkanes, partially fluorinated alkanes, and partially fluorinated alkanols-with the aim of analysing the solute-solvent interactions. A comparison of the phase behaviour of solutions containing phosphonium-based ionic liquids and 1-alkyl-3 methylimidazolium based ionic liquids, including a discussion of their different morphologies at a structural level, is also provided. It was found that fluorination of the aliphatic chains of organic compounds can be used as an effective way to control the solubility limits of these compounds in phosphonium- or imidazolium-based ionic liquids, both in terms of concentration and temperature. PMID- 20539891 TI - Infrared spectroscopy of the alanine dipeptide analog in liquid water with DFT MD. Direct evidence for P(II)/beta conformations. AB - Following our previous work [J. Phys. Chem. B. Lett., 2009, 113, 10059], DFT based molecular dynamics (DFTMD) simulations of 2-Ala peptide (i.e. Ac-Ala-NHMe dialanine peptide analog with methyl group caps at the extremities) immersed in liquid water at room temperature are reported. Our goal here is the theoretical calculation of the infrared spectrum of aqueous 2-Ala, in order to provide a definitive understanding of the average conformation adopted by this peptide in the liquid phase, taking into account solute and solvent at the same theoretical level of representation. We find that the experimental Amide I-II band predominantly results from a mixture of partially unfolded P(II) and unfolded beta conformational equilibrium of aqueous 2-Ala at room temperature. PMID- 20539892 TI - An in silico analysis of microRNAs: mining the miRNAome. AB - Systematic analysis of literature- and experimentally-derived datasets using text mining with ontological enrichment and network modeling revealed global trends in the microRNA (miRNA) interactome. A total of 756 unique miRNAs were resolved from PubMed abstracts and 1165 direct relationships between 270 miRNAs and 581 genes were identified as phrase groups using semantic search techniques. These miRNA:gene interactions were built into a bipartite network (the miRNAome) which displays scale-free degree distribution. Functional classification of miRNA target genes using PANTHER revealed 189 distinct molecular functions, with significant enrichment of nucleic acid binding, transcription and protein phosphorylation. Pathway analysis revealed a network of 176 miRNAs linked to 368 OMIM disorders via their target genes, which are enriched (p = 0.0047) for disease-associated SNP variations. Reference to a database of drug targets revealed that 24.8% of all published miRNA-targets are targets for drug development programs, while a sub-set (18.2%) are targets for FDA-approved drugs. Consistent with topological analysis of the miRNA-disease network, the most prevalent class of FDA-approved drugs is anti-neoplastic agents against published miRNA-target genes. Linking miRNAs to biological process and diseases reveals distinct co-regulation of phenotypes that could aid in understanding the role miRNA-based gene regulation plays in biological phenomena. PMID- 20539893 TI - Recent advances in fluorescent and colorimetric conjugated polymer-based biosensors. AB - Conjugated polymers recently have drawn much attention as an emerging sensory material due to their meritorious signal amplification, convenient optical detection, readily tunable properties, and easy fabrication. We review the molecular design principles of sensory conjugated polymer recognition events, which can trigger conformational change of the conjugated polymer, induce intermolecular aggregation, or change the distance between the conjugated polymer as an energy donor and the reporter dye molecule as an energy acceptor. These recognition/detection mechanisms result in mainly three types of measurable signal generation: turn on or turn off fluorescence, or change in either visible color or fluorescence emission color of the conjugated polymer. In this article, we highlight recent advances in fluorescent and colorimetric conjugated polymer based biosensors. PMID- 20539894 TI - Self-organized spiral columns in laterally grafted rods. AB - Attachment of a flexible coil on the mid-part of a rigid rod block generates T shaped rod-coil block molecules that self-assemble into a stepped column. These layers, in turn, self-curve into a spiral column with tunable core structure in the solid state. PMID- 20539895 TI - Indicator displacement assays for amino acids using Ni-NTA tethered to PAMAM dendrimers on controlled pore glass. AB - PAMAM dendrimer monolayers, immobilized on glass and modified with Ni(II)-NTA moieties at the termini, show generational dependent responses as histidine selective sensors via indicator displacement assays. PMID- 20539896 TI - Three-dimensional large-scale microfluidic integration by laser ablation of interlayer connections. AB - Multilayer Soft Lithography (MSL) is a robust and mature fabrication technique for the rapid prototyping of microfluidic circuits having thousands of integrated valves. Despite the success and wide application of this method, it is fundamentally a planar fabrication technique which imposes serious design constraints on channel routing, feature density, and fluid handling complexity. We present here methods and related instrumentation to remove these limitations by combining the advantages of MSL processing with laser micromachining using a CO(2) laser ablation system. This system is applied to both the dense integration of layer-layer interconnects and the direct writing of microchannels. Real-time image recognition and computer control allow for robust wafer-scale registration of laser ablation features with moulded channel structures. Ablation rates of up to 8 Hz are achieved with positional accuracy of approximately 20 microm independent of mechanical distortions in the elastomer substrate. We demonstrate these capabilities in the design and fabrication of a production scale multi laminate micromixer that achieves sub-millisecond mixing of two streams at flow rates up to 1 mL min(-1). The marriage of laser micromachining with MSL-based valve integration allows for high-yield fabrication of topologically complex microfluidic circuits having thousands of layer-layer interconnects and integrated valves. PMID- 20539897 TI - The unusual coordination abilities of the peptides with betaXaaHisGlyHis sequence. The influence of structural modification of the peptide chain on the copper(II) binding. AB - The coordination abilities of tetrapeptides containing beta-amino acids towards Cu(II) ions are presented. The studied tetrapeptides were: Ac-betaAlaHisGlyHis, betaAlaHisGlyHis, Ac-betaAspHisGlyHis, betaAspHisGlyHis, Ac-betaAspHisGly-dHis and betaAspHisGly-dHis. Thorough potentiometric titrations were carried out to establish the stoichiometry of the resulting metal-ligand complexes and the role of free -alphaCOO(-) side chain group in metal binding. The copper(II) coordination mode of the complexes was investigated by performing detailed spectroscopic analyses (UV-Vis, EPR, CD) in strict correlation with potentiometric measurements. PMID- 20539898 TI - Asymmetric PPCys: strongly fluorescing NIR labels. AB - By a stepwise synthesis strategy biofunctionalized Pyrrolopyrrole Cyanines (PPCy) with an asymmetric substitution pattern were obtained. These exhibit extremely strong and narrowband NIR absorption and fluorescence. Internalization of a peptide bound PPCy is demonstrated using live cell microscopy. PMID- 20539899 TI - Visual and light scattering spectrometric detections of melamine with polythymine stabilized gold nanoparticles through specific triple hydrogen-bonding recognition. AB - Melamine can be sensitively detected in aqueous medium through its selective interaction with polythymine (polyT(n)) modified gold nanoparticles (AuNPs) by forming triple H-bonds, which results in aggregation of the polyT(n)-stabilized AuNPs, displaying variations of localized plasmon resonance features such as colour change from red to purple and enhanced localized surface plasmon resonance light scattering (LSPR-LS) signals. PMID- 20539900 TI - Micro-/nano-patterning of DNA and rapid readout with SERS tags. AB - Hybridisation of oligonucleotide micro- and nano-structures, formed using far- and near-field optical lithography, with Raman dye-labelled silver nanoparticles functionalised with complementary oligonucleotides yields striking contrast, attributed to Raman "hot-spot" formation, and enables rapid, convenient read-out by Raman microscopy. PMID- 20539901 TI - Structural and compositional tuning of layered subnitrides; new complex nitride halides. AB - New quaternary bimetallic nitride halides and the first examples of quintinary nitride mixed halides have been synthesised in the phase system Ca - Sr - N - Cl Br. The variation in structure with composition has been investigated by powder X-ray and powder neutron diffraction techniques. All compounds crystallise in the R-3m spacegroup, with the anti-alpha-NaFeO(2) structure. The layered compounds exhibit unprecedented coexistent disorder of both cations and anions in which only nitride solely occupies a discrete crystallographic position. [N(Ca,Sr)(2)](+) layers alternate with halide ions (Cl, Br)(-), which fill the octahedral voids between the positively charged sheets. A dual cationic-anionic substitution approach allows all aspects of the anisotropic structure to be controlled, including the thickness of the ionic layers and the [N(Ca,Sr)(2)](+) interlayer spacing. PMID- 20539902 TI - Evaluation of a new automated panel of assays for the detection of anti PF4/heparin antibodies in patients suspected of having heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin treatment; the prognosis depends on early and accurate diagnosis, and prompt start of alternative anticoagulants. Because of high sensitivity, the commercially available immunologic assays are widely used, though not suited to be run on single samples and with a turnaround time of 2-3 hours. We evaluated two new, rapid, automated, semi-quantitative chemiluminescent immunoassays in HIT suspected patients: HemosIL AcuStar HIT-IgG(PF4-H) (specific for IgG anti PF4/heparin antibodies) and HemosIL AcuStar HIT-Ab(PF4-H) (detecting IgG, IgM and IgA anti-PF4/heparin antibodies) (both from Instrumentation Laboratory). A total of 102 patients with suspected HIT were included; HIT was diagnosed in 17 (16.7%). No false negative cases were observed using either the HemosIL AcuStar HIT-IgG(PF4-H) or the HIT-Ab(PF4-H) assay (sensitivity and negative predictive values = 100%; negative likelihood ratios <0.01). The specificity was higher for the HemosIL AcuStar HIT-IgG(PF4-H) in comparison with that of the HemosIL AcuStar HIT-Ab(PF4-H) (96.5% vs. 81.2%). Higher values of the HemosIL AcuStar HIT-IgG(PF4 H) were associated with increased probability of HIT. Patients with confirmed HIT and thrombotic complications had significantly higher levels of HemosIL AcuStar HIT-IgG(PF4-H) than those without thrombotic complications. The HemosIL AcuStar HIT-IgG(PF4-H) and HIT-Ab(PF4-H) assays showed a very high sensitivity, and therefore they can reliably be used to rule out HIT in suspected patients. The diagnostic specificity was greatly increased by using the HemosIL AcuStar HIT IgG(PF4-H). Both the assays are reproducible (CVs <6%), rapid (turnaround time 30 minutes), automated, and semi-quantitative, and they can be run for single sample testing. PMID- 20539903 TI - The in vitro effects of niacin on platelet biomarkers in human volunteers. AB - Niacin is a natural pyridine derivative, proven to favorably modulate the blood lipid profile by increasing levels of high-density lipoprotein (HDL) cholesterol, and by reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and Lp (a) lipoprotein concentrations. Considering that platelet activity is important in predicting vascular outcomes, and that HDL heavily constitutes platelet cellular membranes, we sought to evaluate the effect of niacin on human platelet activity indices. The blood obtained from 30 aspirin naive volunteers was preincubated with escalating concentrations of niacin in vitro. Platelet tests included whole blood and plasma aggregometry, rapid cartridge-based analyser, expression of major surface receptors by flow cytometry, and plasma prostaglandins by ELISA. Preincubation of blood with niacin at 0.3, 1.0 and 3.0 mM resulted in significant inhibition of maximal adenosine diphosphate (ADP)- (p=0.03), and collagen-induced platelet aggregation (p=0.01), and reduced activity by VerifyNow (p=0.007) bedside analyser. Surface platelet PAR-1 (MoAb WEDE-15; p=0.04), and vitronectin (CD51/CD61; p=0.02) receptors were up-regulated. Niacin was associated with a two- to three-fold increase of thromboxane B2, prostaglandins D2, and E2. Formation of platelet-monocyte microparticles (CD14+CD151), and expression of PECAM-1 (CD31), thrombospondin (CD36), GP IIb/IIIa (CD41a) antigen, and activity with MoAb PAC-1, GPIb (CD42b), P-selectin (CD62p), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), were not affected by niacin, suggesting no effect on prostacyclin release. In conclusion, niacin in vitro affects platelet activity by mildly inhibiting aggregation, and stimulating significant prostaglandin release, with mostly intact major platelet receptor expression. The effect of niacin is unique, differs from other known antiplatelet agents, and suggests potential opportunities for therapeutic combination, particularly in patients with low levels of HDL-C. These preliminary data, while intriguing, require confirmation in subjects receiving orally dosed extended-release niacin in order to determine whether these findings are clinically relevant. PMID- 20539904 TI - Low cut-off values increase diagnostic performance of protein S assays. AB - Conflicting data have been reported on the accuracy of protein S (PS) assays for detection of hereditary PS deficiency. In this study we assessed the diagnostic performance of two total PS antigen assays, four free PS assays and three PS activity assays in a group of 28 heterozygous carriers of mutations in PROS1 and 165 control subjects. Several control groups were formed, one of healthy volunteers and - because PS levels are influenced by oral contraception and pregnancy, and assays measuring PS activity may be influenced by the presence of the factor V Leiden mutation -, we also investigated the influences of these factors. All nine PS assays detected significantly reduced PS levels in subjects with a PROS1 mutation. Eight out of nine PS assays showed a 100% sensitivity and 100% specificity to detect heterozygous carriers of mutations in PROS1 with values far below the lower limit of the reference values obtained from healthy volunteers. Low specificities were found in subjects with a factor V Leiden mutation and in pregnant women. At lower cut-off levels, equal to the highest PS value found in heterozygous carriers of mutations in PROS1, the specificity considerably increased in these subjects. When using low cut-off levels equal to the highest PS value found in heterozygous carriers of mutations in PROS1, ensuring 100% sensitivity, the specificity in all study groups increases considerably, by which misclassification can be maximally avoided. PMID- 20539905 TI - Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice. AB - Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed. This study was a multicenter, prospective cohort study in consecutive orthopaedic patients treated with 2.5 mg of fondaparinux. Anti-Xa activities were recorded in 809 patients. Population parameters and inter-individual variability were estimated using NONMEM VI software. A two-compartment model with first-order absorption best described fondaparinux pharmacokinetics. Covariates partly explaining inter-individual variability were body weight, age and creatinine clearance estimated by the simplified Modification of Diet in Renal Disease formula (MDRD). A body weight less than 50 kg and moderate renal failure increased drug exposure. Although the population pharmacokinetic model of fondaparinux was described, this one requires to be validated in everyday practice. PMID- 20539906 TI - Translational potential of human embryonic and induced pluripotent stem cells for myocardial repair: insights from experimental models. AB - Heart diseases have been a major cause of death worldwide, including developed countries. Indeed, loss of non-regenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is irreversible. Current therapeutic regimes are palliative in nature, and in the case of end-stage heart failure, transplantation remains the last resort. However, this option is significantly hampered by a severe shortage of donor cells and organs. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency to differentiate into all cell types. More recently, direct reprogramming of adult somatic cells to become pluripotent hES-like cells (a.k.a. induced pluripotent stem cells or iPSCs) has been achieved. The availability of hESCs and iPSCs, and their successful differentiation into genuine human heart cells have enabled researchers to gain novel insights into the early development of the human heart as well as to pursue the revolutionary paradigm of heart regeneration. Here we review our current knowledge of hESC-/iPSC-derived CMs in the context of two fundamental operating principles of CMs (i.e. electrophysiology and Ca2+-handling), the resultant limitations and potential solutions in relation to their translation into clinical (bioartificial pacemaker, myocardial repair) and other applications (e.g. as models for human heart disease and cardiotoxicity screening). PMID- 20539907 TI - Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases. AB - Recent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised. PMID- 20539908 TI - New era of regenerative medicine for cardiovascular diseases. PMID- 20539909 TI - New oral anticoagulant drugs in cardiovascular disease. AB - Oral anticoagulation has been limited to vitamin K antagonists (VKAs) for over 60 years. VKAs are effective and recommended for the prevention of venous and arterial thromboembolism in cardiovascular disease, but their pharmacodynamics are difficult to predict and the highly variable interindividual and intraindividual response to treatment accounts for the need of continuous monitoring. This prompted the intensive exploration of numerous substances within the last decade in an attempt to meet the shortcomings of current oral anticoagulation with VKAs. The development and clinical investigation of two novel groups of oral anticoagulants targeting central factors of the coagulation system either factor Xa or thrombin (factor IIa) has now reached the daily clinical practice with the approval of the oral direct thrombin inhibitor dabigatran etexilate and the oral direct factor Xa inhibitor rivaroxaban. Ongoing clinical trials are investigating these substances and other novel oral anticoagulants with similar mechanisms of action in patients with atrial fibrillation and acute coronary syndromes. This review article discusses the clinical evaluation and pharmacological properties of novel oral anticoagulants in late and earlier stages of clinical development, thereby providing a critical analysis and an outlook on the future of oral anticoagulation in cardiovascular disease. PMID- 20539910 TI - Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Data from the REVERSE cohort study. AB - The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5-7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use. PMID- 20539912 TI - Regulation of von Willebrand factor-platelet interactions. AB - The formation of thrombi is a multistep process involving several components, including von Willebrand factor (VWF). VWF is an adhesive multimeric protein, which acts as a molecular bridge between the subendothelial matrix and the glycoprotein Ib/IX/V receptor complex. Furthermore, VWF promotes the expansion of the platelet plug by cross-linking platelets via binding to integrin alphaIIbbeta3. In terms of thrombus formation, it is essential that VWF-platelet interactions occur timely, that is: it should happen not too early or too late. Given the co-existence of VWF and platelets in the circulation, this implies that there must be regulatory mechanisms that prevent premature formation of VWF-rich platelet aggregates that could occlude the vasculature. Indeed, several mechanisms have been identified at the level of VWF, which are dedicated to the prevention of excessive VWF-platelet interactions following endothelial release of VWF (which may include limited exposure to shear stress, the presence of Mg2+ ions, inhibition of VWF-platelet interactions by endothelial proteins, ADAMTS13 mediated proteolysis) and of circulating VWF-platelet aggregates during normal circulation (shielding of the platelet-binding A1 domain by other regions of the VWF molecule, inhibition of VWF-platelet interactions by beta2-glycoprotein I). In the present review an overview of these mechanisms will be discussed. PMID- 20539911 TI - Tissue factor and thrombosis: The clot starts here. AB - Thrombosis, or complications from thrombosis, currently occupies the top three positions in the cardiovascular causes of morbidity and mortality in the developed world. There are a limited number of safe and effective drugs to prevent and treat thrombosis. Animal models of thrombosis are necessary to better understand the complex components and interactions involved in the formation of a clot. Tissue factor (TF) is required for the initiation of blood coagulation and likely plays a key role in both arterial and venous thrombosis. Understanding the role of TF in thrombosis may permit the development of new antithrombotic drugs. This review will focus on the role of TF in in vivo models of thrombosis. PMID- 20539913 TI - FIX-Triple, a gain-of-function factor IX variant, improves haemostasis in mouse models without increased risk of thrombosis. AB - Engineered recombinant factor IX (FIX) with augmented clotting activity may prove useful for replacement therapy, but it has not been studied for risk of thrombosis. We used three mouse models to evaluate thrombosis risk associated with the FIX variant FIX-Triple, which has a 13-fold higher specific activity than wild-type FIX (FIX-WT). Protein infusion of FIX-Triple into haemophilia B mice was not thrombogenic, even at a dose of 13-fold higher than FIX-WT. Gene knock-in to generate mice that constitutively produce FIX-WT or FIX-Triple protein revealed that all mice expressed equal antigen levels. FIX-Triple knock in mice that exhibited 10-fold higher FIX clotting activity did not show hypercoagulation. Adeno-associated viral (AAV) delivery of the FIX gene into mice was used to mimic gene therapy. Haemophilia B and inbred C57Bl/6 mice injected with different doses of virus particles carrying FIX-WT or FIX-Triple and expressing up to a nearly 13-fold excess (1289% of normal) of FIX clotting activity did not show increased risk of thrombosis compared with untreated wild type mice in a normal haemostatic state. When challenged with ferric chloride (FeCl3), the mesenteric venules of AAV-treated C57Bl/6 mice that gave a nearly five-fold excess (474%) of FIX clotting activity were not thrombotic; however, thrombosis became obvious in FeCl3-challenged mice expressing extremely high FIX clotting activities (976-1289%) achieved by AAV delivery of FIX-Triple. These studies suggest that FIX-Triple is not thrombogenic at therapeutic levels and is a potential therapeutic substitute for FIX-WT. PMID- 20539914 TI - The mechanism of stem cell differentiation into smooth muscle cells. AB - Stem cells represent one of the most promising areas in biological and medical research. All stem cells are defined as having two basic properties: unlimited self-renewal and the broad potential to differentiate in vitro, via "progenitor cells", into somatic cells of many tissue types, in which smooth muscle cell (SMC) differentiation is a complicated and not well defined process. It is known that serum response factors (SRF) and co-activator myocardin are essential transcription factors in SMC differentiation. Upstream activators or regulators for the transcription factors have been recently identified, such as reactive oxygen species, histone deacetylases, microRNAs and extracellular matrix (ECM) proteins and integrins. In this review we, therefore, aim to briefly summarise recent progress in the mechanism of stem cell differentiation into SMCs to highlight the potential targets for promoting/inhibiting SMC differentiation useful for vessel-tissue engineering and treatment of vascular disease. PMID- 20539915 TI - A combined immunostimulatory and immunoinhibitory short interference RNA reduces hypercoagulability in a rat model of acute promyelocytic leukaemia. AB - Acute promyelocytic leukaemia (APL) confers an increased risk of thrombosis and bleeding. Current treatments are insufficient to inhibit these complications. We recently showed that a combined immunoinhibitory and immunostimulatory short interference (si) RNA effectively inhibited leukaemic growth and metastasis in rats with APL. We now asked if the reported anti-leukaemic effects of siRNA treatment could be explained by inhibition of hypercoagulability. We measured markers of coagulation and fibrinolysis in plasma collected from APL rats with overt leukaemia using conventional assays. Coagulopathy developed in untreated leukaemic rats evidenced by increase in several haemostatic markers. Treatment of leukaemic rats with the siRNA reduced (p < 0.05) the concentration of thrombin anti-thrombin complex (a marker of coagulation) by 40% compared with rats treated with an inactive, control siRNA. Substantial reductions (p < 0.05) were also obtained for two markers of fibrinolysis: D-dimer (72%) and plasminogen activator inhibitor type 1 (51%). The activity of tissue factor, the main initiator of coagulation, was not increased (p > 0.05) in untreated leukaemic rats compared with healthy rats, and did not change (p > 0.05) upon treatment with the siRNA. The bifunctional siRNA reduces the hypercoagulable state in APL in addition to its direct anti-leukaemic properties, supporting testing of this small molecule in human APL. PMID- 20539916 TI - Heme oxygenase-1 in neovascularisation: A diabetic perspective. AB - Neovascularisation is crucial both for physiological processes, like development, wound healing, tissue regeneration, hair growth or menstrual cycle, and for pathological states, such as tumour progression, retinopathy and psoriasis. Blood vessel formation is orchestrated by numerous pro-angiogenic and anti-angiogenic factors, acting together to keep tight rein on this complicated, desirable but also dangerous process. One of the proteins important for neovascularisation is heme oxygenase-1 (HO-1), an enzyme degrading heme. This review focuses on the role of HO-1 in angiogenesis and vasculogenesis, having a closer look at the significance of this system in diabetes. PMID- 20539917 TI - Phagocytosis of platelet microvesicles and beta2- glycoprotein I. AB - The majority of the antiphospholipid antibodies, present in patients with antiphospholipid syndrome, are directed against conformational epitopes in beta2 glycoprotein I. beta2-glycoprotein I is an anionic phospholipid-binding 50-kDa plasma protein whose physiological role is not clear. Here we investigate the role of beta2-glycoprotein I in the phagocytosis of phosphatidylserine-expressing platelet microvesicles and the effect of autoantibodies to beta2-glycoprotein I on this process. We labelled the glycans of beta2-glycoprotein I with BODIPY (4,4 difluoro-4-bora-3a,4a-diaza-s-indacene)-hydrazide without affecting its phospholipid binding capacity. BODIPY-beta2-glycoprotein I bound to platelet microvesicles in a concentration-dependent manner and promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at approximately 10 microg/ml. beta2-glycoprotein I-stimulated phagocytosis was inhibited by annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified beta2-glycoprotein I-dependent antiphospholipid antibodies from five patients with antiphospholipid syndrome inhibited the phagocytosis in a concentration-dependent manner. These studies suggest that the binding of beta2-glycoprotein I to phosphatidylserine-expressing procoagulant platelet microvesicles may promote their clearance by phagocytosis and autoantibodies to beta2-glycoprotein I may inhibit this process to induce a procoagulant state. PMID- 20539918 TI - [E-learning in nuclear medicine - a nationwide survey in Germany]. AB - AIM: To assess available e-learning concepts and programmes for nuclear medicine at university hospitals in Germany. METHODS: All (34) departments of nuclear medicine at German university hospitals were asked to participate in an anonymized online survey. Questions were categorized into four topics: 1.) clinic and education; 2.) on-site strategies for e-learning; 3.) available e-learning offers and 4.) free text comments on experiences and expectations. All input was reviewed descriptively; free text was analyzed analytically. RESULTS: The response rate was 56% (19/34). 13/19 responses indicated well-defined e-learning strategies, mainly to support frontal teaching courses. Future e-learning perspectives focus on clinical case studies with sufficient imaging materials. Only 7/19 university hospitals operate a centralized e-learning platform (e. g. Moodle). The acceptance of the available e-learning options by the students is considered relatively poor. CONCLUSIONS: Today e-learning concepts for nuclear medicine are available at selected university hospitals only. All responders wish to expand on e-learning but many report the lack of administrative support to do so. These data could be regarded as a basis for discussions of inter-university teaching scenarios. PMID- 20539919 TI - Self-direction in learning: does it change over time? AB - The purpose of this study was to examine the change in students' self-direction in learning over time. The students were enrolled in two health professional graduate programs at one institution of higher education, occupational therapy (day and weekend formats) and physical therapy. The occupational therapy program uses a cased-based learning (CBL) approach, while the physical therapy program uses a problem-based learning (PBL) approach. From 2003 through 2007, the Self Directed Learning Readiness Scale (SDLRS) was administered to three cohorts of occupational therapy and physical therapy students upon entrance into the professional phase of their respective programs, and again at the conclusion of their academic coursework. The CBL and PBL approaches incorporate the concept of self-direction in learning. Participants included one hundred and six Utica College students. Eighty-six students met inclusion criteria and were included in the results. The mean score for the pre-test SDLRS for occupational therapy (day) students was 219.10. For occupational therapy (weekend) students, the mean score for the pre- test SDLRS was 223.58. The mean score for the pre-test SDLRS for physical therapy students was 227.77. Mean scores for the post- test SDLRS students were: occupational therapy (day) students: 230.90, occupational therapy (weekend) students: 230.75, and physical therapy students: 242.25. The results of this study revealed that there was a significant difference between SDLRS scores from the first semester of the academic program, the pre-test scores, and those from the last semester of the program, the post-test scores (P > .001). For the pre-test, students scored an average of (standard deviation) of 225.1 (20.5) compared to 237.9 (22.8) for the post-test. These results indicate that self direction in learning did change over time from the first semester to the final academic semester for a group of 86 occupational therapy and physical therapy students. The results of this study will add to the body of knowledge regarding the education of students in health related programs. PMID- 20539920 TI - The meaning of caring from the perspectives of patients undergoing physical therapy. AB - This research note describes a pilot study that examined the meaning of caring from the perspectives of patients undergoing physical therapy. METHODS: A phenomenological methodology was used to explore the essential meaning of caring behaviors from the experiences of patients undergoing physical therapy. Patients were asked to describe caring interactions they have experienced with their physical therapists. RESULTS: The responses of the participants were inductively analyzed for themes and sub-themes that explained physical therapy caring. Based on that analysis, a central theme of mindful caring emerged from participants' responses. The theme of mindful caring reflected the physical therapist and patient relationship. Further analysis uncovered four sub-themes that gave a clearer picture of caring behaviors experienced by the participants. These included personal values, patient empowerment, open communication and exceptional service. CONCLUSION: The results of this pilot study demonstrate the dimensions of caring in healthcare practice from the unique perspectives of patients. PMID- 20539921 TI - An art therapy in-service program model for medical students and residents. AB - This paper examines the author's experience implementing an art therapy in service program into the training of medical students and residents in an urban hospital teaching facility. Emphasis is placed on specific aspects of planning and implementation, including formal and informal assessment, as well as methods of engaging medical students in art therapy experientials relevant to their experience as helping professionals. Benefits and challenges encountered throughout the process are also discussed. This paper is based on a presentation given at the 36th annual American Art Therapy Association conference. PMID- 20539922 TI - Introduction of a cultural training experience into interdisciplinary health science education program. AB - In the 21st century the U.S. will have an increasingly diverse population, challenging healthcare communities to deliver culturally sensitive services. Healthcare professionals must be culturally competent to address the needs of this changing population. While education can assist health professional students to attain progressively higher levels of cultural competence, delivering this education must rely heavily on field experiences or engagement to help students simultaneously learn and apply culturally sensitive skills. The implementation of a cultural sensitivity training experience in an interdisciplinary curriculum and the use of the Purnell Model for Cultural Competence are discussed in the assessment of the case study write-up for cultural sensitivity and awareness. Overall, students gained a greater understanding of patient's cultural background and a willingness to incorporate cultural issues into their health assessments as a result of the cultural experience. PMID- 20539923 TI - The impact of a service learning experience to enhance curricular integration in a physical therapist education program. AB - A goal when designing the Physical Therapy Program at Lebanon Valley College (LVC) was to maximize vertical and horizontal integration of course content related to (a) medical Spanish, (b) geriatrics, and (c) health promotion through a service learning engagement. Seventeen Doctor of Physical Therapy students from LVC participated in a fall risk screening at a local senior center in a Spanish speaking neighborhood. The screen included the single leg stance, timed-up-and-go (TUG), and functional reach tests. The students screened 30 participants over a 3 hour time period. Following the screening event, students were asked to reflect on their experience. Reflections revealed that the activity supported integration of concurrent didactic course material and Core Values, reinforced cultural issues presented the previous year, and convinced students that physical therapists have a distinct and important role in primary and secondary prevention in meeting the needs of the Spanish-speaking elderly community. PMID- 20539924 TI - Librarian involvement in a nutrition undergraduate research course: preparing nutrition students for evidence-based practice. AB - Given the foundational importance of literature searching skills to later stages of research and, ultimately, evidence-based practice, the authors wanted to assess a unique strategy for teaching such skills. This pilot study describes the results of an undergraduate nutrition research course in which a librarian lead several class sessions. The goal of this study was to assess students' perceptions, attitudes and use of research literature and resources before and after a course partially taught by a librarian. Twenty-seven students enrolled in an undergraduate Introduction to Research course at Georgia State University were given pre- and post-test questionnaires at the beginning and end of a course that included three librarian-led class sessions. Most of the results indicate that the repeated involvement of a librarian enriched this particular undergraduate research course. By the end of the course, students were more comfortable in libraries and with using library resources; they used the campus library more frequently; they were more confident in their ability to find high-quality information on nutrition-related topics and identify strengths and weaknesses of different information sources; and they felt they gained skills that will help them achieve their educational and career goals. PMID- 20539926 TI - Knowledge dissemination and adoption. PMID- 20539925 TI - Building competency in the novice allied health professional through peer coaching. AB - The development of competence is an ongoing journey, and one that is particularly punctuated in the early part of a health professional's career. These novice practitioners need to recognize that the challenges inherent in building competency might be resolved more readily by engaging with peers. This paper outlines what it means to be a novice practitioner, and how peer coaching can be used to support professional development in the allied health sciences. An overview of the reasoning process and how peer coaching and experiential learning can be used to build competence is described. A structured and formal approach to peer coaching is outlined in this paper. Novices who embrace this professional development strategy will find the model of coaching practice and underlying strategies described in this paper beneficial to their experience. The importance of formalizing the process and the underlying communication skills needed for coaching are described in detail with accompanying examples to illustrate the model in practice. PMID- 20539927 TI - Health reform and its aftermath. AB - The Patient Protection and Affordability Act, H.R. 3509, that was signed into law by President Obama in March 2010 might just as easily have been subtitled the "Attorneys, Accountants, Lobbyists, and Public Relations Personnel Relief Act of 2010." As components of the law unfold over the next decade, thousands of pages of regulations must be written to explain how to implement the various provisions in the 906-page engrossed version of this legislation. Key segments of the health care industry in the form of practitioners, insurance companies, pharmaceutical manufacturers, medical device companies, and academic institutions with programs in the health sciences will be affected in diverse ways. History being a reliable guide, it is safe to posit that these entities will respond in the usual manner by employing armies of lobbyists, public relations specialists, and attorneys to enhance the likelihood that the ensuing regulatory environment will not be too inimical to their respective interests. PMID- 20539928 TI - Relationship of the Nelson Denny Reading Test to scores on the National Physical Therapy Licensure Examination. AB - This study examined the relationship between scaled scores of reading comprehension as measured by the Nelson Denny Reading Test and scaled scores on the National Physical Therapy Licensure Examination (NPTE). Sixty-seven graduate students from Arkansas State University participated in this study. The Nelson Denny Reading Test was given at the initiation of the physical therapy program, and the NPTE was taken after successful completion of the graduate program in physical therapy. A correlation analysis examined the scaled scores of these graduates from the Reading Test and the NPTE. Analysis revealed that a moderate positive relationship and statistically significant difference existed between scaled scores on the Reading Test and the NPTE for those graduates who passed the NPTE their first time. PMID- 20539929 TI - Introducing medical students to the interdisciplinary health care team: piloting a case-based approach. AB - Medicine in the 21st century requires expanded multidisciplinary problem-solving in order to deliver cost-effective, quality health care, yet many medical schools still educate their students in relative isolation with little interaction or understanding of other health care professionals. To begin to address this issue, the University of Medicine and Dentistry of New Jersey (UMDNJ) School of Health Related Professions and School of Nursing were invited by the New Jersey Medical School to introduce medical students at the New Jersey Medical School to a cross section of health professions they are likely to encounter. These health professions included medical imaging, dietetics-nutrition, laboratory technology, nursing, physical therapy, physician assistant, respiratory therapy and social work. During a 60-min educational session, a simulated case-based approach heightened medical school students' awareness of the function and value of interdisciplinary collaboration. Faculty from each of the eight disciplines gave a brief summary of their profession, including their scope-of-practice and academic requirements. At the end of the session, participants were given a brief 12-item survey to evaluate the experience. Though this was only a small, explorative project, survey results suggested that participants increased their understanding of other health professions, including when to refer to and collaborate with these professions. Feedback from this pilot project may be used to optimize future initiatives of this type. PMID- 20539930 TI - An outcome assessment for evaluating occupational therapy students' proficiency and skills required for passing the NBCOT computer-based certification test. AB - The objective the current study was to perform an outcome assessment of occupational therapy students participating in the first offering of a graduate seminar. This seminar was designed to increase their proficiency and skills required for passing the computer-based test (CBT) NBCOT certification exam. Four outcome measures were assessed: pre- and post-seminar NBCOT CBT practice tests score and pre- and post-seminar NBCOT CBT numbers of areas of weakness delineated by NBCOT. Our hypotheses expected that the student score and number of identified areas of weakness at the post-seminar NBCOT practice testing to demonstrate: H1- a score increase over pre-seminar practice testing; and H2--a decrease in the number of areas of weakness delineated by NBCOT over pre-seminar practice testing. All 13 graduating occupational therapy students participated in the seminar and were the subjects of this assessment. The Wilcoxon test (1-tailed) was employed to test the research hypotheses. A significant (Z = 3.11, p = 0.002) post- over pre-seminar practice test score increase was found. No significant post- over pre-seminar practice testing decrease in number of areas of weakness was found. PMID- 20539931 TI - Research knowledge, attitudes, and practices of pediatric occupational therapists in Australia, the United Kingdom, and Taiwan. AB - Limited evidence is available on the attitudes and perceptions of evidence-based practice and research utilization within the occupational therapy (OT) field. The aim of this study was to investigate and compare the research knowledge, attitudes, and practices related to evidence-based practice and research utilization of pediatric OTs from Australia, the United Kingdom, and Taiwan. Questionnaires were mailed to 1,230 participants (300 in Australia, 480 in the UK, and 450 in Taiwan) who were asked to complete the "Research Knowledge, Attitudes, and Practices of Research Survey" (KAP Survey). Responses were received from 696 participants (response rate 56.6%). The findings indicated that pediatric OTs perceived their research knowledge, attitudes, and practices to be of a "moderate" level, with the lowest ratings being for participants' knowledge and practices of "administering research implementation." Participants from Taiwan perceived significantly higher research knowledge, attitudes, and practices than pediatric OTs from Australia and the United Kingdom for a number of research activities. To ensure evidence-based and research utilization among pediatric OTs, continuing education may be required to enhance knowledge and practices of research activities. PMID- 20539932 TI - Learning style preferences of Australian health science students. AB - OBJECTIVES: It has been identified that health science student groups may have distinctive learning needs. By university educators' and professional fieldwork supervisors' being aware of the unique learning style preferences of health science students, they have the capacity to adjust their teaching approaches to best fit with their students' learning preferences. The purpose of this study was to investigate the learning style preferences of a group of Australian health science students enrolled in 10 different disciplines. METHODS: The Kolb Learning Style Inventory was distributed to 2,885 students enrolled in dietetics and nutrition, midwifery, nursing, occupational therapy, paramedics, pharmacy, physiotherapy, radiation therapy, radiography, and social work at one Australian university. A total of 752 usable survey forms were returned (response rate 26%). RESULTS: The results indicated the converger learning style to be most frequently preferred by health science students and that the diverger and accommodator learning styles were the least preferred. CONCLUSION: It is recommended that educators take learning style preferences of health science students into consideration when planning, implementing, and evaluating teaching activities, such as including more problem-solving activities that fit within the converger learning style. PMID- 20539933 TI - Racial-ethnic diversity in allied health: the continuing challenge. AB - Despite gains over the last few decades, the racial-ethnic diversity of health professionals has not kept pace with demographic changes in the general population of the United States, with significant consequences for the health of minority populations and access to health care services. We analyzed data for allied health educational programs accredited in 1989-90 and 2006-07, with particular attention to the race/ethnicity of enrollments, attrition, and graduates and the types of institutions that were more or less likely to have increased diversity over the time period. Our data show that blacks and Hispanics have higher attrition rates than whites and Asian or Pacific Islanders. In addition, federal institutions and for-profit institutions have higher rates of student racial/ethnic diversity, and both have become more diverse over time, although for-profit institutions have higher attrition rates than other types of institutions. Because minority students are more likely to attend for-profit institutions, the higher attrition rate at these institutions versus other types of institutions merits continued attention and additional study. At the same time, all institutions must direct resources toward increasing diversity and ensuring higher graduation rates among racial/ethnic minority students. PMID- 20539934 TI - Formative feedback, rubrics, and assessment of professional competency through a speech-language pathology graduate program. AB - Professional competencies independent of discipline-specific knowledge and skills are addressed by most allied health professions. This paper presents the process of developing and testing a Graduate Student Development Profile (GSDP) in rubric format. In addition to documenting behaviors, a rubric system provides formative feedback helpful to student learning and development as a professional. A rubric for rating responsibility for learning, critical thinking, cognitive flexibility, professionalism, and communication, each with specific subcategories, was created, developed, and implemented by faculty and clinical staff to guide the three sequential evaluations each master's level student receives during the five semester speech-language pathology program. Pilot scoring of master's students was used to calibrate and refine the GSDP before official implementation. Two evaluations were completed during faculty meetings to familiarize users with the GSDP. A third evaluation was conducted via a secured website. In each case, resulting scores and specific comments for each student were shared during a faculty meeting before being presented to students individually. The GSDP documents the speech-language pathology student's professional competency demonstrated across academic, clinical, and interpersonal settings. The web-based version brings convenience and efficiency to the often formidable, but fundamentally necessary, process of providing formative and summative feedback to students. PMID- 20539935 TI - Student-facilitated health promotion intervention for chronic disease self management in at-risk elders reflections from the field. AB - A student-facilitated and faculty-supervised health promotion program for chronic disease management in at-risk elders was developed based on the belief that individual contact with high-risk elders will facilitate improved health behaviors while enhancing the real-life experiences of students through interdisciplinary collaboration and community-based learning. Subjects were seven students enrolled as health professions academic majors at the university who served as student health advocates in the Healthy Elder Living Program (HELP). The data collected included student reflection questionnaires, field notes from the HELP staff, and communication logs between the HELP coordinator and students. As student health advocates, the students made visits to at-risk elders to reinforce recommendations from health care providers, to review adherence to the Health Promotion Inventory (HPI), and to interact socially with the client through discussion of health- and non-health-related issues. A training model for health promotion was developed based on identification of four common themes of student performance as health advocates. Overall, students demonstrated a greater appreciation for the complexity of social, psychological, and physical aspects of chronic disease as a result of participation in this program for at-risk elders. They were able to apply professional skills learned in the classroom while providing a needed service to elders. At-risk clients also benefited from the HELP intervention, showing improved physical performance and less depression. PMID- 20539936 TI - ClC-3 chloride channels are essential for cell proliferation and cell cycle progression in nasopharyngeal carcinoma cells. AB - ClC-3, a gene encoding a candidate protein for volume-activated chloride (C(-)) channels, may be involved in tumor development. Herein we report a study using an antisense "knock-down" strategy to investigate the mechanism by which ClC-3 affects cell proliferation in nasopharyngeal carcinoma CNE-2Z cells. With immunoblots and MTT assays we demonstrated that the expression of ClC-3 was cell cycle dependent and in a similar concentration-dependent manner, an antisense oligonucleotide specific for ClC-3 inhibited ClC-3 protein expression and cell proliferation. The expression level of ClC-3 correlated with cell proliferation. Moreover, in the cells exposed to a ClC-3 antisense oligonucleotide, the cloning efficiency was inhibited, and cells were arrested in the S phase. The ClC-3 antisense oligonucleotide inhibited the volume-activated C(-) current (I(Cl,vol)) and the regulatory volume decrease (RVD) in a concentration-dependent manner. Additionally, the I(Cl,vol) or RVD was positively correlated with cell proliferation in the treated cells. In conclusion, ClC-3 is involved in cell proliferation and cell cycle progression through a mechanism involving modulation of I(Cl,vol) and RVD. CIC-3 may represent a therapeutic target in human cancer. PMID- 20539937 TI - A convenient spectrometric assay system for intracellular quantitative measurement of DNA glycosylase activity. AB - Cytosine methylation is a vital biology event. However, it is also the source of genomic instability due to deamination of 5'-methylcytosine by spontaneous hydrolysis, which produces thymine and results in G:T mismatches. Thymine DNA glycosylase and methyl-CpG-binding protein 4 are major DNA glycosylases involved in the mismatch repair progress, and their activities have been measured in many related researches. In this study, we developed a convenient spectrometric assay system for specific and quantitative measurement of intracellular DNA glycosylase activity. A G:T mismatch was introduced into the upstream region of firefly luciferase-coding sequence in the pGL3-control plasmid. Only if the G:T mismatches were repaired to G:C, will luciferase be expressed in transfected cells. By measuring luciferase activity, which is simple and convenient, the intracellular DNA glycosylase activity can be determined. PMID- 20539938 TI - Prokaryotic expression, purification, and polyclonal antibody production of a hydrophobin from Grifola frondosa. AB - Hydrophobins are small fungal proteins that self-assemble spontaneously at hydrophilic-hydrophobic interfaces and change the polar nature of the surfaces to which they attach. A new hydrophobin gene hgfI was identified recently from the edible mushroom Grifola frondosa. In this paper, the cloning, expression, purification, and polyclonal antibody preparation of the HGFI were described. The hgfI gene was cloned into pET-28a expression plasmid at the EcoRI and NdeI restriction sites and then transformed into Escherichia coli BL21 strain. SDSPAGE analysis showed that recombinant HGFI protein was satisfactorily expressed by optimizing the concentration and induction time of IPTG. The expressed recombinant HGFI protein was purified by electroelution because its inclusion body was insoluble in traditional processing method. After a desalting procedure with Sephadex G-25, the recombinant HGFI protein was used to immunize adult rabbits following standard protocol. ELISA and western blot analysis indicated that the produced antiserum could detect both HGFI protein expressed in the prokaryotic (E. coli) and in the eukaryotic cells (G. frondosa). Furthermore, the antiserum was used to determine the localization of HGFI protein in G. frondosa cells using an immunofluorescence technique. The results demonstrated that HGFI protein was localized in the cell wall, especially at the budding position of hypha. The polyclonal antibody against HGFI will facilitate further production and functional study of HGFI protein. PMID- 20539939 TI - PI3K/Akt signaling transduction pathway is involved in rat vascular smooth muscle cell proliferation induced by apelin-13. AB - Vascular smooth muscle cells (VSMCs) were prepared from thoracic aortas of male Sprague-Dawley rats by the explant method to observe VSMC proliferation via phosphoinositide 3 kinase (PI3K)/Akt signaling transduction pathway induced by apelin-13. Expression of PI3K, phospho-PI3K, phospho-Akt, ERK1/2, phospho-ERK1/2 and cyclin D1 was detected by western blot analysis. Results showed that apelin 13 promoted the expression of phospho-PI3K and phospho-Akt in dose- and timedependent manner. PI3K inhibitor LY294002 significantly decreased the expression of phospho-PI3K, phospho-Akt, phospho-ERK1/2, and cyclin D1 induced by apelin-13. The Akt inhibitor 1701-1 significantly diminished the expression of phospho-Akt, phospho-ERK1/2, and cyclin D1 stimulated by apelin-13. MTT assay results showed that PI3K inhibitor LY294002 and Akt inhibitor 1701-1 significantly inhibited the VSMC proliferation induced by apelin-13. Apelin-13 promoted VSMC proliferation through PI3K/Akt signaling transduction pathway. PMID- 20539940 TI - 14-3-3 mediates apelin-13-induced enhancement of adhesion of monocytes to human umbilical vein endothelial cells. AB - To investigate whether apelin-13 induced THP-1 monocytes (MCs) adhesion to ECV304 human umbilical vein endothelial cells (HUVECs) via 14-3-3 signaling transduction pathway and the potential novel physiological function and signaling transduction pathway of apelin-APJ, HUVECs ECV304 were cultured in DMEM and MCs THP-1 were cultured in RPMI 1640 medium. Monocyte adhesion and the expression of vascular cell adhesion molecule-1 (VCAM-1) and 14-3-3 were measured with monocyte adhesion assay and western blot analysis. Data showed that apelin-13 increased adhesion of MCs to HUVECs in a concentration- and time-dependent manner, which reached their peaks at 1 mM and 12 h, respectively. Similarly, apelin-13 induced the expression of HUVECs adhesion molecule, VCAM-1, in a concentration- and time-dependent manner, reached their peaks at 1 microM and 12 h, respectively. Apelin-13 induced the expression of 14-3-3 in a concentration- and timedependent manner, which reached their peaks at 1 mM and 5 min, respectively. Furthermore, the potent 14-3 3 inhibitor difopein significantly reduced the expression of 14-3-3 and VCAM-1 in apelin-13 stimulated HUVECs, and difopein significantly inhibited the effect of apelin-13 on induction of MCs adhesion to HUVECs. These data suggested that 14-3 3 mediated the induction of adhesion of MCs to HUVECs by Apelin-13. PMID- 20539941 TI - GGDEF and EAL proteins play different roles in the control of Sinorhizobium meliloti growth, motility, exopolysaccharide production, and competitive nodulation on host alfalfa. AB - A new bacterial secondary messenger, bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP), is usually synthesized or decomposed by proteins containing GGDEF or glutamate-alanine-leucine (EAL) domain. They often act as cyclase or phosphodiesterase of c-di-GMP and their genes are distributed among almost all bacteria according to known genomic DNA sequences. However, the systematic identification of GGDEF and EAL genes remains unclear in rhizobia, soil bacteria that interact with compatible legumes to form nitrogen-fixing nodules. In this study, 19 putative GGDEF and EAL genes were identified in a model rhizobium, Sinorhizobium meliloti, by bioinformatic analysis (encoding 5 GGDEF proteins, 4 EAL proteins, and 10 GGDEF and EAL double-domain proteins). Null mutants of 14 genes were constructed through systematic plasmid insertion. All 14 gene mutants showed deficient growth in minimal medium and defective motility, and 11 gene mutants produced a lot more exopolysaccharide and displayed less competitive nodulation on the host plant, alfalfa. Our results suggested that GGDEF and EAL proteins may play different roles in the control of S. meliloti physiology, although they contain conserved catalytic (GGDEF or EAL) domains. Our finding also implied that c-di-GMP may play an important role in the interactions between this rhizobium and its host plants to establish efficient symbiosis. PMID- 20539942 TI - Downregulation of WIF-1 by hypermethylation in astrocytomas. AB - Wnt inhibitory factor-1 (WIF-1) acts as a Wnt antagonist and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression of WIF-1 activate Wnt signaling aberrantly and induce the development of several human tumors. By using RT-PCR, immunohistochemistry and methylation-specific PCR, we analyzed the expression and methylation of WIF-1 in 4 normal brain tissues, 35 freshly resected astrocytoma tissues and 4 glioblastoma-derived cell lines. Significant downregulation of WIF-1 mRNA and protein expression levels was observed in astrocytoma tissues compared with normal brain tissues. Significant association between WIF-1 downregulation and pathological grade of astrocytomas was found. WIF-1 gene aberrant methylation was observed in 19 of 35 (54.29%) tumor samples. The promoter methylation tumors showed low WIF-1 protein and mRNA expression, whereas the promoter unmethylation tumors displayed high protein and mRNA expression levels. Moreover, complete absence of WIF-1 mRNA expression was observed in four cell lines, whereas treatment with demethylating agent, 5-aza-2' deoxycytidine, restored WIF-1 expression. Our results suggested that the WIF-1 gene is frequently silenced in astrocytoma by aberrant promoter methylation. This may be an important mechanism in astrocytoma carcinogenesis. PMID- 20539943 TI - The relationship between internal domain sequences of piggyBac and its transposition efficiency in BmN cells and Bombyx mori. AB - The piggyBac transposon, which includes terminal inverted repeat sequences and internal domain (ID) sequences, is widely used as a tool for insect transformation. To optimize this system for transgenic research on Bombyx mori, we examined the effects of the amount of the transposase plasmid and its ID sequences on the expression of green fluorescent protein (GFP). Four kinds of transposon plasmids, pB[A3GFP]-1 with the full length of ID sequences, pB[A3GFP] 2 having only the 3' ID sequence, pB[A3GFP]-3 without ID sequences, and pB[A3GFP] 4 containing 333 bp of the 5' ID sequence, and 179 bp of the 3' ID sequence were constructed with GFP as the marker. After transfecting these four plasmids into BmN cells, we analyzed the transfecting efficiency by comparing the GFP positive to negative cell ratio. Our results indicated that plasmid pB-4 got the highest ratio on the 22nd day. Moreover, the GFP positive to negative cell ratio increased with higher amount of transposase plasmid without overproduction inhibition. Furthermore, we injected three piggyBac transposon plasmids, pB[A3GFP]-1, pB[3xP3GFP]-3, and pB[3xP3RFP]-4 harboring different markers into preblastoderm stage eggs of B. mori, and found that the transformation efficiency of pB[3xP3RFP]-4 was 3.8 folds higher than pB[A3GFP]-1, whereas pB[3xP3GFP]-3 failed to produce transformants. Our results suggested that pB-4 may be one of the best piggyBac transposon plasmids currently available for germline transformation in B. mori. PMID- 20539944 TI - MicroRNAs and prostate cancer. AB - MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that negatively regulate gene expression by mainly binding to 30 untranslated region (UTR) of target mRNAs at the post-transcriptional level. Recent studies have demonstrated that aberrant expressions of miRNAs are closely associated with the development, invasion, metastasis and prognosis of various cancers including prostate cancer (PCa). The proposed molecular mechanisms that underlie the aberrant expression of miRNAs result from gene changes, epigenetic modification and alteration of Dicer abundance. Although up to 50 miRNAs have been reported to be significantly expressed in human PCa, only a small number of them were experimentally shown to make contribution to the pathogenesis of PCa. The aim of this review is to describe the mechanisms of several known miRNAs, summarize recent studies on the relevance of altered expression of oncogenic miRNAs (e.g. miR-221/-222, miR-21, and miR-125b) and tumor suppressor miRNAs (e.g. miR-101, miR-126*, miR-146a, miR-330, miR-34 cluster, and miR-200 family) for PCa. Additionally, their potential clinical applications and prospects in PCa, such as biomarkers and clinical therapies, are also briefly discussed. PMID- 20539947 TI - [Diagnosis of nasal valve stenosis via anterior rhinomanometry using a nasal valve dilatator]. PMID- 20539948 TI - [Current recommendations of dacryocystorhinostomy]. AB - CURRENT RECOMMENDATIONS OF DACRYOCYSTORHINOSTOMYOBJECTIVE: With the implementation and the development of endoscopic systems, especially in functional endoscopic sinus surgery (FESS) in the last two decades, the gold standard considered external dacryocystorhinistomy (DCR) by Toti in patients with an obstruction of the lacrimal sac or the nasolacrimal duct has been replaced more and more by endonasal techniques. The endonasal approach, first performed in 1893 by Caldwell and publiciced by West 1911, has been modified since than, reached increasing acceptance and is nowadays often performed be ENT surgeons and ophthalmologists. MATERIAL AND METHODS: This review article presents the possible reasons of an obstruction of the lacrimal sac or the nasolacrimal duct with consecutive epiphora or recurrent dacryocystitis, describes diagnostic procedures and indications of therapy, and tries to demonstrate the surgical change towards endoscopic endonasal techniques. We compare both operation techniques and discuss their advantages with the focus on the endonasal approach. The relevance of additional adjuvants described in literatur (laser, use of mitomycin or fluoruracil or silicon intubation) are presented and discussed, too. RESULTS: At the end we discuss the published results of both techniques (endonasal vs. external DCR) and compare their success rates. In spite of the tendency towards endonasal endoscopic techniques the results of this approach seem to be a little worse in comparison to the results after external DCR. PMID- 20539950 TI - [Mucosal remodeling in chronic rhinosinusitis without nasal polyposis - an ultrastructural evaluation]. AB - OBJECTIVE: Because of recurrent scarring of the ostiomeatal complex after paranasal sinus surgery the therapy of chronic rhinosinusitis without nasal polyps (CRSsNP) seems to be difficult. The aim of this study was to evaluate ultrastructural changes of nasal mucosa in patients with CRSsNP. MATERIAL AND METHODS: In case of revision sinus surgery we took specimens of altered mucosa from 21 patients. All subjects suffered from recurrent CRSsNP. Twelve patients without signs of chronic rhinosinusitis dealed as control group. To prepare for electron microscopy the samples were immersed in 3% phosphate-buffered glutaraldehyde and refixed in 1% osmium acid. After dehydration and heat polymerization ultrathin cuts were prepared. After double-contrasting ultrastructures were evaluated by transmission electron microscopy. RESULTS: Typical changes evaluated by electron microscopy were loss of cilia, an increase of microvilli, collagen fibres, fibrocytes, fibroblasts and myofibroblasts as well as perivascular alterations and endothelial changes. CONCLUSION: The study revealed the presence of evident ultrastructural changes in the mucosa of patients with chronic rhinosinusitis without nasal polyps. Mucosal remodeling seems to be not reversible by conservative treatment. PMID- 20539951 TI - [Information on treatment alternatives in tonsillectomy]. PMID- 20539952 TI - [Septoplasty update]. AB - Septoplasty is one of the most frequently performed otorhinolaryngological procedures which might be very challenging for the surgeon. An accurate preoperative diagnosis of pathologies of the septum in the context of the nasal cavity is essential for the success of surgery. Intraoperative visualization through microscope or endoscope is very helpful for the surgeon and for the training of the residents. The modern technique of septoplasty with the phases of approach, mobilization, resection/repositioning and reconstruction/fixation is presented. Furthermore, the extracorporeal septoplasty in extreme deviations of the septum and alternative techniques for use in cases with limited pathologies as well as aspects of septoplasty in children are discussed. As particularly pathologies of the caudal septum are responsible for failures of septal surgery, some special problems of this region such as the vertical fracture of the caudal septum, the lack of caudal septum or anterior convexities of the cartilaginous septum are argued. Finally, advices for the management of intra-and postoperative complications are given. PMID- 20539953 TI - Ankle and foot: state of the art. PMID- 20539954 TI - Retinacular disorders of the ankle and foot. AB - The retinacula of the ankle are distinct structures defined as regions of localized thickening of the crural fascia covering the deep structures of the distal portion of the leg, ankle, and foot. Their role is to maintain the approximation of the tendons to the underlying bone. The retinacula of the ankle and foot contain the extensor retinaculum, the peroneal retinaculum, and the flexor retinaculum. Knowledge of the normal anatomy and imaging appearance of these structures is essential for the depiction of their injuries. Even though they may provide an explanation for chronic and unexplained residual pain after an injury, they are frequently overlooked or misdiagnosed. PMID- 20539955 TI - Ultrasound of peroneal tendons. AB - Disorders of the peroneal tendon (PeT) complex are common and affect patients of many different ages. They can be traumatic, inflammatory, infective, or degenerative. Clinical assessment orients the diagnosis, but an imaging modality is almost always performed to confirm the clinical impression and to obtain additional information that is essential in choosing among different treatments. Due to its peculiar characteristics of high resolution, cost effectiveness, noninvasiveness, and dynamism, ultrasound (US) is now widely considered the first line imaging modality to assess superficial tendons. US not only allows an optimal evaluation of the PeT complex but can also accurately assess its synovial sheath, retinacula, and adjacent tissues. This article describes the normal anatomy, technique of examination, and normal US anatomy of the PeT complex as well as illustrating the US appearance of its main disorders. PMID- 20539956 TI - The Achilles tendon. AB - Achilles tendon disorders are among the most common conditions seen by sports medicine physicians. The request for radiological assessment and for radiologically assisted therapy is on the steady increase. Thus understanding the anatomy and biomechanics of the Achilles tendon is crucial to the effective radiological diagnosis and thus the management of such conditions. PMID- 20539957 TI - Is sonoelastography of value in assessing tendons? AB - Sonoelastography is a newly introduced ultrasound technique that evaluates tissue elasticity and thus provides additional information to that offered by conventional ultrasound images. In the musculoskeletal field, sonoelastography can help improve estimation of tendon stiffness. In this article, the principles and future developments of sonoelastography are discussed using the strongest and thickest tendon of the human body, the Achilles tendon, for illustrative purposes. Preliminary findings of sonoelastography in healthy and pathological Achilles tendons, technical considerations, examination technique and several limitations are addressed. The usefulness of elastography can be expected to increase rapidly in the musculoskeletal field, as soon as we learn to interpret elastographic artifacts as well as to take advantage of the new information provided by sonoelastography. PMID- 20539958 TI - Plantar fascia: imaging diagnosis and guided treatment. AB - Plantar fasciopathy is a common cause of heel pain. This article covers the imaging anatomy of the hindfoot, the imaging findings on ultrasound and magnetic resonance imaging (MRI) of plantar fasciopathy, plantar fibromas, trauma, Achilles tendonopathy, neural compression, stress fractures of the os calcis and other heel pad lesions. Thickening of the plantar fascia insertion more than 5 mm either on ultrasound or MRI is suggestive of plantar fasciopathy. Ultrasound is superior to MRI for diagnosis of plantar fibroma as small low signal lesions on MRI are similar to the normal plantar fascia signal. Ultrasound demonstrates low echogenicity compared with the echogenic plantar fascia. Penetrating injuries can appear bizarre due to associated foreign body impaction and infection. Achilles tendonopathy can cause heel pain and should be considered as a possible diagnosis. Treatment options include physical therapy, ECSWT, corticosteroid injection, and dry needling. Percutaneous US guided treatment methods will be described. PMID- 20539959 TI - Imaging of neuropathies about the ankle and foot. AB - Neuropathies about the ankle and foot may be the cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and etiology of nerve compression and exclude other disease possibly underlying the patient' symptoms. In this article, a review of the anatomical and pathological features of nerve entrapments in the distal lower extremity is presented on ultrasound and magnetic resonance imaging, according to the nerve involved. PMID- 20539960 TI - Postoperative MR imaging of the foot and ankle: tendon repair, ligament repair, and Morton's neuroma resection. AB - This review article describes the postoperative magnetic resonance (MR) findings relating to surgery after tendon repair, ligament repair, and Morton's neuroma resection. The normal postoperative tendon is commonly thickened, showing signal changes that are most pronounced 3 to 6 months after surgery. Two years after tendon suture, the signal intensity should be low on T2-weighted images. The focus of the postoperative MR imaging after ankle repair is to detect the normal condition after the various surgical procedures (e.g., Brostrom, Watson-Jones, Evans, or Chrisman-Snook). The repaired ligament has to be visible, low signal intense on T2-weighted MR images, and the shape should be homogeneous. A high rate (26%) of so-called Morton's neuroma recurrences is seen in asymptomatic individuals after Morton's neuroma resection. Postoperatively, intermetatarsal bursitis MR abnormalities are more commonly encountered in symptomatic intermetatarsal spaces than in asymptomatic intermetatarsal spaces. PMID- 20539961 TI - Neuro-osteoarthropathy of the foot-radiologist: friend or foe? AB - Charcot neuro-osteoarthropathy is a significant problem with a rapid devastating nature. If not recognized it may lead to progressive foot deformity, ulceration or osteomyelitis, or eventually to amputation. The diagnosis is challenging, and imaging plays a pivotal role. Rapid and accurate diagnosis and early intervention is important to prevent progressive and destructive Charcot deformity of the foot. The imaging workup of the warm swollen Charcot foot is presented. The advantages and disadvantages of different imaging modalities are discussed. This review provides the consulting radiologists with tools to cautiously differentiate Charcot's neuro-osteoarthropathy from osteomyelitis. It is crucial to look beyond radiological features and integrate the location of pathology and presence of ulcer in the reading process. Because imaging plays a pivotal role in arriving at the definitive diagnosis and adequate treatment, the radiologist "makes the difference"-can be a friend or a foe. PMID- 20539962 TI - [Blast injury]. AB - The blast injury is characterized by 3 different patterns of injury: blast wave, splintered fragments and displacement of victim's body. Severe external and internal hemorrhage, tension pneumothorax and the lethal trios (hypothermia, acidosis, coagulopathy) require a rapid prehospital and inhospital trauma care according to a standardized protocol. The concepts of damage control resuscitation and damage control surgery have proven to be effective and should be integrated into the treatment. PMID- 20539963 TI - [Non cooperation and refusal during induction of anesthesia in children]. AB - Induction of anesthesia can be very distressing for children. This may lead to a lack of cooperation and refusal. The knowledge about the reasons of this behaviour is important to develop strategies and techniques to minimize the preoperative stress. Adequate preparation and the use of anxiolytic premedication are important modules. Non-pharmacological interventions are interesting and could be an alternative to sedative drugs in the future. PMID- 20539964 TI - [Opioids in the management of chronic pain and driving ability]. AB - Opioids are important in pain management of patients suffering from chronic pain. However, opioid use is associated with several concerns, such as opioid induced impairment of cognitive and psychomotor performance. Several studies could demonstrate that opioid treatment in stable doses does not necessarily impair complex activities such as driving ability. But due to intraindividual variability to opioid response and other confounding factors (e.g. pain intensity, co-morbidity) judgements have to be made on an individual basis only. PMID- 20539965 TI - [Emergency room management--"High-tech" and the focal point of interdisciplinary relations and communication]. PMID- 20539966 TI - [Interdisciplinary treatment of severely injured patients in the trauma resuscitation room]. AB - The trauma resuscitation room in emergency departments is an important link between preclinical treatment and clinical management of patients with multiple trauma. For the trauma team (Trauma Surgery, Anaesthesiology, Radiology) to respond adequately, a high degree of training and standardisation is required. With arrival of the patient, the trauma team starts with priority orientated resuscitation. After life-threatening problems have been resolved, the diagnostic work is started with plain films of the chest and the pelvis and FAST. Additional plain films are made depending on further suspected injuries. Reassessment of the patient is done and necessary emergency interventions are performed before the patient is transferred to the radiology department for organ focused computed tomography. CT has gained importance in the early diagnostic phase of trauma care. The development of Multislice Helical Computed Tomography (MSCT) has led to substantial refinement in the diagnostic work-up. For many institutions it has become an essential part of the imaging of the traumatized patient. Delayed and insufficient medical interventions have a high impact on negative patient outcome. Anticipating and dealing with critical situations might reduce preventable errors in the treatment process and can be achieved by implementation of an algorithm-based structured workflow. In that context some elements of quality management are well established in clinical practice. In the presented paper we describe the effort that needs to be done to provide optimal care for multiple trauma patients after admission to a designed trauma centre. PMID- 20539967 TI - [Interaction of emergency medical services and the emergency department- challenges in the acute care of seriously ill or injured patients]. AB - The needs of seriously ill or injured patients issue a challenge to the Emergency Department in terms of personnel, premises and organization. The acute and often interdisciplinary care necessitates optimal surrounding conditions and a stringent coordination of each single step in the in-hospital setting. Many emergencies are time-critical, thus requiring the immediate initiation of diagnostic and first therapeutic measures with respect to the in-hospital interfaces. This review article describes the structural and organizational prerequisites of the appropriate management of seriously sick and injured patients in the Emergency Department. It also focuses on the interdisciplinary cooperation with other specialties during the initial resuscitation ("team approach") as well as during the ongoing clinical course. PMID- 20539968 TI - [Training for real: simulation, team-training and communication to improve trauma management]. AB - The focus on the role of non-technical skills such as communication, dynamic decision making, situational awareness and teamwork in emergency medicine has gained importance over the past few years. Especially during time-critical and complex treatment of severely injured patients in a multidisciplinary and interprofessional trauma-team these factors play an important role for patient safety and process optimization and are a key factor influencing the perceived quality of a given scenario by the team members. Thus, apart from medical expertise and technical excellence of single actors within a trauma team, non technical skills need to be incorporated in trainings for trauma management. For the improvement of non-technical skills, particularly team communication and teamwork, a simulator-based training represents a valuable tool. The technical performance of portable manikin-based simulators has improved tremendously during the last decade, which facilitates realistic and true-to-life multidisciplinary team-training in trauma management. PMID- 20539969 TI - [Professional indemnity insurance for anaesthetists--tips and risks]. AB - In view of patients' increasing expectations the civic liability of physicians is gaining more and more importance. In order to prevent them from the risk of indemnifications to be paid out of their own pocket in the event of loss, a profound professional indemnity insurance becomes necessary. The professional activity of an employed physician is often covered through his employer; however, whether sufficient or not is always subject to an individual case-by-case review as to the limits of indemnity and the risk of a possible regress. Only after definition and verification of the concrete insurance needs (e.g. subsidiary activities), the physician is in the position to decide upon his individual professional indemnity insurance, taking his personal (remaining) risk into account. Thus, superfluous double insurance and insurance gaps can be avoided. PMID- 20539970 TI - Cloning and characterization of a cDNA coding a hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase involved in chlorogenic acid biosynthesis in Lonicera japonica. AB - The flower buds of Lonicera japonica are widely used in Chinese medicine for their anti-inflammatory properties. The reason why L. japonica has potent and significant effects is that it contains various active components, especially chlorogenic acid (CGA). In the present study, we isolated a hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (HQT) gene encoding a protein of 439 amino acids from L. japonica. The RT-PCR results showed that tissue distribution of HQT was in accordance with the pattern of CGA content. The corresponding cDNAs were expressed in Escherichia coli as fusion proteins. Recombinant HQT exhibited catalysis activity in esterification of quinic acid with caffeoyl-CoA to generate CGA. Purified proteins demonstrated similar kinetic properties as HQT isolated from other species. This work is of significance for further studies concerned with strengthening the efficacy of L. japonica by means of improved CGA content and exploring the biosynthesis of CGA in vitro. PMID- 20539971 TI - Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity. AB - Andrographolide, a major constituent of Andrographis paniculata, was previously shown to exhibit anti-inflammatory, antiviral, and anticancer activities. The anticancer activity of andrographolide includes growth suppression, apoptosis promotion, antiangiogenesis, and antitransformation. However, the effect of andrographolide on cancer metastasis, the most malignant feature of cancer, has not been elucidated extensively. In the present study, we demonstrated that andrographolide at nontoxic to subtoxic concentrations (0.3-3 uM) suppressed the invasion ability of CT26 cells in Matrigel-based invasion assays. In addition, the expression of cell adhesion regulators (beta-catenin and ILK) was not altered by andrographolide treatment. However, andrographolide indeed inhibited matrix metalloproteinase 2 (MMP2) activity without affecting its expression. Furthermore, the activation of ERK, but not Akt, was attenuated by andrographolide treatment. Notably, a similar inhibitory effect of andrographolide on the invasion and MMP2 activity of the human colon cancer cell line HT29 was also observed. In summary, our results indicate that andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity. PMID- 20539972 TI - Antimalarial activity of Aspilia pruliseta, a medicinal plant from Uganda. AB - Aspilia pruliseta Schweinf. (Asteraceae) is a medicinal plant indigenous to Uganda and the neighboring countries of East Africa. It has been used extensively by the rural population for the treatment of fevers and malaria. During the antimalarial evaluation of this plant, four nontoxic diterpenes were isolated that possessed moderate activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) clones of Plasmodium falciparum, with IC(50) values ranging from 14 to 23 uM. These moderately active compounds included the previously undescribed diterpene, ENT-15 beta-senecioyloxy-16,17-epoxy-kauran-18 oic acid that demonstrated an IC(50) value of 23.4 uM against clone D6, but was devoid of activity against clone W2. Four additional diterpenes were obtained from the aerial parts of A. pruliseta, but these known compounds were essentially inactive. The moderate activities of select diterpenes of A. pruliseta could account collectively for the historical and enduring use of this plant in traditional African medicine. PMID- 20539973 TI - In vitro anti-influenza viral activities of stilbenoids from the lianas of Gnetum pendulum. AB - The anti-influenza viral activities of six stilbenoids from the lianas of Gnetum pendulum C. Y. Cheng were evaluated with two different assays, neuraminidase (NA) activity assay and cytopathic effect (CPE) reduction assay. The NA assay results showed that all six stilbenoids exerted an NA inhibitory effect, while the CPE assay indicated that among them, isorhapontigenin (2), gnetupendin B (3), shegansu B (4), and gnetin D 6) exhibit significant in vitro anti-influenza viral activity in MDCK cells, with IC(50) values from 0.67 to 11.99 ug/mL in comparison to the positive controls oseltamivir acid and ribavirin whose IC(50) values were 0.040 and 5.54 ug/mL, respectively. PMID- 20539974 TI - Quality of life and fear of cancer recurrence after endoscopic and surgical treatment for early neoplasia in Barrett's esophagus. AB - BACKGROUND AND STUDY AIMS: Endoscopic treatment of early neoplasia in Barrett's esophagus preserves the esophagus and is minimally invasive compared with surgical treatment. However, the influence of endoscopic therapy on quality of life (QOL) and fear of cancer recurrence is unknown. We explored QOL and fear of cancer recurrence 12 - 60 months after endoscopic and surgical treatment for early Barrett's neoplasia, using a cross-sectional design. PATIENTS AND METHODS: A total of 81 patients with early Barrett's neoplasia underwent endoscopic treatment and 33 patients underwent surgery. The choice of treatment was based on tumor size, depth of penetration or patient preference. QOL was measured using the SF-36, EORTC-QLQ-C30, and the EORTC-QLQ-OES18 questionnaires. Anxiety and fear of recurrence were measured using the Hospital Anxiety and Depression Scale (HADS) and the Worry Of Cancer Scale (WOCS). RESULTS: In total, 66 endoscopy patients and 29 surgery patients were eligible for the study. Questionnaires were completed by 64/66 (97 %) endoscopy patients and 27 / 29 (93 %) surgery patients. Multivariate analyses were conducted, with sex, age, comorbidity, and histology of the resected specimen used as covariates. Patients in the surgery group reported significantly more eating problems (OR = 18.3; P < 0.001) and reflux symptoms (OR = 3.4; P = 0.05) on the EORTC-OES18 questionnaire, whereas endoscopy patients reported more fear of recurrence on the WOCS than surgery patients ( P = 0.003). No significant differences were found between the two groups on the other outcomes. CONCLUSION: Preservation of the esophagus after endoscopy treatment, which is preferred from a clinical perspective, may induce fear of cancer recurrence. Proper patient education with specific attention to fear of cancer recurrence may therefore be required. PMID- 20539975 TI - "Eye-tracking" for assessment of image perception in gastrointestinal endoscopy with narrow-band imaging compared with white-light endoscopy. AB - BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) is a new imaging methodology for improving the detection rate of gastrointestinal lesions. We aimed to evaluate perception of images by NBI and corresponding standard white-light endoscopy (WLE) using a computer-guided eye-tracking system. METHODS: A total of 23 NBI images of various lesions with the 23 corresponding WLE images were assessed in random order by 18 subjects with various endoscopy experience. Before evaluation, a teaching set of three NBI and corresponding WLE images was shown to highlight the characteristics of lesions. An eye-tracking system (Tobii X series with integrated 17-inch monitor) was used to record the eye movements of the subjects while they examined respective images. The following parameters were measured: total time spent on image, time until first fixation of lesion, total number of fixations per image and per lesion, and number of fixations until finding the lesion. RESULTS: In total, 828 experiments were conducted. Lesions could not be detected in 6.5 % (NBI) and 4.1 % (WLE) of images ( P = NS). The total number of fixations and total time spent on respective figures as a whole were significantly greater for NBI images compared with WLE images ( P < 0.003). However, the number of fixations until the lesion was found, the number of fixations on the lesion, and the time until first fixation of the lesion did not differ between the two image groups ( P > 0.1). CONCLUSION: This is the first study using eye tracking to evaluate image perception in gastrointestinal endoscopy. Significant differences in the interpretation of NBI and WLE images were observed, which may be relevant for the detection and characterization of lesions during endoscopy. PMID- 20539976 TI - Sepsis and cardiomyopathy as rare clinical manifestations of pheochromocytoma- two case report studies. AB - The clinical manifestation of pheochromocytomas is highly variable and can closely resemble numerous clinical conditions. Here, we report on two cases of patients with pheochromocytoma, which manifested as sepsis or cardiomyopathy. The first patient initially presented with bacterial urosepsis due to klebsiella oxytoca. Despite effective antibiotic therapy, the patient developed recurring fever accompanied by hypertension. The inconsistency between therapy-refractory hypertension and fever indicated the possibility of excessive catecholamine production. In the second case, the patient presented with a suspected ST-segment elevation myocardial infarction accompanied by E. coli sepsis and a previously undiagnosed unilateral tumor mass of the adrenal gland. Severely impaired myocardial contraction of the apical anterior and inferior regions without significant coronary artery disease was consistent with the Takotsubo cardiomyopathy, a known transient functional myocardial complication associated with pheochromocytoma. Both patients were diagnosed with unilateral pheochromocytoma. Following pre-operative antihypertensive therapy, both patients were cured by surgery and still remain free of disease after two years of follow up. PMID- 20539977 TI - Intraoperative laser-assisted indocyanine green angiography for the evaluation of mastectomy flaps in immediate breast reconstruction. AB - Skin-sparing mastectomy has been associated with flap ischemia and necrosis. Current clinical methods for assessment of flap viability following mastectomy are largely subjective and lack objective data to guide intraoperative decisions. Intraoperative laser-assisted indocyanine green angiography (LA-ICGA) was performed on 20 skin sparing mastectomy flaps. LA-ICGA data were retrospectively compared with clinical outcome. Preoperative, intraoperative, and postoperative digital photographs along with clinical course were evaluated in an effort to identify potential complications. LA-ICGA was performed on 20 breasts in 12 patients. Eleven breasts (55%) demonstrated no wound-healing issues. Nine breasts (45%) experienced wound-healing issues, which were stratified as follows: 1 (5%) mild, 1 (5%) moderate, and 7 (35%) severe. Of these seven severe wound-healing issues, 5 (25%) required debridement and 2 (10%) required complete removal of the prosthetic device. Retrospective analysis demonstrated a 95% correlation between intraoperative imaging and clinical course with 100% sensitivity and 91% specificity. There was a false-positive rate of 9%. This series suggests LA-ICGA is a useful adjunct to determine mastectomy flap viability. Further quantitative advances in this technology may provide objective numerical thresholds to guide intraoperative mastectomy flap debridement when indicated. PMID- 20539992 TI - Guest editor's message: Providing more medical care through distance learning in Micronesia and developing culturally competent curricula are provided in several solution-based articles. PMID- 20539993 TI - Health as a human right: who is eligible? AB - In Hawaii, health care is a commodity, not a human right: those who can afford it receive care, those who cannot often don't. As health workers and health professional students, we witness the consequences that public policies and budget considerations have on people, on patients, on the health of those that we are dedicated to assisting. Beginning with a case study, we examine the historical antecedents leading to the increasing migration of Micronesians to Hawaii, examine the special relation that (Compact of Free Association) citizens have with the United States, and seek to reframe the political discussion regarding their health care status in this state as a debate in which medical considerations, not political or economic ones, should be the primary voice. PMID- 20539994 TI - The "compact impact" in Hawaii: focus on health care. AB - The political, economic, and military relationship between the former Pacific Trust Territories of the United States is defined by the Compact of Free Association (COFA) treaty. The respective COFA treaties allow the United States military and strategic oversight for these countries, while COFA citizens can work, reside, and travel with unlimited lengths of stay in the United States. The unforeseen consequences of the diaspora of the people of the COFA nations to the United States and its territories is called the "Compact Impact." In 2007 the social, health, and welfare system costs attributed to the estimated 13,000 COFA migrants in Hawaii was $90 million. The US federal government does not take full responsibility for the adverse economic consequences to Hawaii due to COFA implementation. The lack of health and education infrastructure in the COFA nations, as well as the unique language, culture, political, and economic development of the region have contributed to the adverse elements of the Compact Impact. The Department of Human Services of Hawaii, once supportive of the COFA peoples, now looks to withdraw state sponsored health care support. This paper reviews the historical, political, and economic development, which surrounds the Compact Impact and describes Hawaii's government and community response. This paper attempts to understand, describe, and search for solutions that will mitigate the Compact Impact. PMID- 20539995 TI - Understanding cervical cancer prevention and screening in Chuukese women in Hawaii. AB - BACKGROUND: Cervical cancer is the primary cause of death due to cancer in women in Chuuk State, Federated States of Micronesia. The Chuukese population is the fastest growing segment of the Micronesian community in Hawaii. Little is known about the health beliefs or practices of this population in Hawaii. The purpose of this project was to describe the knowledge, attitudes, and beliefs of Chuukese women in Hawaii regarding cervical cancer prevention and screening. METHODS: Research assistants from the Chuukese community were recruited and trained as members of the research team. A culturally sensitive survey tool was developed and piloted by the research team and used to interview ten key informants from the Chuukese community in Honolulu, Hawaii. RESULTS: There is limited knowledge about cervical cancer, especially the association with human papillomavirus (HPV). This may be indicative of a lack of health information in general. Fear, privacy concerns, lack of awareness and cultural beliefs represent the main barriers mentioned when discussing cervical cancer. Education, done in a group setting with other women, is the most recommended method of informing this community and improving preventive and screening services for cervical cancer in these women. PMID- 20539996 TI - American Samoan women's health: experiences and attitudes toward breast and cervical cancer screening. AB - BACKGROUND: Cancer is the second leading cause of death among Samoan women and, compared to women of other ethnicities in the United States, Samoan women present at earlier ages with advanced stages of both breast and cervical cancers. Our goal was to gain a better understanding of issues that may prevent women in American Samoa from using available cancer screening resources. METHODS: Following approval from the Office of Samoan Affairs, we conducted four focus group sessions, in which a total of 55 women from urban and rural sites participated. Women were asked about their perceptions regarding barriers, knowledge, and past utilization of available cancer screening services. RESULTS: Among the participants, professional women were more aware and had higher utilization rates of age-specific screening services. Barriers to health care services included lack of awareness and fears regarding poor confidentiality. DISCUSSION: Our findings, which have been reviewed by participants, highlight the further need for outreach and education about female cancers. Screening rates could be increased and all services may benefit from increased collaboration between the American Samoa Department of Public Health and Lyndon B. Johnson (LBJ) Tropical Medical Center. Our findings underline a need for additional staff training in professionalism, particularly in the areas of confidentiality and respect for patients. PMID- 20539997 TI - Perceptions and use of complementary and alternative medicine in American Samoa: a survey of health care providers. AB - PURPOSE: American Samoa health care providers' use and perceptions of common complementary and alternative treatments, with a focus on traditional Samoan healing for women diagnosed with breast cancer or cervical cancer, was investigated to inform the development of the first locally produced women's cancer prevention radio drama and the first cancer patient navigator program in the US Territory. METHODS: A 10-item self-administered survey was completed by a total of 47 health care providers employed at the Lyndon B. Johnson Tropical Medical Center and the American Samoa Department of Health Breast and Cervical Cancer Early Detection Program. FINDINGS: Comprehensive health care is limited in American Samoa, especially cancer treatment. Dissatisfaction or disconnection with Western medicine leads some patients to seek complementary or alternative health care from traditional Samoan healers who provide massage and herbal remedies. Health care providers in American Samoa use and recommend many complementary and alternative medicines (CAM) popular in the United States. The most common CAM recommended to patients is exercise (81%), diet modification (81%), prayer (36%), massage (36%), support group participation (26%), and relaxation techniques (19%). Traditional Samoan healing methods are unique CAM that 19% of mainstream health care providers have used, and 17% have recommended these techniques to patients. Most survey respondents believe traditional Samoan healing methods have a harmful effect on patient quality of life and 72% have advised a patient to discontinue using this type of CAM. While most providers feel that the majority of American Samoan patients use traditional healing methods to complement Western healthcare, 55% are aware of a breast cancer or cervical cancer patient utilizing these techniques as an alternative to hospital treatment. A provider's ethnicity, gender, age and years of professional experience appear to be indicators of different CAM method endorsement and patient consultations concerning CAM use. CONCLUSIONS: CAM use is likely to continue in American Samoa as long as health care deficiencies exist. Most American Samoa health care professionals accept common CAM in the United States, but local providers are more likely to endorse traditional healing methods than their mainland counterparts. Little is known of the impact different CAM have on quality of life, especially amongst cancer patients. The majority of American Samoa health care providers request more information about tradition al healing which would facilitate more comprehensive medical documentation and patient care. PMID- 20539998 TI - Resident-driven group medical visits for diabetes mellitus in an ethnically diverse clinic population. AB - Group medical visits benefit both patients and providers. In this study, a family medicine resident physician initiated group medical visits for diabetes mellitus at a family medicine residency clinic with the cooperative health care clinic format. Patients were ethnically diverse; mostly of Asian or Pacific Islander ancestry. A registered dietician was present at most group visits, and topics discussed were patient driven. Thirteen patients participated over a nine-month period but data from only the seven patients who attended more than once was used for analysis to show changes over time. Data for all pre- and post-participation surveys collected were used (thirteen and nine, respectively). Non-laboratory measures, such as increased whole grain consumption, were more greatly affected than laboratory measures, such as hemoglobin A1C. Pre- and post-participation surveys revealed that most patients were concerned about general diabetes knowledge, diet and exercise, and group medical visits helped them increase knowledge of these topics. Major challenges of resident initiated group medical visits were scheduling and low patient attendance despite reminder systems. PMID- 20539999 TI - Designing a cultural competency curriculum: asking the stakeholders. AB - BACKGROUND: The design of a cultural competency curriculum can be challenging. The 2002 Institute of Medicine report, Unequal Treatment, challenged medical schools to integrate cross-cultural education into the training of all current and future health professionals. However, there is no current consensus on how to do this. The Department of Native Hawaiian Health at the John A. Burns School of Medicine formed a Cultural Competency Curriculum Development team that was charged with developing a curriculum for the medical school to address Native Hawaiian health disparities. By addressing cultural competency training of physicians, the team is hoping to help decrease the health disparities found in Native Hawaiians. Prior attempts to address culture at the time consisted of conferences sponsored by the Native Hawaiian Center of Excellence for faculty and clinicians and Problem Based Learning cases that have imbedded cultural issues. OBJECTIVE: Gather ideas from focus groups of Native Hawaiian stake- holders. The stakeholders consisted of Native Hawaiian medical students, patients and physicians. Information from the focus groups would be incorporated into a medical school curriculum addressing Native Hawaiian health and cultural competency training. METHODOLOGY: Focus groups were held with Native Hawaiian medical students, patients and physicians in the summer and fall of 2006. Institutional Review Board approval was obtained from the University of Hawaii as well as the Native Hawaiian Health Care Systems. Qualitative analysis of tape recorded data was performed by looking for recurrent themes. Primary themes and secondary themes were ascertained based on the number of participants mentioning the topic. RESULTS: Amongst all three groups, cultural sensitivity training was either a primary theme or secondary theme. Primary themes were mentioned by all students, by 80% of the physicians and were mentioned in all 4 patient groups. Secondary themes were mentioned by 75% of students, 50% of the physicians and by 75% of patient group. All groups wanted medical students to receive cultural sensitivity training, and all wanted traditional healing to be included in the training. The content of the training differed slightly between groups. Students wanted a diversity of teaching modalities as well as cultural issues in exams in order to emphasize their importance. They also felt that faculty needed cultural competency training. Patients wanted students to learn about the host culture and its values. Physicians felt that personal transformation was an important and effective tool in cultural sensitivity training. Cultural immersion is a potential teaching tool but physicians were concerned about student stages of readiness and adequate preparation for cultural competency training modalities such as cultural immersion. CONCLUSIONS: Cultural competency or sensitivity training was important to patients, students and physicians. The focus group data is being used to help guide the development of the Department of Native Hawaiian Health's cultural competency curriculum. PMID- 20540000 TI - Health disparities in the Native Hawaiian homeless. AB - While it is well accepted that Native Hawaiians have poor health statistics compared to other ethnic groups in Hawaii, it is not well documented if these disparities persist when comparing Native Hawaiian homeless individuals to the general homeless population. This paper examines the Native Hawaiian homeless population living in three shelters on the island of Oahu, to determine if there are significant differences in the frequency of diseases between the Native Hawaiian and non-Native Hawaiian homeless. A retrospective data collection was performed using records from the Hawaii Homeless Outreach and Medical Education (H.O.M.E.) project. Data from 1182 patients was collected as of 12/05/09. Information collected included patient demographics, frequency of self reported diseases, family history of diseases, risk factors, prevalence of chronic diseases, and most common complaints. The data from Native Hawaiians and non Native Hawaiians were examined for differences and a 1-tail Fisher exact analysis was done to confirm significance. The data reveals that the Native Hawaiian homeless population is afflicted more frequently with asthma and hypertension compared to other ethnic groups. While diabetes constituted more visits to the clinics for Native Hawaiians compared to the non-Native Hawaiians, there was no significant difference in patient reported prevalence of diabetes. The Native Hawaiian homeless also had increased rates of risky behaviors demonstrated by higher past use of marijuana and methamphetamines. Interestingly, there was a lower use of alcohol in the Native Hawaiian homeless and no significant difference between Native Hawaiians and non-native Hawaiians in current use of illicit drugs, which may represent a hopeful change in behaviors. These troubling statistics show that some of the health disparities seen in the general Native Hawaiian population persist despite the global impoverished state of all homeless. Hopefully, these results will aid organizations like the H.O.M.E. project to better address the health needs of the Native Hawaiian homeless population. PMID- 20540001 TI - Physician and pharmacist collaboration: the University of Hawaii at Hilo College of Pharmacy--JABSOM experience. AB - The purpose of this article is to describe the experiential program created at the newly formed University of Hawaii at Hilo College of Pharmacy (UHH CoP). The Introductory Pharmacy Practice Experience (IPPE) rotations were developed to prepare student pharmacists for their final year of Advanced Pharmacy Practice Experience (APPE) rotations by improving clinical skills and patient interactions. In partnership with the John A. Burns School of Medicine (JABSOM) Department of Family Practice, physician and pharmacist teams collaborate to deliver patient care for chronic diseases and elevate educational opportunities provided by UHH CoP. Another goal of the experiential program is to determine whether the investment of pharmacist faculty and adjunct physician/nurse preceptors prepares students for the final year of APPE rotations. A survey was administered to non-faculty pharmacist preceptors who taught the third IPPE rotation during the summer of 2009. Twenty-nine surveys were received from six facilities on Oahu and the Big Island. Initial survey results revealed an overall rating average of 3.72 (Likert scale: 1--lowest to 5--highest), an average of 4.14 for professionalism, an average of 3.41 for overall clinical skills, and an average of 3.45 for overall readiness for experiential rotations. Average ratings when compared with fourth-year students from several mainland colleges ranged from 1.7 to 2.2 (1--worse than, 2--same, 3--better). This data demonstrates that UHH CoP is investing faculty and preceptor resources wisely to enhance the preparation of students for APPE rotations. PMID- 20540002 TI - Getting the patients' perspective: a survey of diabetes services on Guam. AB - The prevention and control of diabetes is a major public health priority for the US Territory of Guam. As part of a strategic planning process, a survey of diabetes patients was conducted to determine patients' perceptions of the availability and adequacy of preventive and clinical services to control diabetes. A total of 125 survey questionnaires were distributed to diabetes patients attending either one of the Guam Department of Public Health and Social Services Community Health Centers or a private Internal Medicine/Endocrinology clinical practice of the only endocrinologist on the island. All 125 questionnaires were returned. Respondents were highly aware of the duration of their diabetes, and almost 75% have had the opportunity to discuss the chronic nature of the illness and the importance of key lifestyle changes to help prevent or retard the progression of the disease. However, almost 40% of patients were not aware of the type of diabetes they had, and one in five have not received diabetes self-management education from their health care providers. Key interventions, such as nutritional counseling, brief tobacco cessation interventions, regular eye and foot examinations and immunization services were not being provided to 30% to 60% of patients, despite clinical practice guidelines that recommend these interventions for all diabetics. While over half of respondents were generally satisfied with the quality of preventive and routine medical care that they receive from their service providers, they identified the need for better quality diabetes self-management education, preventive services, enhanced access to specialists and specialized care, especially for diabetes-related complications, and better financial support to assist them in meeting the costs of chronic care and medications. The feedback from these respondents should provide guidance regarding service gaps and needs as the Department of Public Health and Social Services and its community partners collaboratively develop a strategic plan to better address diabetes prevention and control on Guam. The information should also serve to direct quality improvement efforts to enhance existing diabetes services on the island. PMID- 20540003 TI - Guam's influenza epidemic(s) of 2009. AB - OBJECTIVE: To characterize syndromic and laboratory surveillance for influenza on Guam during 2009, including the relation of cases to the timing of swine flu related stories published in a local newspaper. METHODS: Data utilized in the study included clinical diagnoses of acute respiratory infection (ARI) in the Emergency Department log of Guam's only civilian hospital (syndromic surveillance) and laboratory confirmed cases of Influenza A (rapid test) and novel 2009 H1N1 influenza virus (RT-PCR subtyping) from both civilian and military sources. In addition, the number of "swine flu" stories appearing weekly in a local paper were tallied. RESULTS: What initially appeared to be an epidemic occurring in 2 distinct waves was shown to be separate epidemics of "seasonal flu" and "swine flu." There was a strong correlation between the timing of "swine flu" stories appearing in local media and the diagnosis of ARI. CONCLUSION: Syndromic surveillance is useful for the early detection of disease outbreaks but laboratory results may be necessary in order to gain a clear epidemiologic picture of a disease incident. PMID- 20540004 TI - New hospital medical libraries in Micronesia. PMID- 20540005 TI - Developing the rural primary care workforce in Hawaii--a 10-point plan. AB - The shortage of physicians and resultant lack of access to care particularly on the rural neighbor islands of Hawaii has been well described. A recent report in the December issue of this journal by Withy, et al. documents a current shortage of 45 physicians on the Big Island. (1) Similar reports suggest that Hawaii's physician workforce lags 20% behind physician to population ratios in the continental US. It is projected that the aging population and the heavy burden of chronic disease will increase demand for health services by 40% by 2020 and even higher for specialties that focus on the care of elders. The existing physician shortage is heightened by the high percentage of doctors reaching retirement age. High business and living costs coupled with low reimbursement for health services makes it difficult to be competitive when recruiting physicians to Hawaii. Are there evidence based solutions to the state rural primary care workforce crisis? This article describes what is currently in place as well as new initiatives and a ten point plan to lay the framework for an improved state rural training pipeline. PMID- 20540006 TI - A partnership between the cancer research center of Hawaii and the University of Guam in Cancer Research, Education, Training, and Outreach. AB - Cancer Health Disparities. The term cancer health disparities describes the unequal burden of cancer incidence, morbidity, and mortality in different population groups. By and large, the higher burden of cancer is observed in racial or ethnic minorities, immigrant communities, inner city populations, and insular, rural, or otherwise geographically isolated populations. In rare instances, however, the majority Caucasian population suffers a higher burden of cancer, e.g., melanoma. There are multiple and overlapping causes for cancer health disparities, including genetic make up, cultural norms and beliefs, behavior, environmental factors, as well as social aspects such as socio-economic status, poverty, and education. Reducing cancer health disparities is an important and integral component of the nation's effort to improve the health of all Americans. The science of cancer health disparities aims to better understand the causes of health disparities and to develop better means of prevention, diagnosis, and therapy, although some of the social aspects of cancer health disparities may be beyond the reach of the biomedical community. PMID- 20540008 TI - [Transcriptomics: a further step in the right direction]. PMID- 20540007 TI - [KDIGO guidelines for the diagnosis and treatment of chronic kidney disease mineral and bone disorder: what's new?]. PMID- 20540009 TI - [Live or die? Dephosphorylation is the key]. PMID- 20540010 TI - [Ferritin: new part for old actor]. PMID- 20540011 TI - [Bicarbonate in the prevention of iodinated contrast medium-induced kidney damage: a never-ending story?]. PMID- 20540012 TI - [Urea: underestimated toxin?]. PMID- 20540013 TI - [Renal hypoperfusion and acute kidney injury: any news?]. PMID- 20540014 TI - [Treatment of atrial fibrillation in dialyzed patients: the role of oral anticoagulants. The cardiologist's point of view]. AB - Atrial fibrillation is associated with an increased thromboembolic risk, mainly in the cerebral vascular district. Oral anticoagulant therapy has been demonstrated to be effective in the prevention of thromboembolic events; however, it has some limitations and a relevant bleeding risk. In order to overcome the limits of oral anticoagulant therapy, other antithrombotic strategies have been tested. Antithrombotic therapy in atrial fibrillation must be tailored according to the thromboembolic risk of the single patient and the specific characteristics of the different drugs. Clinicians are supported in their decisions regarding antithrombotic therapy by the current practice guidelines, which are based on different risk indices. This paper will discuss the issues of thromboembolic risk stratification and the different options of antithrombotic strategies, including possible future alternatives. PMID- 20540015 TI - [Treatment of atrial fibrillation in dialyzed patients: the role of oral anticoagulants. The nephrologist's point of view]. AB - Atrial fibrillation is the most frequent arrhythmia in patients on dialysis. Whereas it is associated with a higher thromboembolic risk in the general population, this association has not been unequivocally confirmed in dialysis patients. Furthermore, the potential benefits of oral anticoagulant therapy in uremia have been recently reviewed, given the increased risk of bleeding in these patients. Cardiologic guidelines to guide the choice of oral anticoagulant therapy by stratifying the thromboembolic and hemorrhagic risks were developed in the general population and their generalization to dialysis patients has not been validated. This paper will discuss the association between atrial fibrillation and thromboembolic risk in dialysis, presenting some strategies to evaluate the risk-benefit balance of oral anticoagulant therapy in dialysis patients affected by atrial fibrillation. PMID- 20540016 TI - [Anticoagulant therapy in patients with atrial fibrillation on dialysis: between the risk of hemorrhage and vascular calcification]. AB - Oral anticoagulant therapy (OAT) in patients with atrial fibrillation during dialitic treatment or suffering from severe chronic renal failure is not easy to mange. OAT interferes with the mechanisms of protection and prevention of vascular calcification and increases the risk of bleeding and of the development of vascular calcifications typical of these patients. The aim of this report is to highlight the complexity of the management and therapy in uremic patients, discussing the importance of OAT in order to prevent thrombo-embolic complications during atrial fibrillation episodes. PMID- 20540017 TI - [Role of C-peptide in the pathogenesis of diabetic nephropathy]. AB - Insulin and C-peptide are secreted by pancreatic beta cells in equimolar amounts. Although C-peptide has long been believed to have no biological function, in recent years this molecule has been recognized as an independent hormone with a specific G-protein-coupled receptor. Recent evidence suggests that C-peptide may also have a specific nephroprotective effect, particularly in cases of diabetic nephropathy. In animal models of diabetes this beneficial effect has been repeatedly confirmed. Contradictory results have been obtained in humans: on the one hand it was shown that patients with diabetic nephropathy have lower plasma levels of C-peptide than patients with diabetes of similar duration and normal renal function; on the other hand it is also evident that patients affected by type 2 diabetes develop nephropathy even in the presence of high plasma levels of C-peptide, suggesting that in humans C-peptide is likely to have multifaceted activity. This review describes the different arguments supporting or contrasting the notion of C-peptide as a potential new therapy for diabetic nephropathy. It is possible that only a well performed, large-scale clinical study with careful evaluation of the positive and negative effects of C-peptide will finally clarify whether C-peptide reintegration in patients with type 1 diabetes is able to prevent the development and/or control the progression of diabetic nephropathy. PMID- 20540018 TI - [Treatment of lupus nephritis: an update]. AB - Renal involvement contributes significantly to the severity of systemic lupus erythematosus and influences patient survival. Although in recent years, thanks to the use of immunosuppressive agents and steroids, the prognosis has greatly improved, it is still associated with multiple side effects and possible relapses. Therefore, recent studies have evaluated the possibility of using protocols that may be equally effective both in the short and long term but are potentially less toxic in both the proliferative and membranous forms of lupus. Moreover, further knowledge of the complex pathogenesis of lupus has accelerated research into and use of new biological immunomodulators. In this review we present the most recent therapeutic trials and the new, promising therapies based on biological immunomodulators. PMID- 20540019 TI - [Natural history, diagnosis and treatment of chronic hepatitis B and C in hemodialysis patients]. AB - Chronic hepatitis B and C are important causes of liver disease in hemodialysis units. The most important route of transmission is the inapparent parenteral route; known risk factors are the high prevalence of HBV and HCV infections in hemodialysis units, previous blood transfusions, long-term dialysis treatment, frequent changes of hemodialysis unit, and previous renal transplants. The source, time and duration of infection are often difficult to ascertain. The studies investigating the natural history of viral hepatitis in hemodialysis patients are few and limited by a short follow-up, but they show an independent and negative impact on survival due to an increased risk of liver cirrhosis and hepatocellular carcinoma. The treatment options include conventional or pegylated interferon (alone or in association with ribavirin) and the nucleoside/nucleotide analogs. The aim of treatment is viral eradication or persistent suppression of viral replication. The altered pharmacokinetics, the increased risk of drug related toxicity, and the need for renal transplant complicate the management of antiviral therapy. In patients with chronic HBV infection and active replication the most common approach is persistent suppression of viral replication using nucleoside/nucleotide analogs. As regards hepatitis C, several clinical trials evaluating conventional interferon monotherapy have shown higher sustained virological response and dropout rates in dialysis patients than in patients with normal kidney function. Data about pegylated interferon as monotherapy or in association with ribavirin are promising but limited. Hemodialyzed patients obtaining a sustained virological response often maintain the response after kidney transplantation. PMID- 20540020 TI - [Kidney transplant: a mere stage of CKD?]. AB - At present, renal transplantation is the best treatment for end-stage renal disease but not the cure. The main factors limiting a full recovery after transplantation include the need for lifelong immunosuppressive therapy (which may lead to severe side effects in the long term), and only partial recovery of renal function after grafting. The latter event is not infrequent nowadays due to the increasing age of donors, who frequently die of cerebrovascular accidents and may have subclinical renal vascular lesions despite a GFR >60 mL/min, with increased susceptibility to calcineurin inhibitor toxicity. As a consequence, uremic alterations such as anemia, arterial hypertension and bone disease may persist at various degrees after surgery and affect the patients' outcome in the long term. The outcome of renal transplantation may be improved if, in addition to accurate tuning of immunosuppressive regimens, we take into account the prevention and treatment of all conditions that may impair the clinical course of transplant recipients. PMID- 20540021 TI - [Diagnostic and therapeutic approach in patients with urinary calculi]. AB - The natural history of urolithiasis includes the risk of recurrence and of the development of chronic kidney and/or bone disease, which is why a thorough clinical and metabolic evaluation of these patients is of the utmost importance at disease onset. This paper is aimed at identifying the type of urolithiasis, the related risk factors, and the corresponding treatment options. The diagnostic and therapeutic approach described here includes 1) accurate history taking to detect secondary nephrolithiasis and screen for the main risk factors for kidney and bone disease; 2) metabolic evaluation graded according to different complexity levels based on the severity of the disease and the presence of risk factors; 3) carrying out appropriate imaging procedures. The resulting information allows to plan treatment based either on general rules of lifestyle and diet, or on selected medical intervention, if necessary. This report, which is based on current guidelines, was produced by the Gruppo Italiano di Studio Multidisciplinare per la Calcolosi Renale. It is addressed to all professionals involved in the management of patients suffering from nephrolithiasis, first of all general practitioners, who often become involved immediately at the onset of the disease. PMID- 20540022 TI - [Quality of life assessment in patients on hemodialysis and peritoneal dialysis]. AB - Assessment of the quality of life (QoL) of patients with end-stage renal disease undergoing replacement therapy is very important. The aim of our study was to assess the QoL of patients on hemodialysis (HD) and peritoneal dialysis (PD). To determine the state of health of the patients as well as psychological aspects we used two international questionnaires: the Health-Related Short Form (SF-36) and the Psychological General Well-being Index (PGWBI). The study included 48 patients (26 men, 22 women) with chronic kidney disease (KDOQI: 5). All patients were on dialysis treatment. Their mean age was 63 years (range 59-73) and the mean duration of dialysis was 18 months (range 12-34). Twenty-four patients (13 men, 11 women) were on DP and 24 (13 men, 11 women) on HD. The results demonstrate that the PD and HD groups diverged on almost all scales. The scales that measure both the mental and physical dimensions of QoL showed PD to be associated with a higher level of psychophysical well-being than HD. The SF-36 revealed that both the physical and mental dimensions were directly influenced by the type of treatment. On the depression scale of PGWBI we found that patients on HD were more prone to depression than patients on PD. In conclusion, PD appears to have clear advantages in terms of QoL, especially in elderly patients, thanks to the possibility to perform the treatment independently at the patient's home. PMID- 20540023 TI - [How to measure effects in clinical research (corrected)]. PMID- 20540024 TI - [Recurrent multifocal cancer lesions in a patient on hemodialysis after kidney pancreas transplant failure]. AB - Cancer is an important cause of mortality in patients on hemodialysis and kidney transplant recipients. Immunodepression and the genotoxic action of uremia are critical pathogenic agents. A 59-year-old man, ex-smoker, who had been on hemodialysis for seven months because of uremic degeneration of diabetic nephropathy, underwent a combined kidney-pancreas transplant in 1991, complicated by slow-resolution CMV infection. In 1993, after kidney graft failure due to chronic rejection, hemodialysis treatment was restarted with good pancreatic function. Steroid therapy was interrupted and azathioprine and cyclosporine immunosuppressive therapy maintained. In September 2007 the patient was diagnosed with two neoplasms of the oral mucosa: a well-differentiated squamous carcinoma and a spinocellular carcinoma associated with field cancerization. The tumors were resected, followed by laser treatment. Histological examination revealed squamous cell carcinoma without lymph node involvement. Azathioprine was interrupted. In January 2008 adjuvant radiotherapy to the surgical areas of the oral mucosa and neck was started. In February a verrucous nevus on the patient's chest turned out to be a spinocellular carcinoma in situ. In May 2008 recurrence of keratinizing squamous carcinoma of the oral mucosa was found, this time with nodal involvement. Cyclosporine administration was interrupted and after consultation with the oncology committee it was decided to continue with supportive therapy only, until the patient's death in August 2008. PMID- 20540025 TI - [Voriconazole compromises renal function in an elderly CDK patient with Candida albicans infection]. AB - There has been a progressive increase in the number of intensive care patients being transferred to nephrology units because of improper dosage of drugs, especially patients with chronic kidney disease (CKD). Voriconazole is a new synthetic triazole derivative with stronger therapeutic activity against fungal infections than fluconazole or itraconazole. Its effectiveness is associated with high nephrotoxicity, affecting patients with CKD in particular. The adverse effects of voriconazole involve several segments of the nephron, particularly the proximal tubule, medullary thick ascending limb, and collecting duct, causing loss of potassium and magnesium and backdiffusion of hydrogen ions. We report the case of an 86-year-old man with moderate CKD who developed acute renal failure as a result of inadequate dosage of voriconazole. He developed oliguria, electrolyte imbalance and fluid overload requiring hemodialysis. Vericonazole withdrawal associated with short daily hemodialysis treatment led to the recovery of diuresis, kidney function, and electrolyte balance. In conclusion, in elderly patients with liver disease and moderate CKD, thorough evaluation is needed before the administration of voriconazole in order to establish the most appropriate dose. PMID- 20540026 TI - [The DASCO meetings: a contribution of industry to Italian nephrology]. AB - Between 1971 and 1977 eight DASCO meetings were held in different cities in Italy. The meetings dealt with the technical aspects of renal dialysis, then in its early days. They were organized as round tables and the proceedings were published timely. Lively discussion among the audience was a characteristic feature. Most of the attendants, who came from all over Italy, later pursued careers in nephrology and held posts in the Italian Society of Nephrology. The meetings contributed to the development of national standards for dialysis and ended in 1977 with the definitive establishment of renal dialysis in Italy. PMID- 20540027 TI - [The role of the patient in handling long-term treatment. From compliance to adherence]. PMID- 20540028 TI - Peritoneal transport testing. AB - Different tests can be used to provide valuable information about the function of the peritoneal membrane. The data obtained can be useful for tailoring dialysis adequacy, for the analysis of clinical problems such as ultrafiltration failure or to predict the development of more severe peritoneal membrane derangement. The most widely used peritoneal function test is the peritoneal equilibration test (PET), developed and described by Twardowski in 1987. PET is performed using a 2.27% glucose solution, and it lasts 4 hours. It measures peritoneal solute transport and ultrafiltration (UF), and it gives the possibility to categorize patients (high, high-average, low-average and low transporters). However, a PET with 3.86% glucose provides better information on UF, on the phenomenon of sodium sieving and an assessment of free water transport. Two recently developed tests (Mini-PET, Double Mini-PET) are promising tools to assess free water transport and the osmotic conductance to glucose. It is possible to integrate the 3.86%-PET with the new tests to obtain a complete PET: the Uni-PET (all these tests in 1 PET). The new insights into peritoneal function need a new standardization of the PET. It would be worth having a machine (PET machine) which performs the PET automatically to avoid possible mistakes during the performance of the manual PET and to allow an universal standardization of the test. PMID- 20540029 TI - Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma. AB - BACKGROUND: Recent studies demonstrated that the expression pattern of bone morphogenetic protein-7 (BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC). METHODS: Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression was analyzed by immunohistochemistry. RESULTS: RT-PCR showed strong down regulation of BMP-7 mRNA in cancer tissue. Immunohistochemistry revealed expression of BMP-7 in normal renal tissue, with almost complete loss of BMP-7 expression in malignant cells of 6 patients (30%). After 3 years of follow-up, 5 out of 6 patients with high BMP-7 mRNA expression were alive and disease-free, compared with 9 out of 14 patients with low BMP-7 mRNA expression. CONCLUSIONS: BMP-7 mRNA and protein expression were down-regulated in CCRC. Further prospective studies are needed to characterize the role of BMP-7 in human CCRC. PMID- 20540030 TI - Cardiorenal protective effect of the oral uremic toxin absorbent AST-120 in chronic heart disease patients with moderate CKD. AB - BACKGROUND: The detailed mechanisms and treatment methods of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) are not fully understood. We conducted a prospective study in CHF patients manifesting CKD to examine if AST-120 (Kremezin) improves cardiac and renal functions. METHODS: Twenty outpatients with CHF manifesting moderate CKD (serum creatinine 1.3-2.0 mg/dL) were studied. The patients had received AST-120 at a dosage of 6 g/day in combination with existing medications for 24 months. Some parameters of kidney and heart function were monitored. Also the cumulative length of hospital stay and number of admissions for the 2-year periods before and after initiation of AST-120 treatment were calculated. RESULTS: Results of renal function tests, atrial natriuretic peptide, edema, cardiothoracic ratio and hospital stay indicated significant improvements in patients treated with AST-120. The length of hospital stay and number of admissions both decreased significantly during the 2 years of AST-120 treatment compared with the 2 years before treatment, from 39.7 +/- 12.9 days to 4.14 +/- 2.5 days, and from 0.79 +/- 0.21 admissions to 0.21 +/- 0.11 admissions, respectively. CONCLUSIONS: AST-120 contributes to the improvement of cardiac and renal functions, and consequently improves the quality of life of patients. PMID- 20540031 TI - Gypenosides inhibit renal fibrosis by regulating expression of related genes in rats with unilateral ureteral obstruction. AB - BACKGROUND: Transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF) and Smad7 are potent components of fibrogenesis-related signal transduction pathways. Renal fibrosis is the major pathological change in the rat models with unilateral ureteral obstruction (UUO). Investigating the effects of gypenosides (GPs) on the expression of fibrogenesis-related genes in the UUO model may lead to the development of effective therapy for renal diseases. METHODS: Rats were randomly divided into 3 experimental groups: (i) sham operation rats treated with saline (sham group), (ii) UUO model rats treated with saline (control group) and (iii) UUO model rats treated with GPs (GPs group). Blood urea nitrogen and serum creatinine were detected as the measurement of renal function. UUO-treated kidney tissues were taken for assessment of renal damage index and determination of related gene expression through immunohistochemistry and RT-PCR. RESULTS: UUO-induced tubulointerstitial damage and fibrosis were attenuated by the application of GPs (day 3 and day 7, p<0.01; day 14, p<0.05). The expression of TGF-beta1 and CTGF was significantly reduced with GPs treatment (TGF-beta1, p<0.01; CTGF, p<0.05). Smad7 expression was elevated with GPs treatment at days 7 and 14 (p<0.01). GPs' protective effects on renal function were also demonstrated with this UUO model. CONCLUSIONS: These results suggest that UUO-induced tubulointerstitial fibrosis can be effectively attenuated by GPs application. GPs-mediated down-regulation of TGF-beta1 and CTGF and up-regulation of Smad7 are essential for their effects of antifibrogenesis. PMID- 20540032 TI - Life expectancy, expected years of life lost and survival of hemodialysis and peritoneal dialysis patients. AB - BACKGROUND: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD patients were then matched with PD patients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model. RESULTS: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 +/- 13.7 vs. 53.1 +/- 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28 6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). CONCLUSIONS: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD. PMID- 20540033 TI - Criteria for referring patients with renal disease for nephrology consultation: a review of the literature. AB - INTRODUCTION: Referrals to nephrologists comprise not only patients with chronic kidney disease but also those with other nephrological conditions. There may be confusion about when to refer a patient to a nephrologist. We conducted a literature review to identify preexisting priority-setting, triage or referral criteria developed to guide referrals from primary care to a nephrologist. METHODS: Medline and Cochrane databases were searched (1997 to 2008) using search terms: referral, consultation, triage and a list of specified nephrological conditions. Abstracts were assessed by 2 reviewers using criteria to determine relevance. Citation and hand searches were done on papers selected for review; relevant Web sites were also consulted. Two reviewers read all selected papers to determine if they met the objectives. One reviewer abstracted relevant data from each retained reference and compiled the results into a report, which was reviewed by 3 practicing nephrologists. RESULTS: There were 18 retained papers, reports or Web sites; 4 of these were professional national guidelines. All but 1 reference cited serum creatinine or estimated glomerular filtration rate as a criterion for referral. Other referral criteria were proteinuria (8 sources), blood pressure (5 sources), electrolytes (3 sources) or hematuria (3 sources). There was inconsistency in referral recommendations. CONCLUSIONS: The differing advice identified in the literature results in confusion as to when patients should be referred to a nephrologist. Nephrologists, an already strained human resource, must prioritize requests for consultation using an undefined and no doubt inconsistent metric. Standardized, diagnosis-neutral criteria would benefit both primary care providers and nephrologists. PMID- 20540034 TI - Noncardiogenic pulmonary edema induced by hydrochlorothiazide. AB - We report the case of a 74-year-old woman with pulmonary edema induced by hydrochlorothiazide. We missed the diagnosis in the first episode, and it was only upon unintentional hydrochlorothiazide rechallenge that we correctly identified the cause of the pulmonary edema. PMID- 20540035 TI - A protocolized approach to vancomycin dosing in conventional hemodialysis. AB - BACKGROUND: We implemented a protocol at our center to automate intravenous vancomycin dosing in hemodialysis patients. The effectiveness of this protocol is evaluated. METHODS: This was a prospective cohort study of all hemodialysis patients in our unit. Patients were enrolled from August 2005 to May 2007. Thirty eight episodes of infection required vancomycin in 32 patients over the study period. All patients were dialyzed with an F8 or F160 (Fresenius) membrane. A load of vancomycin was administered based on weight to a maximum of 1,500 mg in the last 90 minutes of dialysis. Subsequent doses were 500 mg with each dialysis. Trough levels were taken predialysis prior to the third and fifth doses. If a therapeutic range of 10-20 mg/L was not achieved, the next vancomycin dose was decreased by 50% (if greater than 20 mg/L) or increased by 50% (if less than 10 mg/L). RESULTS: Ninety-three levels were taken; 81 were in range. Of those requiring a dose change, 4 were above 20 mg/L, and 8 were below 10 mg/L. Membrane type did not predict a requirement for dose adjustment (chi-square test: p=0.9341). A dose change after the third dose did not predict subsequent dose adjustments. Thirty-five of the 36 episodes were eradicated with this protocol. No follow-up data were available on 2 infection episodes (censored). No side effects from vancomycin were identified. CONCLUSIONS: The protocol successfully achieved therapeutic vancomycin levels and treated infection in our patients. It worked for both high- and low-flux membranes. PMID- 20540036 TI - Effect of a single hemodialysis session on endothelial dysfunction. AB - BACKGROUND: The mechanisms of endothelial dysfunction induced by hemodialysis are unclear. To gain a mechanistic view we have evaluated some of the biochemical markers which directly or indirectly lead to endothelial dysfunction during a single dialysis session. METHODS: Time course changes in plasma nitrate levels, arginine (ARG), citrulline, asymmetric dimethylarginine (ADMA), homocysteine (Hcy), malondialdehyde (MDA) and lipoprotein-associated phospholipase A2 (LpPLA2) were evaluated in 27 patients with end-stage renal disease on maintenance hemodialysis. Statistical evaluation of changes was done using analysis of variance for repeated measures and linear regression using generalized estimating equations for repeated measures. RESULTS: Nitrate levels significantly increased as a result of dialysis (p<0.001). Hcy (p<0.05) and ADMA (p<0.001) levels were found to be significantly decreased. ARG/ADMA ratio showed an increase (p<0.001). Presence of oxidative stress (OS) was observed in the form of increased plasma MDA levels. Nitrate levels were negatively associated with Hcy, ADMA and LpPLA2 activity. CONCLUSION: Our results show an increased production of nitric oxide (NO) during dialysis, which however is affected by increased OS ultimately favoring endothelial dysfunction. Measures to reduce the OS during hemodialysis are needed to get the complete benefit of clearance of circulating inhibitors of NO synthase during dialysis. PMID- 20540037 TI - Vitamin D receptor activators and response to injury in kidney diseases. AB - Clinical studies have confirmed that administration of vitamin D receptor (VDR) activators offers a survival benefit in hemodialysis patients and may help in preservation of renal function in predialysis patients. Accumulated clinical and mainly experimental data support that in the context of kidney disease, VDR activators exert their beneficial effect not only due to their action on calcium and phosphorus homeostasis, but also through modulation of the response to injury. They attenuate systemic and renal inflammation, and they affect the tissue repair process, reducing renal fibrosis. This aspect of the functions of VDR activators in kidney disease is reviewed in the present manuscript. PMID- 20540038 TI - Contrast-induced acute kidney injury (CI-AKI) following intra-arterial administration of iodinated contrast media. AB - BACKGROUND: We report the incidence of contrast-induced acute kidney injury (CI AKI) following administration of iodixanol or low-osmolar contrast media (LOCM) in patients for suspected peripheral arterial occlusive disease (PAOD) undergoing intra-arterial digital angiography (IA-DSA). METHODS: IA-DSA was performed according to site standard for contrast agent type and volume following computed tomography (CT) of the abdominal aortoiliac and lower extremity arteries and a washout period of at least 3 days. Serum creatinine was measured at baseline and 24 +/- 4 hours after contrast administration. CI-AKI was defined as laboratory increase of serum creatinine value =25% from baseline measurement at 24 hours. The incidence of CI-AKI was analyzed with chi-square statistics. RESULTS: Of the 250 patients who underwent IA-DSA with complete data for analysis, 147 (58.8%) received iodixanol and 103 (41.2%) received LOCM (iopamidol, 91; ioversol, 7; iohexol, 3; iopromide, 2). Baseline mean serum creatinine was statistically higher for iodixanol compared with LOCM (100 vs. 82.7 umol/L; p=0.0124). CI-AKI occurred in 8 patients (5.4%) with iodixanol and 14 patients (13.6%) with LOCM (p=0.025). Further analysis showed that iopamidol administration was responsible for the 13 out of 14 cases of CI-AKI in LOCM patients. CONCLUSIONS: In patients with suspected PAOD undergoing IA-DSA, the incidence of CI-AKI at 24 hours following contrast administration was significantly less for patients who received iodixanol compared with various LOCM; this difference was primarily driven by iopamidol. PMID- 20540039 TI - The impact of peritransplant warfarin use on renal transplant outcome. AB - BACKGROUND: The unplanned nature of kidney transplantation necessitates that patients undergo surgery without prior cessation of warfarin. Our study analyses the impact of warfarin treatment in the peritransplant period on graft outcome and perioperative transfusion requirements. METHODS: We identified 31 patients undergoing deceased donor kidney transplantation who were concurrently receiving warfarin therapy, between 2000 and 2008. A random, sex-matched, adult, deceased donor control group of 62 patients was generated from the Irish transplant database. RESULTS: The warfarin group were older (mean 47.5 vs. 42.5 years, p=0.067) and had spent longer on dialysis prior to transplantation (mean 3.5 vs. 2.1 years, p=0.004). Graft survival in the warfarin group was not significantly different at 1-, 3- and 5-year follow-ups. There was no statistically significant difference in red blood cell transfusions between the groups (45% vs. 29%, p=0.2). Warfarin patients had a prolonged mean cold ischaemia time (22.3 vs. 18.5 hours, p=0.002). CONCLUSION: This study demonstrates excellent short- and long term results for kidney transplantation in patients requiring warfarin at the time of transplantation. PMID- 20540040 TI - A comparative study of 2 new phosphate binders (sevelamer and lanthanum carbonate) in routine clinical practice. AB - INTRODUCTION: Lack of adherence may influence the efficiency of phosphate binders. Our clinical hypothesis was that if lanthanum carbonate (LC) might offer some advantage over sevelamer (S), that that would be in those patients in whom serum phosphate (P) levels were not controlled by S or in those requiring high doses of it, presuming that therapeutic compliance with S could be inadequate. The aim of this study was to compare the cost-consequences of changing from S to LC. METHODS: This was a prospective comparative before-after interventional study. Fifty-one hemodialysis patients prescribed a large number of tablets of S (>= 9 tablets/day) and/or had serum phosphorus (P) levels >5.5 mg/dL were changed from S to LC; 68 patients who did not meet those criteria served as controls. RESULTS: Mean daily number of total phosphate binder tablets was reduced after the introduction of LC (13.9 +/- 5.5 at time 0 vs. 7.7 +/- 4.6 at 12 months; p<0.001). LC was suspended in 14 patients (31.1%), due to a wish to return to the previous medication (S). Percentage compliance with the objectives recommended by the NFK-KDOQI guidelines improved after the change (patients with P <5.5 mg/dL: 46.9% at month 0 and 72.5% at month 12; p<0.01). The incremental cost of changing from S (month 0) to LC (month 12) was -107.8 monthly, considering only the costs of phosphate binders. LC reached the P objective at a lower cost (euro 582.2 vs. euro 1,038.5; -44%; p<0.01). CONCLUSIONS: A complete change from S to LC in these particular kinds of patients significantly decreased the cost of treatment while also improving the achievement of NFK-KDOQI guideline objectives for mineral metabolism. PMID- 20540041 TI - Effect of a dialysis session on the prognostic values of NT-proBNP, troponins, endothelial damage and inflammation biomarkers. AB - BACKGROUND: In hemodialysis, the relationship between the increased concentration of natriuretic peptides and volume overload, inflammatory activity, endothelial dysfunction, left ventricular function and mass, and silent ischemic events is not clear. To investigate the relationship, a 3-year prospective cohort study was conducted in 50 adult hemodialysis patients in NYHA class I-II who were free from diabetes and ischemic heart events. METHODS: Doppler echocardiogram, plasma NT proBNP, troponin T and I, CRP, TNF alpha, big-endothelin 1, and cystatin-C, were determined both before and after a dialysis session. The outcome was all-cause death. RESULTS: 13 out of 50 patients died. Survival curves significantly differed by age (above vs. below the median 68 yrs), NT-proBNP (9719 pg/mL), troponin T (0.03 ng/mL), C-reactive protein (4.8 mg/L), left atrial volume index (51 mL/sqm), ejection fraction (61%), and diastolic pattern. In the Cox model only NT-proBNP (cutoff 10000 pg/mL) had a significant hazard ratio (4.1). Post-HD measurements of NT-proBNP, troponin T, and CRP maintained their prognostic value. The high correlation between pre and post values of NT-proBNP, and the lack of correlation with ultrafiltration volume excluded a role for acute fluid removal on its regulation. CONCLUSIONS: The increased level of NT-proBNP is the most important prognostic factor even in the absence of severe heart dysfunction and myocardial ischemic events, without any relationship with endothelial dysfunction, inflammatory biomarkers, or with acute fluid removal. A cutoff value of NT-proBNP of 10000 pg/mL could be used to identify hemodialysis patients with a higher risk of death. PMID- 20540042 TI - Evidence of a causal link between health outcomes, insurance coverage, and a policy to expand access: experimental data from children in the Philippines. AB - In this paper, we present evidence on the health effects of a health insurance intervention targeted to poor children using data from a randomized policy experiment known as the Quality Improvement Demonstration Study. Among study participants, using a difference-in-difference regression model, we estimated a 9 12 and 4-9 percentage point reduction in the likelihood of wasting and having an infection, respectively, as measured by a common biomarker C-reactive Protein. Interestingly, these benefits were not apparent at the time of discharge; the beneficial health effects were manifest several weeks after release from the hospital. PMID- 20540043 TI - Descriptive validity of alternative intertemporal models for health outcomes: an axiomatic test. AB - Intertemporal preferences for health are an important concept when modelling health-affecting behaviour and with respect to informing discounting practice in economic evaluation. The aim of this paper is to test robustly stationarity, the key axiom of the Discounted Utility model, and to test whether the quasi hyperbolic or generalised hyperbolic model provides a better description of individual time preferences for health outcomes when stationarity is violated. Very little is known about the descriptive validity of the quasi-hyperbolic model. The different models can lead to different predictions and it is therefore crucial to test which functional form is more descriptively valid. An axiomatic approach is used. Intertemporal preferences were elicited from 203 university students. The results showed that stationarity is violated. Individuals discounted both initial delay and further delays between outcomes at a decreasing rate. This suggests that the quasi-hyperbolic model may not be appropriate to use in intertemporal analyses of health behaviour. PMID- 20540044 TI - Scission of carbon monoxide using TaR3, R=(N(tBu)Ph) or OSi(tBu)3: a DFT investigation. AB - The experimentally known reduction of carbon monoxide using a 3-coordinate [Ta(silox)(3)] (silox=OSi(tBu)(3)) complex initially forms a ketenylidene [(silox)(3)Ta-CCO], followed by a dicarbide [(silox)(3)Ta-CC-Ta(silox)(3)] structure. The mechanism for this intricate reaction has finally been revealed by using density functional theory, and importantly a likely structure for the previously unknown intermediate [(silox)(3)Ta-CO](2) has been identified. The analysis of the reaction pathway and the numerous intermediates has also uncovered an interesting pattern that results in CO cleavage, that being scission from a structure of the general form [(silox)(3)Ta-C(n)O] in which n is even. When n is odd, cleavage cannot occur. The mechanism has been extended to consider the effect of altering both the metal species and the ligand environment. Specifically, we predict that introducing electron-rich metals to the right of Ta in the periodic table to create mixed-metal dinuclear intermediates shows great promise, as does the ligand environment of the Cummins-style 3-coordinate amide structure. This latter environment has the added complexity of improved electron donation from amide rotation that can significantly increase the reaction exothermicity. PMID- 20540045 TI - A zeolite-supported molecular ruthenium complex with eta6-C6H6 ligands: chemistry elucidated by using spectroscopy and density functional theory. AB - An essentially molecular ruthenium-benzene complex anchored at the aluminum sites of dealuminated zeolite Y was formed by treating a zeolite-supported mononuclear ruthenium complex, [Ru(acac)(eta(2)-C(2)H(4))(2)](+) (acac=acetylacetonate, C(5)H(7)O(2)(-)), with (13)C(6)H(6) at 413 K. IR, (13)C NMR, and extended X-ray absorption fine structure (EXAFS) spectra of the sample reveal the replacement of two ethene ligands and one acac ligand in the original complex with one (13)C(6)H(6) ligand and the formation of adsorbed protonated acac (Hacac). The EXAFS results indicate that the supported [Ru(eta(6)-C(6)H(6))](2+) incorporates an oxygen atom of the support to balance the charge, being bonded to the zeolite through three Ru-O bonds. The supported ruthenium-benzene complex is analogous to complexes with polyoxometalate ligands, consistent with the high structural uniformity of the zeolite-supported species, which led to good agreement between the spectra and calculations at the density functional theory level. The calculations show that the interaction of the zeolite with the Hacac formed on treatment of the original complex with (13)C(6)H(6) drives the reaction to form the ruthenium-benzene complex. PMID- 20540046 TI - Lanthanide(III) complexes of 4,10-bis(phosphonomethyl)-1,4,7,10 tetraazacyclododecane-1,7-diacetic acid (trans-H6do2a2p) in solution and in the solid state: structural studies along the series. AB - Complexes of 4,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,7 diacetic acid (trans-H(6)do2a2p, H(6)L) with transition metal and lanthanide(III) ions were investigated. The stability constant values of the divalent and trivalent metal-ion complexes are between the corresponding values of H(4)dota and H(8)dotp complexes, as a consequence of the ligand basicity. The solid-state structures of the ligand and of nine lanthanide(III) complexes were determined by X-ray diffraction. All the complexes are present as twisted-square-antiprismatic isomers and their structures can be divided into two series. The first one involves nona-coordinated complexes of the large lanthanide(III) ions (Ce, Nd, Sm) with a coordinated water molecule. In the series of Sm, Eu, Tb, Dy, Er, Yb, the complexes are octa-coordinated only by the ligand donor atoms and their coordination cages are more irregular. The formation kinetics and the acid assisted dissociation of several Ln(III)-H(6)L complexes were investigated at different temperatures and compared with analogous data for complexes of other dota-like ligands. The [Ce(L)(H(2)O)](3-) complex is the most kinetically inert among complexes of the investigated lanthanide(III) ions (Ce, Eu, Gd, Yb). Among mixed phosphonate-acetate dota analogues, kinetic inertness of the cerium(III) complexes is increased with a higher number of phosphonate arms in the ligand, whereas the opposite is true for europium(III) complexes. According to the (1)H NMR spectroscopic pseudo-contact shifts for the Ce-Eu and Tb-Yb series, the solution structures of the complexes reflect the structures of the [Ce(HL)(H(2)O)](2-) and [Yb(HL)](2-) anions, respectively, found in the solid state. However, these solution NMR spectroscopic studies showed that there is no unambiguous relation between (31)P/(1)H lanthanide-induced shift (LIS) values and coordination of water in the complexes; the values rather express a relative position of the central ions between the N(4) and O(4) planes. PMID- 20540047 TI - Cubic mesoporous titanium phosphonates with multifunctionality. AB - Cubic mesoporous titanium phosphonate materials with bridged organic groups inside the framework were synthesized by means of a one-pot hydrothermal autoclaving process, with the assistance of cationic surfactant cetyltrimethylammonium bromide. 1-Hydroxyethylidene-1,1-diphosphonic acid was used as the coupling molecule. A typical cubic mesophase with surface area of 1052 m(2) g(-1) and pore size of 2.6 nm was confirmed by XRD, TEM, and N(2) sorption analysis. The organophosphonate groups were homogeneously incorporated in the network of the mesoporous solids, as revealed by FTIR and magic-angle spinning (MAS) NMR spectroscopy, and thermogravimetry and differential scanning calorimetry (TG-DSC) measurements. The synthesized hydroxyethylidene-bridged cubic mesoporous titanium phosphonates proved to be thermally stable up to 350 degrees C, with a well-preserved hybrid framework and cubic mesoporous architecture. The obtained cubic mesophase could be transformed into a hexagonal mesophase by simply adjusting the molar ratios of the added raw materials, namely, a Ti/P molar ratio of 1:4 and a CTAB/Ti molar ratio of 1.9-2.3 for the cubic phase and Ti/P molar ratio of 3:4 and CTAB/Ti molar ratio of 0.1-0.4 for the hexagonal phase. The cubic hybrid materials could be used as efficient photocatalysts for the photodegradation of rhodamine B. Moreover, they were also used for adsorption of CO(2) and heavy metal ions and exhibited a significant capture amount of around 1.0 mmol g(-1) for CO(2) molecules at 35 degrees C and high adsorption capacity of 28.5 micromol g(-1) for Cu(2+) ions with good reusability, which demonstrated their promising potential in environmental remediation. PMID- 20540048 TI - Formation of quaternary chiral centers by N-heterocyclic carbene-Cu-catalyzed asymmetric conjugate addition reactions with Grignard reagents on trisubstituted cyclic enones. AB - The copper-catalyzed conjugate addition of Grignard reagents to 3-substituted cyclic enones allows the formation of all-carbon chiral quaternary centers. We demonstrate in this article that N-heterocyclic carbenes act as efficient chiral ligands for this transformation. High enantioselectivities (up to 96% ee) could be obtained for a variety of substrates. PMID- 20540049 TI - Ion-pair complexation with a cavitand receptor. AB - The capability of resorcinarenes to bind anions within the alkyl feet at the lower rim has been exploited as the starting point for developing a new cavitand able to engulf contact ion pairs of primary ammonium salts in chlorinated solvents with association constants (K(ass)) in the range of 10(3)-10(4) M(-1). Methylene bridges were introduced into the upper rim to freeze the resorcinarene in the cone conformation with the four H(down) protons converging in the lower pocket, thereby maximizing the CH-anion interactions responsible for the anion binding. Four additional phosphate moieties were introduced into the lower rim in close proximity to the anionic site to provide hydrogen-bonding-acceptor P=O groups and promote cation complexation at the bottom of the cavitand. The binding ability of the synthesized ligands was analyzed by (1)H NMR spectroscopy and, when possible, by isothermal titration calorimetry (ITC); the data were in agreement when complementary techniques were used. PMID- 20540050 TI - Supramolecular catalysis with extended aggregates and gels: inversion of stereoselectivity caused by self-assembly. AB - L-Proline-L-valine dipeptide derivatives, which self-assemble in toluene, have been studied as stereoselective catalysts in the conjugate addition of cyclohexanone to trans-beta-nitrostyrene. Remarkable effects on the stereoselectivity are observed associated to the aggregation of the catalyst. Outstanding differences were observed between the catalytic activity of compound 1, which forms supramolecular gels in toluene, and compound 2, which is not a gelator. In the former case, the enantioselectivity of the reaction was almost insensitive to changes in catalyst concentration and temperature, but in the case of compound 2, the catalytic activity was very much affected by those variables. Structural studies indicate that the results can be rationalized by taking into account significant conformational changes experienced by the catalytic L-proline derivatives associated with the aggregation process. The results highlight that catalyst self-assembly is a very important issue to consider in the stereoselective outcome of organocatalytic reactions. Especially relevant is the fact that the use of supramolecular gels as organocatalysts emerges as a technique that affords reliable and constant stereoselectivity in different conditions with the added value of easy catalyst recovery. PMID- 20540051 TI - Twist ferrocene wires from self-assembly of chiral rod-coil organometallics. PMID- 20540052 TI - Isomeric squaraine-based [2]pseudorotaxanes and [2]rotaxanes: synthesis, optical properties, and their tubular structures in the solid state. AB - On the basis of formation of [2]pseudorotaxane complexes between triptycene derived tetralactam macrocycles 1a and 1b and squaraine dyes, construction of squaraine-based [2]rotaxanes through clipping reactions were studied in detail. As a result, when two symmetrical squaraines 2d and 2e were utilized as templates, two pairs of isomeric [2]rotaxanes 3a-b and 4a-b as diastereomers were obtained, owing to the two possible linking modes of triptycene derivatives. It was also found, interestingly, that when a nonsymmetrical dye 2g was involved, there existed simultaneously three isomers of [2]rotaxanes in one reaction due to the different directions of the guest threading. The (1)H NMR and 2D NOESY NMR spectra were used to distinguish the isomers, and the yield of [2]rotaxane 5a with the benzyl group in the wider rim of the host 1a was found to be higher than that of another isomer 5b with an opposite direction of the guest, which indicated the partial selection of the threading direction. The X-ray structures of 3b and 4a showed that, except for the standard hydrogen bonds between the amide protons of the hosts and the carbonyl oxygen atoms of the guests, multiple pi...pi stacking and C-H...pi interactions between triptycene subunits and aromatic rings of the guests also participated in the complexation. Crystallographic studies also revealed that the [2]rotaxane molecules 3b and 4a further self-assembled into tubular structures in the solid state with the squaraine dyes inside the channels. In the case of 4a, all the nonsymmetrical macrocyclic molecules pointed in one direction, which suggests the formation of oriented tubular structures. Moreover, it was also found that the squaraines encapsulated in the triptycene-derived macrocycles were protected from chemical attack, and subsequently have potential applications in imaging probes and other biomedical areas. PMID- 20540053 TI - Spin crossover versus low-spin behaviour exhibited in 2D and 3D supramolecular isomers of [Fe(II)(2,4-bpt)2].guest. PMID- 20540054 TI - A simple primary amine thiourea catalyzed highly enantioselective conjugate addition of alpha,alpha-disubstituted aldehydes to maleimides. PMID- 20540055 TI - Structure determination of the top-loop of the conserved 3'-terminal secondary structure in the genome of flaviviruses. AB - To what extent small differences in RNA sequences (mutations) can have a profound impact on biology remains an intriguing question. This effect can be studied by using untranslated RNA regions as a model. We have studied the influence of mutations on the structure of an RNA hairpin that occurs in the 3'-untranslated region (UTR) of Flaviviridae, and is known to have a large impact on the vector dependency of flaviviruses. Three related RNA sequences were studied by NMR spectroscopy. The selected sequences represent each one of the three clusters in the flavivirus genes (mosquito-borne, tick-borne, and no-known-vector viruses). A new strategy was used to obtain chemical shift signatures of carbonyl atoms in unlabeled uridine nucleobases to characterize their involvement in hydrogen bonding. Clear differences occur in the structures and stacking pattern of the three RNA hairpins. The observed differences cannot be predicted based on sequence analysis. A different biology can be correlated with a different RNA tertiary structure. The underlying biological mechanism, however, remains to be studied. PMID- 20540056 TI - Functions of genes and enzymes involved in phenalinolactone biosynthesis. AB - Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tu6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an Fe(II)/alpha-ketoglutarate-dependent dioxygenase, is responsible for the key step in gamma-butyrolactone formation, whereas PlaO5, a cytochrome P450-dependent monooxygenase, catalyses the 1-C-hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the gamma-butyrolactone moiety. PMID- 20540057 TI - Designed short peptides that form amyloid-like fibrils in coassembly with amyloid beta-peptide (Abeta) decrease the toxicity of Abeta to neuronal PC12 cells. PMID- 20540058 TI - Targeted photoswitchable probe for nanoscopy of biological structures. PMID- 20540059 TI - Marine molecular machines: heterocyclization in cyanobactin biosynthesis. AB - Natural products that contain amino-acid-derived (Cys, Ser, Thr) heterocycles are ubiquitous in nature, yet key aspects of their biosynthesis remain undefined. Cyanobactins are heterocyclic ribosomal peptide natural products from cyanobacteria, including symbiotic bacteria living with marine ascidians. In contrast to other ribosomal peptide heterocyclases that have been studied, the cyanobactin heterocyclase is a single protein that does not require an oxidase enzyme. Using this simplifying condition, we provide new evidence to support the hypothesis that these enzymes are molecular machines that use ATP in a product binding or orientation cycle. Further, we show that both protease inhibitors and ATP analogues inhibit heterocyclization and define the order of biochemical steps in the cyanobactin biosynthetic pathway. The cyanobactin pathway enzymes, PatD and TruD, are thiazoline and oxazoline synthetases. PMID- 20540060 TI - Development of a DNA photoaffinity probe for the analysis of 8-OxodG-binding proteins in a human proteome. PMID- 20540061 TI - Modelling inhalational anaesthetics using bayesian feature selection and QSAR modelling methods. AB - The development of robust and predictive QSAR models is highly dependent on the use of molecular descriptors that contain information relevant to the property being modelled. Selection of these relevant features from a large pool of possibilities is difficult to achieve effectively. Modern Bayesian methods provide substantial advantages over conventional feature selection methods for feature selection and QSAR modelling. We illustrate the importance of descriptor choice and the beneficial properties of Bayesian methods to select context dependent relevant descriptors and build robust QSAR models, using data on anaesthetics. Our results show the effectiveness of Bayesian feature selection methods in choosing the best descriptors when these are mixed with less informative descriptors. They also demonstrate the efficacy of the Abraham descriptors and identify deficiencies in ParaSurf descriptors for modelling anaesthetic action. PMID- 20540062 TI - Synthesis and evaluation of bis-thiazolium salts as potential antimalarial drugs. AB - An innovative therapeutic approach based on the use of dicationic derivatives was previously designed to inhibit the biosynthesis of phosphatidylcholine in Plasmodium spp. Among these, bis-thiazolium salts were shown to block proliferation of the malaria parasite at concentrations in the low nanomolar range. However, due to unsuitable molecular properties such as the presence of the two polar heads and flexibility in the linker, these compounds have low oral bioavailability. To characterize the structural requirements of the linker that lead to more rigid analogues with fewer rotatable bonds but which retain antimalarial activity, a new series of compounds incorporating an aryl moiety and eventually oxygen atoms were prepared, and their biological activity was evaluated. Structure-activity relationships suggest that the optimal linker construct is an aromatic group with two n-butyl chains branched at the para position; two new leads (compounds 39 and 40) were selected for further development. PMID- 20540063 TI - High-throughput virtual screening using quantum mechanical probes: discovery of selective kinase inhibitors. AB - A procedure based on semi-empirical quantum mechanical (QM) calculations of interaction energy is proposed for the rapid screening of compound poses generated by high-throughput docking. Small molecules (consisting of 2-10 atoms and termed "probes") are overlapped with polar groups in the binding site of the protein target. The interaction energy values between each compound pose and the probes, calculated by a semi-empirical Hamiltonian, are used as filters. The QM probe method does not require fixed partial charges and takes into account polarization and charge-transfer effects which are not captured by conventional force fields. The procedure is applied to screen approximately 100 million poses (of 2.7 million commercially available compounds) obtained by high-throughput docking in the ATP binding site of the tyrosine kinase erythropoietin-producing human hepatocellular carcinoma receptor B4 (EphB4). Three QM probes on the hinge region and one at the entrance pocket are employed to select for binding affinity, while a QM probe on the side chain of the so-called gatekeeper residue (a hypervariable residue in the kinome) is used to enforce selectivity. The poses with favorable interactions with the five QM probes are filtered further for hydrophobic matching and low ligand strain. In this way, a single-digit micromolar inhibitor of EphB4 with a relatively good selectivity profile is identified in a multimillion-compound library upon experimental tests of only 23 molecules. PMID- 20540064 TI - Discovery of a class of diketopiperazines as antiprion compounds. AB - Prion diseases are fatal neurodegenerative and infectious disorders for which effective pharmacological tools are not yet available. This unmet challenge and the recently proposed interplay between prion diseases and Alzheimer's have led to a more urgent demand for new antiprion agents. Herein, we report the identification of a novel bifunctional diketopiperazine (DKP) derivative 1 d, which exhibits activity in the low micromolar range against prion replication in ScGT1 cells, while showing low cytotoxicity. Supported by properly addressed molecular modeling studies, we hypothesized that a planar conformation is the major determinant for activity in this class of compounds. Moreover, studies aimed at assessing the mechanism-of-action at the molecular level showed that 1 d might interact directly with recombinant prion protein (recPrP) to prevent its conversion to the pathogenic misfolded prion protein (PrP(Sc))-like form. This investigation suggests that DKP based antiprion compounds can serve as a promising lead scaffold in developing new drugs to combat prion diseases. PMID- 20540065 TI - Structure-based virtual screening and electrophysiological evaluation of new chemotypes of K(v)1.5 channel blockers. AB - Atrial fibrillation (AF) is the most prevalent nonfatal cardiac rhythm disorder associated with an increased risk of heart failure and stroke. Considering the ventricular side effects induced by anti-arrhythmic agents in current use, K(v)1.5 channel blockers have attracted a great deal of deliberation owing to their selective actions on atrial electrophysiology. Herein we report new chemotypes of K(v)1.5 channel blockers that were identified through a combination of structure-based virtual screening and in silico druglike property prediction including six scoring functions, as well as electrophysiological evaluation. Among them, five of the 18 compounds exhibited >50 % blockade ratio at 10 microM, and have structural features different from conventional K(v)1.5 channel blockers. These novel scaffolds could serve as hits for further optimization and SAR studies for the discovery of selective agents to treat AF. PMID- 20540066 TI - Local and remote charge-transfer-enhanced Raman scattering on one-dimensional transition-metal oxides. AB - The one-dimensional (1D) transition-metal oxide MoO(3) belt is synthesized and characterized with X-ray diffraction, scanning electron microscopy, and Raman spectroscopy. Charge-transfer-(CT) enhanced Raman scattering of 4-mercaptobenzoic acid (4-MBA) on a 1D MoO(3) belt was investigated experimentally and theoretically. The chemical enhancement of surface-enhanced Raman scattering (SERS) of 4-MBA on the MoO(3) belt by CT is in the order of 10(3). The SERS of 4 MBA was investigated theoretically by using a quantum chemical method. The remote SERS of 4-MBA along the 1D MoO(3) belt (the light excitation to one side of the MoO(3) belt, and the SERS spectrum is collected on the other side of the MoO(3) belt) is also shown experimentally, which provides potential applications of SERS. The incident polarization dependence of remote SERS spectra has also been investigated experimentally. PMID- 20540067 TI - An effective preparation of sulfonyl- or sulfinyl-substituted fluorinated alkenes and their stereoselective addition-elimination reactions with organocuprates. AB - Treatment of trifluorovinyl- or pentafluoropropen-1-yl sulfone or sulfoxide, which are easily prepared from commercially available 1,2-dibromofluoroalkanes, with various organocuprates affords substitution or beta-reduction products in good to excellent yields through an addition-elimination reaction sequence. PMID- 20540068 TI - Morphology-dependent gas-sensing properties of ZnO nanostructures for chlorophenol. AB - The crystal-plane effect of ZnO nanostructures on the toxic 2-chlorophenol gas sensing properties was examined. Three kinds of single-crystalline ZnO nanostructures including nanoawls, nanorods, and nanodisks were synthesized by using different capping agents via simple hydrothermal routes. Different crystal surfaces were expected for these ZnO nanostructures. The sensing tests results showed that ZnO nanodisks exhibited the greatest sensitivity for the detection of toxic 2-chlorophenol. The results revealed that the sensitivity of these ZnO samples was heavily dependent on their exposed surfaces. The polar (0001) planes were most reactive and could be considered as the critical factor for the gas sensing performance. In addition, calculations using density functional theory were employed to simulate the gas-sensing reaction involving surface reconstruction and charge transfer both of which result in the change of electronic conductance of ZnO. PMID- 20540069 TI - A series of novel organically templated germanium antimony sulfides. AB - A series of novel organically templated germanium antimony sulfides have been solvothermally synthesized and structurally, thermally, and optically characterized. The compound [Me(2)NH(2)](6)[(Ge(2)Sb(2)S(7))(Ge(4)S(10))] (1) features two distinct tetranuclear [Ge(2)Sb(2)S(7)](2-) and [Ge(4)S(10)](4-) isolated clusters. The compound [(Me)(2)NH(2)][DabcoH](2)[Ge(2)Sb(3)S(10)] (2) (Dabco = triethylenediamine) features a 1D-[Ge(2)Sb(3)S(10)](n)(3n-) ribbon constructed with two [GeSbS(5)](n)(3n-) chains bridged by Sb(3+) ion in psi SbS(4) configuration. Compounds [M(en)(3)][GeSb(2)S(6)] (M = Ni (3), Co (4) en = ethylenediamine) feature the unique 2D grid layer structures of [GeSb(2)S(6)](n)(2n-). The compound [(Me)(2)NH(2)](2)[GeSb(2)S(6)] (5) previously reported by us features a 3D chiral microporous structure with the chiral channels. The optical absorption spectra indicate that all the compounds are wide bandgap semiconductors. Thermal stabilities of these compounds have been investigated by thermogravimetric analyses (TGA). PMID- 20540070 TI - Use of side-chain incompatibility for tailoring long-range p/n heterojunctions: photoconductive nanofibers formed by self-assembly of an amphiphilic donor acceptor dyad consisting of oligothiophene and perylenediimide. AB - To tailor organic p/n heterojunctions with molecular-level precision, a rational design strategy using side-chain incompatibility of a covalently connected donor acceptor (D-A) dyad has been successfully carried out. An oligothiophene perylenediimide dyad, when modified with triethylene glycol side chains at one terminus and dodecyl side chains at the other (2(Amphi)), self-assembles into nanofibers with a long-range D/A heterojunction. In contrast, when the dyad is modified with dodecyl side chains at both termini (2(Lipo)), ill-defined microfibers result. In steady-state measurements using microgap electrodes, a cast film of the nanofiber of 2(Amphi) displays far better photoconducting properties than that of the microfiber of 2(Lipo). Flash-photolysis time-resolved microwave conductivity measurements, in conjunction with transient absorption spectroscopy, clearly indicate that the nanofiber of 2(Amphi) intrinsically allows for better carrier generation and transport properties than the microfibrous assembly of 2(Lipo). PMID- 20540071 TI - C-H bond activation/borylation of furans and thiophenes catalyzed by a half sandwich iron N-heterocyclic carbene complex. AB - A coordinatively unsaturated iron-methyl complex having an N-heterocyclic carbene ligand, [Cp*Fe(L(Me))Me] (1; Cp*=eta(5)-C(5)Me(5), L(Me)=1,3,4,5-tetramethyl imidazol-2-ylidene), is synthesized from the reaction of [Cp*Fe(TMEDA)Cl] (TMEDA=N,N,N',N'-tetramethylethylenediamine) with methyllithium and L(Me). Complex 1 is found to activate the C-H bonds of furan, thiophene, and benzene, giving rise to aryl complexes, [Cp*Fe(L(Me))(aryl)] (aryl=2-furyl (2), 2-thienyl (3), phenyl (4)). The C-H bond cleavage reactions are applied to the dehydrogenative coupling of furans or thiophenes with pinacolborane (HBpin) in the presence of tert-butylethylene and a catalytic amount of 1 (10 mol% to HBpin). The borylation of the furan/thiophene or 2-substituted furans/thiophenes occurs exclusively at the 2- or 5-positions, respectively, whereas that of 3 substituted furans/thiophenes takes place mainly at the 5-position and gives a mixture of regioisomers. Treatment of 2 with 2 equiv of HBpin results in the quantitative formation of 2-boryl-furan and the borohydride complex [Cp*Fe(L(Me))(H(2)Bpin)] (5). Heating a solution of 5 in the presence of tert butylethylene led to the formation of an alkyl complex [Cp*Fe(L(Me))CH(2)CH(2)tBu] (6), which was found to cleave the C-H bond of furan to produce 2. On the basis of these results, a possible catalytic cycle is proposed. PMID- 20540072 TI - Cyclam-cored dendrimers appended with four dendrons of two different types: intradendrimer energy transfer. AB - We have synthesized two cyclam-cored dendrimers appended with dendrons of two different types by proper protection/deprotection of the cyclam unit. The resulting dendrimers contain six naphthyl and two dansyl units (N6 D2) or two dansyl and six naphthyl units (N2 D6) at the periphery. Their photophysical properties have been compared to those of a dendrimer containing 8 dansyl units (D8) and a previously investigated dendrimer containing 8 naphthyl units (N8). The absorption spectra are those expected on the basis of the number of chromophores, demonstrating that no ground state interaction takes place. The emission spectra of N2 D6 and N6 D2 show naphthalene localized and naphthalene excimer emission similar to those observed in the case of N8, together with a much stronger dansyl emission with maximum at 525 nm. Addition of CF(3)SO(3)H to dendrimer solutions in CH(3)CN/CH(2)Cl(2) 1:1 (v/v) leads to protonation of the aliphatic amine units of the cyclam core at first and then of the aromatic amine of each dansyl chromophores. Cyclam can be diprotonated and this affects dansyl absorption and, most significantly, emission bands by a charge perturbation effect. Each dansyl unit is independently protonated in both dendrimers. The most interesting photophysical feature of these heterofunctionalized cyclam-cored dendrimers is the occurrence of an intradendrimer photoinduced energy transfer from naphthyl to dansyl chromophores of two different dendrons (interdendron mechanism). The efficiency of this process is 50 % for N6 D2 and it can be increased up to 75 % upon protonation of the cyclam core and formation of N6 D2(2H(+)). This arises from the fact that protonation of the amine units of the cyclam prevents formation of exciplexes upon naphthyl excitation, thus shutting down one of the deactivation processes of the fluorescent naphthyl excited state. PMID- 20540073 TI - Selectivity of chlorantraniliprole to parasitoid wasps. AB - BACKGROUND: Chlorantraniliprole is a novel anthranilic diamide insecticide registered for use in vegetables, fruits, grains and turf against a variety of insect pests. The objective of this article is to summarize results of acute toxicity testing of chlorantraniliprole on seven species of parasitic wasps with wide geographic distribution and relevance to different crops and integrated pest management (IPM) programmes. RESULTS: Tier-1, worst-case laboratory studies evaluated wasp survival and reproduction following different exposure concentrations and scenarios to chlorantraniliprole (i.e. fresh-dried spray deposits on glass plates, direct contact, ingestion, egg card, dipped leaf residue bioassays, sprayed mummies). No statistically significant effects on adult survival, percentage parasitism or emergence were observed following exposures to chlorantraniliprole compared with controls. CONCLUSION: Chlorantraniliprole was harmless to the parasitoid wasp species tested according to IOBC classification criteria (<30% effects) and may be a useful tool in IPM programmes. PMID- 20540074 TI - Monitoring of resistance to spirodiclofen and five other acaricides in Panonychus citri collected from Chinese citrus orchards. AB - BACKGROUND: Citrus red mite, Panonychus citri (McGregor), is one of the most important pesticide-resistant pests in China. In order better to understand its resistance status, six populations of the mite were collected from Chinese citrus orchards for monitoring of resistance to spirodiclofen and another five acaricides. RESULTS: All the samples collected in the field in 2006 were susceptible to spirodiclofen. However, the LC(50) values in populations sampled in 2009 ranged from 3.29 to 418.24 mg L(-1) spirodiclofen, a 127-fold difference between the least and most sensitive populations. Compared with a susceptible strain, 50-fold and 90.8-fold resistance to spirodiclofen was detected in populations sampled from Pinghe and Fuzhou in 2009, as well as cross-resistance to spirotetramat. The LC(50) values for abamectin, fenpropathrin, hexythiazox and pyridaben in the collected samples ranged from 0.041 to 3.52 mg L(-1), from 23.91 to 696.16 mg L(-1), from 13.94 to 334.19 mg L(-1) and from 48.90 to 609.91 mg L( 1) respectively. CONCLUSION: Great variations in resistance to the tested acaricides were observed among the sampled populations. The Pinghe population developed resistance to all the acaricides tested. The Jianning population was susceptible to most acaricides tested, except pyridaben. Resistance management strategies were conducted on the basis of these observations. PMID- 20540075 TI - Matrix-assisted diffusion-ordered spectroscopy: mixture resolution by NMR using SDS micelles. AB - Diffusion-ordered spectroscopy (DOSY) is a powerful technique for mixture analysis, but in its basic form it cannot separate the component spectra for species with very similar diffusion coefficients. It has been recently demonstrated that the component spectra of a mixture of isomers with nearly identical diffusion coefficients (the three dihydroxybenzenes) can be resolved using matrix-assisted DOSY (MAD), in which diffusion is perturbed by the addition of a co-solute such as a surfactant [R. Evans, S. Haiber, M. Nilsson, G. A. Morris, Anal. Chem. 2009, 81, 4548-4550]. However, little is known about the conditions required for such a separation, for example, the concentrations and concentration ratios of surfactant and solutes. The aim of this study was to explore the concentration range over which matrix-assisted DOSY using the surfactant SDS can achieve diffusion resolution of a simple model set of isomers, the monomethoxyphenols. The results show that the separation is remarkably robust with respect to both the concentrations and the concentration ratios of surfactant and solutes, supporting the idea that MAD may become a valuable tool for mixture analysis. PMID- 20540076 TI - Diuretic drug binding to human glutathione transferase P1-1: potential role of Cys-101 revealed in the double mutant C47S/Y108V. AB - The diuretic drug ethacrynic acid (EA), both an inhibitor and substrate of pi class glutathione S-transferase (GST P1-1), has been tested in clinical trials as an adjuvant in chemotherapy. We recently studied the role of the active site residue Tyr-108 in binding EA to the enzyme and found that the analysis was complicated by covalent binding of this drug to the highly reactive Cys-47. Previous attempts to eliminate this binding by chemical modification yielded ambiguous results and therefore we decided here to produce a double mutant C47S/Y108V by site directed mutagenesis and further expression in Escherichia coli and the interaction of EA and its GSH conjugate (EASG) examined by calorimetric studies and X-ray diffraction. Surprisingly, in the absence of Cys 47, Cys-101 (located at the dimer interface) becomes a target for modification by EA, albeit at a lower conjugation rate than Cys-47. The Cys-47 -> Ser mutation in the double mutant enzyme induces a positive cooperativity between the two subunits when ligands with affinity to G-site bind to enzyme. However, this mutation does not seem to affect the thermodynamic properties of ligand binding to the electrophilic binding site (H-site) and the thermal or chemical stability of this double mutant does not significantly affect the unfolding mechanism in either the absence or presence of ligand. Crystal structures of apo and an EASG complex are essentially identical with a few exceptions in the H-site and in the water network at the dimer interface. PMID- 20540077 TI - Policy challenges to the quality of child health services in Bulgaria. AB - BACKGROUND: Our study aimed to explore policy challenges to the quality of child health services in Bulgaria. METHODS: The study was based on qualitative in-depth interviews, analysis of regulatory documents, and review of the literature. Respondents included policy-makers, providers and users of health services, from both rural and urban areas. RESULTS: Problems identified included insufficient training of general practitioners, medical errors, delays in response to emergencies, inadequate information provided to patients, and underdeveloped child public health. A common view was that paediatricians provide better quality care than general practitioners. Respondents described a lack of clinical guidelines for rational use of pharmaceuticals, overprescribing of antibiotics, reliance on pharmaceutical companies for information, and unrestricted sales of drugs over-the-counter. 'Clinical pathways', introduced as a payment mechanism in hospitals, were perceived as lacking transparency, complicating clinical practice, and forcing doctors to record wrong diagnoses and conduct unnecessary investigations. CONCLUSIONS: Our findings indicate the need to develop evidence based clinical guidelines for primary and secondary care, establish payment mechanisms that facilitate quality improvements, promote rational use of pharmaceuticals, improve continuing training of physicians and strengthen child public health. PMID- 20540078 TI - The double spiral of change--experiences of privatization in a Swedish hospital. AB - Privatization is a trend in countries with a public health system. It involves organizational change, a cultural transformation and changes for the employees as well as a more strictly controlled work. The objective of this study is to describe, analyse and interpret how privatization is perceived by the employees of a health care organization in Sweden. METHODOLOGY: In-depth interviews have been performed with physicians, paramedics, secretaries, nurses, assistant nurses and local managers, in all 14 respondents, after a private entrepreneur had taken over the management of a hospital. The interviews were tape-recorded and have been analysed and interpreted following a grounded theory approach. FINDINGS: The transcribed interviews show that trust is a core category and linked with emotions, commitment and security. The analysis shows that employees' experience of privatization within a health care organization differs and is full of nuances and complexities. CONCLUSION: A simultaneous virtuous and a vicious circle of experiences and reactions may describe how employees experience privatization. It can also be concluded that leadership is an important factor in the success of organizational change. PMID- 20540079 TI - Editorial. A diversity of topics and countries. PMID- 20540081 TI - Professional knowledge creation in the hospital sector: a qualitative study in Taiwan. AB - This paper aims to develop a professional knowledge creation model for the hospital sector. For this purpose, we qualitatively explore the determinants and process of knowledge creation in the hospital sector. Drawing from organization theory, we develop a hospital's professional knowledge creation model and develop three propositions first. We further explore the theoretical model at organization level by case study in Taiwan. The findings suggest that the hospital's professional knowledge creation is influenced by knowledge stock, social ties and isomorphic pressures as propositions argued. However, hospitals' attempts to keep aligned with their highly institutionalized environments may pay more attention to both existing knowledge stock and the process of professional knowledge creation for their survival. Finally, it is hoped that the significances of this study will contribute to the development of hypotheses in the future quantitative study for building a generalized knowledge creation model for the hospital organization. PMID- 20540082 TI - Primary health-care network monitoring: a hierarchical resource allocation modeling approach. AB - Management of a primary health-care network (PHCN) is a difficult task in every country. A suitable monitoring system can provide useful information for PHCN management, especially given a large quantity of health-care data that is produced daily in the network. This paper proposes a methodology for structured development of monitoring systems and a PHCN resource allocation monitoring model based on this methodology. The purpose of the monitoring model is to improve the allocation of health-care resources. The proposed methodology is based on modules that are organized into a hierarchy, where each module monitors a particular aspect of the system. This methodology was used to design a PHCN monitoring model for Slovenia. Specific aspects of the Slovenian PHCN were taken into account such as varying needs of patients from different municipalities, existence of small municipalities having less than 1000 residents, the fact that many patients visit physicians in other municipalities, and that physicians may work at more than one location or organization. The main modules in the model are focused on the overall assessment of the PHCN, monitoring of patients visits to health-care providers (HCPs), physical accessibility of health services, segment of patients in municipalities who have not selected a personal physician, assessment of the availability of HCPs for patients, physicians working on more than one location, and available human resources in the PHCN. Most of the model's components are general and can be adapted for other national health-care systems. PMID- 20540083 TI - Occupational functioning, sickness absence and medication utilization before and after cognitive-behaviour therapy for generalized anxiety disorders. AB - BACKGROUND: Cognitive-behaviour therapy (CBT) is efficacious in reducing symptoms of generalized anxiety disorders (GAD). The question is whether it is also efficient, i.e., whether there are also enduring effects with respect to improving utilization of medication and psychotherapy, or occupational functioning and sick leave after the end of treatment. METHOD: The study was based on 44 outpatients (age 18-65 years; HAM-A score >=18; GAD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria as assessed by standardized interview) who were treated with 25 sessions of CBT (treatment by 12 state-licensed behaviour therapists in office-based practice; no psychotropic treatment for the duration of the therapy). The rate of medication treatment, occupational functioning and sick leave was assessed for 8 months before and after the end of treatment. RESULTS: In the comparison of the pre treatment and post-treatment periods, 46.5% versus 7.2% of patients used psychotropic medication for at least 4 weeks and had been 3.1 versus 1.1 days on sickness absence per month, respectively. About 70% of patients showed impairment in occupational role performance during the pre-treatment phase compared with 5% to 20%, depending on the dimension, in the follow-up period. CONCLUSIONS: The data suggest that CBT is not only efficacious in terms of symptom reduction but also efficient in terms of reducing inappropriate medication intake and improving occupational functioning. PMID- 20540084 TI - The effect of market reforms and new public management mechanisms on the Swiss health care system. AB - In 1996, the Federal Law on Health Insurance (LAMal) was adopted in order to contain costs in Swiss health care. At the same time, the reform aimed to maintain or even improve solidarity and encourage institutional reform through new public management (NPM) and market mechanisms. More freedom in contractual conditions between insurers and providers and a clearer distinction of responsibilities between federal and regional (cantonal) authorities were stipulated to achieve efficiency, effectiveness, and transparency. The focus of this paper is an analysis of the effects of market reforms and NPM mechanisms introduced with the LAMal on the cost-containment, quality of care and equity objectives in the Swiss health care system. PMID- 20540085 TI - The structure of native G-actin. AB - Heat shock proteins act as cytoplasmic chaperones to ensure correct protein folding and prevent protein aggregation. The presence of stoichiometric amounts of one such heat shock protein, Hsp27, in supersaturated solutions of unmodified G-actin leads to crystallization, in preference to polymerization, of the actin. Hsp27 is not evident in the resulting crystal structure. Thus, for the first time, we present the structure of G-actin in a form that is devoid of polymerization-deterring chemical modifications or binding partners, either of which may alter its conformation. The structure contains a calcium ion and ATP within a closed nucleotide-binding cleft, and the D-loop is disordered. This native G-actin structure invites comparison with the current F-actin model in order to understand the structural implications for actin polymerization. In particular, this analysis suggests a mechanism by which the bound cation coordinates conformational change and ATP-hydrolysis. PMID- 20540086 TI - Control of cortical rigidity by the cytoskeleton: emerging roles for septins. AB - The cortex is the outermost region of the cell, comprising all of the elements from the plasma membrane to the cortical actin cytoskeleton that cooperate to maintain the cell's shape and topology. In eukaryotes without cell walls, this cortex governs the contact between their plasma membranes and the environment and thereby influences cell shape, motility, and signaling. It is therefore of considerable interest to understand how cells control their cortices, both globally and with respect to small subdomains. Here we review the current understanding of this control, including the regulation of cell shape by balances of outward hydrostatic pressure and cortical tension. The actomyosin cytoskeleton is the canonical regulator of cortical rigidity and indeed many would consider the cortex to comprise the actin cortex nearly exclusively. However, this actomyosin array is intimately linked to the membrane, for example via ERM and PIP2 proteins. Additionally, the lipid membrane likely undergoes rigidification by other players, such as Bin-Amphiphysin-Rvs proteins. Recent data also indicates that the septin cytoskeleton may play a formidable and more direct role in stabilization of membranes, particularly in contexts where cells receive limited external stabilization from their environments. Here, we review how septins may play this role, drawing on their physical form, their ability to directly bind and modify membranes and actomyosin, and their interactions with vesicular machinery. Deficiencies and alterations in the nature of the septin cytoskeleton may thus be relevant in multiple disease settings. PMID- 20540088 TI - Development in the cynomolgus macaque following administration of ustekinumab, a human anti-IL-12/23p40 monoclonal antibody, during pregnancy and lactation. AB - BACKGROUND: Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of interleukin (IL) 12 and IL-23 and inhibits their pharmacological activity. To evaluate potential effects of ustekinumab treatment during pregnancy, developmental studies were conducted in cynomolgus macaques. METHODS: Ustekinumab was tested in two embryo/fetal development (EFD) studies and in a combined EFD/pre and postnatal development (PPND) study. In the EFD studies, pregnant macaques (12/group) were dosed with saline or ustekinumab (9 mg/kg IV, 22.5 mg/kg SC, or 45 mg/kg IV or SC during the period of major organogenesis, gestation day [GD] 20-50). Fetuses were harvested on GD100-102 and examined for any effects on development. In the EFD/PPND study, pregnant macaques were injected with saline or ustekinumab (22.5 or 45 mg/kg SC) from GD20 through lactation day 33. Infants were examined from birth through 6 months of age for morphological and functional development. Potential effects on the immune system were evaluated by immunophenotyping of peripheral blood lymphocytes and immunohistopathology of lymphoid tissues in fetuses and infants and by T dependent antibody response (TDAR) to KLH and TTX and by DTH response in infants. Ustekinumab concentrations were measured in serum from dams, fetus, and infants and in breast milk. RESULTS: Ustekinumab treatment produced no maternal toxicity and no toxicity in the fetuses or infants, including no effects on the TDAR or DTH responses. Ustekinumab was present in serum from GD100 fetuses and was present in infant serum through day 120 post-birth. Low levels of ustekinumab were present in breast milk. CONCLUSIONS: Exposure of macaque fetuses and infants to ustekinumab had no adverse effects on pre- and postnatal development. PMID- 20540087 TI - Influence of centriole number on mitotic spindle length and symmetry. AB - The functional role of centrioles or basal bodies in mitotic spindle assembly and function is currently unclear. Although supernumerary centrioles have been associated with multipolar spindles in cancer cells, suggesting centriole number might dictate spindle polarity, bipolar spindles are able to assemble in the complete absence of centrioles, suggesting a level of centriole-independence in the spindle assembly pathway. In this report we perturb centriole number using mutations in Chlamydomonas reinhardtii, and measure the response of the mitotic spindle to these perturbations in centriole number. Although altered centriole number increased the frequency of monopolar and multipolar spindles, the majority of spindles remained bipolar regardless of the centriole number. But even when spindles were bipolar, abnormal centriole numbers led to asymmetries in tubulin distribution, half-spindle length and spindle pole focus. Half spindle length correlated directly with number of centrioles at a pole, such that an imbalance in centriole number between the two poles of a bipolar spindle correlated with increased asymmetry between half spindle lengths. These results are consistent with centrioles playing an active role in regulating mitotic spindle length. Mutants with centriole number alteration also show increased cytokinesis defects, but these do not correlate with centriole number in the dividing cell and may therefore reflect downstream consequences of defects in preceding cell divisions. PMID- 20540089 TI - Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats. AB - BACKGROUND: Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague Dawley rats. METHODS: Bryostatin-1 was intravenously administered to rats on gestation days 6-15 at 4.0, 8.0, and 16.0 microg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. RESULTS: The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. CONCLUSIONS: Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy. PMID- 20540090 TI - Embryo-fetal developmental toxicity of figitumumab, an anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody, in cynomolgus monkeys. AB - BACKGROUND: Insulin-like growth factor (IGF) signaling has been linked to tumor cell survival and tumorigenesis. The anti-IGF-1 receptor monoclonal antibody, figitumumab, has been developed as an anti-cancer therapeutic. As part of the safety evaluation, an embryo-fetal developmental toxicity study was conducted in the cynomolgus monkey. METHODS: Figitumumab was administered once weekly intravenously at a dose of 5, 15, or 100 mg/kg during the period of major organogenesis (gestation days [GD] 20-48) with scheduled cesarean section around GD100. Maternal endpoints included clinical observations, food consumption, body weights, hematology, placental weights, toxicokinetics, and immunogenicity. Fetal evaluations included viability; body weights; external, visceral, and skeletal examination (and measurements); drug exposure; and immunogenicity. RESULTS: There was a dose-dependent increase in embryo-fetal loss in the presence of decreased maternal food consumption and slight reduction in body weight. Figitumumab related embryo-fetal developmental toxicity was observed as growth retardation exhibited by reduced fetal body weights at all doses with corresponding developmental delays in morphology. Treatment-related fetal structural malformations were also observed in the mid- and high-dose groups. CONCLUSIONS: Maternal figitumumab dosing only during the period of organogenesis was associated with pregnancy loss and fetal growth deficits; both considered consistent with inhibition of IGF signaling. Fetal malformations were also observed, and were considered secondary to altered placental function and/or reduced fetal growth; however, direct inhibition of IGF signaling in the conceptus cannot be ruled out. This appears to be the first report of treatment related fetal anomalies with a monoclonal antibody when administered only during the period of major organogenesis. PMID- 20540091 TI - Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients. AB - We examined the presence of circulating plastic adherent multipotent mesenchymal stem cells (MSCs) in fracture patients. Three patient groups (n = 10-18) were evaluated, including elderly females with a femoral neck fracture treated with cemented hemiarthroplasty, an age- and sex-matched group with hip osteoarthritis (OA) treated with cemented total hip arthroplasty (THA), and younger adults with surgically treated lower extremity fractures. The presence of circulating MSCs pre- and postoperatively was compared to bone marrow (BM) MSCs from the same subjects. Criteria for identifying MSCs included cell surface markers (CD105+, CD73+, CD90+, CD45-, CD14-), proliferation through several passages as well as osteogenic, chondrogenic, and adipogenic differentiation. Plastic adherent MSCs were found in peripheral blood (PB) from 22% of hip fracture patients, 46% of younger fracture patients, and in none of 63 pre- and postmenopausal women with hip OA. When detectable, circulating MSCs appeared between 39 and 101 h after fracture. PB derived MSCs did not differ from BM derived MSCs, except for a small population (<15%) of CD34+ cells among PB derived MSCs. This initial study indicates mobilization of MSCs into the circulation in response to fracture, even in very old patients, while circulating MSCs were not detectable before or after elective THA. PMID- 20540092 TI - New predictive model for monitoring bone remodeling. AB - The aim of this article was to present a new thermodynamic-based model for bone remodeling which is able to predict the functional adaptation of bone in response to changes in both mechanical and biochemical environments. The model was based on chemical kinetics and irreversible thermodynamic principles, in which bone is considered as a self-organizing system that exchanges matter, energy and entropy with its surroundings. The governing equations of the mathematical model have been numerically solved using Matlab software and implemented in ANSYS software using the Finite Element Method. With the aid of this model, the whole inner structure of bone was elucidated. The current model suggested that bone remodeling was a dynamic process which was driven by mechanical loading, metabolic factors and other external contributions. The model clearly indicated that in the absence of mechanical stimulus, the bone was not completely resorbed and reaches a new steady state after about 50% of bone loss. This finding agreed with previous clinical studies. Furthermore, results of virtual computations of bone density in a composite femur showed the development of a dense cortical bone around the medullary canal and a dense trabeculae bone between the femoral head and the calcar region of the medial cortex due to compressive stresses. The comparison of the predicted bone density with the structure of the proximal femur obtained from X-rays and using strain energy density gave credibility to the current model. PMID- 20540093 TI - Biodegradable xylitol-based elastomers: in vivo behavior and biocompatibility. AB - Biodegradable elastomers based on polycondensation reactions of xylitol with sebacic acid, referred to as poly(xylitol sebacate) (PXS) elastomers have recently been developed. We describe the in vivo behavior of PXS elastomers. Four PXS elastomers were synthesized, characterized, and compared with poly(L-lactic co-glycolic acid) (PLGA). PXS elastomers displayed a high level of structural integrity and form stability during degradation. The in vivo half-life ranged from approximately 3 to 52 weeks. PXS elastomers exhibited increased biocompatibility compared with PLGA implants. PMID- 20540094 TI - Controlled release of 2, 3 desulfated heparin exerts its anti-inflammatory activity by effectively inhibiting E-selectin. AB - Control of inflammation using appropriate anti-inflammatory agent prevents wound from becoming chronic. Heparin is a heterogeneous mixture of polysaccharide molecules with a mean molecular weight between 12-30 kDa containing 200-300 disaccharide units of glycosaminoglycan chains. Chemical modifications leading to generation of a unique pentasaccharide sequence effectively reduces its anticoagualant activity, while retaining its anti-inflammmatory property. In this study, Standard heparin was partially desulfated to 2, 3 desulfated heparin (2, 3 DSH) and its anti-inflammatory property was determined by assessing its ability to prevent static adhesion of leukocytes to endothelium and clotting assay. The effectiveness of 2, 3 DSH to down regulate E-selectin and key proinflammatory cytokines (IL-1beta and IL-6) was assessed by western blot and immunocytochemistry. These results were compared with commercially available 2 Desulfated Heparin (2DSH) and standard heparin (SH). Finally, a controlled delivery system of 2, 3 DSH was designed using chitosan microspheres and collagen as scaffold. Optimal loading of 2, 3 DSH was achieved and the release kinetics were tuned to follow a controlled release pattern. The steady state concentration of 2, 3 DSH was found to be optimal to elicit anti-inflammatory property and could achieve inhibition of E-selectin expression while unaffecting the normal clotting cascade. PMID- 20540095 TI - Photocrosslinkable chitosan modified with angiopoietin-1 peptide, QHREDGS, promotes survival of neonatal rat heart cells. AB - Myocardial infarction (MI) results in the death of cardiomyocytes (CM), which causes scar formation and pathological remodeling of the heart. The delivery of healthy myocytes or bone marrow cells reduces pathological remodeling after MI, however, current cell injection methods have low cell survival rates and high cell loss. The main objective of this work was to develop a novel hydrogel that can promote survival of CMs. Photocrosslinkable azidobenzoic acid modified chitosan (Az-chitosan) was conjugated with the angiopoietin-1-derived peptide, QHREDGS. This novel peptide is thought to mediate attachment and survival responses of CM to angiopoietin-1 via integrin binding. Thin layers of Az chitosan, Az-chitosan-QHREDGS, and Az-chitosan-DGQESHR (scrambled peptide control) were spin coated on glass slides and photocrosslinked with application of UV light (365 nm). Neonatal rat heart cells cultured up to 5 days, demonstrated significantly higher attachment and viability on Az-chitosan-QHREDGS compared to cells on other hydrogel controls. Surfaces were also stained for the CM-specific marker troponin I, demonstrating significantly higher percentage of CMs on Az-chitosan-QHREDGS compared to Az-chitosan. The cells cultivated on Az chitosan-QHREDGS demonstrated significantly lower levels of caspase 3/7 activation after taxol treatment in comparison to cells cultivated on the control hydrogels, glass substrate, or Az-chitosan linked to RGD, an established integrin binding peptide that did not protect against apoptosis. Thus, Az-chitosan-QHREDGS supports attachment and survival of neonatal rat heart cells. PMID- 20540096 TI - Development of a three-dimensional model for rapid evaluation of bone substitutes in vitro: effect of the 45S5 bioglass. AB - The evaluation of innovative bone substitutes requires the development of an optimal model close to physiological conditions. An interesting alternative is the use of an immortalized cell line to construct multicellular spheroids, that is, three-dimensional (3D) cultures. In this study, a modified hanging drops method has resulted in the generation of spheroids with a well-established human fetal osteoblasts line (hFOB 1.19), and tests have been focused on the effect of 45S5 bioglass ionic dissolution products in comparison with two-dimensional (2D) cultures. Depending on cell culture type, quantitative analysis (cell proliferation, viability/cytotoxicity, and cellular cycle) and qualitative analysis (electron microscopy and genes expression) showed a differential effect. Cell proliferation was enhanced in 2D-conditioned cultures in accordance with literature data, but decreased in 3D cultures submitted to the same conditions, without change of gene expression patterns. The decrease of cell proliferation, observed in conditioned spheroids, appears to be in agreement with clinical observations showing the insufficiency of commercially available bioglasses for bone repairing within nonbearing sites, such as periodontal defects or small bone filling, in general. Therefore, we suggest that this model could be adapted to the screening of innovative bioactive materials by laboratory techniques already available and extended monitoring of their bioactivity. PMID- 20540098 TI - Collagen and mineral deposition in rabbit cortical bone during maturation and growth: effects on tissue properties. AB - We characterized the composition and mechanical properties of cortical bone during maturation and growth and in adult life in the rabbit. We hypothesized that the collagen network develops earlier than the mineralized matrix. Growth was monitored, and the rabbits were euthanized at birth (newborn), and at 1, 3, 6, 9, and 18 months of age. The collagen network was assessed biochemically (collagen content, enzymatic and non-enzymatic cross-links) in specimens from the mid-diaphysis of the tibia and femur and biomechanically (tensile testing) from decalcified whole tibia specimens. The mineralized matrix was analyzed using pQCT and 3-point bend tests from intact femur specimens. The collagen content and the Young's modulus of the collagen matrix increased significantly until the rabbits were 3 months old, and thereafter remained stable. The amount of HP and LP collagen cross-links increased continuously from newborn to 18 months of age, whereas PEN cross-links increased after 6 months of age. Bone mineral density and the Young's modulus of the mineralized bone increased until the rabbits were at least 6 months old. We concluded that substantial changes take place during the normal process of development in both the biochemical and biomechanical properties of rabbit cortical bone. In cortical bone, the collagen network reaches its mature composition and mechanical strength prior to the mineralized matrix. PMID- 20540097 TI - Tailoring nanocrystalline diamond coated on titanium for osteoblast adhesion. AB - Diamond coatings with superior chemical stability, antiwear, and cytocompatibility properties have been considered for lengthening the lifetime of metallic orthopedic implants for over a decade. In this study, an attempt to tailor the surface properties of diamond films on titanium to promote osteoblast (bone forming cell) adhesion was reported. The surface properties investigated here included the size of diamond surface features, topography, wettability, and surface chemistry, all of which were controlled during microwave plasma enhanced chemical-vapor-deposition (MPCVD) processes using CH4-Ar-H2 gas mixtures. The hardness and elastic modulus of the diamond films were also determined. H2 concentration in the plasma was altered to control the crystallinity, grain size, and topography of the diamond coatings, and specific plasma gases (O2 and NH3) were introduced to change the surface chemistry of the diamond coatings. To understand the impact of the altered surface properties on osteoblast responses, cell adhesion tests were performed on the various diamond-coated titanium. The results revealed that nanocrystalline diamond (grain sizes <100 nm) coated titanium dramatically increased surface hardness, and the introduction of O2 and NH3 during the MPCVD process promoted osteoblast adhesion on diamond and, thus, should be further studied for improving orthopedic applications. PMID- 20540099 TI - Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation. AB - In Part I, the in vitro degradation of bioactivAR52115e glass scaffolds with a microstructure similar to that of human trabecular bone, but with three different compositions, was investigated as a function of immersion time in a simulated body fluid. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13 93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. This work is an extension of Part I, to investigate the effect of the glass composition on the in vitro response of osteogenic MLO-A5 cells to these scaffolds, and on the ability of the scaffolds to support tissue infiltration in a rat subcutaneous implantation model. The results of assays for cell viability and alkaline phosphatase activity showed that the slower degrading silicate 13-93 and borosilicate 13-93B1 scaffolds were far better than the borate 13-93B3 scaffolds in supporting cell proliferation and function. However, all three groups of scaffolds showed the ability to support tissue infiltration in vivo after implantation for 6 weeks. The results indicate that the required bioactivity and degradation rate may be achieved by substituting an appropriate amount of SiO2 in 13-93 glass with B2O3, and that these trabecular glass scaffolds could serve as substrates for the repair and regeneration of contained bone defects. PMID- 20540100 TI - Gold nanoparticles on titanium and interaction with prototype protein. AB - Modifying titanium (Ti) implant surfaces with functional proteins can strengthen the interface between prosthesis and bone. A prototype system was developed using gold nanoparticles (AuNPs) to immobilize proteins onto Ti. An electroless (galvanic displacement) deposition method was first used to form AuNPs of controlled size and coverage on commercial Ti foil (giving Ti-AuNPs). Parameters were then modified to create two groups of discs (n = 26) with different average AuNP diameters. Scanning electron microscopy and X-ray photoelectron spectroscopy were used to characterize the morphology and surface structure of Ti-AuNPs. To study the interaction of Ti-AuNPs with proteins, Ti discs (n = 8) modified with plain AuNPs and discs (n = 8) modified with thiol (HS--R--COOH)-functionalized AuNPs were treated with lysozyme solution. The amount and activity of the lysozyme on the discs were examined with Micro-BCA and enzymatic assays. Lysozyme was immobilized onto the discs, and the assays showed that the discs with thiol functionalized AuNPs, discs with bare AuNPs, and Ti controls had average lysozyme adsorptions of 23 x 10(4), 2.3 x 10(4), and 5.7 x 10(4) microg/m2, respectively. The activity assays showed that 21.5, 18.4, and 12.5% of the adsorbed lysozyme was active on the discs with thiol-functionalized AuNPs, discs with bare AuNPs, and Ti controls, respectively. This technique holds promise for binding functional biomolecules to surgical implants, hence possibly creating implant surfaces that react to their local environment. PMID- 20540101 TI - Directional fluid flow enhances in vitro periosteal tissue growth and chondrogenesis on poly-epsilon-caprolactone scaffolds. AB - The purpose of this study was to investigate the effect of directional fluid flow on periosteal chondrogenesis. Periosteal explants were harvested from 2-month-old rabbits and sutured onto poly-epsilon-caprolactone (PCL) scaffolds with the cambium layer facing away from the scaffolds. The periosteum/PCL composites were cultured in suspension in spinner flask bioreactors and exposed to various fluid flow velocities: 0, 20, 60, and 150 rpm for 4 h each day for 6 weeks. The application of fluid flow significantly increased percent cartilage yield in periosteal explants from 17% in the static controls to 65-75% under fluid flow (there was no significant difference between 20, 60, or 150 rpm). The size of the neocartilage was also significantly greater in explants exposed to fluid flow compared with static culture. The development of zonal organization within the engineered cartilage was observed predominantly in the tissue exposed to flow conditions. The Young's modulus of the engineered cartilage exposed to 60 rpm was significantly greater than the samples exposed to 150 and 20 rpm. These results demonstrate that application of directional fluid flow to periosteal explants secured onto PCL scaffolds enhances cell proliferation, chondrogenic differentiation, and cell organization and alters the biomechanical properties of the engineered cartilage. PMID- 20540103 TI - Occurrence of substance P in bone repair under different load comparison of straight and angulated fracture in rat tibia. AB - Substance P (SP) has been shown in vitro to stimulate both formation and resorption of bone. This seemingly contradictory observation could be explained by in vivo variations in skeletal loading and rate of bone turnover, features which may be explored during different phases of fracture healing. In 50 SD rats, the right tibia was fractured and fixed with an intramedullary pin in straight alignment and in anterior angulation resulting in a convex and concave side under different load. Fracture repair was assessed by radiography, histology, and semi quantitative immunohistochemistry of SP nerve fiber occurrence at days 7, 21, 35, 56, and 84 post-fracture. During regeneration, days 7-35, abundant SP-nerve ingrowth was observed in the fracture callus reaching a side-symmetrical peak at day 21 in straight fractures. In angulated fractures, the SP peak was also observed at day 21 on the concave loaded side, but not until day 35 on the convex unloaded side. Each SP-peak coincided with cortical bridging. During remodeling, days 35-84, a side-symmetrical disappearance of SP-positive fibers was seen in straight fractures. The same pattern was seen on the concave loaded side of angulated fractures. However, on the convex unloaded side, where resorption now took place, SP-fibers remained until the end of the experiment. Our study suggests that neuronal SP during bone regeneration has a stimulatory role on bone formation, while during remodeling increased SP fiber density in unloaded areas may be related to bone resorption. PMID- 20540105 TI - Flash nano-welding: investigation and control of the photothermal response of ultrathin bismuth sulfide nanowire films. AB - Ultrathin Bi2S3 nanowires undergo a pronounced photothermal response to irradiation from a commercial camera flash. Controlled nano-welding was shown by using single walled carbon nanotube mats as an electrically and thermally conductive substrate. The resulting welded nanowire film is denser and has significantly lower resistance than unflashed bilayer films. PMID- 20540104 TI - A comparison of the effects of prenatal exposure of CD-1 mice to three imidazolium-based ionic liquids. AB - BACKGROUND: Ionic liquids (ILs; salts with melting points below 100 degrees C) exhibit wide liquid ranges, non-flammability, and thermal stability among other properties. These unique salts are best known as "green" alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1-ethyl-3 methylimidazolium chloride ([C(2)mim]Cl), 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl), and 1-decyl-3methylimidazolium chloride ([C(10)mim]Cl). METHODS: From gestation days (GD) 6-16, mated CD-1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C(2)mim]Cl; 113, 169, or 225 mg/kg/day [C(4)mim]Cl; 50, 75, or 100 mg/kg/day [C(10)mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: Fetal weight was significantly decreased in the two highest dosage groups exposed to [C(4)mim]Cl and [C(10)mim]Cl in comparison with their controls, but the [C(2)mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C(4)mim]Cl and [C(10)mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C(2)mim]Cl-treated groups, despite maternal morbidity at the highest dosage level. CONCLUSIONS: This study indicates that [C(4)mim]Cl and [C(10)mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium-based ILs is influenced by alkyl chain length. PMID- 20540106 TI - Solution-processed solid solution of a novel carbazole derivative for high performance blue phosphorescent organic light-emitting diodes. AB - Blue light: Incorporation of two fluorenyl rings into a phenyl group at the C9 position of fluorene builds a bulky and rigidly tetrahedral framework, which is functionalized by two carbazole groups. This molecule possesses excellent thermal and morphological stability, miscibility to the phosphorescent dopant, and high triplet energy, leading to narrow blue phosphorescent emission. PMID- 20540107 TI - Cooperation and cheating in microbial exoenzyme production--theoretical analysis for biotechnological applications. AB - The engineering of microorganisms to produce a variety of extracellular enzymes (exoenzymes), for example for producing renewable fuels and in biodegradation of xenobiotics, has recently attracted increasing interest. Productivity is often reduced by "cheater" mutants, which are deficient in exoenzyme production and benefit from the product provided by the "cooperating" cells. We present a game theoretical model to analyze population structure and exoenzyme productivity in terms of biotechnologically relevant parameters. For any given population density, three distinct regimes are predicted: when the metabolic effort for exoenzyme production and secretion is low, all cells cooperate; at intermediate metabolic costs, cooperators and cheaters coexist; while at high costs, all cells use the cheating strategy. These regimes correspond to the harmony game, snowdrift game, and Prisoner's Dilemma, respectively. Thus, our results indicate that microbial strains engineered for exoenzyme production will not, under appropriate conditions, be outcompeted by cheater mutants. We also analyze the dependence of the population structure on cell density. At low costs, the fraction of cooperating cells increases with decreasing cell density and reaches unity at a critical threshold. Our model provides an estimate of the cell density maximizing exoenzyme production. PMID- 20540108 TI - Biofuel production improvement with genome-scale models: The role of cell composition. AB - Genome-scale models have developed into a vital tool for rational metabolic engineering. These models balance cofactors and energetic requirements and determine biosynthetic precursor availability in response to environmental and genetic perturbations. In particular, allocation of additional reducing power is an important strategy for engineering potential biofuel production from microbes. Many potential biofuel solvents induce biomolecular changes on the host organism that are not yet captured by genome-scale models. Here, methods of construction for several biomass constituting equations are reviewed along with potential changes to cellular composition with potential biofuels exposure. The biomass constituting equations of potential host organisms with existing genome-scale models are compared side-by-side to explore their evolution over the years and to explore differences that arise when these equations are compiled by different research groups. Genome-scale model simulation results attempt to address and provide guidance for further research into: (i) whether inconsistencies in the biomass constituting equations are relevant to predictions of solvent production, (ii) what level of detail is necessary to accurately describe cellular composition, and (iii) future developments that may enable more accurate characterizations of biomolecular composition. PMID- 20540109 TI - Cellulases of Penicillium verruculosum. AB - Nine major cellulolytic enzymes were isolated from a culture broth of a mutant strain of the fungus Penicillium verruculosum: five endo-1, 4-beta-glucanases (EGs) having molecular masses 25, 33, 39, 52, and 70 kDa, and four cellobiohydrolases (CBHs: 50, 55, 60, and 66 kDa). Based on amino acid similarities of short sequenced fragments and peptide mass fingerprinting, the isolated enzymes were preliminary classified into different families of glycoside hydrolases: Cel5A (EG IIa, 39 kDa), Cel5B (EG IIb, 33 kDa), Cel6A (CBH II, two forms: 50 and 60 kDa), Cel7A (CBH I: 55 and 66 kDa), Cel7B (EG I: 52 and 70 kDa). The 25 kDa enzyme was identical to the previously isolated Cel12A (EG III). The family assignment was further confirmed by the studies of the substrate specificity of the purified enzymes. High-molecular-weight forms of the Cel6A, Cel7A, and Cel7B were found to possess a cellulose-binding module (CBM), while the catalytically active low-molecular-weight forms of the enzymes, as well as other cellulases, lacked the CBM. Properties of the isolated enzymes, such as substrate specificity toward different polysaccharides and synthetic glycosides, effect of pH and temperature on the enzyme activity and stability, adsorption on Avicel cellulose and kinetics of its hydrolysis, were investigated. PMID- 20540110 TI - In silico genome-scale metabolic analysis of Pseudomonas putida KT2440 for polyhydroxyalkanoate synthesis, degradation of aromatics and anaerobic survival. AB - Genome-scale metabolic models have been appearing with increasing frequency and have been employed in a wide range of biotechnological applications as well as in biological studies. With the metabolic model as a platform, engineering strategies have become more systematic and focused, unlike the random shotgun approach used in the past. Here we present the genome-scale metabolic model of the versatile Gram-negative bacterium Pseudomonas putida, which has gained widespread interest for various biotechnological applications. With the construction of the genome-scale metabolic model of P. putida KT2440, PpuMBEL1071, we investigated various characteristics of P. putida, such as its capacity for synthesizing polyhydroxyalkanoates (PHA) and degrading aromatics. Although P. putida has been characterized as a strict aerobic bacterium, the physiological characteristics required to achieve anaerobic survival were investigated. Through analysis of PpuMBEL1071, extended survival of P. putida under anaerobic stress was achieved by introducing the ackA gene from Pseudomonas aeruginosa and Escherichia coli. PMID- 20540112 TI - Plasmacytoid dendritic cell-induced migration and activation of NK cells in vivo. AB - NK cells are cytotoxic cells of the innate immune system. They have been found to be critical in the defense against infections and also against some tumors. Recent studies have shown that NK cells require signals from accessory cells to induce their recruitment and activation at the site of infection or tumor growth. In this study, we examined whether plasmacytoid DC (pDC) could recruit and activate NK cells in vivo. When CpG-stimulated pDC were injected i.p. to C57BL/6 mice, they efficiently recruited NK cells, a process that was dependent on NK cell CXCR3 and CD62L and in part on CCR5. NK cells isolated from the peritoneum of mice inoculated with TLR7/8 or TLR9-stimulated pDC exhibited greater cytotoxicity against YAC-1 tumor cells than NK cells recovered from mice inoculated with control pDC. The present results are discussed in relation to pDC induced NK cell migration and activation in vivo. PMID- 20540111 TI - Reversal of type 1 diabetes by a new MHC II-peptide chimera: "Single-epitope mediated suppression" to stabilize a polyclonal autoimmune T-cell process. AB - Polyclonality of self-reactive CD4(+) T cells is the hallmark of several autoimmune diseases like type 1 diabetes. We have previously reported that a soluble dimeric MHC II-peptide chimera prevents and reverses type 1 diabetes induced by a monoclonal diabetogenic T-cell population in double Tg mice [Casares, S. et al., Nat. Immunol. 2002. 3: 383-391]. Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4(+) T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65(217-230) specific CD4(+) T cells) using a soluble I-A(alphabeta) (g7)/GAD65(217 230)/Fcgamma2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. Activated GAD65(217-230)-specific T cells and a fraction of the diabetogenic (B(9-23)-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. More importantly, this led to the reversal of hyperglycemia for more than 2 months post-therapy in 80% of mice in the context of stabilization of pancreatic insulitis and improved insulin secretion by the beta cells. These findings argue for the stabilization of a polyclonal self-reactive T-cell process by a single epitope-mediated bystander suppression. Dimeric MHC class II-peptide chimeras like approach may provide rational grounds for the development of more efficient antigen-specific therapies in type 1 diabetes. PMID- 20540113 TI - TGF-beta interactions with IL-1 family members trigger IL-4-independent IL-9 production by mouse CD4(+) T cells. AB - TGF-beta and IL-4 were recently shown to selectively upregulate IL-9 production by naive CD4(+) T cells. We report here that TGF-beta interactions with IL 1alpha, IL-1beta, IL-18, and IL-33 have equivalent IL-9-stimulating activities that function even in IL-4-deficient animals. This was observed after in vitro antigenic stimulation of immunized or unprimed mice and after polyclonal T-cell activation. Based on intracellular IL-9 staining, all IL-9-producing cells were CD4(+) and 80-90% had proliferated, as indicated by reduced CFSE staining. In contrast to IL-9, IL-13 and IL-17 were strongly stimulated by IL-1 and either inhibited (IL-13) or were unaffected (IL-17) by addition of TGF-beta. IL-9 and IL 17 production also differed in their dependence on IL-2 and regulation by IL-1/IL 23. As IL-9 levels were much lower in Th2 and Th17 cultures, our results identify TGF-beta/IL-1 and TGF-beta/IL-4 as the main control points of IL-9 synthesis. PMID- 20540114 TI - Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection. AB - Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL 2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85 90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN gamma double and IFN-gamma single expressors as compared with the other CD4(+) T cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti mycobacterial therapy. PMID- 20540115 TI - TGF-beta affects development and differentiation of human natural killer cell subsets. AB - Human peripheral blood NK cells may be divided into two main subsets: CD56(bright)CD16(-) and CD56(dim)CD16(+). Since TGF-beta is known to influence the development of many leukocyte lineages, its effects on NK cell differentiation either from human CD34(+)Lin(-) hematopoietic progenitor/stem cells in vitro or from peripheral blood NK cells were investigated. TGF-beta represses development of NK cells from CD34(+) progenitors and inhibits differentiation of CD16(+) NK cells. Moreover, TGF-beta also results in conversion of a minor fraction of CD56(bright)CD16(+) cells found in peripheral blood into CD56(bright)CD16(-) cells, highlighting a possible role of the former as a developmental intermediate and of TGF-beta in influencing the genesis of NK subsets found in blood. PMID- 20540116 TI - Rapid transcriptome and proteome profiling of a non-model marine invertebrate, Bugula neritina. AB - Non-model organisms represent the majority of life forms in our planet. However, the lack of genetic information hinders us to understand the unique biological phenomena in non-model organisms at the molecular level. In this study, we applied a tandem transcriptome and proteome profiling on a non-model marine fouling organism, Bugula neritina. Using a 454 pyrosequencing platform with the updated titanium reagents, we generated a total of 48M bp transcriptome data consisting of 131 450 high-quality reads. Of these, 122 650 reads (93%) were assembled to produce 6392 contigs with an average length of 538 bases and the remaining 8800 reads were singletons. Of the total 15 192 unigenes, 13 863 ORFs were predicated, of which 6917 were functionally annotated based on gene ontology and eukaryotic orthologous groups. Subsequent proteome analysis identified and quantified 882 proteins from B. neritina. These results would provide fundamental and important information for the subsequent studies of molecular mechanism in larval biology, development, antifouling research. Furthermore, we demonstrated, for the first time, the combined use of two high-throughput technologies as a powerful approach for accelerating the studies of non-model but otherwise important species. PMID- 20540118 TI - Proteome analysis of brain in murine experimental autoimmune encephalomyelitis. AB - Multiple sclerosis is considered a prototype inflammatory autoimmune disorder of the CNS. Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein is one of the best-characterized animal models of multiple sclerosis. Comprehensive understanding of gene expression in EAE can help identify genes that are important in drug response and pathogenesis. We applied a 2-DE-based proteomics approach to analyze the protein expression pattern of the brain in healthy and EAE samples. Of more than 1000 protein spots we analyzed, 70 showed reproducible and significant changes in EAE compared to controls. Of these, 42 protein spots could be identified using MALDI TOF-TOF-MS. They included mitochondrial and structural proteins as well as proteins involved in ionic and neurotransmitter release, blood barriers, apoptosis, and signal transduction. The possible role of these proteins in the responses of mice to animal models of multiple sclerosis is discussed. PMID- 20540117 TI - EAE mediated by a non-IFN-gamma/non-IL-17 pathway. AB - Previous studies have shown that EAE can be elicited by the adoptive transfer of either IFN-gamma-producing (Th1) or IL-17-producing (Th17) myelin-specific CD4(+) T-cell lines. Paradoxically, mice deficient in either IFN-gamma or IL-17 remain susceptible to EAE following immunization with myelin antigens in CFA. These observations raise questions about the redundancy of IFN-gamma and IL-17 in autoimmune demyelinating disease mediated by a diverse, polyclonal population of autoreactive T cells. In this study, we show that an atypical form of EAE, induced in C57BL/6 mice by the adoptive transfer of IFN-gamma-deficient effector T cells, required IL-17 signaling for the development of brainstem infiltrates. In contrast, classical EAE, characterized by predominant spinal cord inflammation, occurred in the combined absence of IFN-gamma and IL-17 signaling, but was dependent on GM-CSF and CXCR2. Our findings contribute to a growing body of data, indicating that individual cytokines vary in their importance across different models of CNS autoimmunity. PMID- 20540119 TI - Inhibition of photosynthesis and modification of the wheat leaf proteome by Ptr ToxB: a host-specific toxin from the fungal pathogen Pyrenophora tritici repentis. AB - Tan spot, caused by Pyrenophora tritici-repentis, is an important foliar disease of wheat. The fungus produces the host-specific, chlorosis-inducing toxin Ptr ToxB. To better understand toxin action, we examined the effects of Ptr ToxB on sensitive wheat. Photosynthesis, as measured by infrared gas analysis, declined significantly within 12 h of toxin treatment, prior to the development of chlorosis at 48-72 h. Analysis by 2-DE revealed a total of 102 protein spots with significantly altered intensities 12-36 h after toxin treatment, of which 66 were more abundant and 36 were less abundant than in the buffer-treated control. The identities of 47 of these spots were established by MS/MS, and included proteins involved in the light reactions of photosynthesis, the Calvin cycle, and the stress/defense response. Based on the declines in photosynthesis and the identities of the differentially abundant proteins, we hypothesize that Ptr ToxB causes a rapid disruption in the photosynthetic processes of sensitive wheat, leading to the generation of ROS and oxidative stress. Although the photoprotective and repair mechanisms of the host appear to initially still be functional, they are probably overwhelmed by the continued production of ROS, leading to chlorophyll photooxidation and the development of chlorosis. PMID- 20540121 TI - Innovative inorganic-organic nanohybrid materials: coupling quantum dots to carbon nanotubes. PMID- 20540120 TI - Multiple P450 genes overexpressed in deltamethrin-resistant strains of Helicoverpa armigera. AB - BACKGROUND: Resistance to the pyrethroid insecticide deltamethrin has been a growing problem in the management of Helicoverpa armigera (Hubner) pest populations in West Africa. Detoxification by P450 enzymes appears to be a major mechanism of resistance, but the genes responsible for resistance are unknown. RESULTS: First, it was shown that deltamethrin resistance in strains from Burkina Faso (Kaya) and from Spain (Seville) were suppressible by piperonyl butoxide and by trichlorophenyl propynyl ether, thus indicating a major role of P450 enzyme(s) in resistance. The larval expression of 21 CYP genes encoding P450 enzymes from six CYP families were then compared by quantitative RT-PCR. Five genes, CYP4L5, CYP4L11, CYP6AE11, CYP332A1 and CYP9A14, were significantly overexpressed in the Kaya and Seville strains when compared with Heliar, a susceptible strain. Significant overexpression of multiple CYP genes (CYP4M6, CYP4M7, CYP6AE11, CYP9A12, CYP332A1 and CYP337B1) was also found in six field strains with different levels of resistance from Benin, Burkina Faso and Mali. CONCLUSION: Although functional or genetic evidence for the role of these P450s in resistance remains to be formally established, results suggest that multiple P450 enzymes contribute to deltamethrin resistance. This study is a first step towards the development of molecular tools for the detection of P450-based resistance in H. armigera. PMID- 20540122 TI - Stable oxoborate with edge-sharing BO4 tetrahedra synthesized under ambient pressure. PMID- 20540123 TI - A protease-based strategy for the controlled release of therapeutic peptides. PMID- 20540124 TI - Orthogonal action of noncovalent interactions for photoresponsive chiral columnar assemblies. PMID- 20540125 TI - A coupling strategy to produce hydrogen and ethylene in a membrane reactor. PMID- 20540127 TI - A rapid aqueous fluoride ion sensor with dual output modes. PMID- 20540126 TI - Structural control of crystal nuclei by an eggshell protein. PMID- 20540128 TI - A universal approach to the synthesis of noble metal nanodendrites and their catalytic properties. PMID- 20540129 TI - A programmable DNA-based molecular valve for colloidal mesoporous silica. PMID- 20540130 TI - Detection of kinase activity using versatile fluorescence quencher probes. PMID- 20540131 TI - Photographing oxygen distribution. PMID- 20540132 TI - Synthesis of transparent and field-responsive BaTiO3 particle/organosiloxane hybrid fluid. PMID- 20540133 TI - A [2]rotaxane flip switch driven by coordination geometry. PMID- 20540134 TI - Room-temperature C-C bond cleavage of an arene by a metallacarborane. PMID- 20540135 TI - Molecular-sieve membrane with hydrogen permselectivity: ZIF-22 in LTA topology prepared with 3-aminopropyltriethoxysilane as covalent linker. PMID- 20540138 TI - Facile template-free synthesis of Bi(2)O(2)CO(3) hierarchical microflowers and their associated photocatalytic activity. AB - Hierarchical Bi(2)O(2)CO(3) flowerlike microstructures have been synthesized for the first time using a facile, template-free, and low-temperature solution method. With an average diameter of about 3 microm, the as-prepared Bi(2)O(2)CO(3) microflowers are composed of numerous two-dimensional nanosheets with oriented terminal engagement. On the basis of electron microscopy observations, a plausible growth mechanism is proposed as a spatial self-assembly process accompanied by Ostwald ripening. The molar ratio of the initial reagents plays an important role in determining the morphologies of the Bi(2)O(2)CO(3) microstructures. UV/Vis spectroscopy is employed to analyze the band gaps of the products. Both mesopores and macropores are revealed in the Bi(2)O(2)CO(3) microflowers by means of nitrogen sorption and pore-size distribution. Moreover, evaluated by the degradation of methyl orange under UV illumination, the photocatalytic performance of the Bi(2)O(2)CO(3) hierarchical microflowers is almost six times higher than that of commercial Bi(2)O(2)CO(3). The higher specific surface area, the meso/macropores, and the intra-electric field formed between the (Bi(2)O(2))(2+) layer and the slabs comprising CO(3) (2-) in the Bi(2)O(2)CO(3) crystal structure, are believed to facilitate the separation of the photoinduced electrons and holes and thus improve the corresponding photocatalytic activity. PMID- 20540139 TI - Substrate influence for the Zn-tetraphenyl-porphyrin adsorption geometry and the interface-induced electron transfer. AB - In molecular devices, the importance of interfaces cannot be neglected as they determine charge injection and charge flow and, therefore, the device performance. Herein we report on the interaction of one single layer of Zn tetraphenyl-porphyrin with Ag(110) and Si(111). Photoemission, near-edge X-ray absorption, and resonant photoemission are used to study the bonding nature, the adsorption geometry as well as the dynamics of electron transfer between the molecules and the metal or semiconductor surfaces. Molecule-substrate charge transfer is driven by the overlap with the molecular pi orbitals. In particular, the coupling of the phenyl legs with the substrate and the relative excited charge injection are dramatically different for the two surfaces considered. PMID- 20540140 TI - New microporous materials for acetylene storage and C(2)H(2)/CO(2) separation: insights from molecular simulations. AB - Force-field based grand-canonical Monte Carlo simulations are used to investigate the acetylene and carbon dioxide uptake capacity, as well as the C(2)H(2)/CO(2) adsorption selectivity of three novel microporous materials: Magnesium formate, Cu(3)(btc)(2), and cucurbit[6]uril. Because no comparable computational studies of acetylene adsorption have been reported so far, the study focuses on systems for which experimental data are available to permit a thorough validation of the simulation results. The results for magnesium formate are in excellent agreement with experiment. The simulation predicts a high selectivity for acetylene over CO(2), which can be understood from a detailed analysis of the structural features that determine the affinity of Mg-formate towards C(2)H(2). For Cu(3)(btc)(2), preliminary calculations reveal the necessity to include the interaction of the sorbate molecules with the unsaturated metal sites, which is done by means of a parameter adjustment based on ab-initio calculations. In spite of the high C(2)H(2) storage capacity, the C(2)H(2)/CO(2) selectivity of this material is very modest. The simulation results for the porous organic crystal cucurbit[6]uril show that the adsorption characteristics that have been observed experimentally, particularly the very high isosteric heat of adsorption, cannot be understood when an ideal structure is assumed. It is postulated that structural imperfections play a key role in determining the C(2)H(2) adsorption behavior of this material, and this proposition is supported by additional calculations. PMID- 20540141 TI - Efficient two-photon excited amplified spontaneous emission from organic single crystals. AB - E, E-1, 4-bis[4'-(N,N-dibutylamino)styryl]-2,5-dimethoxy-benzene (DBASDMB) organic crystals with high crystalline quality, large size and excellent optical properties are prepared. The linear and nonlinear properties in the crystal are comparatively studied. The relaxation dynamics pumped by two-photon are very similar with that pumped by one-photon. The crystal exhibits very strong two photon excited fluorescence and amplified spontaneous emission. Efficient two photon absorption, reasonably high fluorescent quantum efficiency, and high crystal quality together with stimulated emission make organic crystals ideal for the application in frequency upconversion and other optoelectronic fields. PMID- 20540142 TI - Organic semiconductors: impact of disorder at different timescales. AB - The charge transport in organic materials, from molecular crystals to polymers, is determined by their degree of disorder. The dynamic disorder in ideal molecular crystals at room temperature and the static disorder in disordered polymers are just two limiting cases of the timescale of the fluctuations in the electronic Hamiltonian caused by nuclear motions. In fact, a very large number of important materials (e.g. liquid crystalline semiconductors) are actually in an intermediate regime where the disorder is neither purely static nor purely dynamic. This Minireview discusses the recent contribution of computational chemistry (molecular dynamics and quantum chemistry) to the characterization of these transport regimes and outlines the theoretical methods that can be used to relate the system characteristics to the measurable mobility. PMID- 20540143 TI - Efficient photochemical oxidation of anisole in protic solvents: electron transfer driven by specific solvent-solute interactions. AB - The dynamics of the bimolecular quenching of triplet excited benzophenone by anisole was studied by nanosecond flash photolysis. We carried out a detailed study of the solvent dependence of the reaction rates and efficiencies in a number of protic and non-protic solvents. These studies were augmented by theoretical modelling and experimental investigation of solute/solvent interactions in the triplet excited and the ground state, respectively. The triplet quenching that follows Stern-Volmer kinetics in all cases is profoundly dependent on the nature of the solvent, with the highest reactivity being consistently found in protic solvents. The results in non-protic solvents are compatible with unproductive quenching via a charge-transfer state, whereas the generally fast quenching in protic solvents is accompanied by efficient formation of free-radical products. Analysis of the solvent dependence in terms of Marcus theory reveals the impact of specific solvation of benzophenone by protic solvents on the ET driving force and kinetics. Specific solvation is found to support efficient free radical ion formation in media of moderate and low polarity as well. PMID- 20540144 TI - Bolus ingestion of white and green tea increases the concentration of several flavan-3-ols in plasma, but does not affect markers of oxidative stress in healthy non-smokers. AB - White tea (WT) is rich in flavan-3-ols as green tea (GT) and might provide health protective effects due to the strong antioxidant properties of flavan-3-ols. Since intervention studies with WT are lacking, we evaluated the effects of WT consumption on antioxidant status, antioxidant capacity and biomarkers of oxidative stress compared to water and GT. After an overnight fast, 70 healthy non-smokers were randomized to consume 600 mL of WT, GT or water (control). Plasma (epi-)catechin and epi(gallo)catechingallate, antioxidant capacity (Folin assay, trolox equivalent antioxidant capacity test), 8-iso-prostaglandin F(2alpha), ascorbic acid and uric acid were determined before and several times within 8 h after consumption. DNA strand breaks were measured in vivo and ex vivo (H(2)O(2) stimulation) in leukocytes. Plasma flavan-3-ols significantly increased after WT and GT ingestion. Trolox equivalent antioxidant capacity was lower after 5 h in controls versus WT (p = 0.031) and GT (p = 0.005). Folin-Ciocalteu reducing capacity, ascorbic and uric acid as well as markers of oxidative stress (8-iso-prostaglandin-F(2alpha), DNA strand breaks) were not affected by the beverages. A short-term increase of catechins does not change plasma antioxidant capacity in healthy subjects. Conclusions with respect to health protective effects of WT and GT on the basis of these biomarkers can, thus, not be drawn. PMID- 20540145 TI - Peptides from Pisum sativum L. enzymatic protein digest with anti-adhesive activity against Helicobacter pylori: structure-activity and inhibitory activity against BabA, SabA, HpaA and a fibronectin-binding adhesin. AB - SCOPE: Identification of anti-adhesive peptides against Helicobacter pylori obtained by enzymatic hydrolysis of seed proteins from Pisum sativum L. (Fabaceae). METHODS AND RESULTS: Bioassay-guided fractionation of protein tryptic digest by ultrafiltration, size exclusion chromatography (SEC) and reversed phase chromatography (RPC) were used. Identification of bioactive peptides was achieved by MALDI-TOF-MS. Adhesion of H. pylori was monitored by two different assays, using a quantitative in vitro assay on human AGS cells with evaluation of bacterial binding by flow cytometry, beside a semi-quantitative in situ adhesion assay using FITC-labelled H. pylori on human stomach tissue sections. From two highly active fractions (F3, F3.3) two anti-adhesive peptides (S3, S5) were identified. Neither F3 nor S3 or S5 had any cytotoxic effect against H. pylori. By hemagglutination assay and semiquantitative dot blot overlay assay with immobilized ligands it was shown that F3 interacts specifically with H. pylori adhesins BabA, SabA, HpaA and a fibronectin-binding adhesin, while S3 and S5 inhibit only BabA. It was demonstrated that BabA, usually interacting with carbohydrate motifs such as fucosylated blood group antigens, interacts with the peptide moieties. CONCLUSION: Bioactive peptides from pea protein could be applied as functional ingredients for protecting infants and children against infections such as H. pylori. PMID- 20540146 TI - Effects of plant-derived polyphenols on TNF-alpha and nitric oxide production induced by advanced glycation endproducts. AB - Advanced glycation endproducts (AGEs) accumulate on protein deposits including the beta-amyloid plaques in Alzheimer's disease. AGEs interact with the "receptor for advanced glycation endproducts", and transmit their signals using intracellular reactive oxygen species as second messengers. Ultimately, AGEs induce the expression of a variety of pro-inflammatory markers including the tumor necrosis factor (TNF-alpha) and inducible nitric oxide (NO) synthase. Antioxidants that act intracellularly, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti inflammatory capacity. This study tested the pure compounds apigenin and diosmetin as well as extracts from silymarin, uva ursi (bearberry) and green olive leaf for their ability to attenuate AGE-induced NO and TNF-alpha production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner. Apigenin and diosmetin were most potent, and exhibited EC(50) values approximately 10 microM. In contrast, TNF-alpha expression was only reduced by apigenin, diosmetin and silymarin; not by the bearberry and green olive leaf extracts. In addition, the silymarin and bearberry extracts caused significant cell death at concentrations >or=10 microg/mL and >or=50 microg/mL, respectively. In conclusion, we suggest that plant-derived polyphenols might offer therapeutic opportunities to delay the progression of AGE-mediated and receptor for advanced glycation endproducts-mediated neuro-inflammatory diseases including Alzheimer's disease. PMID- 20540147 TI - Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. AB - In obesity, adipocyte hypertrophy and chronic inflammation in adipose tissues cause insulin resistance and type-2 diabetes. Trigonella foenum-graecum (fenugreek) can ameliorate hyperglycemia and diabetes. However, the effects of fenugreek on adipocyte size and inflammation in adipose tissues have not been demonstrated. In this study, we determined the effects of fenugreek on adipocyte size and inflammation in adipose tissues in diabetic obese KK-Ay mice, and identified the active substance in fenugreek. Treatment of KK-Ay mice with a high fat diet supplemented with 2% fenugreek ameliorated diabetes. Moreover, fenugreek miniaturized the adipocytes and increased the mRNA expression levels of differentiation-related genes in adipose tissues. Fenugreek also inhibited macrophage infiltration into adipose tissues and decreased the mRNA expression levels of inflammatory genes. In addition, we identified diosgenin, a major aglycone of saponins in fenugreek to promote adipocyte differentiation and to inhibit expressions of several molecular candidates associated with inflammation in 3T3-L1 cells. These results suggest that fenugreek ameliorated diabetes by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues, and its effects are mediated by diosgenin. Fenugreek containing diosgenin may be useful for ameliorating the glucose metabolic disorder associated with obesity. PMID- 20540148 TI - Nonextractable polyphenols, usually ignored, are the major part of dietary polyphenols: a study on the Spanish diet. AB - SCOPE: Dietary polyphenols (PP) can be divided into two groups: extractable polyphenols (EPP) or compounds solubilized by aqueous organic solvents, and nonextractable polyphenols (NEPP) or compounds that remain in their corresponding extraction residues. Most studies on food polyphenols and dietary intakes address exclusively EPP. The objective of this work was to determine the actual amount of PP, including NEPP, in food and in a whole diet. METHODS AND RESULTS: HPLC-MS analyses were performed to identify EPP in methanol-acetone extracts and NEPP in the acidic hydrolyzates of their extraction residues in cereals, fruits, vegetables, nuts, and legumes. NEPP contents, estimated as hydrolyzable PP plus nonextractable proanthocyanidins (PA), ranged from 880 mg/100 g dry weight in fruits to 210 mg/100 g in cereals and were substantially higher than the contents of EPP. NEPP intake (day/person) in the Spanish diet (942 mg) is higher than EPP intake (258 mg) fruits and vegetables (746 mg) are the major contributors to the total PP intake (1201 mg). CONCLUSION: Non extractable polyphenols are the major part of dietary polyphenols. The knowledge of intakes and physiological properties of NEPP may be useful for a better understanding of the potential health effects of dietary PP. PMID- 20540149 TI - Plasma phospholipids n-3 polyunsaturated fatty acid is associated with metabolic syndrome. AB - The relationship between n-3 PUFA and metabolic syndrome (MS) is not clear. The aim of this study was to examine relationships between plasma phospholipids (PL) n-3 PUFA and MS in Chinese subjects. Nine hundred and twenty-nine subjects were recruited in Hangzhou, China. Two hundred and ten (183 males, 27 females) with MS and 719 (545 males, 174 females) healthy subjects were identified in this cross sectional study. The prevalence of MS in females (24.56%) was significantly higher than that in males (10.04%) in this population. Total PUFA (p<0.001), n-3 PUFA (p<0.001), and n-3:n-6 (p<0.001) were significantly lower in MS subjects compared to healthy subjects. Plasma phospholipid (PL), n-3 PUFA was significantly inversely associated with MS (p = 0.013). In addition, subjects with high levels of PL total fatty acids (FA) had a more than threefold higher likelihood of MS (OR = 3.44, 95% CI = 1.60-7.39) than the subjects with low levels of PL total FA. Our results suggest that plasma PL n-3 PUFA was significantly inversely associated with MS, while high total FA were positively associated with MS in Chinese. PMID- 20540150 TI - Functional and proliferative effects of repeated low-dose oral administration of furan in rat liver. AB - SCOPE: Furan, a food contaminant formed during heat processing, induces hepatocellular tumors in rodents and high incidences of cholangiocarcinomas in rats even at the lowest dose (2 mg/kg b.w.) administered. Initial estimates suggested that human intake of furan may be as high as 3.5 MUg/kg b.w./day, indicating a relatively narrow margin of exposure. The aim of this study was to establish dose-response data for cytotoxicity, regenerative cell proliferation and secondary oxidative DNA damage in livers of male F344 rats treated with furan at doses <=2 mg/kg b.w. for 28 days. METHODS AND RESULTS: No significant signs of hepatotoxicity other than a mild, dose-dependent increase in serum cholesterol and unconjugated bile acids, and no evidence of oxidative DNA damage were seen. Histopathological alterations and proliferative changes were restricted to subcapsular areas of the left and caudate liver lobes. CONCLUSION: Although statistically significant effects were only seen at the 2 mg/kg b.w. dose during the course of our study, a ~two and ~threefold increase in 5-bromo-2' deoxyuridine labeling index was observed at 0.1 and 0.5 mg/kg b.w., respectively, suggesting that chronic exposure to doses even below 2 mg/kg b.w. may cause proliferative changes in rat liver and highlighting the need to assess furan carcinogenicity at lower doses. PMID- 20540151 TI - Downhill binding energy surface of the barnase-barstar complex. AB - We have employed biased molecular dynamics simulations in explicit solvent to characterize the one-dimensional potential of mean force for the dissociation process of the barnase-barstar protein-protein complex. Unbinding of barstar from wild-type barnase was compared with dissociation from four charge-deletion mutants of barnase. Interestingly, we find in all cases that unbinding of barnase and barstar is an uphill process on a smooth, tilted energy landscape. The total free energy difference between the dissociated and bound state was similar for wild-type barnase-barstar and for the R87A mutant of barnase. The values for the three other mutant barnase mutants K27A, R59A, and R83Q were only about half as much. Besides, we have analyzed the conformational dynamics of important residues at the barnase-barstar interface. In the bound state, their conformational fluctuations are reduced relatively to the free state because of the formation of intermolecular contacts. Interestingly, we find that some residues also show decreased mobility at intermediate stages of the unbinding process suggesting that these residues may be involved in the first contacts being formed on binding. (c) 2010 Wiley Periodicals, Inc. Biopolymers 93: 977-985, 2010. PMID- 20540152 TI - Effect of 2-hydroxypropyl-beta-cyclodextrin on thermal stability and aggregation of glycogen phosphorylase b from rabbit skeletal muscle. AB - The study of the kinetics of thermal aggregation of glycogen phosphorylase b (Phb) from rabbit skeletal muscles by dynamic light scattering at 48 degrees C showed that 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) accelerated the aggregation process and induced the formation of the larger protein aggregates. The reason of the accelerating effect of HP-beta-CD is destabilization of the protein molecule under action of HP-beta-CD. This conclusion was supported by the data on differential scanning calorimetry and the kinetic data on thermal inactivation of Phb. It is assumed that destabilization of the Phb molecule is due to preferential binding of HP-beta-CD to intermediates of protein unfolding in comparison with the original native state. The conclusion regarding the ability of the native Phb for binding of HP-beta-CD was substantiated by the data on the enzyme inhibition by HP-beta-CD. (c) 2010 Wiley Periodicals, Inc. Biopolymers 93: 986-993, 2010. PMID- 20540153 TI - A fully defined, fed-batch, recombinant NS0 culture process for monoclonal antibody production. AB - To manufacture a glycoprotein, mammalian cells expressing the desired protein are often grown in fed-batch mode. Feeding an undefined, nonanimal hydrolysate helps the cells receive sufficient nutrition, but makes systems difficult to optimize. Even different lots of the same hydrolysate may have significant variability; furthermore, individual components may actually be detrimental to the cells. Switching to fully defined feeds could eliminate these issues. For monoclonal antibody (mAb) production by fed-batch NS0 cells, this article describes the replacement of a hydrolysate-based feed with a fully defined, animal-component free feed system. The defined feed initially had 67 components, but additional experiments allowed a reduction to 25 components. The mAb titer is approximately 20% higher than in the undefined system, and the feed volume is circa 20% lower. The two systems generated antibodies with similar glycosylation profiles. Other benefits of the defined feed system include lower raw material costs, the ability to optimize key nutrient concentrations, greater confidence in raw material quality, and the elimination of potential, hydrolysate-associated endotoxin issues. PMID- 20540154 TI - Molecular basis of cytokine receptor activation. AB - Cytokines are secreted soluble peptides that precisely regulate multiple cellular functions. Amongst these the GM-CSF/IL-3/IL-5 family of cytokines controls whether hematopoietic cells will survive or apoptose, proliferate, differentiate, migrate, or perform effector functions such as phagocytosis or reactive oxygen species release. Their potent and pleiotropic activities are mediated through binding to high affinity membrane receptors at surprisingly low numbers per cell. Receptor binding triggers a cascade of intracellular signaling events, including reversible phosphorylation of receptor subunits and associated signaling molecules, leading to multiple biological responses, with the prevention of apoptosis or "cell survival" being a key cellular function that underpins all others. Many chronic inflammatory diseases and a number of haematological malignancies are driven by deregulated GM-CSF, IL-3, or IL-5 cytokine receptor signaling, highlighting their importance in disease. A major step in understanding how these cytokine receptors function is to elucidate their three dimensional structure and to relate this to the many signaling pathways emanating from their receptors. We have recently solved the structure of the human GM-CSF receptor complexed to GM-CSF which revealed distinct forms of receptor assembly: a hexamer that comprises two molecules each of GM-CSF, GM-CSF receptor alpha chain and GM-CSF receptor beta chain; and an unexpected dodecamer in which two hexameric complexes associate through a novel site 4. This latter form is necessary to bring JAK2 molecules sufficiently close together to enable full receptor activation. In this review we focus on the most recent insights in cytokine receptor signaling, and in receptor assembly. The stage is now set to link distinct forms of cytokine receptor assembled structures to specific forms of cytokine receptor signaling and function. Armed with this knowledge it may be possible to map distinct cytokine receptor signaling pathways from the cell surface to the cell nucleus which may themselves become new therapeutic targets. PMID- 20540156 TI - Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition. PMID- 20540155 TI - A systems-based approach to investigate dose- and time-dependent methylmercury induced gene expression response in C57BL/6 mouse embryos undergoing neurulation. AB - BACKGROUND: Aberrations during neurulation due to genetic and/or environmental factors underlie a variety of adverse developmental outcomes, including neural tube defects (NTDs). Methylmercury (MeHg) is a developmental neurotoxicant and teratogen that perturbs a wide range of biological processes/pathways in animal models, including those involved in early gestation (e.g., cell cycle, cell differentiation). Yet, the relationship between these MeHg-linked effects and changes in gestational development remains unresolved. Specifically, current information lacks mechanistic comparisons across dose or time for MeHg exposure during neurulation. These detailed investigations are crucial for identifying sensitive indicators of toxicity and for risk assessment applications. METHODS: Using a systems-based toxicogenomic approach, we examined dose- and time dependent effects of MeHg on gene expression in C57BL/6 mouse embryos during cranial neural tube closure, assessing for significantly altered genes and associated Gene Ontology (GO) biological processes. Using the GO-based application GO-Quant, we quantitatively assessed dose- and time-dependent effects on gene expression within enriched GO biological processes impacted by MeHg. RESULTS: We observed MeHg to significantly alter expression of 883 genes, including several genes (e.g., Vangl2, Celsr1, Ptk7, Twist, Tcf7) previously characterized to be crucial for neural tube development. Significantly altered genes were associated with development cell adhesion, cell cycle, and cell differentiation-related GO biological processes. CONCLUSIONS: Our results suggest that MeHg-induced impacts within these biological processes during gestational development may underlie MeHg-induced teratogenic and neurodevelopmental toxicity outcomes. PMID- 20540157 TI - Pericytes and vessel maturation during tumor angiogenesis and metastasis. AB - Despite promising results in preclinical and clinical studies, the therapeutic efficacy of antiangiogenic therapies has been restricted by a narrow focus on inhibiting the growth of endothelial cells. Other cell types in the tumor stroma are also critical to the progression of cancer, including mural cells. Mural cells are vascular support cells that range in phenotype from pericytes to vascular smooth muscle cells. Although the role of pericytes and pericyte-like cells in the pathophysiology of cancer is still unclear, evidence indicates that aberrations in pericyte-endothelial cell signaling networks could contribute to tumor angiogenesis and metastasis. The purpose of this review is to evaluate critically recent evidence on the role of pericytes in tumor biology and discuss potential therapeutic targets for anticancer intervention. PMID- 20540158 TI - Physical discipline, escalation, and child abuse potential: psychometric evidence for the Analog Parenting Task. AB - Data from three studies provide new evidence to support the validity of the Analog Parenting Task (APT) as an instrument to assess risk for harsh, physically aggressive parenting. In this series of studies, there was a strong association between APT scores of expected use and escalation of discipline strategies and self-reported disciplinary attitudes. APT scores were also associated with physical abuse potential as assessed by both a well-established measure of child abuse potential (Child Abuse Potential Inventory) and another instrument designed specifically for use in pre-parent populations (e.g., Adult-Adolescent Parenting Inventory-2). This study provides new psychometric evidence to support the use of the APT to assess harsh parenting. Additionally, these data highlight the connection between acceptance and use of physical disciplinary strategies, propensity for disciplinary escalation, and risk for abuse perpetration. The findings are discussed in the context of Milner's Social Information Processing model [Milner, 2003] of abuse, which suggests that parental selection of disciplinary responding and the monitoring of disciplinary responding are key events in the disciplinary process. The APT may prove a useful adjunct to more commonly used self-report measures to allow for multimethod assessment of risk for punitive parenting. PMID- 20540159 TI - Do personality characteristics and beliefs predict intra-group bullying between prisoners? AB - This study assesses how beliefs about aggression and personality can predict engagement in intra-group bullying among prisoners. A sample of 213 adult male prisoners completed the DIPC-SCALED (bullying behavior), the EXPAGG (beliefs toward aggression), and the IPIP (a five-factor measure of personality). It was predicted that bullies would hold greater instrumental beliefs supporting the use of aggression than the other categories, with perpetrators reporting lower scores on agreeableness, conscientiousness, and openness to experience, and higher scores on neuroticism (i.e. low scores on emotional stability) than the remaining sample. Bullies and bully-victims endorsed greater instrumental aggressive beliefs than the victim category. Only one perpetrator group, bullies were predicted by reduced levels of agreeableness and increased levels of neuroticism, whereas bully/victims were predicted by decreased levels of neuroticism. Limitations of this study and directions for future research are discussed. PMID- 20540160 TI - Adding injury to insult: unexpected rejection leads to more aggressive responses. AB - Previous research indicates that rejection by a group causes aggressive responses. However, in these previous studies, rejected participants were led to believe that they were liked and accepted before the rejection; likely, this rejection was highly unanticipated. Sociometer theory (Leary et al., 1995) proposes the existence of a psychological mechanism (a "sociometer") that enables individuals to detect potential rejection via others' reactions; a properly working sociometer affords a person predictive control over an interaction. We hypothesized the lack of predictive control inherent in previous rejection studies was a critical contributor to participants' aggressive responses; predictive control should lead to decreased aggression. To test this, we manipulated predictive control by varying confederate behavior toward participants before a rejection manipulation. Results indicate that unpredictable rejection undermined participants' belief that they could predict other's behavior (i.e., led to the perception of a broken sociometer) and led to higher levels of aggression. PMID- 20540161 TI - Support for religio-political aggression among teenaged boys in Gaza: Part I: psychological findings. AB - Politically aggressive militant groups usually rely on support from a larger community, although evidence suggests that only some members of that larger community support that aggression. A major subtype of political aggression is that associated with religious differences--or Religio-Political Aggression (RPA). Little previous research has explored demographic or psychological factors that might distinguish supporters from non-supporters of RPA. In an exploratory study, we investigated whether factors previously associated with aggression might correlate with support for RPA in the case of the Israeli/Palestinian conflict. During the second intifada, fifty-two 14-year-old Palestinian boys in Gaza completed self-report measures of life events, emotional status, and political attitudes. Teenaged boys who reported family members having been wounded or killed by the Israeli Defense Forces (IDF) expressed greater support for RPA (t(50) = -2.30, P = .026). In addition, boys who felt their group was treated unjustly reported greater support for RPA compared with those who did not (t(50) = -2.273, P = .027). Implications of these preliminary data are discussed. PMID- 20540162 TI - Mechanisms of moral disengagement and their differential use by right-wing authoritarianism and social dominance orientation in support of war. AB - Right-wing authoritarianism (RWA) and social dominance orientation (SDO) are associated with the approval of war as a political intervention [McFarland, 2005]. We examined whether the effects of RWA and SDO on war support are mediated by moral-disengagement mechanisms [i.e., responsibility reduction, moral justification, minimizing consequences, and dehumanizing-blaming victims; Bandura, 1999] and whether the ideologies use the mechanisms differently. Our data were consistent with the possibility that minimizing consequences (Study 1) and moral justification (Study 2) mediate the effects of RWA and SDO on approval of war. Both ideologies were positively associated with all moral-disengagement mechanism though more strongly so for RWA. Comparisons within ideologies suggest that RWA was most strongly associated with moral justification and SDO was most strongly associated with dehumanizing-blaming victims. We discuss implications and limitations. PMID- 20540163 TI - Rapid identification of furanocoumarins in Angelica dahurica using the online LC MMR-MS and their nitric oxide inhibitory activity in RAW 264.7 cells. AB - INTRODUCTION: Angelica dahurica (Fisch. Ex hoffm.) Benth. Et Hook. is a perennial herb that grows throughout Korea whose dried roots have been used to treat various diseases in Korean traditional medicine. The root extract contains diverse constituents, and it is necessary to determine the active compounds. OBJECTIVE: To investigate the nitric oxide (NO) inhibitory activity in a root extract of A. dahurica and identify the most active compounds using LC-NMR-MS. METHODOLOGY: In search of the anti-inflammatory constituents of A. dahurica extract, the HPLC-based activity profiling approach was used to investigate the extract's NO inhibitory activity. To directly identify the compounds, a hyphenated LC-NMR-MS technique was applied. Reversed-phase isocratic chromatography was performed using the acetonitrile-water solvent system on a C(30) column. The identification of the compounds was based on information from ESI/MS and 1H-NMR. RESULTS: NO inhibitory activities for five main fractions of the extract were evaluated, which were identified by LC-NMR-MS as containing furanocoumarins: byakangelicol, oxypeucedanin, imperatorin, phellopterin and isoimperatorin. CONCLUSION: The results obtained showed that the anti inflammatory activities of A. dahurica could be linked to imperatorin and phellopterin. PMID- 20540164 TI - In vitro folding of methionine-arginine human lyspro-proinsulin S-sulfonate disulfide formation pathways and factors controlling yield. AB - We investigated the in vitro folding of an oxidized proinsulin (methionine arginine human lyspro-proinsulin S-sulfonate), using cysteine as a reducing agent at 5 degrees C and high pH (10.5-11). Folding intermediates were detected and characterized by means of matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), reversed-phase chromatography (RPC), size-exclusion chromatography, and gel electrophoresis. The folding kinetics and yield depended on the protein and cysteine concentrations. RPC coupled with MALDI-MS analyses indicated a sequential formation of intermediates with one, two, and three disulfide bonds. The MALDI-MS analysis of Glu-C digested, purified intermediates indicated that an intra-A-chain disulfide bond formed first among A6, A7, and A11. Various non-native intra-A (A20 with A6, A7, or A11), intra-B (between B7 and B19), and inter-A-B disulfide bonds were observed in the intermediates with two disulfide bonds. The intermediates with three disulfide bonds had mainly the non-native intra-A and intra-B bonds. At a cysteine-to-proinsulin-SH ratio of 3.5, all intermediates with the non-native disulfide bonds were converted to properly folded proinsulin via disulfide bond reshuffling, which was the slowest step. Aggregation via the formation of intermolecular disulfide bonds of early intermediates was the major cause of yield loss. At a higher cysteine-to proinsulin-SH ratio, some intermediates and folded MR-KPB-hPI were reduced to proteins with thiolate anions, which caused unfolding and even more yield loss than what resulted from aggregation of the early intermediates. Reducing protein concentration, while keeping an optimal cysteine-to-protein ratio, can improve folding yield significantly. PMID- 20540165 TI - Insurance status and hospital care for myocardial infarction, stroke, and pneumonia. AB - BACKGROUND: Despite widely documented variations in health care outcomes by insurance status, few nationally representative studies have examined such disparities in the inpatient setting. OBJECTIVE: To determine whether there are insurance-related differences in hospital care for 3 common medical conditions. DESIGN AND SUBJECTS: Retrospective database analysis of 154,381 adult discharges (age 18-64 years) with a principal diagnosis of acute myocardial infarction (AMI), stroke, or pneumonia from the 2005 Nationwide Inpatient Sample (NIS). MEASUREMENTS: For each diagnosis, we compared in-hospital mortality, length of stay (LOS), and cost per hospitalization for Medicaid and uninsured patients with the privately insured. RESULTS: Compared with the privately insured, in-hospital mortality among AMI and stroke patients was significantly higher for the uninsured (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] [1.24 1.85] for AMI and 1.49 [1.29-1.72] for stroke) and among pneumonia patients was significantly higher for Medicaid recipients (1.21 [1.01-1.45]). Excluding patients who died during hospitalization, LOS was consistently longer for Medicaid recipients for all 3 conditions (adjusted ratio 1.07, 95% CI [1.05-1.09] for AMI, 1.17 [1.14-1.20] for stroke, and 1.04 [1.03-1.06] for pneumonia), although costs were significantly higher for Medicaid recipients for only 2 of the 3 conditions (adjusted ratio 1.06, 95% CI [1.04-1.09] for stroke and 1.05 [1.04-1.07] for pneumonia). CONCLUSIONS: In this nationally representative study of working-age Americans hospitalized for 3 common medical conditions, significantly lower in-hospital mortality was noted for privately insured patients compared with the uninsured or Medicaid recipients. Interventions to reduce insurance-related gaps in inpatient quality of care should be investigated. PMID- 20540166 TI - The characteristics and clinical outcome of adult patients with aplastic anemia and abnormal cytogenetics at diagnosis. AB - The characteristics and clinical outcome of 600 adult patients with aplastic anemia (AA) that had successful cytogenetic studies at the time of diagnosis were retrospectively evaluated. Among these, 572 (95.3%) had normal cytogenetics and 28 (4.7%) had abnormal cytogenetics. The most frequent abnormality was trisomy 8 (n = 15), followed by monosomy 7/deletion of 7q (n = 5), and deletion of 1q (n = 5). There were no statistically significant differences with respect to gender, hepatitis viral infection, paroxysmal nocturnal hemoglobinuria, or severity of disease between the patients in the normal and abnormal cytogenetics groups; however, the patients with abnormal cytogenetics were generally younger than those with normal cytogenetics (P < 0.001). Abnormal cytogenetics was associated with a higher cumulative leukemic transformation rate (P < 0.001) and lower leukemic transformation-free survival (P = 0.021). Furthermore, abnormal cytogenetics was an independent predictor of a poor response to immunosuppressive therapy (HR = 0.255; 95% CI = 0.077-0.839; P = 0.024). These analyses suggest that patients with AA and abnormal cytogenetics have different clinical characteristics compared to patients with AA and normal cytogenetics. PMID- 20540167 TI - Development and validation of a HPLC method for quantification of rivastigmine in rat urine and identification of a novel metabolite in urine by LC-MS/MS. AB - A sensitive, specific and accurate HPLC method for the quantification of rivastigmine (RSM) in rat urine was developed and validated. The method involves the simple liquid-liquid extraction of RSM and pyridostigmine as an internal standard (IS) from rat urine with tertiary methyl butyl ether. The chromatographic separation of RSM and IS was achieved with 20 mm ammonium acetate buffer (pH 6.5) and acetonitrile (65:35, v/v) delivered at flow-rate of 1 mL/min on a Kromasil KR-100. The method was in linear range from 50 to 5000 ng/mL. The validation was done as per FDA guidelines and the results met the acceptance criteria. The method was successfully applied for the quantification of RSM in rat urine. Besides method validation, we have identified two metabolites of RSM in urine. Both the metabolites were characterized by HPLC-PDA and LC-MS/MS and it was found that one metabolite is novel. PMID- 20540168 TI - Communication about sexuality and intimacy in couples affected by lung cancer and their clinical-care providers. AB - OBJECTIVE: Little is known about the effects of lung cancer on intimate and sexual relationships. This study explores health-care provider, patient, and partner perspectives on: (1) the effects of lung cancer on physical and emotional intimacy, (2) the ways in which intimacy affects the experience of living with lung cancer, and (3) communication about intimacy and sexuality in the context of lung cancer. METHODS: Qualitative, in-depth interviews with eight cancer-care providers and 13 married couples (ages 43-79) affected by lung cancer were conducted and audiotaped in the clinical setting. Interviews were transcribed, iteratively analyzed, and coded according to the above domains. Coding was performed independently by members of an interdisciplinary team; inter-rater reliability was assessed using the kappa statistic; and analyses were summarized by domain. RESULTS: Most cancer-care providers and couples affected by lung cancer believed intimacy and sexuality issues were salient, yet few reported discussing these. Couples described negative and positive effects of cancer on intimacy. Negative effects were driven by cancer or its treatment, including physical and psychological effects. Positive effects included an increase in non coital physical closeness and appreciation of the spouse. Age was perceived as an important factor influencing the relationship between lung cancer and intimacy. CONCLUSIONS: Emotional intimacy and sexuality are important concerns for couples affected by lung cancer. The findings suggest previously unrecognized positive effects of lung cancer on emotional and physical intimacy. Couples affected by lung cancer and providers believe these issues are relevant for lung cancer care. PMID- 20540170 TI - Posttraumatic stress disorder and dementia: what is the origin of the association? PMID- 20540169 TI - Getting better at biotech. PMID- 20540171 TI - Patient information page from The Hormone Foundation. Patient guide to testosterone therapy in adult men with androgen deficiency syndromes. PMID- 20540172 TI - Safety and efficacy of laryngeal mask airway Supreme versus laryngeal mask airway ProSeal: a randomized controlled trial. AB - BACKGROUND AND OBJECTIVE: The Supreme laryngeal mask airway (LMA) is a new single use polyvinyl chloride supraglottic device that combines the functionality of the ProSeal and Fastrach airways. High oropharyngeal leak pressures are important as they indicate airway protection, feasibility of positive pressure ventilation and likelihood of successful LMA placement. The oropharyngeal leak pressure of the LMA Supreme is not well established versus the LMA ProSeal. This study was designed to compare the safety and efficacy of the LMA Supreme versus the LMA ProSeal in elective ambulatory procedures. METHOD: Hospital ethics board approval was obtained. One hundred and five patients were consented and randomly allocated to LMA Supreme or ProSeal groups. Anaesthesia was induced with intravenous propofol 2-3 mg kg(-1) and fentanyl 1-2 microg kg(-1) and maintained with desflurane in an air-oxygen mixture. Anaesthesiologists with more than 5 years of experience performed all of the LMA insertions. Manometry was used to standardize intracuff pressure at 60 cmH2O. The primary outcome was the oropharyngeal leak pressure. Secondary outcomes were the time and number of attempts for insertion, ease of insertion and the anaesthesiologist's satisfaction score of the airway device. The success on first attempt insertion was measured. Patients were interviewed postoperatively for any pharyngolaryngeal adverse events. RESULTS: A total of 99 patients were analysed for the primary outcome. The baseline demographic data for both groups were comparable. The mean oropharyngeal leak pressure with the LMA Supreme was 21 +/- 5 cmH2O (95% confidence interval 20-22). This was significantly lower than that of the LMA ProSeal, 25 +/- 6 cmH2O (95% confidence interval 23-27; P<0.001). The success rate of the first attempt insertion was higher for the LMA Supreme than for the LMA ProSeal (98 and 88%, respectively; P=0.04). There was no difference in the median time taken for insertion with the LMA Supreme versus the LMA ProSeal: 26 s (interquartile range 23-45) versus 30 s (interquartile range 20-38), respectively (P=0.16). The ease of insertion, postoperative pharyngolaryngeal adverse events, patient satisfaction scores and anaesthesiologist's satisfaction scores were comparable in both groups. There were no complications of aspiration or nerve injuries. CONCLUSION: The LMA Supreme has lower oropharyngeal leak pressures than the LMA ProSeal. The success of the first attempt insertion was higher for the LMA Supreme. The LMA Supreme is a safe, efficacious and easy-to-use disposable supraglottic airway device in elective ambulatory procedures. The higher rate of success on first attempt insertion may make it more suitable as an airway rescue device. PMID- 20540173 TI - Effectiveness of premature epidural catheter termination as a quality indicator in a developing country. AB - BACKGROUND AND OBJECTIVE: Premature epidural catheter termination in the postoperative period is a common cause of epidural analgesia failure. The incidence varies from 5.7 to 13%. A higher incidence of unplanned epidural catheter termination was observed in our hospital. We took this as a quality improvement project, monitored the causes and applied remedial measures at the same time to reduce the incidence. METHOD: An audit was conducted by the Acute Pain Service between January 2004 and December 2007 to find the incidence and different causes of accidental epidural catheter pullout. Different strategies were applied simultaneously to counter the identified causes. A predesigned pro forma was used for audit while remedial measures included change in practice, counselling of the person responsible, group teaching and reinforcement of epidural care policy. RESULTS: The overall incidence of premature epidural termination was 3.9% during a 4-year period with a higher incidence in 2004 (5.59%), which was reduced in later years. The main reason for premature epidural catheter removal was mishandling of the catheter and filter (64%). The most common site for catheter disconnection was found to be at the filter end of the catheter (54.7%), although 39 (61%) epidural catheters were removed by the Acute Pain Service following disconnection or breakage to avoid danger of infection. CONCLUSION: Identification of premature epidural catheter termination as a quality indicator and continuous quality improvement efforts later on proved to be a useful approach in reducing the incidence. The present audit also helped to quantify the improvement in the quality of care. PMID- 20540174 TI - Comparison of a bupivacaine peripheral nerve block and systemic ketoprofen on peripheral inflammation and hyperalgesia in rats. AB - BACKGROUND AND OBJECTIVE: Local anaesthetics via a nerve block can attenuate inflammation. However, their effects have never been compared with the anti inflammatory effects of systemic NSAIDs. The aim of this study was to compare the effects of bupivacaine via sciatic block with a systemic NSAID on oedema and hyperalgesia and on indices of systemic inflammation as measured by cytokines and prostaglandin E2 production in a model of peripheral inflammation in rats. METHODS: Rats (n=56) randomly received three injections: a left subcutaneous hind paw injection (carrageenan or physiological saline); a left sciatic block (bupivacaine or physiological saline); and a systemic injection (ketoprofen or physiological saline). Six hours later, local oedema, thermal and mechanical hyperalgesia as well as cerebrospinal fluid prostaglandin E2 concentration and tumour necrosis factor-alpha and interleukin 1beta-stimulated production in whole blood cultures were measured. RESULTS: A sciatic block with bupivacaine as well as a systemic injection of NSAID significantly decreased the oedema and the thermal and mechanical hyperalgesia induced by carrageenan. Oedema was decreased by approximately 12%, and thermal and mechanical thresholds were increased by three-fold to fourfold and 1.5-2-fold, respectively. They both inhibited the increased production of prostaglandin E2 in cerebrospinal fluid and tumour necrosis factor-alpha and interleukin 1beta in stimulated whole blood induced by carrageenan. There was no further benefit of the combination of a sciatic block and systemic NSAID. CONCLUSION: In the current study, a bupivacaine block alone achieved the same anti-inflammatory effect as systemic NSAID or as when the same block is combined with a NSAID. PMID- 20540175 TI - Intermediate or brainless phenotypes for psychiatric research? AB - For highly heritable brain disorders, such as schizophrenia and autism, investigating genetic effects on the level of neural systems seems an obvious approach. Nevertheless, the usefulness of the intermediate phenotypes ('endo' phenotypes) continues to be debated energetically. We argue that, while not all intermediate phenotypes are created equal, the hypothesis-driven investigation of the translational cascades linking genetic variation to disturbed behavior is a viable and important strategy that should not be supplanted by an exclusive focus on brainless, clinical/categorical phenotypes investigated in very large numbers of participants. PMID- 20540176 TI - Development of the Hypertonia Assessment Tool (HAT): a discriminative tool for hypertonia in children. AB - AIM: The aim of this study was to develop a tool to identify paediatric hypertonia subtypes. METHOD: Items generated by experts were subscaled (spasticity, dystonia, rigidity). The tool was administered to 34 children (19 males, 15 females, mean age 8y 2mo, range 2y 5mo-18y 7mo) with hypertonia and cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels: I, n=7; II, n=5; III, n=7 level IV, n=7; and level V, n=8 level. Kuder-Richardson Formula 20 determined internal consistency. To assess reliability, two physicians administered the tool to 25 additional children with CP (15 males, 10 females; mean age 10y 8 mo; GMFCS levels I, n=4; II, n=3; III, n=7; IV, n=4; and V, n=7) on two occasions, 2 weeks apart. To evaluate validity, a third physician diagnosed the hypertonia by neurological examination. RESULTS: The internal consistency of the spasticity items was moderate (alpha = 0.58), and dystonia was high (a=0.79). Item reduction eliminated seven of the 14 original items. The agreement of the spasticity and rigidity subscales was adequate (prevalence adjusted bias-adjusted kappa [PABAK] ranging from moderate [0.57] to excellent [1.0]) for validity, test-retest reliability, and interrater reliability. For dystonia agreement was lower, with PABAK ranging from fair (0.30) to good (0.65). Eighty-seven per cent had spasticity and 78% had dystonia. INTERPRETATION: The Hypertonia Assessment Tool has good reliability and validity for identifying spasticity and the absence of rigidity, and moderate findings for dystonia. PMID- 20540178 TI - Detecting emotional disorder in young people in primary care. AB - PURPOSE OF REVIEW: Screening young people for emotional disorder in primary care has seemed sensible given most attend annually and most mental disorder is undetected. Yet evidence supporting screening has been scant. This review considers recent progress around conceptual frameworks, epidemiological findings, accuracy of available instruments and evidence for effectiveness of screening in reducing the burden of emotional disorders. RECENT FINDINGS: Despite better evidence about the accuracy of screens in identifying adolescent depression and possible benefits of early intervention with current treatments, demonstration of improved health outcomes and cost-effectiveness is still lacking. Even when screening detects mental disorder other factors such as readiness for care and availability of effective treatments may affect responses. Best results are obtained when screening is linked to collaborative models of care. Evidence around harms from screening is scant but debate exists over potential harms of false-positives such as stigma and increased strain on healthcare resources. SUMMARY: There is growing consensus that, if screening for emotional disorder is to be effective in primary care, facilitated access of identified young people to effective treatment options is necessary. Further research is required to demonstrate that routine screening will improve mental health outcomes and be cost-effective. PMID- 20540179 TI - The role of early parental bonding in the development of psychiatric symptoms in adulthood. AB - PURPOSE OF REVIEW: To identify and discuss recent research concerning the association between parent-child relationships and psychiatric symptoms in adulthood. RECENT FINDINGS: Despite their methodological limitations such as small sample sizes and inadequate follow-up periods, recent studies have shown that early parental bonding may play an important role either as a risk or protection factor for the development of psychiatric symptoms in adulthood. Affective enhancement and encouragement of autonomy seem to exert a protective effect, whereas emotional neglect and overprotection seem to be risk factors for the development of psychiatric symptoms in adulthood. SUMMARY: Current available data indicate that parent-child relationships may prevent or promote the development of psychiatric symptoms, mainly anxiety and depressive symptoms. In order to investigate the quality of parental bonding and its correlation with the level of psychological well being or psychiatric morbidity, further longitudinal studies with larger samples and adequate follow-up periods should be conducted. PMID- 20540177 TI - Disconnexion syndromes in animals and man: Part I. 1965. PMID- 20540181 TI - Occult inflammation causes IBS symptoms in patients with IBD. PMID- 20540182 TI - genetic susceptibility to postinfectious IBs. PMID- 20540185 TI - Hung parliament. Political stalemate is a threat to the health service's renewal. PMID- 20540186 TI - Uncertainty must not halt urgent reform, managers insist. PMID- 20540187 TI - Confed 'misled' over failed scheme. PMID- 20540188 TI - Stephen Eames on the leadership race. PMID- 20540189 TI - Health and wealth are partners. PMID- 20540190 TI - New government. Survive the calm after the storm. PMID- 20540191 TI - Patient safety. A simple checklist gives a sure touch. PMID- 20540192 TI - [Instruments, books and other objects memorable to (almost) forgotten opinions, therapies, buildings, etc: warm water bath for butyrometers]. PMID- 20540193 TI - ["My wish is that each health establishment institutes an ethics monitor" (interview by Sylvie Warnet)]. PMID- 20540194 TI - Gaining control. CDC: infection rates drop, but progress still unclear. PMID- 20540195 TI - Easing the process. CMS' path to credentialing viewed as promising. PMID- 20540196 TI - Hospitals cry foul. Preventable readmission penalty brings concerns. PMID- 20540197 TI - Fed funds on the way ... but states worried about expansion, how to pay. PMID- 20540198 TI - Blues get tougher on fraud. $510 million recovered in 2009 as insurers adopt new strategies. PMID- 20540199 TI - Under a watchful eye. Insurers put on notice regarding antitrust concerns. PMID- 20540200 TI - The gator bowl. Add flushed meds--and perhaps recluse reptiles--to your list of concerns. PMID- 20540201 TI - Seeing the light. Medicare Advantage plans that coordinate care can thrive under reform. PMID- 20540202 TI - Ready to jump in? States advancing plans for high-risk insurance pools, but not everyone is ready--or willing--to make the dive. PMID- 20540203 TI - Detail oriented. Medical loss-ratio definition needed by HHS. PMID- 20540204 TI - Try, try again. SGR fix on tap, but AMA 'disappointed' by measure. PMID- 20540205 TI - Universal's big play. Psychiatric Solutions deal would boost revenue, debt. PMID- 20540206 TI - Psych strategy. Acquisition lets UHS capitalize on growing sector. PMID- 20540207 TI - AMGA revenue up 4%. Group cites member increase, education programs. PMID- 20540208 TI - Have debt will travel. Not-for-profits meet in N. Y, talk about changes. PMID- 20540209 TI - Peach punch. Ga. hospitals choose more taxes over less pay. PMID- 20540210 TI - Boot camp in session. NPSF looks to inspire organizational change with demonstrations. PMID- 20540211 TI - Still a war worth fighting. New anti-drug policy is right to focus on the public health issue, but... PMID- 20540212 TI - Enforcing reform. It's time for federal authorities to bring antitrust scrutiny to insurers. PMID- 20540213 TI - Working on IT. PMID- 20540214 TI - Largest national healthcare associations. Organizations ranked by 2008 revenue, based on Modern Healthcare's review of IRS form 990 filings. PMID- 20540215 TI - Restless leg syndrome. Stopping a sleep wrecker. PMID- 20540216 TI - Tick-borne illnesses. Early treatment is key. PMID- 20540217 TI - How does swimming compare with walking as a form of exercise? PMID- 20540218 TI - [Not Available]. PMID- 20540219 TI - [Not Available]. PMID- 20540220 TI - [Picture of the month: cerebral hemorrhage]. PMID- 20540221 TI - [Patients' assessment of general practitioners]. PMID- 20540222 TI - Laparoscopic adjustable gastric band surgery. PMID- 20540223 TI - Extension of expiration dates for several body system listings. Final rule. AB - We are extending the expiration dates of the following body systems in the Listing of Impairments (listings) in our regulations: Cardiovascular System, Endocrine System, Growth Impairment, Hematological Disorders, Musculoskeletal System, Mental Disorders, Neurological, and Respiratory System. We are making no other revisions to these body system listings. This extension will ensure that we continue to have in the listings the criteria we need to evaluate impairments in the affected body systems at the appropriate steps of the sequential evaluation processes for initial claims and continuing disability reviews. PMID- 20540224 TI - Dental devices: classification of dental amalgam, reclassification of dental mercury, designation of special controls for dental amalgam, mercury, and amalgam alloy; technical amendment. Final rule; technical amendment. AB - The Food and Drug Administration (FDA) published a final rule in the Federal Register of August 4, 2009 (74 FR 38686) which classified dental amalgam as a class II device, reclassified dental mercury from class I to class II, and designated special controls for dental amalgam, mercury, and amalgam alloy. The effective date of the rule was November 2, 2009. The final rule was published with an inadvertent error in the codified section. This document corrects that error. This action is being taken to ensure the accuracy of the agency's regulations. PMID- 20540225 TI - Crohn's disease and the timing of discovery. PMID- 20540226 TI - Balloon-assisted enteroscopy: double or single? PMID- 20540227 TI - [Hepatic metastasis of colorectal cancer--current therapeutic possibilities]. AB - In this article we presented the therapeutical modalities available nowadays for the treatment of patients with colorectal liver metastases (CRLM), based on a wide search in the literature. To date, due to the developments in liver surgery, anesteziology and intensive care therapy, chemotherapy, interventional radiology and radiationtherapy, the treatment of CRLM is multimodal. These advances led to a changing of the definition of the resectability, in present, resectability being defined by the quality and volume of the functional liver remnant after hepatectomy. In the last years, the timing of liver resection was recconsidered, hepatectomy being suitable (especially in patients with multiple CRLM) after neoadjuvant chemotherapy, and in patients with synchronous CRLM, resection of the primary tumor and liver metastases is reccomended to be performed simultaneously whenever this approach is safe and allows a complete resection of the tumoral tissue. Presence of the extrahepatic colorectal metastases do not represent a contraindication to liver resection, as long as complete removal of the metastases is possible. Conversion to resectability was possible for about 30% of the patients with initially unresectable CRLM, using several therapeutical strategies, giving the chance of a long-term survival to these patients. Liver re resection is the treatment of choice for patients with recurrent liver metastases, survival rates being similar to those achieved after the first liver resection. Hyperthermic ablation is recommended in patients whose CRLM could not be resected, but the results seem to be inferior to those achieved by liver resection. CONCLUSIONS: In present, the treatment of CRLM is multimodal, involving the surgeon, oncologist, radiotherapist and radiologist. Taking into account the great variability of the patients and the multiple therapeutical possibilities, the treatment should be taylored to each patient. PMID- 20540228 TI - Problems concerning diagnosis and treatment of compartment syndromes after lower limb trauma. AB - Compartment Syndrome (CS) is characterised by an imbalance produced by increased pressure in an inextensible space (called "the Compartment"). Without being specific for orthopaedics, CS has increasing frequency in modern traumatology. Microcirculation disturbances generate the syndrome's self-augmenting physiopathological character. The pathognomonic feature of the clinical panel in CS of the lower limbs is increased consistency of the muscular groups, while peripheral pulse maintainance does not exclude CS. Although positive diagnosis is based on measuring the intra-compartmental pressure, (ICP) clinical suspicion is crucial. The correct treatment is surgical, consisting in early and large decompressive fasciotomy. Without proper treatment, CS endangers not only the vitality of the limb (due to Acute Peripheral Ischemia with onset in microcirculation and centripetal extension), but also the patient's life, thus becoming a life-threatening disorder. The authors underline the importance of correct clinical evaluation and early treatment in order to prevent the serious local and general complications of the CS. PMID- 20540230 TI - [Pregnancy--a factor in favour of biliary lithiasis]. AB - OBJECTIVE: The purpose of the analysis accomplished is to identify how much pregnancy influences the occurrence of gravel at young women. MATERIAL AND METHOD: This retrospective analysis was realized between January 2007 and April 2009 in the two surgery departments of Pitesti county Hospital and it was based on the analysis of the medical history and operational standards. During this period, there were operated 762 cholecystectomys, out of which, 348 through laparoscopics and 414 usual. RESULTS: Out of 605 female patients, 10 patients were operated during the first 6 months after giving birth. The cholecystectomys at 10 patients were realized through laparoscopics. Two patients had postoperatoric icterus. Under medical treatment icterus was relegated in the 3 postoperator day. The second patient who had icterus, a retrograde endoscopy of common biliary duct was aplied in the 5 a postoperator day CONCLUSIONS: During pregnancy period, profound functional gastro intestinal, gall bladder and pancreas changes occur. Following this changes, there can be formed gravel which can lead the characteristic symptomatology: gall bladder colic, icterus, fever, vomit. PMID- 20540229 TI - [Liver transplantation--indications, surgical technique, results--the analysis of a clinical series of 200 cases]. AB - INTRODUCTION: Initially considered experimental, liver transplantation (LT) has become the treatment of choice for the patients with end-stage liver diseases. MATERIAL AND METHODS: Between April 2000 and October 2009, 200 LTs (10 reLTs) were performed in 190 patients, this study being retrospective. There were transplanted 110 men and 80 women, 159 adults and 31 children with the age between 1 and 64 years old (mean age--39.9). The main indication in the adult group was represented by viral cirrhosis, while the pediatric series the etiology was mainly glycogenosis and biliary atresia. There were performed 143 whole graft LTs, 46 living donor LTs, 6 split LTs, 4 reduced LTs and one domino LT RESULTS: The postoperative survival was 90% (170 patients). The patient and graft one-year and five-year survivals were 76.9%, 73.6% and 71%, 68.2%, respectively. The early complications occurred in 127 patients (67%). The late complications were recorded in 71 patients (37.3%). The intraoperative and early postoperative mortality rate was 9.5% (18 patients). CONCLUSIONS: The Romanian liver transplantation program from Fundeni includes all types of current surgical techniques and the results are comparable with those from other international centers. PMID- 20540231 TI - [Fibrocystic breast disease--breast cancer sequence]. AB - Fibrocystic breast disease has developed a major issue: the breast cancer sequence. Its involvement regarding the increse of breast cancer risk has 2 aspects: it may be either the marker of a prone tissue or a premalignant hystological deffect. Difficult differential diagnosis of benign proliferative breast lession and carcinoma led to the idea of sequency between the two: cancer does not initiate on normal mammary epithelia; it takes several proliferative stages for it to occur. In our series we analized a number of 677 breast surgical procedures where the pathologic examination reveals 115 cases (17%) of coexistence between cancer and fibrocystic breast disease. This aspect has proved to be related to earlier debut of breast cancer, suggesting that epithelial hyperplasia is a risk factor for breast cancer. PMID- 20540232 TI - [Solitary pulmonary nodule--150 resected cases]. AB - Solitary pulmonary nodule represents a radiological entity with unknown prevalence in general population. As definition, solitary pulmonary nodule has 3 cm diameter or less and is surrounded by lung parenchyma, with no other abnormalities on the same chest X-ray or CT scan film. The differential diagnosis of the solitary pulmonary nodule includes over 100 conditions and the most frequent is lung cancer. Identification and correct management of the solitary pulmonary nodule opposes early detection and treatment of the lung cancer and the uselessness of a surgical procedure on a benign disease which needs no treatment. After analyzing 150 solitary pulmonary nodules resected and after comparing the results with the literature, given the fact that 48.66% of the nodules are malignant and 52.66% of the nodules have the maximum accepted dimensions (3 cm), the authors proposed an algorithm for solitary pulmonary nodule management adapted to Romania's accessibility to diagnostic procedures. As conclusion, the surgical resection of an indeterminate solitary pulmonary nodule (not certified as benign at CT scan or by biopsy) has an absolute indication and curative intention. PMID- 20540233 TI - Preliminary results after Nuss procedure. AB - INTRODUCTION: Pectus excavatum (PE) is the most frequent anterior chest deformity and occurs in approximately 1 in 1000 live births. In 1998 Donald Nuss introduced a new minimal invasive operative technique for PE which avoids any cartilage resection or sternum osteotomy. PURPOSE: The purpose of this study is to assess the short and medium time results after minimal invasive correction of pectus excavatum and to present our improvements to the original Nuss technique. MATERIAL AND METHODS: During a two years period seven PE patients were treated by us using Nuss technique. The intervention represents a premiere because it was the first Nuss operation performed by a team composed exclusively by Romanian surgeons. We present you the seven cases, our operative technique and the short and medium term outcomes. MAIN RESULTS: No itraoperative incidences were recorded. Postoperative course was good for all patients. Complication occurred in three cases: two pleural effusions and a wound dehiscence. They have been all successfully resolved with no further events. Overall the therapeutic and cosmetic results were considered good by patients and their parents. CONCLUSION: Preliminary results indicate that Nuss operation for PE correction is a safe surgical technique with excellent cosmetic outcomes. More cases and long time results are necessary to fully evaluate this technique. PMID- 20540234 TI - Single-balloon enteroscopy following videocapsule endoscopy for diagnosis of small bowel tumors: preliminary experiences. AB - BACKGROUND AND AIM: Small bowel tumors (SBTs), either benign or malignant, are rare, accounting for 3-6% of all digestive neoplasms. Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) have revolutionized the diagnosis and management of patients with small bowel diseases, including SBTs. A novel method using the single-balloon enteroscopy (SBE) has recently been developed. The aim of present study was to present our preliminary experience with SBE in patients with suspected SBTs on VCE examination. PATIENTS AND METHODS: Patients in whom VCE showed one or more lesions suggesting SBTs underwent SBE. RESULTS: Three patients (2 males, 1 female; mean age 52 +/- 11 years) underwent SBE, and then surgery. There were two gastrointestinal stromal tumors and one adenocarcinoma. Clinically, all patients had iron-deficiency anemia and abdominal pain, and one patient had episodes of nausea/ vomiting. SBE was well tolerated without adverse events. CONCLUSIONS: SBE is a safe procedure and overcomes the limitations of VCE. Both procedures are complimentary in patients with suspected SBTs. VCE should be used first for initial diagnosis, followed by SBE for histopathological confrmation of the diagnosis and, if necessary, endoscopic therapy. PMID- 20540235 TI - [Bipolar plasma vaporization--new endoscopic technique in non-invasive bladder cancer]. AB - OBJECTIVES: The aim of our study was to evaluate the efficacy and safety of a newly introduced endoscopic technique in the treatment of non-muscle invasive bladder cancer (NMIBC), the bipolar plasma vaporization of bladder tumors (BPV BT). MATERIALS AND METHODS: Between May and November 2009, 72 consecutive patients presenting papillary bladder tumors over 1 cm underwent BPV-BT and a 3 months follow-up. Initial biopsy followed by plasma vaporization of the tumor and biopsies of the tumoral bed were performed in all cases. The follow-up protocol included abdominal ultrasonography, urinary cytology and cystoscopy at 3 months. RESULTS: BPV-BT was successfully performed in all cases. Multiple tumors were found in 45.9% and tumors over 3 cm in 33.3% of the cases. The mean tumoral volume was 10.5 ml. The mean operative time was 16 minutes, the mean hemoglobin decrease was 0.4 g/dl, the mean catheterization period was 2.3 days and the mean hospital stay was 3.4 days. There was no major intra- or postoperative complications. The pathological exam diagnosed 58.3% pTa, 30.6% pT1 and 11.1% pT2 cases. No tumoral base biopsies were positive for malignancy. The recurrence rate was 15.6% for the NMIBC patients, 13.3% for patients with single tumor under 3 cm and 16.3% in cases of single tumors over 3 cm or multiple tumors. Orthotopic recurrent tumors were encountered in 3.1% of the cases. CONCLUSIONS: BPV-BT seems to represent a promising endoscopic treatment alternative for NMIBC patients, with good efficacy, reduced morbidity, fast postoperative recovery and satisfactory follow-up parameters. PMID- 20540236 TI - [Intensive care issues in the management of potential organ donors]. AB - Organ transplantation is a multidisciplinary speciality that has undergone a remarkable development in the last two decades, saving the lives of patients in advanced failure of various organs. Medical management of organ donors is an essential component of achieving success in transplantation. It requires a good knowledge and understanding of the pathological changes caused by brain death, changes that usually require a diagnosis and a rapid treatment. In our study we intend to analyse the problems that we encountered during preparation of the donors. Hypovolemia, insipid diabetes, pulmonary edema, maintaining viability of organs in optimal conditions are important aspects which influences donation success to a large number of recipients. Between January 2007 - July 2009 in the ICU department of Bagdasar Arseni Emergency Hospital, Bucharest we had 47 potential organ donors, of which only 20 actually came to organ donation. A significant percentage of potential donors are lost due to complications and/or because of denial of consent by the family. PMID- 20540237 TI - [Laparoscopic modified partial posterior Toupet fundoplication]. AB - We describe the technique of the laparoscopic posterior partial fundoplication used by us for the treatment of gastroesophageal reflux disease. We use the division of short gastric vessels for the mobilisation of the gastric fundus in addition to the Toupet partial posterior fundoplication modified by Coster. The fundoplication is achived with only 5 stiches, 3 for the right hemivalve and 2 for the left one. We also present the advantages, the indications, the contraindications and the main complications of the procedure. PMID- 20540238 TI - [Acute intestinal occlusion by diverticulum-appendiceal string. 1931]. PMID- 20540239 TI - Single incision laparoscopic surgery (SILS) cholecystectomy. A novel technique. AB - INTRODUCTION: Since early nineties, laparoscopic cholecystectomy has become gold standard for cholecystectomy. Also, a high tendency of minimizing surgical trauma encourages the use of new approaches in laparoscopic surgery. A novel approach such as Single incision laparoscopic surgery (SILS) cholecystectomy has been describes. CASE REPORT: We report on a case of a 33-year-old female patient scheduled for elective laparoscopic cholecystectomy due to symptomatic ultrasonography verified cholelithiasis. A single 2.5-cm long semicircular infraumbilical skin incision was used. Pneumoperitoneum was established alter introduction of the predesigned trocar. Antegrade cholecystectomy was performed without stay suture placement. Postoperative course was uneventful. DISCUSSION: This article reports the authors' method of performing SILS cholecystectomy. SILS approach is feasible with new standard devices from the industry that offers slightly modified instruments for standard laparoscopic cholecystectomy. CONCLUSION: Single-incision laparoscopic surgery is a feasible way to perform cholecystectomy. A learning-curve is required and further work in the form of randomized controlled trials is needed to investigate the advantages of this new technique. PMID- 20540240 TI - [Splenic angioembolization--a safe, efficient and rational approach]. AB - The authors present a case of postraumatic splenic rupture grade III (AAST-OIS), with injury severity score 10, revised trauma score 7841 managed nonoperatively, by angioembolization, with successful outcome. The indications and different types of splenic angioembolization in trauma are discussed, together with the role of this procedure in increasing the success rate of nonoperative management. Up to our knowledge, this is the first reported case of therapeutic splenic angioembolization in the Romanian medical literature. PMID- 20540241 TI - Primary biliary cystadenocarcinoma mimicking a complicated hydatid cyst. AB - Cystadenocarcinoma of the liver is a rare neoplasm that originates from hepatobiliary epithelium. Primary location of this tumor is generally intrahepatic and most cases are in the right hepatic lobe. Herein we present a case of intrahepatic cystadenocarcinoma in a 53-year-old man who had been followed up for 8 years as hydatic cyst disease of the liver. He was admitted to our hospital with jaundice and loss of appetite. Ultrasound and computed tomography showed a cystic lesion that looked like type II cyst hidatic. Thereafter magnetic resonance imaging revealed a cystic lesion associated with biliary tree. On diagnostic laparotomy peritoneal infiltrations were observed and pathologic examination revealed a biliary cystadenocarcinoma and peritonitis carcinomatosa was diagnosed. Unfortunately correct diagnosis was extremely late and no curative management was possible. PMID- 20540242 TI - Late presentation of a shrapnel wound-induced traumatic intra-thoracic abdominal evisceration, as colon perforation with left faecopneumothorax. AB - The diaphragmatic hernia is a well recognized and common complication of both the penetrating and blunt thoracoabdominal trauma.The clinical presentation is eather in the acute phase, or later, when it features the symptoms of obstructive complications. The aim of the study is to report a case of delayed presentation of a blast wound with diaphragmatic hernia, complicated by herniation and perforation of the left colonic angle in the pleural cavity. The report highlights the multiple complications following the initial event and the staged management of the case. PMID- 20540243 TI - [Soft tissue sarcoma--problems of diagnosis and treatment]. AB - Soft tissue sarcomas are a rare group of cancers compromising 1% of all malignancies and there has been a slight increase in incidence. We present 3 cases of soft tissue sarcomas (the tumors were located to the right axilary region, perianal and dorsale face of the left leg) hospitalized in 2nd Surgical Clinic of Emergency Hospital of Craiova and we discuss the difficulties of diagnosis and treatment. The classification and characterization of soft-tissue sarcomas have evolved as the information supplied by histologic analysis has been supplemented with that provided by immunohistochemical analysis. Surgical resection involving wide margins, with or without radiotherapy, offers the best chance of cure in the absence of metastatic disease. There is little evidence that local recurrence increases the likelihood of metastatic spread, although debate on this point continues. Except for rhabdomyosarcomas and Ewing's sarcomas, the use of adjuvant chemotherapy generally does little to influence the natural history of the disease. In conclusion surgical treatment is mainstay of treatment for soft-tissue sarcomas and is usefull the prompt diagnosis for decrease the risk of local recurrence and metastatic disease. PMID- 20540244 TI - [Double gall blader--surprise during operation]. AB - Gall blader abnormalities are very rare. The diagnosis is difficult, more often appears during operation or necropsy. The authors present a clinical case with double gall blader, into a 50 years old man. The diagnosis appeared during laparoscopic cholecystectomy. The colecistectomy was performed for chronic cholelithiasis. Even it is rare, this pathology should be known, to avoid biliary ducts iatrogenic injuries during operations. The authors made a mustering of literature. PMID- 20540245 TI - Horseshoe appendix: a extremely rare anomaly. AB - Appendiceal anomalies are extremely rare malformations. We presented the case of a patient 43-year-old who had undergone emergency surgery for bowel occlusion. Incidentally we have found an "horseshoe-shaped" appendix which removed. After review of the literature we have introduced this appendiceal variant in a complete classification of appendiceal anomalies. PMID- 20540246 TI - [Pulmonary vein anomaly in a patient with pulmonary aspergillosis]. AB - Vein pulmonary anomalies are seldom met. They have a prevalence of 0.4-0.7% of the cases (according to the American authors). The case under discussion is a 68 year-old patient, who was admitted in the hospital for hemoptysis in low quantity but recurrent, physical asteny, fever and weight loss. The onset had been two months before admission to the hospital. The thoracic X-ray shows opacity at the left apex with marked subcostal and costal intensity, with a homogenous area of 5/6 cm. The thoracic CT exam shows multiple bilateral fibronodular images and the left upper lobe shows a cavitary image with regular and thin walls; intracavitary there is an oval formation with mixed densities of approximate 3.5/4/4.5 cm, which suggests a lung aspergilloma. Surgery will be performed--left upper lobectomy associated with atypical resection from the left Fowler segment. During the surgery it is noticed that the left upper pulmonary vein is abnormaly in the left pulmonary hilum. It has a cranial trajectory, runs in parallel with the left phrenic nerve on the mediastinal surface of the left upper lobe then goes in the mediastinum and pours into the left vein branchocefalic trunk. The post-surgery recovery was slowly favourable with complete pulmonary re-expansion, but with the persistence of the aerial losses which imposed pleural drainage for a period of over 2 weeks. PMID- 20540247 TI - [Cholangiocarcinoma of the distal bile duct--case presentation]. AB - Cholangiocarcinoma is a rare disease (0.15-0.16% in the general population). We present the case of a man, 64 years old, who was admitted to our clinic for emergency with intense jaundice, abdominal pain in the supra-umbilical region. Laboratory analysis revealed elevated total bilirubin (23.5 mg/dl), with predominant direct bilirubin and an increased serum level of alkaline phosphatase and GGT, AST, ALT. The abdominal CT shows an tumor infiltrating distal bile duct, with important dilatation of proximal biliary tree and enlarged retro pancreatic lymph node (8 mm). The first therapeutic procedure was an surgical exploration of the abdomen to asses the resectability of the tumor and an internal biliary drainage colecisto-gastrostomy to allow improving of patient's biological and clinical state and a latter radical operation, after remission of jaundice. After a month we performed cephalic duodenopancreatectomy. Pathology result: moderately differentiated adenocarcinoma of intestinal type (G2) pT2NOMO (stage II). The postoperative evolution was favorable encumbered by a small pancreatic fistula healed by conservative method. PMID- 20540248 TI - [Efficacy of posterior microendoscopic foraminotomy for cervical radiculopathy]. AB - OBJECTIVE: To evaluate the clinical results of posterior microendoscopic foraminotomy in the treatment of cervical radiculopathy and cervical intervertebral disc protrusion. METHODS: From February 2004 to June 2007, 24 cases of cervical radiculopathy received posterior microendoscopic foraminotomy. There were 16 males and 8 females, aging 42-68 years (59 years on average), including 16 cases of cervical radiculopathy and 8 cases of cervical intervertebral disc protrusion. The course of disease was 6-15 months. The affected intervertebral discs were C4, 5 in 8 cases, C5, 6 in 12 cases, and C6, 7 in 4 cases. The radiological examinations showed that 8 protrusions included 6 soft tissue protrusions and 2 rigid tissue protrusions, and that cervical radiculopathy were caused by yellow ligament hypertrophy, Luschka's joint hyperplasia, and abnormal position of facet joint. According to Japanese Orthopedic Association (JOA), the score before operation was (12.60 +/- 1.52) points. RESULTS: The operation time was 90 to 120 minutes (100 minutes on average), the bleeding during operation was 100 to 150 mL (120 mL on average). Nerve root pain were relieved completely in 19 cases and were relieved partly in 4 cases. One case of calcified nucleus pulposus had neurological traction injury and recovered completely after 3 months. All cases were followed up 24-36 months (28 months on average). The radiological examinations after operation showed the intervertebral disc site was decompressed completely and the height of intervertebral disc and the cervical segmental alignment were normal. At 24 months postoperatively, the JOA score was (16.10 +/- 0.29) points, showing significant difference when compared with that of preoperation (P < 0.01). CONCLUSION: The posterior microendoscopic foraminotomy can get to the operation site with mini-incision, decrease tissue damage during operation, and avoid narrow intervertebral space, so it has satisfactory clinical results. PMID- 20540249 TI - [Research of single incision via MAST Quadrant retractor in management of lumbar spondylolisthesis]. AB - OBJECTIVE: To evaluate the effect of posterior lumbar interbody fusion (PLIF) using single incision via MAST Quadrant retractor in the management of lumbar spondylolisthesis. METHODS: From July 2008 to June 2009, 20 cases of lumbar spondylolisthesis were treated with posterior lumbar interbody fusion via MAST Quadrant retractor using single incision, including 2 cases of degenerative spondylolisthesis and 18 cases of isthmic spondylolisthesis. There were 8 males and 12 females aged from 34 to 62 years (average 45.5 years). The disease course was 1 to 6 years (mean 34.5 months). The spondylolisthesis locations were L4, 5 in 8 cases and L5, S1 in 12 cases. According to Meyerding classification, all cases were classified as degree I. The Visual Analogue Scale (VAS) score was (6.6 +/- 1.2) points. The operative time, the blood loss, and the therapeutic effects were recorded. RESULTS: The operative time was (155 +/- 23) minutes and the amount of blood loss was (360 +/- 102) mL. The hospitalization time were (12.0 +/ 3.4) days. All incisions healed by first intention. X-ray films showed spondylolisthesis reduction immediately after operation. All patients were followed up 14.3 months on average (from 9 to 20 months). The VAS score decreased to (1.6 +/- 2.3) points at the last follow-up, showing significant difference when compared with that of preoperation (P < 0.05). The X-ray films showed that lumbar interbody fusion was achieved in all the patients. No loosening, breakage, and displacement of pedicle screw fixation was observed. According to Nakai standard, the results were excellent in 18 cases and good in 2 cases at the last follow-up. CONCLUSION: As long as the indication is strictly chosen, PLIF via MAST Quadrant retractor is a safe, effective, and minimally invasive surgical technique in treating lumbar spondylolisthesis. PMID- 20540250 TI - [Treatment of sacral fractures with pedical screw systems fixed between lumbar and ilium]. AB - OBJECTIVE: To evaluate the clinical effect of pedical screw systems fixed between lumbar and ilium for treatment of sacral fractures. METHODS: From June 2003 to June 2009, 21 cases of sacral fracture (29 sides including monolateral 13 cases and bilateral 8 cases) were treated with pedical screw systems to have reduction and fixation. There were 12 males and 9 females, aging 23-59 years (38.2 years on average). Fracture was caused by traffic accident in 12 cases, by falling from height in 7 cases, and by crash in 2 cases. Screws were inserted into lumbar pedicles and iliac crests. Decompression was used in 4 cases complicated by sacral nerves injury, and reductions and fixations were used in 12 cases complicated anterior pelvic or acetabulum injury. The preoperative proximal displacement at the injured side of the pelvis was (16.29 +/- 6.47) mm compared with contralateral pelvis. RESULTS: All incisions healed primarily with no complication of infection. Twenty-one patients were followed up 6 months to 6 years. Clinical healing time of fracture was 6-9 weeks. In 4 cases complicated by S1 or S2,3 nerves injury, the function recovered completely after 4-9 weeks. In other 17 patients, no complication of intraoperative nerve injury occurred. All patients could walk and squat after 6-12 weeks of operation. No breakage or displacement of implant occurred. The postoperative proximal displacement at the injured side of the pelvis was (3.51 +/- 0.68) mm compared with contralateral pelvis, showing significant difference (P < 0.01) when compared with preoperative one. CONCLUSION: It is a novel choice to have reduction and internal fixation for sacral fracture with pedical screw systems fixed between lumbar and ilium. The strict regulation of indication and skill is the key to prevent complication. PMID- 20540251 TI - [Experimental study on screw insertion in lower cervical pedicle assisted by multi-spiral computerized tomography three dimensional reconstruction techniques]. AB - OBJECTIVE: To assess the clinical significance of transpedicular screw insertion in lower cervical vertebra assisted by multi-spiral CT (MSCT) three dimensional (3D) image reconstruction techniques. METHODS: Eight cervical vertebra specimens were examined by MSCT, and the messages were sent to SGI02 Workstation; according to the parameter requirements of lower cervical pedicle fixation, by using post process of volume rendering (VR) the condition was judged and multi-planar reformation (MPR) was used to do individual analysis; and the ideal path of screw insertion was obtained and the related parameters were measured. After preoperative plan being finished, referring to these measured parameters, 3.5 mm screws were inserted into C37 pedicles of these 8 specimens. After insertion of screws, MSCT scanning and 3D reconstruction were performed again to evaluate the accuracy of lower cervical pedicle screw inserting. From May 2007 to November 2009, 28 patients who received screw insertion in lower cervical spines were given MSCT scanning and 3D reconstruction to evaluate the illness situation, to confirm shortest fixation volumes, and to collect the parameters of aim pedicle screw insertion. RESULTS: The time of insertion for each screw was (392 +/- 62) seconds. It was found that one pedicle was clausura (1.25%, 1/80) and five pedicle diameters in coronal view were less than 3 mm (6.25%, 5/80), which all were not fit for screw insertion. A total of 74 screws were placed successfully. One-time success rate of screw insertion was 95.95% (71/74). The total accuracy rate was 91.89% (68/74). Six screws penetrated (8.11%). According to the Richter penetrating classification: grade one was 6.76% (5/74) and grade two was 1.35% (1/74). There were significant differences (P < 0.05) in penetrated rate between our study and anatomic landmark localization (47.37%), Miller methods (25.00%), and there was no significant difference (P > 0.05) when compared with Abumi method (6.70%), hopper method (7.10%), pipeline depopulation method (5.20%) and navigation technique (11.30%). In clinical 28 cases, 121 screws were inserted; one pedicle was clausura and one was fissure fracture, which all were unfit for insert screw in preoperative plan, the surgery project was adjusted. After operation, 17 patients (76 screws) were given MSCT scanning again. A total of 67 screws (88.16%) were placed successfully. Nine screws (11.84%) penetrated, grade one was 7.89% (6/76) and grade two was 3.95% (3/76). CONCLUSION: It is accurate to apply MSCT 3D reconstruction techniques to measure the ideal screw canal in preoperative individualized plan. Strictly following individual quantitative data, the safety and accuracy of the surgery can be improved. And it is feasible and available to use MSCT MPR imaging to evaluate the accuracy of pedicle screw insertion. PMID- 20540252 TI - [Reliability research of multi-planar reformation of multi-spiral computerized tomography in measuring kyphosis angle after thoracolumbar fracture]. AB - OBJECTIVE: To study the feasibility and reliability of the multi-planar reformation (MPR) of multi-spiral CT (MSCT) in measuring the kyphosis angle (KA) after thoracolumbar fracture. Methods From December 2007 to December 2009, 45 thoracolumbar fracture patients who underwent computed radiology (CR) and MSCT were recruited. There were 32 males and 13 females with a mean age of 48 years (range, 24-63 years), including 36 simple compression fractures and 9 burst fractures. The fracture locations were T11 in 6 cases, T12 in 11 cases, L1 in 20 cases, and L2 in 8 cases. Fracture was caused by traffic accident in 25 cases, by falling from height in 12 cases, and by others in 8 cases. The imaging examination was performed after 2 hours to 7 days of injury in 22 cases and after more than 7 days in 23 cases. The KA was measured on the lateral X-ray films of CR and MPR by two observers, then the measurements were done again after three weeks. The data were statistically analyzed. RESULTS: The average KA values on CR by two observers were (20.75 +/- 8.31)degrees and (22.49 +/- 9.07)degrees, respectively; showing significant difference (P < 0.05), and the correlation was good (r = 0.882, P < 0.05). The average KA values on MPR by two observers were (16.65 +/- 8.62)degrees and (17.08 +/- 7.88)degrees, respectively, showing no significant difference (P > 0.05), the correlation was excellent (r = 0.976, P < 0.05). The average KA values on CR and MPR were (21.61 +/- 8.43)degrees and (16.87 +/- 8.20)degrees, respectively; showing significant difference (P < 0.05), the correlation was good (r = 0.852, P < 0.05). CONCLUSION: It is more feasible and reliable in measuring the KA on MRP of MSCT than CR, but the value is larger on CR. PMID- 20540253 TI - [Arthroscopic treatment of intra-articular meniscal cysts]. AB - OBJECTIVE: To investigate the treatment and therapeutic efficacy of intra articular meniscal cysts by arthroscopy. METHODS: From January 2005 to December 2009, 9 cases of intra-articular meniscal cysts were treated by arthroscopy, including 5 males and 4 females, with an average age of 33.8 years (range, 24-46 years). Six patients suffered in left knees, 3 in right ones. Just 1 case had trauma history, the others had no obvious predisposing causes. The average course of the disease was 24.2 months (range, 4-36 months). The Lysholm score was (74.2 +/- 11.6) points. Arthroscopy showed that the locations of cysts were the anterior horn of lateral meniscus in 8 cases and the anterior horn of medial meniscus in 1 case; all being single cyst (of them, 3 being multilocular cyst). RESULTS: All incisions healed primarily with no complications of infection and joint effusion. All 9 patients were followed up from 3 to 48 months with an average of 12.7 months. Preoperative symptoms disappeared or reduced and the range of motion of the knee returned to normal. The Lysholm score was (95.1 +/- 3.4) points after 3 months of operation, showing significant difference (P < 0.01) when compared with the score before operation. According to assessment standard described by Choy, the treatment outcome was excellent in 6 cases, good in 2 cases, and general in 1 case; the excellent and good rate was 88.9%. No recurrence was found during follow-up. CONCLUSION: Arthroscopic surgery shows the advantages to maintain good function of knee for the treatment of meniscal cyst, it is the best choice for intra-articular meniscal cysts because of its mini trauma, rapid recovery, thorough treatment and less recurrence. Simultaneously, partial or total meniscectomy or meniscus repairing under arthroscopy is performed. PMID- 20540254 TI - [A combination of arteriovenous impulse system and low-molecular-weight heparins calcium for prophylaxis of deep venous thrombosis following total knee arthroplasty]. AB - OBJECTIVE: To analyze the effect of arteriovenous impulse system (AVIS) combined with low-molecular-weight heparins calcium (LMWHC) for prophylaxis of deep vein thrombosis (DVT) following total knee arthroplasty (TKA). METHODS: From March 2006 to March 2008, 76 cases of osteoarthritis patients (76 knees) accepted TKA, including 25 males and 51 females with an average age of 66.6 years (range, 58-79 years). The affected knees were left side in 41 cases and right side in 35 cases. They were randomly divided into experimental group and control group before surgery. Then LMWHC and rehabilitation training were routinely given in two groups before and after surgery. However, only experimental group was treated with AVIS continually during the first four days and then two times a day for 30 minutes one time during 5-7 days. At 7 days after operation, color Doppler ultrasound was used to detect the occurrence condition of DVT. RESULTS: Five cases (13.16%) had thrombosis of calf and recovered after treated with urokinase and salvia in the experimental group. Eleven cases had thrombosis of calf and 3 cases had thrombosis of whole low extremities (36.84%), and improved after treated with urokinase and salvia in the control group. There was significant difference in DVT incidence rate between two groups (P < 0.05). No pulmonary embolism or death was found in both groups. CONCLUSION: AVIS can effectively accelerate the venous blood return velocity, a combination of AVIS and LMWHC has a better effect in the prevention of DVT following TKA. PMID- 20540255 TI - [Clinical research of accurate limb length equalization in total hip arthroplasty]. AB - OBJECTIVE: To explore the effective method and the feasibility of the accurate limb length equalization in patients undergoing total hip arthroplasty (THA). METHODS: From September 2006 to September 2008, 52 patients underwent unilateral THA, including 36 males and 16 females, with an average age of 61.5 years (range, 46-76 years). Among these cases, there were 22 cases of avascular necrosis of the femoral head, 12 cases of hip osteoarthritis, 11 cases of femoral neck fracture, 4 cases of congenital dislocation of hip, and 3 cases of acetabular dysplasia. Forty cases had leg length discrepancy, and the shortened length of the legs was in the range of 10 mm to 35 mm with an average of 20 mm. The mean Harris score before operation was 45 points (range, 36-58 points). Based on the clinical measurement and radiographic examination, the surgical protocols were designed, the type of the hip prosthesis was chosen, and the neck length of the femoral prosthesis, and the position of osteotomy were estimated. By the proper wearing of the acetabula, the best rotation point was found out. The cut plane of the femoral neck was adjusted according to the results of the radiographic and other examinations. The neck length was readjusted after the insertion of the prosthesis so as to achieve intended leg-length equalization. The discrepancy of the leg length was measured and evaluated after operation. RESULTS: The incision healed by first intention in all patients. One patient had ischiadic nerve palsy and achieved full restoration after 5 months of symptomatic management. Forty four patients were followed up 16 months on average (7-32 months). The mean Harris score was 87.5 points (80-91 points), showing significant difference (P < 0.05) when compared with that before operation. The limb length equalization were got in 35 patients (equalization rate was 79.5%). Seven patients had the prolong leg (from 10 mm to 18 mm), 2 patients had the shortened legs (15 mm and 25 mm, respectively). CONCLUSION: By measurement of leg-length and radiographic examination before and during operation, the problem of unequal leg-length can be solved during the THA. PMID- 20540256 TI - [Experimental study on simvastatin in prevention and treatment of aseptic loosening of prosthesis]. AB - OBJECTIVE: To evaluate the mechanisms of p42/p44 kinase phosphorylation in cell models and to investigate the effect of simvastatin on the prevention and treatment of aseptic loosening of prosthesis by observing the influence of simvastatin on the levels of tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1) of human peripheral blood mononuclear cell (PBMC) challenged with titanium particles. METHODS: PBMC from 45 mL peripheral blood of healthy adult voluntary donators, were separated and cultured, and divided into 5 groups according to different culture medium: group A, PBMC and titanium particles; group B, PBMC and titanium particles with 1 x 10(-5) mol/L simvastatin; group C, PBMC and titanium particles with 1 x 10(-6) mol/L simvastatin; group D, PBMC and titanium particles with 1 x 10(-7) mol/L simvastatin; and group E, PBMC and titanium particles with the extracellular signal-regulated kinase (ERK1/2) inhibitor U0126. The contents of TNF-alpha and MCP-1 were tested by ELISA after 24 hours of culture. PBMC were pretreated with different medium grouping as groups A, B, C, D, and E for 60 minutes, and were challenged with titanium particles for 30 minutes and 60 minutes, then the level of ERK1/2 expression was tested by Western blot. RESULTS: In groups A, B, C, D, and E, the absorbance (A) values of TNF-alpha were 1.115 5 +/- 0.243 6, 0.693 6 +/- 0.354 3, 0.695 7 +/- 0.387 3, 0.716 4 +/- 0.478 9, and 0.263 5 +/- 0.1016, respectively; and the A values of MCP-1 were 1.4210 +/- 0.105 3, 0.915 1 +/- 0.411 3, 1.003 5 +/- 0.464 2, 1.102 0 +/- 0.353 9, and 0.2713 +/- 0.145 1, respectively. The levels of TNF-alpha and MCP-1 in group A were significantly higher than others, showing significant differences (P < 0.05). There were significant differences between group E and groups B, C, and D (P < 0.05), between group B and groups C, D (P < 0.05); no significant difference between group C and group D (P > 0.05). Western blot results showed the expression of ERK1/2 in all groups at 30 minutes and 60 minutes of culture. The levels of ERK1/2 expression were 1.612 1 +/- 0.068 2, 1.078 1 +/- 0.072 8, 1.268 7 +/- 0.223 1, 1.439 7 +/- 0.180 1, and 0.732 0 +/- 0.110 4 in groups A, B, C, D, and E, respectively; showing significant differences between groups (P < 0.05). CONCLUSION: ERK1/2 is a phosphorylated protein after stimulated by wear particles; it is also one of the most important cell signaling activation of macrophage. Simvastatin can inhibit the expression of bone absorptive factors induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis. PMID- 20540257 TI - [Development in treatment of floating shoulder injury]. AB - OBJECTIVE: To review present situation and progress in clinically treating floating shoulder injury. METHODS: Recent literature concerned treatment of floating shoulder injury was reviewed and analyzed in terms of anatomy, pathogenesis, diagnosis, and treatment. RESULTS: Conservative treatment and operative treatment can get good outcome. But the value of the results was limited, because different evaluation criteria were used in the literature. CONCLUSION: There is no uniform standards about the treatment of the floating shoulder injury. Both conservative treatment and operative treatment have advantages and disadvantages, which method will be used to treat the floating shoulder injury based on local damage and the patient's general condition. PMID- 20540258 TI - [Reconstruction of large nasal defects with lateral nasal artery pedicled nasolabial flap]. AB - OBJECTIVE: To evaluate the curative effect of the lateral nasal artery pedicled nasolabial flap for reconstruction of nasal defects. METHODS: From August 2005 to March 2009, 12 cases of large nasal tip and alar defects were repaired with the lateral nasal artery pedicled nasolabial flap. There were 5 male patients and 7 female patients with a mean age of 48.6 years (range, 35-60 years). Five cases of nasal defects were caused by trauma and other defects were caused by excision of carcinoma or hemangioma; the courses of disease were 1 to 10 years and 3 months to 40 years, respectively. The nasal defect size ranged from 2.0 cm x 1.5 cm to 4.5 cm x 2.5 cm. All defects were reconstructed with lateral nasal artery pedicled nasolabial flap in 9 cases and with island flap in 3 cases. The flap size ranged from 2.5 cm x 2.0 cm to 7.0 cm x 3.0 cm. Five patients required cartilage grafts for alar rim support and the distal end of the nasolabial flap was thinned and folded to repair the nasal lining. The donor sites were sutured directly. RESULTS: The mild venous stasis at the distal end of three island flaps occurred at 5-24 hours postoperatively and alleviated spontaneously. All flaps survived. Incision at donor and accepted sites healed by first intention. Flap revision was performed in 5 cases after 6-15 months because of mild swelling at the pedicles of skin flaps. All patients were followed up 8-24 months, with an average of 13 months. All patients achieved satisfactory results in nasal appearance, flap texture and color, and ventilatory function. No obvious scar was found at donor sites. CONCLUSION: The nasolabial flap is an excellent choice for reconstruction of defects of nasal tip and ala. PMID- 20540259 TI - [Application of pectoralis major myocutaneous flap in repair of defect caused by resection of tonsillar cancer]. AB - OBJECTIVE: To discuss and value the effects and the advantages of pectoralis major myocutaneous flap in repair of defect caused by resection of tonsillar cancer. METHODS: The data were retrospectively summarized from 10 patients with recurrent tonsillar cancer after radical radiotherapy from January 1998 to December 2005, including 7 cases of squamous cell carcinoma, 2 cases of undifferentiated carcinoma, and 1 case of adenoid cystic carcinoma. There were 8 males and 2 females, aged 43-68 years with an average of 58 years. All cases were classified as stages III and IV before radiotherapy according to staging standard of oropharyngeal cancer (International Union Against Cancer, 1997). The time of relapse was 6-32 months after radiotherapy. Recurrent tonsil cancer invaded tongue base, soft palate, posterior wall of pharyngeal, parapharyngeal space, and palate. Tumor size was from 4 cm x 2 cm to 8 cm x 5 cm. Seven cases were accompanied by lymph node metastasis. After carcinoma were completely resected and defects were reconstructed by pectoralis major myocutaneous flap of 7 cm x 5 cm-12 cm x 9 cm. The donor sites were sutured directly. RESULTS: After operation, pectoralis major myocutaneous flap completely survived in 9 cases. Partial necrosis of pectoralis major myocutaneous flap was found in 1 case; after treatment, the necrotic flap remained small pharyngeal defect. Incision at donor site healed by first intention in 10 cases. All patients showed satisfactory functions of respiratory, voice, and swallowing with no complication. Ten patients were followed up 2 years to 5 years and 8 months. The 3-year survival rate was 66.7% (6/9), and the 5-year survival rate was 20.0% (1/5). CONCLUSION: Pectoralis major muscle flap has a high survival rate, which is safe, reliable, easy-to-operate, and can repair larger defect. Pectoralis major myocutaneous flap is an ideal material in repair of defect caused by resection of recurrent tonsillar carcinoma after radiotherapy. PMID- 20540261 TI - [Application of modified superficial peroneal neuro-fasciocutaneous flap in repairing soft tissue defect of forefoot]. AB - OBJECTIVE: To investigate the operative procedures and clinical outcomes of the modified superficial peroneal neuro-fasciocutaneous flap in repairing soft tissue defect of forefoot. METHODS: From May 2006 to May 2009, 5 male patients (aged 40 63 years) with soft tissue defect of forefoot were treated with the modified superficial peroneal neuro-fasciocutaneous flap. Tendons and bones were exposed in all cases. Defect was caused by object crash (4 cases) and traffic accident (1 case). The sizes of soft tissue defects of forefoot were 4 cm x 2 cm-8 cm x 4 cm. Rotating point of the modified superficial peroneal neuro-fasciocutaneous flap pedicled with the peripheral vessels network of ankle joint was at the level of tibiotalar joint. The flaps ranging from 5 cm x 4 cm to 10 cm x 6 cm were adopted to repair soft tissue defects of forefoot. The donor sites were either sutured directly or covered with intermediate split thickness skin grafts. RESULTS: All flaps survived and all wounds healed by first intention. Skin graft at donor site survived completely in all cases. All patients were followed up 6-18 months (mean 11 months). The appearance, texture, and function of the flap were satisfactory. There was a protective sensibility in all flaps without abrasion or ulceration, and the two-point discrimination of the flaps was 10-13 mm. The walking pattern was normal. No obvious discomfort was observed at the skin-graft donor sites. CONCLUSION: With reliable blood supply, no sacrifice of vascular trunks, favorable texture, and thickness, the modified superficial peroneal neuro fasciocutaneous flap pedicled with the peripheral vessels network of ankle joint is useful to repair skin soft tissue defect of the forefoot. PMID- 20540260 TI - [Neurovascular free flap based on dorsal branch of digital artery of ring finger for finger pulp defect]. AB - OBJECTIVE: To investigate the surgical procedures and clinical outcomes of the neurovascular free flap based on dorsal branch of digital artery of ring finger graft for repair of finger pulp defect. METHODS: From February 2006 to May 2009, 11 cases (11 fingers) of finger pulp defect with tendon and bone exposure were treated, including 8 males and 3 females with an average age of 29 years (range, 23-40 years). The defect locations were thumb in 2 cases, index finger in 5 cases, and middle finger in 4 cases. The defect size ranged from 1.0 cm x 1.0 cm to 2.5 cm x 2.0 cm. The time from injury to operation was 1-9 hours. The flap size ranged from 1.5 cm x 1.5 cm to 3.0 cm x 2.5 cm. Five flaps carried the dorsal branch of digital nerve, 6 flaps carried nervi digital dorsales. The flaps were cut from proximal radial dorsal ring finger in 4 cases and from proximal ulnar dorsal ring finger in 7 cases. Defect of donor site was repaired with full thickness skin grafting. RESULTS: All flaps and grafted skins survived; wound and incision of donor site achieved healing by first intention. Eleven patients were followed up 6 to 24 months with an average of 12 months. The other finger flaps had good texture and shape except for 1 flap with slightly bloated. The activities of finger distal interphalangeal joint were normal, the two-point discrimination of finger pulp was 7-12 mm. The extension and flexion activities of donor fingers were normal, the ringlike thread scar left at the donor site. CONCLUSION: It is an ideal method to use the neurovascular free flap based on dorsal branch of digital artery of ring finger graft for repair of finger pulp defect, which has the advantages of simple operation, good appearance, and functional recovery. PMID- 20540262 TI - [Percutaneous penetration ability of dexamethasone-amlodipine besylate compound gel and its effect on survival of ischemic random skin flap]. AB - OBJECTIVE: Dexamethasone (DXM) can regulate the balance of neutrophil and cytokine and enhance the ischemia-reperfusion tolerance of the skin flap; amlodipine besylate (AB) can selectively expand the peripheral blood vessels and relieve the vascular smooth muscle spasm. To investigate the percutaneous penetration ability of DXM/AB compound gel and evaluate its effect on survival of ischemic skin flap. METHODS: Sodium carboxymethylcellulose was used to make blank gel, which was mixed in DXM, AB, azone (AZ), and propylene glycol (PG) respectively to make the compound gel containing 0.3%DXM/0.5%AB only (group D), the compound gel containing 3%AZ/2%PG, 3%AZ, and 2%PG (groups A, B, and C), the 0.3%DXM gel containing 3%AZ/2%PG (group E), the 0.5%AB gel containing 3%AZ/2%PG (group F). The accumulative penetration of DXM and AB in compound gel, 0.3%DXM gel, 0.5%AB gel through excised rat skin and its penetration within flap tissue were investigated by ultraviolet spectrophotometry. Fifty SD rats were selected to make 100 mm x 10 mm random flap at the back, and were randomly divided into 5 groups according to different gels which were used to treat flaps (n = 10): compound gel group (group A1), 0.3%DXM gel group (group B1), 0.5%AB gel group (group C1), blank gel group (group D1), and peritoneal injection of DXM (5 mg/kg) and AB (2 mg/kg) (group E1). The survival area of ischemic random skin flap was measured on the 7th day by planimetry. Twenty-four SD rats were selected to make 100 mm x 10 mm random flap at the back, and were randomly divided into 2 groups (n = 12). The accumulative penetration of DXM and AB within skin flap were also detected at 2 and 6 hours after application of 2 g of compound gel containing 3%AZ/2%PG (group A2) and peritoneal injection AB (2 mg/kg) / DXM (5 mg/kg) (group B2). RESULTS: The accumulative penetration of DXM and AB in compound gel were increased in time-dependent manner (P < 0.05), and it was the highest in group A, and was significantly higher than that in group B and group C (P < 0.01), but there was no significant difference when compared with group E or group F (P > 0.05). The accumulative penetration of DXM and AB in groups A, B, and C were significant higher than that in group D (P < 0.05). After 7 days, the survival area of flaps in groups A1, B1, C1, D1, and E1 were (695.0 +/- 4.6), (439.3 +/- 7.1), (477.5 +/- 14.5), (215.2 +/- 3.8), and (569.4 +/- 9.7) mm2, respectively; group A1 was significantly higher than other groups (P < 0.05). After 2 and 6 hours, the quantities of DXM and AB in skin flap of group A2 were significantly higher than that of group B2 (P < 0.05). CONCLUSION: In 0.3%DXM/0.5%AB compound gel, DXM and AB might penetrate into skin tissue, which could significantly increase the survival area of ischemic skin flap. PMID- 20540263 TI - [Antibacterial effect of autologous platelet-rich gel derived from health volunteers in vitro]. AB - OBJECTIVE: The use of autologous platelet-rich gel (APG) is a relatively new technology and a promising treatment method for infections, which is currently being used by a variety of surgical specialties. The mechanism of antibacterial effect of APG is not yet fully discovered. Subsequent evidence suggests that platelets have multiple functional attributes in antimicrobial host defense (including the capacity to generate antimicrobial oxygen metabolites and the antimicrobial peptides) and interact directly with microorganisms, contribute to clearance of pathogens from the blood. To investigate the bacteriostasis of APG against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa in vitro. METHODS: Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from whole blood of 17 healthy donors. APG was prepared by mixing PRP with bovine thrombin in a 10% calcium gluconate solution or bovine thrombin in a 10% calcium gluconate solution and apocynin (APG-APO). Antibacterial effects of APG, PRP, and APG-APO on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were evaluated by bacteriostasis assay. RESULTS: The culture results showed apparent decrease in the number of Staphylococcus aureus for both APG and APG-APO, which was maximal at first 4 hours and lasted to 24 hours and 8 hours, respectively; showing significant difference (P < 0.05) when compared APG with PRP and PPP, however no significant difference at first 8 hours (P > 0.05) and significant difference at 12 and 24 hours (P < 0.05) when compared APG with APG APO; showing significant difference at first 4 hours (P < 0.05), no significant difference at 6, 8, 12, and 24 hours when compared APG-APO with PRP and PPP (P > 0.05). The bacteriostasis rates of APG and APG-APO were 27.36%-52.97% and 18.82% 51.52% against Escherichia coli, respectively; showing no significant difference (P > 0.05) when compared with PRP. The bacteriostasis rates of APG and APG-APO were less than 35% against Pseudomonas aeruginosa, showing no significant difference (P > 0.05) when compared with PRP; the bacteriostasis rates of PRP were less than 15% against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. CONCLUSION: APG may have potential bacteriostatic effect against Staphylococcus aureus by platelet mediating. Either APG or APG-APO has no obvious bacteriostatic effect against Escherichia coli or Pseudomonas aeruginosa. PRP has no antibacterial activity against Staphylococcus aureus, Escherichia coli or Pseudomonas aeruginosa. PMID- 20540264 TI - [Efficacy comparison between anterior subcutaneous and submuscular transposition of ulnar nerve to treat cubital tunnel syndrome]. AB - OBJECTIVE: To evaluate and compare the efficacy of anterior subcutaneous and submuscular transposition of the ulnar nerve in treating cubital tunnel syndrome. METHODS: From August 2006 to August 2008, 66 patients with cubital tunnel syndrome were treated with anterior subcutaneous transposition (subcutaneous group, 24 cases) and with anterior submuscular transposition (submuscular group, 42 cases). According to McGowan stages, all patients were at Stage 2 or 3 entrapment neuropathy with paresthesia in the ring and small fingers. Respectively, 3 cases and 8 cases complicated by interosseous muscle atrophy in subcutaneous group and in submuscular group. No significant difference was found in gender, age, duration of the disease, and complication between two groups (P < 0.05). The surgical features, distribution of Bishop rates, two-point discrimination test, muscular strength, and complications were recorded. RESULTS: The operation time was (28.4 +/- 5.2) minutes in subcutaneous group and (43.8 +/- 5.6) minutes in submuscular group, showing significant difference (P < 0.01). The incision length was (12.2 +/- 2.5) cm in subcutaneous group and (13.6 +/- 2.8) cm in submuscular group, showing significant difference (P < 0.05). All patients were followed up 1-3 years. According to Bishop scoring system, the results were excellent in 18 cases, good in 4 cases, and poor in 2 cases in subcutaneous group; excellent in 36 cases, good in 3 cases, and poor in 3 cases in submuscular group; and showing no significant difference between two groups (P > 0.05). At 6 months postoperatively, two-point discrimination and grip strength were improved when compared with that of preoperation (P < 0.05), but there was no significant difference between two groups (P > 0.05). Pain and dysesthesia of the scar were noted in 1 patient of the subcutaneous group and 3 patients of the submuscular group. No infection or hematoma was found and no patient needed reoperation. CONCLUSION: Both operative methods are effective alternative for treating cubital tunnel syndrome. The anterior subcutaneous anterior transposition of the ulnar nerve has fewer traumas, and it is a better choice for some old patients. PMID- 20540265 TI - [Expert tibial nails in treatment of complex tibial fractures of type C]. AB - OBJECTIVE: To study the clinical effect of expert tibial nail (ETN) in the treatment of the complex tibial fractures of type C. METHODS: From May to October 2008, 10 cases of complex tibial fractures of type C were treated with unreamed ETN and closed reduction. There were 7 males and 3 females aging from 23 to 50 years with an average age of 39 years. Fracture was caused by traffic accident in 6 cases, by crush in 2 cases, and by falling from height in 2 cases. According to Association for the Study of Internal Fixation (AO/ASIF) classification, there were 2 cases of 42-C1 fractures, 4 cases of 42-C2 fractures, and 4 cases of 42-C3 fractures; including 4 cases of closed fractures and 6 cases of open fractures (2 cases of Gustilo type I and 4 cases of Gustilo type II). RESULTS: The mean duration of surgery and blood loss were 75 minutes (range, 60-110 minutes) and 55 mL (range, 20-100 mL), respectively. All the incision healed by first intension without complication of infection. All cases were followed up for 12-17 months (average 14 months). X-ray films showed that no breakage of nail, iatrogenic fracture, limb shortening, and angulation deformity occurred. All fractures healed after 3-8 months (average 4.2 months). At last follow-up according to Johner-Wruhs standard for the functional recovery, the results were excellent in 8 cases and good in 2 cases. CONCLUSION: ETN has an angular stable locking system for intramedullary nails, which can enhance axial and transverse stability for the treatment of complex tibial fractures of type C. It will provide firm fixation and minimal invasion. PMID- 20540266 TI - [Experimental study on promotion of somato-visceral heterogenic reinnervation with nerve growth factor in rat phrenic-to-vagus anastomosis model]. AB - OBJECTIVE: To investigate the influence of nerve growth factor (NGF) on neuronal regeneration of somato-visceral heterogenic reinnervation using a rat phrenic-to vagus anastomosis model. METHODS: Forty male SD rats, aging 3 months and weighing 200 g, were selected and randomly divided into 3 groups. In group A (n = 10, control group), phrenic and vagus nerves were exposed and no neurography was performed. In group B (n = 15) and group C (n = 15), both nerves were transected and proximal stump of phrenic nerves were microsurgically anastomosed to the distal stump of vagus nerves. Postoperatively, group C was intraperitoneally injected with NGF (20 microg/kg x d), while groups A and B were given matching saline solution. Twelve weeks later, cardiac function was examined under electrical stimulation of the regenerated nerve. Light and electron microscopies were used to examine the heterogenic regenerated nerve, and the passing rate of axon and thickness of myelin sheath were calculated. RESULTS: Under electrical never stimulation in groups A, B, and C, the decreases of blood pressure were (20.12 +/- 2.57), (10.63 +/- 2.44), and (14.18 +/- 2.93) mmHg (1 mmHg = 0.133 kPa), respectively; and the decreases of heart rate were (66.77 +/- 9.96), (33.44 +/- 11.82), and (43.27 +/- 11.02)/minutes, respectively. In group B, the decrease amplitudes of blood pressure and heart rate were 52.83% and 50.08% of group A, respectively. Blood pressure and heart rate in group C also decreased dramatically; the decrease amplitudes of blood pressure and heart rate in group C were 70.48% and 64.80% of group A. There were significant differences in the decrease amplitudes of blood pressure and heart rate (P < 0.05) between group B and group C. Morphological observation showed that heterogenic nerve fibers had the structure of matured myelin sheath and their axons could regenerate into the vagus nerve. In group B and group C, the passing rates of axon were 66.83% +/- 4.46% and 81.63% +/- 3.56%, respectively; and the thicknesses of myelin sheath were (0.25 +/- 0.10) microm and (0.46 +/- 0.08) microm, respectively; showing significant differences (P < 0.05) between group B and group C. CONCLUSION: Heterogenic nerve is primarily a somatic motor nerve; NGF can promote the axons of heterogenic nerve to regenerate into the parasympathetic nerve. PMID- 20540267 TI - [Telomerase reverse transcriptase expression and cell apoptosis during hypoxia ischemia brain damage in neonatal rats]. AB - OBJECTIVE: To investigate the expression of telomerase reverse transcriptase (TERT) and cell apoptosis in neonatal rats with hypoxia ischemia brain damage (HIBD). METHODS: A total of 42 7-day-old SD rats (12-18 g, male or female) were randomly allocated into sham-operation group (n = 6) and hypoxia-ischemia (HI) group (n = 36). In HI group, the rats were anesthetized with ethyl ether. The right common carotid artery (CCA) was exposed and permanently ligated with a 7-0 silk suture through a midline cervical incision. A duration of 2.5 hours of hypoxia (8%O2 / 92%N2) was used to produce HIBD model. For sham-operation group, the CCA was exposed without ligation or hypoxia. The brain tissues were harvested at 4, 8, 12, 24, 48, and 72 hours after completion of an HI insult. The expressions of TERT and CC3 were detected by immunohistochemical staining. The apoptosis cells were detected with TUNEL staining method. RESULTS: The expression of TERT was increased at 4 hours after HI injury, significantly increased at 24 48 hours and then decreased at 72 hours. The expression of CC3 was increased at 4 hours after HI injury, significantly increased at 24 hours and still maintained high expression at 48 hours and 72 hours. However, in the sham-operation group, both the expressions of TERT and CC3 were extremely low. The expression of TERT and CC3 were higher in the HI group than in the sham-operation group at different time points, and the differences were significant (P < 0.05). The TUNEL staining showed that the positive cells in hippocampus and cortical areas were increased at 4 hours after HI injury, significantly increased at 24-48 hours and maintained a high level at 72 hours. However, there was few positive cells in the sham operation group. There were significant differences between the HI group and the sham-operation group at different time points (P < 0.05). CONCLUSION: TERT could be induced by HI in neonatal rats, and might have a protective role in regulating the cell apoptosis in the neonatal HIBD. PMID- 20540268 TI - [Experimental study on reconstruction of ureter by intestinal sero-muscular segment with autograft of bladder mucosa]. AB - OBJECTIVE: It is a thorny problem to reconstruct long ureteral defect in urinary surgery. To investigate the feasibility of intestinal sero-muscular segment with autograft of bladder mucosa as a replacement material for reconstruction of long ureteral defect. METHODS: Twelve adult Beagle dogs (weighing 6.5-9.3 kg and being male or female) were randomly divided into 3 groups, each group including 4 dogs. In group A, lower segment of ureter was reconstructed by autograft of bladder mucosa to the intestinal sero-muscular segment; furthermore, the proximal and distal reconstructed ureter were anastomosed to the bladder and the upper ureter, respectively. In group B, upper segment of ureter was reconstructed by the same method as that of group A, the proximal and distal reconstructed ureter anastomosis with pelvic and lower ureter, respectively. In group C, whole ureter was reconstructed by the same method as that of group A, the proximal and distal reconstructed ureter were anastomosis with pelvic and bladder, respectively. Blood urea nitrogen, Cr2+, K+, Na+, Cl-, Ca2+ and carbon dioxide combining power were detected before operation, the general state, drainage volume, healing of wound, and complications were observed after operation. At 6 weeks, the blood biochemical indexes and intravenous urography (IVU) were detected, and the gross and histological observations of ureter were done. RESULTS: In group B, urine leakage and infection occurred in 1 dog 2 days after operation because ureter stent prolapsed; other dogs had no complications. There was no significant difference in the biochemical indexes between before operation and 6 weeks after operation. IVU showed: in group A, hydronephrosis and ureterectasis occurred on the operation side of 1 dog; in group B, anastomotic stricture between the reconstructed ureter and lower ureter and hydronephrosis occurred in 1 dog; and in other dogs of all groups, renal function was good and the reconstructed ureter had peristalsis function. The histopathological observation showed that the reconstructed ureter had similar structure to normal ureter at 6 weeks in 3 groups; the inflammatory cells infiltrating of the reconstructed ureter was observed in 1 dog of groups A and C, respectively. CONCLUSION: Reconstruction of ureter by intestinal sero-muscular segment with autograft of bladder mucosa has similar structure and function to the normal ureter. The results might provide an experimental basis for clinical use. PMID- 20540269 TI - [Experimental study on construction of neurotization tissue engineered bone for repairing large bone defects in rabbit]. AB - OBJECTIVE: Construction of viable tissue engineered bone is one of the most important research fields in the clinical application of bone tissue engineering, to investigate the function of nerve factors in bone tissue engineering by cell detection in vitro and construction of neurotization tissue engineered bone in vivo. METHODS: Fifty-four healthy New Zealand white rabbits, male or female, weighing 2-3 kg, were involved in this study. Bone marrow mesenchymal stem cells (BMSCs) from the bone marrow of white rabbits were cultured. The second passage of BMSCs were treated with sensory nerve or motor nerve homogenates, using the LG DMEM complete medium as control. The proliferation and osteogenic differentiation of the cells were observed and tested by the MTT assay, alkaline phosphatase (ALP) stain, and collagen type I immunocytochemistry identification. The osteogenic induced BMSCs were inoculated in beta tricalcium phosphate (beta-TCP) biomaterial scaffold and cultured for 72 hours, then the beta-TCP loaded with seed cells was implanted in the rabbit femur with 15 mm bone and periosteum defects. Fifty-four New Zealand white rabbits were randomly divided into three groups (n = 18): sensory nerve bundle (group A) or motor nerve bundle (group B) were transplanted into the side groove of beta-TCP scaffold, group C was used as a control without nerve bundle transplantation. X-ray detection was performed at the 4th, 8th, and 12th weeks after operation. Bone mineral density (BMD) detection and S-100, calcitonin gene-related peptide (CGRP) immunohistochemistry stain were used at the 12th week to evaluate the effects of bone formation and discuss the mechanism. RESULTS: MTT assay indicated that the absorbance (A) value of each group increased with culture time. From the 6th day, the A values of both the sensory nerve and motor nerve homogenate groups were lower than that of the control group, showing significant difference (P < 0.01). On the 8th and 10th days, the A value of the sensory nerve homogenate group was lower than that of the motor nerve homogenate group, showing significant difference (P < 0.05). ALP stain and collagen type I immunocytochemistry identification indicated that the positive cells in both the sensory nerve and motor nerve homogenate groups were less than that of control group after culturing 7 days. And the positive expression of collagen type I was just visible in the cells of control group. The Yang's scores increased gradually in three groups, the score of group A was significantly higher than those of group B and group C (P < 0.01) at the 8th week. The BMD value of group A was significantly higher than those of group B and group C (P < 0.01) at the 12th week. The S-100 and CGRP expressions were high in group A, and low in group B and group C. CONCLUSION: Homogenates of sensory nerve and motor nerve have inhibitory effects on the proliferation and osteogenic differentiation of BMSCs. The osteogenesis and remodeling of the neurotization tissue engineered bone are more closely related with sensory nerves. PMID- 20540271 TI - [Modification and activity observation of hepatocyte growth factor gene on bone marrow mesenchymal stem cells]. AB - OBJECTIVE: To evaluate the transfection efficiency and expression level of hepatocyte growth factor (HGF) by transfecting a recombinant adenovirus carrying HGF gene (Ad-HGF) into bone marrow mesenchymal stem cells (BMSCs) and to explore the effect of the expression supernatant on BMSCs in vitro so as to lay a foundation for the manufacture of gene medicine which expresses efficient cell factors. METHODS: Rat BMSCs were isolated using Percoll density gradient method and cultured according to the adherent property of BMSCs. The expression of c-Met was detected by immunohistochemical examination. BMSCs were infected with a recombinant adenovirus carrying green fluorescent protein gene (Ad-GFP) at multiplicity of infection (MOI, 0, 25, 50, 100, and 200 pfu/cell). To select an optimal MOI, the transfection efficiency and the degree of cell damage were assayed by flow cytometry and MTT, respectively, at 48 hours after transfecting. The expression of HGF in BMSCs transfected with optimal MOI Ad-HGF was measured with ELISA assay. MTT method was used to evaluate the proliferation effect of HGF expression supernatant on BMSCs. RESULTS: Immunohistochemical staining showed that BMSCs expressed c-Met receptor for HGF. At 48 hours after transfecting with different MOI Ad-GFP (0, 25, 50, 100, and 200 pfu/cell), the transfection efficiencies were 0.34% +/- 0.04%, 40.72% +/- 0.81%, 61.72% +/- 1.04%, 85.33% +/- 0.83%, and 17.91% +/- 0.63%, respectively; and the highest transfection efficiency was observed at 100 pfu/cell MOI. The cell damage was obviously observed when MOI was 200 pfu/cell. The expression of HGF in BMSCs reached the highest level after being transfected with 100 pfu/cell MOI Ad-HGF for 48 hours. The expression product could stimulate the proliferation of BMSCs. The proliferation of BMSCs gradually rose with the increase of HGF protein, and reached the highest level at 10% (320 pg). CONCLUSION: BMSCs can be transfected efficiently with Ad-HGF and express HGF protein, which stimulates the proliferation of BMSCs. It suggests that BMSCs is an ideal repair cells with gene vector. PMID- 20540270 TI - [Construction of recombinant adenovirus vector pAdxsi-green fluorescent protein homo sapiens NEL-like 1 and transfected into rat bone marrow mesenchymal stem cells]. AB - OBJECTIVE: To construct a recombinant adenovirus vector pAdxsi-GFP-NELL1 that co expressing green fluorescent protein (GFP) and homo sapiens NEL-like 1 (NELL1) protein (a protein strongly expressed in neural tissue encoding epidermal growth factor like domain), to observe its expression by transfecting the recombinant adenovirus into rat bone marrow mesenchymal stem cells (BMSCs) so as to lay a foundation for further study on osteogenesis of NELL1 protein. METHODS: From pcDNA3.1-NELL1, NELL1 gene sequence was obtained, then NELL1 gene was subcloned into pShuttle-GFP-CMV (-)TEMP vector which was subsequently digested with enzyme and inserted into pAdxsi vector to package the recombinant adenovirus vector (pAdxsi-GFP-NELL1). After verified by enzyme cutting and gel electrophoresis, pAdxsi-GFP-NELL1 was amplified in HEK293 cells and purified by CsCl2 gradient purification, titrated using 50% tissue culture infective dose (TCID50) assay. The rat BMSCs were cultured and identified by flow cytometry and directional induction, then were infected with adenoviruses (pAdxsi-GFP-NELL1 and pAdxsi GFP). NELL1 expression was verified by RT-PCR and immunofluorescence; GFP gene expression was verified by the intensity of green fluorescence under fluorescence microscope. Cell counting kit-8 (CCK-8) was used for investigate the influence of vectors on the proliferation of rat BMSCs. RESULTS: Recombinant adenoviral vector pAdxsi-GFP-NELL1, which encodes a fusion protein of human NELL1, was successfully constructed and amplified with titer of 1 x 10(11) pfu/mL. The primary BMSCs were cultured and identified by flow cytometric analysis, osteogenic and adipogenic induction, then were used for adenoviral transfection efficiency and cell toxicity tests. An multiplicity of infection of 200 pfu/cell produced optimal effects in transfer efficiency without excessive cell death in vitro. Three days after transfection with 200 pfu/cell pAdxsi-GFP-NELL1 or pAdxsi-GFP, over 60% BMSCs showed green fluorescent by fluorescence microscopy. Immunofluorescence with NELL1 antibody also revealed high level expression of human NELL1 protein in red fluorescent in these GFP expressing cells. RT-PCR analysis confirmed that the exogenous expression of NELL1 upon transfection with pAdxsi-GFP-NELL1 at 200 pfu/cell, whereas NELL1 remained undetectable in Ad-GFP-transfected rat BMSCs. The proliferative property of primary rat BMSCs after adenoviral NELL1 transfection was assayed by CCK-8 in growth medium. Growth curve demonstrated no significant difference among BMSCs transfected with pAdxsi-GFP-NELL1, pAdxsi-GFP, and no treatment control at 7 days (P > 0.05). CONCLUSION: Recombinant adenovirus vector pAdxsi-GFP-NELL1 can steady expressing both GFP and NELL1 protein after being transfected into rat BMSCs. It provides a useful tool to trace the expression of NELL1 and investigate its function in vitro and in vivo. PMID- 20540272 TI - [Biological effects of recombinant adeno-associated virus 2 mediated human transforming growth factor beta1, encoding gene transfer to rabbit degenerative nucleus pulposus cells on proteoglycan level]. AB - OBJECTIVE: To verify the potential of the recombinant adeno-associated virus 2 (rAAV2) vector as a strategy for human transforming growth factor beta1 (hTGF beta1) gene transfer in degenerative intervertebral discs of rabbit, to investigate the gene transduction efficacy and to quantify the biologic effects on the proteoglycan level after gene transferring. METHODS: Rabbit models of disc degeneration were established by injecting the 25 microL fibronectin fragment (Fn f, 1 mmol/L), 4 weeks later, saline with or without virus was injected directly into 96 lumbar discs of 24 mature New Zealand white rabbits (male or female and weighing 1.7-2.2 kg) which were divided into 3 groups (n = 8). Group A received the 25 microL rAAV2-hTGF-beta1 (1 x 10(12) vg/mL); group B received rAAV2 enhanced green fluorescent protein (rAAV2-EGFP); and group C received PBS. Two rabbits of groups A, C were killed 1 week after injection, the immunohistochemical staining for hTGF-beta1 was performed on the slices of nucleus pulposus (NP) tissues. At 4, 8, and 12 weeks after gene transferring, NP tissues were harvested and cultured to quantify the changes of the proteoglycan level using 35S-sulfate incorporation assay. The expression of EGFP in group B was observed 12 weeks after injection. RESULTS: Immunohistochemical staining showed that extensive and intense positive immunohistochemical staining for hTGF beta1 were seen in group A when compared with group C 1 week after gene transferring. The nucleus pulposus tissues from the group A exhibited an increased synthesis of proteoglycan, which was significantly more than that from groups B and C (P < 0.05), and no significant difference was observed between group B and group C. The expression of EGFP in group B was high at 12 weeks. CONCLUSION: The discs injected with rAAV2-hTGF-beta1 can highly expressed the therapeutic proteins for more than 12 weeks, it is suggested that rAAV2 should be an valid vector for transferring exogenous genes in the degenerative disc. The therapeutic factors hTGF-beta1 can efficiently increase the proteoglycan synthesis of the degenerative NP cells. PMID- 20540273 TI - [Research advance of treatment of peripheral nerve injury with neuromuscular electric stimulation]. AB - OBJECTIVE: To review researches of treatment of peripheral nerve injury with neuromuscular electrical stimulation (NMES) regarding mechanism, parameters, and clinical application at home and abroad. METHODS: The latest original literature concerning treatment of peripheral nerve injury with NMES was extensively reviewed. RESULTS: NMES should be used under individual parameters and proper mode of stimulation at early stage of injury. It could promote nerve regeneration and prevent muscle atrophy. CONCLUSION: NMES plays an important role in clinical application of treating peripheral nerve injury, and implantable stimulation will be the future. PMID- 20540274 TI - Biological variation of laboratory analytes based on the 1999-2002 National Health and Nutrition Examination Survey. AB - OBJECTIVE: Biological variation consists of within-person (WP) and between-person (BP) variation. These components of biological variation are used to set analytical goals for imprecision and bias, evaluate serial changes for individual analytes, and assess the clinical utility of population-based reference intervals. Estimates of WP coefficients of variation (CVw) and BP coefficients of variation (CVg) for laboratory analytes were estimated from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: NHANES is a survey of the noninstitutionalized civilian U.S. population that uses a stratified, multistage probability design to collect a nationally representative sample. Between- and within-person variations were estimated for 34 laboratory analytes, including general biochemical, nutritional, and environmental analytes. Between-person variation was estimated taking into account the complex sample design of NHANES by Taylor series linearization. For WP variation, a nonrandom sample was obtained with an average of 18.8 days (range: 3-51 days) between two analyte measurements. Data outliers were excluded using Tukey's method to obtain more stable estimates of variation. RESULTS: The BP and WP variations were estimated on as many as 18,761 and 853 sample persons, respectively. When compared with the BP sample, the WP sample was older (mean age: 39 compared with 30 years) and had more non-Hispanic white (45% compared with 37%) and fewer Mexican-American (19% compared with 30%) persons. There was no statistically significant difference in gender proportions between the BP and WP samples. Serum sodium had the lowest CVg (1.8%) and the lowest CVw (1.0%). The index of individuality (CVw/CVg) ranged from 0.20 for blood lead to 0.76 for serum iron. The CVg exceeded the analytical method coefficient of variation for all analytes. Within-person variation was also compared between males and females, and several analytes revealed significant differences (p < 0.01). Serum ferritin had the greatest difference for CVw (males, 17.9% compared with females, 28.8%). PMID- 20540275 TI - Notice of reason for denial of benefits. AB - Lafleur v. La. Health Serv. & Indem. Co., 563 F.3d 148, 2009 U.S. App. LEXIS 6104: The health plan administrator that had failed to raise new grounds for denying benefits to the plan participant prior to the start of litigation did not substantially comply with the Employee Retirement Income Security Act's (ERISA) requirement of notice to the participant, containing reasons for the denial of benefits. PMID- 20540276 TI - Plan amendments--vesting of welfare benefits--settlor intent--ability to terminate health benefits for those on long-term disability. AB - Halbach v. Great-West Life & Annuity Ins. Co., 561 F3d 872 (8th Cir. Mo. 2009): Because the vesting of benefits is subject to contractual arrangement under an employee benefit plan, summary judgment was improper where a genuine issue of material fact remained as to the settlor's intent to vest benefits. PMID- 20540277 TI - It's time to move. PMID- 20540278 TI - Maximizing independent function. AB - In summary, the positioning and seating requirements for patients with SCI and TBI are a highly specialized and complex process. In order for patients to achieve the goals of maximizing independent function, experiencing the highest quality of life possible, and preventing costly complications, they need customized and durable equipment for their individualized bodies and function, and home and community environments. The process of helping patients procure the equipment they need requires a well-coordinated and experienced team of interdisciplinary staff, a comprehensive evaluation over time with various pieces of trial equipment in community settings, clear accountabilities and systems for obtaining the equipment, and the timely procurement and trialing of equipment prior to inpatient discharge to home. PMID- 20540279 TI - To lock or unlock? That is the question. PMID- 20540280 TI - Treating the whole person. PMID- 20540281 TI - Assessing mobility. PMID- 20540282 TI - Fine-tuning your options with billing software. PMID- 20540283 TI - The benefits of continuing education online. PMID- 20540284 TI - [Automatic section for virtual eversion visualization]. AB - The proposed automatic section method achieves accurate automatic section on colon outer surface centerline and evert the colon, by calculating the centerline windowed average curvature. The method is validated on CT colon datasets, and experimental results show that the sectioned virtual eversion facilitates colon visualization and analysis. PMID- 20540285 TI - [A design of electrophysiological stimulator]. AB - Electrophysiological stimulator is widely used in study of biological electrical activities. This electrophysiological stimulator is capable of outputting both biphasic and monophasic waveforms with amplitudes within 0V and 30V. The sequence of the biphasic waveforms is alterable and their widths and interval can be respectively arbitrarily modified by the operator. The machine will inform the operator as soon as the charge completes through the indicator and buzzer. The safety of experimental objects is guaranteed by float ground thanks to battery power supply. PMID- 20540286 TI - [Phase contrast imaging and three-dimensional reconstruction of mouse liver under different conditions]. AB - The liver sample of mouse under different conditions is investigated in this paper, and the three-dimensional vessel system of mouse liver is established. The experiments were performed at X-ray imaging and biomedical application beamline (BL13W1) of Shanghai Synchrotron Radiation Facility (SSRF). The results show that dry liver sample has the best imaging quality. By the approach of filter back projection (FBP), the tomography images are obtained. The vessel tree is reconstructed by the use of surface rendering. It reveals that in-line phase contrast imaging technique has the ability to visualize structures inside mouse liver and has the potential to be used in liver imaging in the future. PMID- 20540287 TI - [A study on individual internal fixation with steel plate according to 3D reconstruction of CT images and Ugnx, Pro/E machining method]. AB - PURPOSE: Discuss the new method of individual internal fixation with steel plate customization. METHOD: Customize individual internal fixation with steel plate according to 3D reconstruction of CT images and Ugnx. Pro/E machining method. RESULT: Success in customization about the first individual internal fixation with clavicular hook plate for the treatment of multisegmental fracture of clavicle. CONCLUSION: The new method of individual internal fixation with steel plate customization according to 3D reconstruction of CT images and Ugnx, Pro/E machining technique is a good news for patients of orthopaedic trauma. We are fully confident of the future development of the method of individual internal fixation with steel plate customization. PMID- 20540288 TI - [Research on the digitized technical remodeling in the positioned picture shooting part of homemade X-ray radiotherapy simulative position finder by use of CR and PACS]. AB - To improve the part of the hardware about Xin Hua SL-IC model X-ray radiotherapy simulative position finder, using CR and PACS, so that located-picture shooting for the simulative position finder have been realized digital upgrade. PMID- 20540289 TI - [Some special problems and countermeasure about dose calibration of high-energy electron for linear accelerator]. AB - This article presents and discusses some special problems about the dose calibration of high-energy elections for Linear Accelerator according to the practice of the authors. Thus the paper explain the issues of this work, and clarify the wrong understanding of real work for the aim of attaining the rules of quality assurance in radiotherapy by WHO. PMID- 20540290 TI - [The applied research of digital subtraction technique on head and neck with 64 slice spiral CTA]. AB - OBJECTIVE: To explore the imaging value of digital subtraction technique on head and neck with 64-slice spiral CTA. METHODS: 958 patients of head and neck vessels were examined with the direct method, Surestart law, low-dose tes methods, Surestart subtraction method, low-dose test subtraction method by CTA, the former three kinds are non-subtraction method, the latter two kinds are subtraction method, a comparative analysis on the five methods from the image quality, imaging time, imaging values, seek for the CTA method with optimal image quality, the shortest imaging time, the best value. RESULTS: The image quality with the direct method (2.82 points), Surestart law (3.25 points), low-dose test method (3.33 points), Surestart subtraction method (4.10 points), low-dose test subtraction method (4.18 points), gradually changed well in order, the image quality of subtraction method is better than non-subtraction method; imaging time with direct method (40.26 minutes), Surestart law (35.06 minutes), small dose test method (33.49 minutes), Surestart subtraction method (17.52 minutes), small dose test subtraction method (15.32 minutes), gradually become shorter in order, the imaging time of subtraction method is shorter than the non-subtraction method; Evaluation on the sensitivity of aneurysms and stenosis, subtraction method is more better than the non-subtraction method, the little narrow extent and the smaller aneurysm, the subtraction method is more better than non subtraction method. CONCLUSION: The digital subtraction method is an ideal head and neck imaging method with 64-slice spiral CTA. PMID- 20540291 TI - [Experimental study of animal cabin with ATM/LP and low oxygen and high carbon dioxide]. AB - OBJECTIVE: To explore the feasibility of the animal experimental cabin to copy the animal models with ATM/LP and low oxygen and high carbon dioxide environment. METHODS: 60 SPF-class male SD rats were divided into two groups, 20 for normobaric hypoxia control experiments and the other 40 for hypobaric hypoxia control experiments. For each group, examine the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the multi-detector measurement of physiological, and observe the pulmonary vascular changes in the structure. RESULTS: The ATM/LP and low oxygen and high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, promoting right ventricular hypertrophy. CONCLUSION: Clinical applications showed that the animal experimental cabin was observing and controlling accurately, safe, reliable, and the results was reproducible. It can successfully copy the regular low-pressure hypoxia and hypercapnia environment pulmonary hypertension model, in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by oxygen-poor and provide an experimental technology platform. PMID- 20540292 TI - [The research of organization behavior model in planning medical equipments purchasing]. AB - The law named The Safety Management Standardization of Medical Apparatus and Instruments in Clinic issued by the government recently, has classified the technical evaluation as one of the aspects of controlling medical risks in demonstration of medical equipments purchasing. This article has researched the organization behavior model, put forward the inevitability of the role in clinical engineering subjection, provided the idea and method of medical equipment purchasing plan, corresponding with the new standardization in now period. PMID- 20540293 TI - [Design and manufacture of medical shipping refrigerated box]. AB - OBJECTIVE: To develop a set of low temperature medical shipping refrigerated box for storage and shipping for biologicals in field environment. METHODS: Semiconductor cooling device (SCD) and phase change energy storage materials (PCESM) were adopted as the means for refrigeration and coolness storage, coolness was produced by SCD and stored by PCESM while power source present, and low temperature state for biologicals was keep by PCESM. RESULTS: The problem for biologicals storage and shipping in low temperature state for medical experiment and clinic was resolved. CONCLUSION: Medical shipping refrigerated box can be used not only in medical, but also in other field such as food storage and shipping, etc. PMID- 20540294 TI - [A new kind of minimally invasived external fixator for orthopaedics fabricated with quick casting method]. AB - OBJECTIVE: A new kind of external fixator for orthopaedics is designed in order to overcome the shortcomings of high weight, hard to operate and high degree of hurt for the conventional external fixator. METHODS: The quick casting method is used to realize fast shaping, and FEM (Finite Element Method) is used to verify the practicability of the design. RESULTS: In order to verify the correctness of the design, FEM is used to simulate it. It is concluded from the simulated result that the biggest relative displacement between the borders of the separated bones is just 0.37 mm, which is much less than the requested value 1 mm. This fits the request to cure the patients whose bones are broken and shows the correctness of the design. Finally, ten sheep are used as specimen to verify the feasibility of the design. It is concluded from the X ray sketches of 2 weeks, 4 weeks and 8 weeks that there is no relative displacement happened between the border of the broken bone and the bone is well cured. CONCLUSIONS: This kind of device is feasible to cure the broken bones and the design scheme can be used as the final treatment means. PMID- 20540295 TI - [A design of software for management of hospital equipment maintenance process]. AB - According to the circumstance of hospital equipment maintenance, we designed a computer program for management of hospital equipment maintenance process by Java programming language. This program can control the maintenance process, increase the efficiency; and be able to fix the equipment location. PMID- 20540296 TI - [The generation characteristics and purchasing points of Gamma Knife]. AB - With the rapid development of the computer technology and the constant updating of the radiotherapy equipment, a huge improvement has been manifested by the new generation of the Gamma Knife radiotherapy system. Not only its functions are being improved, but also the treatment indications are expanding. These advances have been widely recognized by the clinical medical experts, breaking off the forbbiden zone of surgical operations, saving a lot of tumor patients with both malignant and benign lesions, who are not suitable for surgical operations due to local anatomical limitations. However, there are still a lot of clinicians being not clear about the funcitons and generations of Gamma Knife radiotherapy system. Moreover, variant guidances by different manufacturerers have given rise to confusions, especially on the equipment purchasing. Therefore, in this report we summarize the features of Gamma radiotherapy systems produced by different manufacturers in recent years, to supply reference data for the organization and expert buyers. PMID- 20540297 TI - [Cytotoxicity evaluation of the disposable medical syringe piston]. AB - When some testing institutions performed biological evaluation to the disposable medical syringe piston, cytotoxicity was found. According to the biological evaluation testing Selection Guide proposed by Ministry of Health and the Comments of Sample Provider, We performed biological evaluation to one sample by using 5 tests of basic biological evaluation. Cytotoxicity was found, which was probably caused by the residue of the lotion. This research provides reference for objective evaluation of disposable medical syringe piston and safe guarantee of the product. PMID- 20540298 TI - [Pay attention to physical test and drafting product standards of the centrifuge apparatus]. AB - Compare and analyze the standards related to centrifuge apparatus and make corresponding suggestions in allusion to the problems existed in the test method and physical performance during product standard drafting process. PMID- 20540299 TI - [Site inspection procedures and methods for evaluation of the quality management system of in vitro diagnostic regents]. AB - In this paper, the procedures, logos, methods, essentials as well as notable problems for inspecting the qualification management system of in vitro diagnostic regent manufactures are discussed, with aims of promoting inspector's practical level and consequentially ensuring the quality, standard and efficacy of the inspection. PMID- 20540300 TI - [Status and challenges of medical metrology in China]. AB - In recent years, more and more new medical devices appears, among them there are many measurement instruments related to consistency and stability of value, and safety to device. Presently China is facing the health policy reforms and medical quantity management system establishment. The primary duty of the clinical engineering is to ensure security and validity of medical devices, and preventing maintenance included of measurement and safety is important measure for the duty. The paper overviews the status in medical metrology and challenge for health policy reform in China, and gives some suggestions to resolve medical metrology. PMID- 20540301 TI - [Application of ethylene oxide standard sampling subpackage]. AB - Using the all closed covering low-temperature method, we successfully made the packaging and sampling of ethylene oxide standard. PMID- 20540302 TI - [Application of digital images in quality assurance of radiotherapy]. AB - The application of KV, MV real-time digital images and 3D reconstructed radiography in quality assurance of radiotherapy, provides effective means to verify the beam center and therapeutic range, calibrate the positioning accuracy and inspect the characteristics of radiotherapy equipment and radiation physics, greatly improves the quality and accuracy of radiotherapy. PMID- 20540303 TI - [Quality management of nuclear medicine facilities and experience during JCI certification]. AB - In 2003, JCI certification was introduced to create our new hospital quality management system. Our department imaging facilities management level and service quality markedly improved through JCI certification and re-evaluation. It played an important role in improving the efficiency and extending the life of medical facilities, reducing maintenance costs. PMID- 20540304 TI - [Breathing waveform and respiratory ring in the role of mechanical ventilation]. AB - To learn reading respiratory waveform and ring is a key step to good use of respirator, which will help clinicians to analyze the status of the use of respirator and real time changes in patient's lung mechanics from the changes of respiratory wave and ring, for making use of respirator reasonably, scientifically and objectively to provide advanced methods. This article only explains the physical basis of respiratory wave and ring. PMID- 20540305 TI - [Breathing machine management system design and application]. AB - Ventilator management systems can improve the utilization of hospital ventilator, reduce equipment idle and the workload of staff, improving the work efficiency. It lays a good foundation for the systematic centralized management of medical equipment, and makes the hospital information management more perfect. PMID- 20540306 TI - [Application of free anterolateral thigh adipofascial flap in the correction of facial depression]. AB - OBJECTIVE: To investigate the operative technique and therapeutic effect of free anterolateral thigh adipofascial flap in the correction of facial depression. METHODS: From Oct. 1996 to Jan. 2007, 32 patients with facial depression deformities were treated with free anterolateral thigh adipofascial flaps. The bone defects in 8 cases were corrected with Medpor implants at the same stage. RESULTS: 33 free anterolateral thigh adipofascial flaps were used in 32 patients. 2 flaps were used bilaterally in one patient. The size of the flaps ranged from 12 cm x 8 cm to 20 cm x 11 cm (average, 16.5 cm x 10.5 cm). 30 flaps survived completely. Flap edge resorption happened in 3 flaps within half a year postoperatively. Satisfactory results were achieved in 23 patients after one stage treatment. Another 9 patients underwent secondary operation 6 months postoperatively. Among them, 6 patients underwent flap liposuction because of fatty appearance, 3 patients underwent fat transplantation because of flap edge resorption. The patients were followed up for 6 months to 2.5 years. All the deformities were improved greatly, and the faces were almost symmetrical. The wounds at the donor sites were primarily healed with no functional morbidity. CONCLUSIONS: Free anterolateral thigh adipofascial flap is a large size flap. The flap thickness can be adjusted for three-dimensional reconstruction. The vascular anatomy is relatively stable. The bone defects can also be corrected at the same stage. PMID- 20540307 TI - [Management of congenital scalp defects in infants]. AB - OBJECTIVE: To investigate the management of congenital scalp defects in infants. METHODS: From 1996 to 2008, 6 infants with congenital scalp defects were treated with dressing change, flap transposition, or tissue expansion combined with skull defect reconstruction. RESULTS: Parietal scalp defects in 6 cases were healed after treatment. 5 cases were followed up for 3 months to one year. 2 cases had scalp alopecia in some areas. The scar was inconspicuous in the other 3 cases. CONCLUSIONS: Dressing change is suitable for small scalp defect, while flap transposition should be used for medium defect. For large full-thickness cranial defect, dressing change and tissue expansion should be performed at the first stage, followed by skull defect reconstruction and expanded flap transposition. PMID- 20540308 TI - [Correction of low angel-square jaw with mandibular "V-Line" ostectomy combined with mandibular outer cortex ostectomy]. AB - OBJECTIVE: To evaluate the feasibility of mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy for correction of low angle-square jaw. METHODS: From Jul. 2005 to Nov. 2007, 31 patients with low angle-square jaw were corrected with mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy. The patients were followed up for 6-24 months. Pre- and Post operative standard images and X-ray cephalometric examination were used to assess the therapeutic effect. RESULTS: The wounds were healed primarily in all the 31 cases with no severe complication. The lower labial numbness was happened in 13 cases, which was recovered within 4 months. All the patients achieved esthetic improvement at the frontal and lateral view. The mandibular angle and the mandibular plane angle reached 110 degrees - 120 degrees and 25 degrees - 30 degrees after operation. The distance between the angles was decreased. CONCLUSIONS: The low angle-square jaw can be corrected satisfactorily with mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy. PMID- 20540309 TI - [The influence on masticatory function after curved osteotomy of prominent mandibular angle]. AB - OBJECTIVE: To investigate the influence of mandibular curved osteotomy on masticatory function by analyzing the bite force before and after operation. METHODS: From Jan. to Oct. 2008, 20 female cases underwent mandibular curved osteotomy. The maximal bite force in incisor area, bilateral premolar area and molar area was measured before operation and 6 months after operation. RESULTS: The maximal bite force in incisor area, right premolar area, left premolar area, right molar area, left molar area was (11.7 +/- 3.9) kg, (23.2 +/- 1.6) kg, (30.9 +/- 2.3) kg, (35.6 +/- 4.2) kg, (38.5 +/- 3.1) kg, respectively before operation; and was (11.9 +/- 2.1) kg, (23.0 +/- 4.5) kg (31.0 +/- 1.8) kg,(35.9 +/- 3. 5) kg. (38.5 +/- 2.7) kg, respectively 6 months after operation. The postoperative maximal bite force reached the preoperative level, and even slightly above it. There was no significant difference between the measured data before operation and 6 months afterward (P > 0.05). CONCLUSIONS: The curved osteotomy of prominent mandibular angle has no long-term effect on masticatory function. PMID- 20540310 TI - [Treatment of enophthalmos after severe malar-maxillary complex fracture with titanium mesh and high density polyethylene (Medpor)]. AB - OBJECTIVE: To study the surgical management of enophthalmos after severe malar maxillary complex fracture. METHODS: The X-ray and CT examination were performed before operation to diagnose the orbital fracture and intraorbital tissue displacement. The fractured orbital rim was repositioned intraoperatively, followed by implantation of shaped titanium mesh to rebuild the orbital floor. The Medpor was inserted above the titanium mesh to correct the enophthalmos. RESULTS: From Sept. 2007 to Jan. 2009, 6 cases of enophthalmos after severe malar maxillary complex fracture were treated. The enophthalmos was corrected or improved obviously in all the patients. CONCLUSIONS: The enophthalmos after severe malar-maxillary complex fracture can be corrected or obviously improved. Shaped titanium mesh can be used to rebuild the orbital floor with the Medpor to reconstruct the intraorbital tissue volume. PMID- 20540311 TI - [Three-dimensional analysis of facial structure for unilateral cleft lip patients repaired by Millard's method]. AB - OBJECTIVE: To evaluate the aesthetic effect of Millard' s method in patients with unilateral cleft lip by three dimensional sensing system. METHODS: 19 patients with unilateral cleft lip (class II: 7 cases, class III: 12 cases) were randomly selected. The pre- and postoperative 3-D facial profiles were recorded using a 3 DSS scanner. Then 3D geometric models were established by Geomagic Studio 10.0. In the software, columella length, nostril floor width, alar base-subnasale distance, alar length, upper lip height, lateral upper lip height and lip length were measured before and after lip repair respectively. Paired-samples T test and one-sample T test were used for statistical analysis with SPSS 12. 0 software package. RESULTS: There were significant differences in the nostril floor width, alar base-subnasale distance, alar length and lip length before and after operation (P < 0.05, P < 0.01). The ratio of asymmetry in normal people was no more than 0.1. There was significant difference in the asymmetry ratio of columella length and lateral upper lip height between postoperative class II patients and normal people (P < 0.05). There was significant difference in the asymmetry ratio of columella length, nostril floor width, alar base-suhnasale distance, lateral upper lip height and lip length between postoperative class III patients and normal people (P < 0.05 or P < 0.01). CONCLUSIONS: Millard's technique is useful for repairing unilateral cleft lip in rebuilding nasal floor, the Cupid' bow and in correction of the columella deviation, except for a relatively insufficient lip height and columella length at the operated side. Besides, the nostril floor width at the operated side in class III patients is still wider than that at the opposite side. PMID- 20540312 TI - [The pathological characteristics and clinical significances of maturational change of port-wine stain]. AB - OBJECTIVE: In this study histologic observations were presented to elucidate the possible mechanism of maturational change of port-wine stain(PWS). METHODS: Normal PWS(3 cases) , thicken PWS (11 cases) and nodular PWS (9 cases) were included to present histologic observations. RESULTS: Normal PWS, only shows mild dilated, thin-walled vessels within superficial dermis. Thicken PWS, shows further dilated vessels and sebaceous gland throughout dermis and superficial subcutaneous fat. Nodular PWS can be divided into three groups. I Similar to thicken PWS, shows further dilated vessels and sebaceous gland throughout dermis and superficial subcutaneous fat. II Shows Large number of dilated vessels, honeycombing and less vascular mesenchymal. III Tenacious texture shows mild dilated vessels, diffused collagen, mesenchymal rarefaction, lymphocyte infiltration and lymphedema change. CONCLUSIONS: Histologic examination revealed not only the expected vascular abnormalities, but also a number of widely distributed hamartomatous changes in thicken and nodular PWS. The complex hamartomatous changes suggest a genetically determined, multilineage developmental field defect in the pathogenesis of PWS. PMID- 20540313 TI - [Application of modified peroneal tendofascial compound flap with partial tendon of peroneal long muscle in lower leg refractory defects with Achilles tendon rupture]. AB - OBJECTIVE: To investigate the feasibility of using modified peroneal tendofascial compound flap with partial tendon of peroneal long muscle in lower leg refractory defect with Achilles tendon rupture. METHODS: Based on the application experience of peroneal tendofascial compound flap for lower leg refractory defects, partial tendon of peroneal long muscle was included in the flap to repair the Achilles tendon rupture. RESULTS: 6 cases were treated. The maximum size of modified compound flap reached 5 cm x 5 cm. The maximal included tendon in the flap was 5 cm in length. All the flaps survived completely. Partial epidermis necrosis happened in one case between the skin graft at the donor site and the edge of the flap pedicle. The patients were followed up for 5 months to 2 years with satisfactory cosmetic and functional results. CONCLUSIONS: The modified compound flap has reliable blood supply and can be easily transposed, leaving less morbidity at the donor site. It is very suitable for lower leg refractory defect with the Achilles tendon rupture. PMID- 20540314 TI - [Application of island flap pedicled with dorsal cutaneous branches of digital internal artery for skin defect at the same finger]. AB - OBJECTIVE: To investigate the therapeutic effect of island flap pedicled with dorsal cutaneous branches of digital internal artery for skin defect at the same finger. METHODS: From June 2005 to June 2008, 52 fingers in 45 cases with skin defects were treated with island flap pedicled with dorsal cutaneous branches of digital internal artery for skin defect at the same finger. RESULTS: Partial necrosis happened at the distal end of 4 island flaps. All the other flaps survived completely. The patients were followed up for 4-8 months with satisfactory cosmetic and functional results. The two-points discrimination distance was 6. 0-9.0 mm (average, 7.4 mm) in flaps with nerve anastomosis, and 8 10 mm (average, 9 mm) in flaps without nerve anastomosis. Minor pigmentation occurred in 5 fingers, cicatricial contracture around the skin graft in 4 fingers, and pain in donor site scar in 2 fingers. The hand function was assessed as excellent in 42 fingers, as good in 7 fingers and medium in 3 fingers. CONCLUSIONS: The main artery will not be sacrificed when the island flap is used. It is ideal for the treatment of finger skin defect. PMID- 20540315 TI - [Superior or inferior gluteal artery perforator flaps for the gluteal sores]. AB - OBJECTIVE: To investigate the clinical application of superior or inferior gluteal artery perforator flaps for the gluteal sores. METHODS: Before operation, the perforator artery was detected by Doppler flowmeter and labeled. The perforator flap was designed, including the perforator artery, but not the gluteal maximum muscle. RESULTS: From Aug. 2006 to May 2009, 15 cases were treated. The flap size ranged from 6 cm x 8 cm to 7 cm x 15 cm. All the flaps survived completely without hematoma, seroma or other complication. CONCLUSIONS: The gluteal maximum muscle-reserved gluteal artery perforator flap is a good choice for gluteal sore with reliable blood supply and less morbidity in donor site. PMID- 20540316 TI - [Anatomic research and clinical application of modified penile elongation: a report of 205 cases]. AB - OBJECTIVE: To investigate the application of penile cavernous bodies elongation combined with fat flap for the treatment of micro-penis. METHODS: Anatomic study was performed to study the thickness of penile suspension ligaments and the relationship between the penile erection stability and the mobilization of cavernous bodies crus. The suspension ligaments were divided and cavernous bodies crus were partially mobilized, so as to release part of the cavernous bodies from inferior ramus of pubis. Then the penis was elongated sufficiently. Local fat flap was transposed to fill the front space of pubis to make sure the effective elongation of penis. RESULTS: 205 cases of micro-penis were treated. The average length of the penis was 4.26 cm in the static state, 8.13 cm in erectile state before operation. After operation, it increased to 8.63 cm in the static state, 12.11 cm in erectile state. CONCLUSIONS: The cavernous bodies can be elongated 1 2 cm more with the modified method, while the stability of penile erection is not affected. PMID- 20540317 TI - [Impact of third-party bone marrow mesenchymal stem cells on allogenic skin transplantation]. AB - OBJECTIVE: To investigate the effect of the third-party bone marrow-derived mesenchymal stem cells (BMSCs) on the allogeneic skin transplantation. METHODS: 40 female C57BL/6 mice and 50 male BALB/C mice were respectively used as donors and recipients of skin transplantation. 50 BALB/C mice were divided randomly into 5 groups: Blank control group, Cyclophosphamide group BMSCs group, Cyclophosphamide + BMSCs group and CM-DiI staining group, with 10 mice in each group. Before skin transplantation, high-dose abdominal injection of Cyclophosphamide (200 mg/kg, 2 d) was performed in recipient mice. On the transplantation day, a bonus of 1 x 10(5) BMSCs of the SD rat (SD-BMSCs) were injected through the tail vein. The observation of skin grafts, mixed lymphocyte culture (MLC), HE staining, the observation of CM-DiI-labeled SD-BMSCs and FACS were used. RESULTS: The skin graft survival time was significantly prolonged in the Cyclophosphamide + BMSCs group, as compared with the blank control group, the Cyclophosphamide group, the BMSCs group respectively. When BMSC and lymphocyte mixed at the ratio of 1:1 and 1:10, rat BMSCs inhibited T lymphocyte proliferation. More angiogenesis and less lymphocyte infiltration were found in the experimental group than them in other groups. Red fluorescent cells were found in CM-DiI staining group under long-term observation. The SD-BMSCs can he detected by flow cytometry in the cell group and the Cyclophosphamide + BMSCs group. CONCLUSIONS: BMSCs can survive in the heterogeneous recipient body; the third-party BMSCs transplantation can prolong skin graft survival time; BMSCs can inhibit T lymphocyte activation and proliferation. PMID- 20540318 TI - [The differences between adipose tissue derived stem cells and lipoma mesenchymal stem cells in characteristics]. AB - OBJECTIVE: To compared the biological characteristics of adipose-derived stem cells and lipoma-derived mesenchymal stem cells (LMSCs) in vitro, so as to assess the safety of adipose-derived stem cells( ASCs) for transplantation. METHODS: Regular slice and stain of adipose and lipoma tissue were performed. ASCs and LMSCs were isolation from the two tissues by enzymatic digestion, and the appearance of the cultured cells was observed. The cell viability was evaluated with MTS chromatometry and cell growth curve was generated. Flow cytometry was performed for cell cycle analysis and the expression of the cell surface marker profiles. QRT-PCR was used to detect the expression of tumor-specific gene (the high-mobility group AT-hook 2, HMGA2), and immunocytochemistry was used to detect the expression of telomerase. RESULTS: Marked difference was observed in histologic sections of adipose tissue and lipoma tissue. ASCs showed a good consistent in cell morphology while LMSCs not. ASCs showed a significant lower proliferation capacity than LMSCs by MTS chromatometry (P = 0.000). The expression of CD29, CD44, CD105 was similar in ASCs and LMSCs, while the level of CD133 was significantly lower in ASCs (5.35%) than in LMSCs (26.87%). The expression of HMGA2 was lower in ASCs (RQ = 1) than in LMSCs (RQ = 1.79) by qRT PCR, it has statistically difference between them (P < 0.01); And in ASCs and LMSCs, the integrated optical intensity (IA) values of hTERT expression are 1379.597 +/- 498.617 and 3 328.108 +/- 902.856, size (area) are 132,390.27 +/- 35,568.945 and 238,000.53 +/- 49,264.289, density (mean) are 0.009 +/- 0.003 and 0.014 +/- 0.003, revealed the expression of hTERT also shown a significant lower level in ASCs than in LMSCs by immunocytochemistry. CONCLUSIONS: It indicates significant difference between ASCs and LMSCs in the biological characteristics in vitro. There is no evidence of malignant transformation of ASCs. PMID- 20540319 TI - [Expression of mast cell tryptase in scar]. AB - OBJECTIVE: To investigate the expression and distribution of mast cell tryptase (MCT) in scar, and to discuss the different MCT gene expression in keloid, hypertrophic scar and normal skin. METHODS: 20 samples of keloid, 20 samples of hypertrophic scar and 20 samples of normal skin were collected. The distribution of MCT was investigated by immunofluorescence histochemistry, and the MCT mRNA expression was detected by Relative Quantification real-time fluorescent PCR. RESULTS: MCT gene was mainly located in the collagen fiber bundles of the scar, especially in the superficial layer of scar. MCT mRNA expression was significantly higher in keloid than that in hypertrophic scar and normal skin (P < 0.01). Averagely, the MCT gene expression in keloid was 2.5 times and 5.4 times of that in hypertrophic scar and normal skin. CONCLUSIONS: MCT gene may play a role in the pathogenesis of scar. PMID- 20540320 TI - [The significance of TGF-beta expression in scar in adenosine receptor A(2A) knockout mice]. AB - OBJECTIVE: To discuss the mechanism of scar hypertrophy in adenosine receptor A(2A) (A(2A) R) knockout mice. METHODS: Animal models of hypertrophic scar were established in 12 A(2A) R knockout mice and 12 wild-type mice as control. The thickness and the size of transverse section of the hypertrophic scar were observed by H-E staining. The hydroxyproline (HYP) in the scar was measured colorimetrically. The TGF-beta expression was tested by Western blotting method. RESULTS: The hypertrophic scar in wild-type mice was more severe than that in knockout mice. Compared with self-control, the increase of the thickness and the size of transverse section of hypertrophic scar was markedly higher in wild-type group than in the knockout group (P < 0.01). There was significant difference in HYP content between the two groups (P < 0.01). Compared with self-control, the increase of TGF-beta expression in wild-type group was much more than that in knockout group (P < 0.01). CONCLUSIONS: The TGF-beta expression decreases in the A(2A) R knockout mice. The scar hypertrophy is also much less in the A(2A) R knockout mice. PMID- 20540322 TI - [Budget screening and medicine]. PMID- 20540321 TI - [Anatomic study on the mechanism of tear trough deformity and palpbromalar groove deformity]. AB - OBJECTIVE: To study the anatomic mechanism of tear trough deformity and palabromalar groove deformity. METHODS: Six cadavers (12 sides, 3 male, 3 female, an average age of 67.2 years) with tear trough deformity and palpbromalar groove deformity underwent lower eyelid and periorbital area dissection. RESULTS: Tear trough deformity and palabromalar groove deformity locate at the junction of thin eyelid skin and thick cheek skin. Skin is closely attached to the orbicularis oculi muscle. The superior horder of the malar fat pad covers the junction of the palpebral and orbital portions of the orbicularis muscle, and does not descend with malar fat pad, which is also corresponded to the location of tear trough and palphromalar groove. The gap between the orbicularis oculi muscle and the levator labii superioris alaeque nasi muscle is not correspond to tear trough. The orbicularis retaining ligament arises from the orbital rim and ends at the junction of the palpebral and orbital portions of the orbicularis muscle, and the ligament connects with the deep part of the orbicularis muscle which directly attaches to the infraorbital rim. Suborbicular oculi fat pads locate at the inferolateral of the orbital region, thin and flabby. Orbital septal arises from the infraorbital rim, and the orbital fat extrudes anteriorly and inferiorly. CONCLUSIONS: Tear trough deformity and palabromalar groove deformity are resulted from combination of age-related relaxation, atrophy and ptosis of layers of tissues. The orbital septal and the orbicularis retaining ligament prevent tissues from descending, which makes tear trough deformity and palabromalar groove deformity more visible. PMID- 20540323 TI - [Surgery and risk management]. PMID- 20540324 TI - [Medical malpractice lawsuits]. AB - Surgeons have a greater risk of facing medical malpractice lawsuits than internists. Surgeons have therefore become increasingly aware of this possibility from the standpoint of risk management. The most frequently encountered judicial disputes in surgical malpractice claims include: 1) surgical indications; 2) surgical procedures; 3) postsurgical management; and 4) presurgical explanations. In the fourth issue, possible discrepancies between the cognizance of the surgeon and the judge should be carefully noted, in which case the decisions of the Supreme Court should be used as a reference. Regardless of judicial disputes, thorough explanations in the aftermath of intra- or postoperative events are always warranted. A medical malpractice trial is a protracted process. The physician defendant will likely shoulder much of the psychological burden during a trial, although he or she is not engaged in a dispute solely for personal reasons. A physician involved in a malpractice lawsuit should not be left to traverse the path alone. PMID- 20540325 TI - [Risk management and postoperative infection control]. AB - Review of nine cases of judicial precedent on the issue of the postoperative infection in Japan indicates the following issues: indication of surgery; violation of informed consent; preventive measures against nosocomial infection during the preoperative period; cleanliness control during surgery; and treatment of postoperative infection. The most important yardstick for judgment is whether the provided treatment is conformed to the level of standard medical treatment available at the time. Therefore, we should be well versed in the standard postoperative infection treatment, particularly infection surveillance data and CDC standard precautions and related guidelines. Moreover, in each hospital, an infection control team should play an important role in infection control and prevention through preparing manuals and clinical paths incorporating precautions to ensure that the whole staff comply with the prescribed procedures. PMID- 20540326 TI - [Perioperative nutritional support from the viewpoint of risk management]. AB - The nutritional condition of perioperative patients affects the results of surgical treatment. For a better prognosis, surgeons must always consider patients' nutritional status preoperatively. After first assessing the nutritional status, a regimen to improve and/or maintain proper nutrition should be selected taking symptoms and treatment procedure into consideration. Peripheral parenteral nutrition provides limited energy. If patients' nutritional status requires improvement and they must fast for a long-term, total parenteral nutrition should be administered. Parenteral nutrition is nonphysiologic therapy and may have severe complications. During the administration of enteral nutrition via a gastrointestinal fistula or nasogastric tube, vomiting and incorrect infusion due to the improper positioning of the feeding tube may occur. When administering nutrition therapy via a gastrostomy or intestinal fistula, care must be taken to determine the appropriate dose and infusion rate. To provide suitable nutritional therapy, our knowledge of the various options available must be expanded. PMID- 20540327 TI - [Risk management for endoscopic surgery]. AB - The number of medical accidents in endoscopic surgery has recently increased. Surgical complications caused by inadequate preparation or immature technique or those resulting in serious adverse outcomes may be referred to as medical accidents. The Nationwide Survey of Endoscopic Surgery showed that bile duct injury and uncontrollable bleeding were seen in 0.68% and in 0.58%, respectively, of cholecystectomy patients; interoperative and postoperative complications in 0.84% and in 3.8%, respectively, of gastric cancer surgery patients; and operative complications in 6.74% of bowel surgery patients. Some required open repair, and 49 patients died. The characteristic causes of complications in endoscopic surgery are a misunderstanding of anatomy, handling of organs outside the visual field, burn by electrocautery, and injuries caused by forceps. Bleeding that requires a laparotomy for hemostasis is also a complication. Furthermore, since the surgery is usually videorecorded, immature techniques resulting in complications are easily discovered. To decrease the frequency of accidents, education through textbooks and seminars, training using training boxes, simulators, or animals, proper selection of the surgeon depending on the difficulty of the procedure, a low threshold for conversion to laparotomy, and use of the best optical equipment and surgical instruments are important. To avoid malpractice lawsuits, informed consent obtained before surgery and proper communication after accidents are necessary. PMID- 20540328 TI - [Risk management and medical safety under surgery; plumonary thromboembolism]. AB - It was reported that pulmonary embolism rarely occurs in Japan, and physicians did not think about the prevention of venous thromboembolism until about 20 years ago. Recently, however, it has been reported that pulmonary embolisms are on the increase in Japan. The Japanese prophylactic practice guidelines were published in February 2004, and subsequently the prevention of pulmonary embolisms and deep vein thrombosis has gradually become widespread, generally using mechanical prevention. However, the most effective measure to prevent venous thromboembolism is early ambulation and active exercise, while the administration of an anticoagulant is the most effective to prevent fatal and symptomatic pulmonary embolism. However, anticoagulant therapy is associated with complications such as hemorrhage and heparin-induced thrombocytopenia. Therefore, it is important for individual medical institutions to develop in-house manuals on the prevention of venous thrombosis and the bases for the selection of mechanical prevention, anticoagulant therapy, or ambulation/exercise. The number of patients with venous thromboembolism (secondary prevention) requiring treatment before undergoing surgery has also increased recently. It is important for hospitals to cooperate to solve problems, such as by undertaking medical safe national joint action, in a specific clinical area instead of simply undertaking risk management in the prophylaxis of thrombosis in single institutions. PMID- 20540329 TI - [Informed consent]. AB - Most Japanese embrace the concept of informed consent, which became common knowledge in the 1990s but has not been signed into law. Lawsuits filed by patients and their families leading to prosecution, even if no medical malpractice occurred, have increased after poor medical outcomes. To obtain adequate informed consent, the following must be explained: 1) the name and status of disease or condition; 2) why a treatment regimen is proposed and what it involves; 3) risks associated with the treatment; 4) other treatment options and its associated benefits and risks; and 5) the probable outcome after undergoing or refusing the proposed treatment. Additionally, the written informed consent document should include the explanations of points 1)- 5). To gain the trust of patients when seeking their informed consent, it is extremely important to improve communication skills and acknowledge their emotions. PMID- 20540330 TI - [Surgery for the gender identity disorder]. PMID- 20540331 TI - [Surgical treatment for gender identity disorder 1. Sex reassignment surgery for male to female]. PMID- 20540332 TI - [What we can learn from a case of medical malpractice--a case report of fatal pulmonary thromboembolism following physical restraint]. PMID- 20540333 TI - [Suprarenal aortic aneurysmectomy]. PMID- 20540334 TI - [Launch of the Japan Association of Women Surgeons]. PMID- 20540335 TI - [Surgeons who are wanted as leaders]. PMID- 20540336 TI - [Proposal on reviewing the overall healthcare expenditure and its allocation: focusing on medication expenses]. PMID- 20540337 TI - [Historic background of nurse practitioners in acute care setting]. PMID- 20540338 TI - [The number of cardiovascular surgeons is decreasing in Nagano]. AB - Shortage of medical doctors has been conspicuous since the residency program has been changed in 2004. We investigated the changes in the number of cardiovascular surgeons, surgical cases and institutes of Nagano from 1996 to 2008. The number of cardiovascular surgeons decreased from 28 to 19. The number of newly joined cardiovascular surgeons were 2.7 +/- 1.4/year from 1996 to 2001 and 1.1 +/- 0.4/year from 2002 to 2008. The number of retirement were 0.7 +/- 0.8/year and 2.3 +/- 1.0/year from 1996 to 2001 and from 2002 to 2008, respectively. The number of surgery cases increased from 340 in 1996 to 771 in 2008. Kaplan-Mayer analysis showed the 50% of cardiovascular surgeons retired in 19 years of their career, and the only 20% of surgeons survived after 29 years. The number of newly joined general surgeons was the only 3 since 2004. We are consolidating the institutes of cardiovascular surgery in Nagano to perform more surgery by fewer surgeons. It is important that working condition of cardiovascular surgeon adapt to young doctor's favor, and new positions should be created for elder cardiovascular surgeons to prevent early retirement. PMID- 20540339 TI - [Proteasomes: their role in cellular processes]. AB - The presented review concerns the structure functional analysis of proteasomes and the participation of ubiquitin proteasome system in the basic cellular processes. 26S proteasomes is a key enzyme of the ubiquitin-dependent pathway of protein degradation in cells. This protein particle is composed of 20S catalytic core and associated regulatory complexes. In addition to several types of peptidase activities, eukaryotic proteasomes also have endoribonuclease, protein chaperone and DNA-helicase activities. The ubiquitin proteasome system controls the levels of most regulatory proteins in a cell and, thus, is absolutely necessary element for cell life. Proteasomal population in a cell is structurally and functionally heterogeneous. These particles are subjected to multistep regulation, particularly, by set of posttranslation modifications. In this review, we also consider the current knowledge on the involvement of proteasomes in controlling the cell cycle, transcription, apoptosis, differentiation, DNA repair and immune response. PMID- 20540340 TI - [Neurogenic differentiation of mesenchymal stem cells: a transgenic approach]. AB - Mesenchymal stem cells (MSC), alongside with "traditional" osteogenic, chondrogenic and adipogenic differentiation potentials, are considered by many researches as capable of giving rise to neurogenic lineage as well. We overview transgenic approaches to the study of neurogenic differentiation of MSC, including expression of neurotrophic factors, signalling molecules and other transgenes with neurogenic properties. PMID- 20540341 TI - [Genotoxic and cytotoxic effects in buccal cells of children living in ecologically different Kuzbass areas]. AB - The article presents the results of the study of micronuclei and other types of cytogenetic aberrations in mucous tunic epithelium cells from children living in two different parts of the Kemerovo region (Tashtagol city, above-standard radon concentration exposition, n = 80), and Krasnoye settlement Leninsk-Kuznetsk area (comparison group, n = 41). The samples studied did not differ in the frequency of micronuclei containing cells. Tashtagol children sample showed significant increase in the number of binuclear cells, buccal epithelial cells with nuclear protrusions and with nuclear vacuoles, pyknotic cells, and apoptosis bodies. Reliable increase in average number of cells with chromatin condensation and kayolysis was found in the comparison group. It has been shown that the frequency of metaphase chromosome aberrations registered in peripheral blood lymphocytes corresponds to the amount of nuclear aberrations detected in buccal epithelium cells using micronuclei test. PMID- 20540342 TI - [Beneficial action of the liposomal form of dihydroquercetin on the process of skin regeneration after thermal burn]. AB - It was found that the flavonoid of plant origin, dihydroquercetin, being localized in lecitin nanoparticles in the presence of amino acid, reduced inflammatory reactions in the wound zone after thermal burn. Application of the liposomal complex on burn trauma stabilized the endogenous antioxidant system and minimized the area of the secondary necrosis in burn wound. Also, intensification of skin regeneration and repair of hair follicles and sebaceous glands were observed. PMID- 20540343 TI - [Cells of coelomic liquid and cells of different tissues of sea star Asterias rubens L. isolated from intact and post-traumatic animals: behaviour and proliferation under cultivation in vitro]. AB - Proposed sources of coelomocytes in Asteroidea after traumatic injures are coelomic epithelium, axial organ or Tidemann's bodies. To study the involvement of cell division in the process, proliferation of cells from different tissues of starfish Asterias rubens L. has been studied after bromdeoxyuridine incorporation in vivo. To study the differentiation of coelomocytes in vitro a method for isolation and cultivation of different tissue cells has been worked out and cell behaviour and proliferation in culture has been analyzed. The reliable BrdU incorporation has been found in coelomic epithelium cells in vivo. Coelomocytes and coelomic epithelium cells behaviour in culture dependent on the post-trauma period after which the cells were loaded into the culture whereas no difference was revealed for axial organ and Tidemann's bodies cells. Two-month cultivation of coelomic epithelium cells resulted in formation of colony-like accumulations of the cells with high nuclear-cytoplasm ratio which of colony-like accumulation of the cells with high nuclear-cytoplasm ratio which incorporated BrdU. Thus, coelomic epithelium cells seem to be more promising object for the study of A. rubens cell differentiation in vitro. PMID- 20540344 TI - [Influence of primary adhesive interactions with fibronectin on clonal growth and osteogenic potential of rat mesenchymal stromal cells]. AB - Interactions with extracellular matrix including fibronectin (Fn) play an important role in regulation of cell growth and differentiation. Influence of Fn and its individual domains on adhesion and osteogenic potencies of rat mesenchymal stromal cells (MSCs) was estimated. Investigation of bone marrow or fetal liver MSCs adhesion dynamics showed that after 7 days of cultivation on Fn the number of adhered clonogenic cells derived from both sources was comparable to their number observed on plastic but their content in suspension was commonly decreased. Population of fetal liver MSCs differed from bone marrow-derived population by greater fraction of cells that adhered for the first 7 days. Bone marrow MSC cultures on Fn were characterized by reduced activity of alkaline phosphatase as compared with cultivation on plastic; furthermore, they deposed significantly smaller amount of calcium salts under cultivation in osteogenic medium. Cultivation of MSCs on Fn fragments demonstrated the primary role of its cell-binding domain in the inhibition of osteogenesis. PMID- 20540345 TI - [Effects of anion channel blockers NPPB and DIDS on tobacco pollen tube growth and its mitochondria state]. AB - Influence of anion channel blockers NPPB and DIDS on pollen tube growth and its mitochondria functioning was studied by means of fluorescence microscopy and flow cytometry. NPPB (40 microM) blocked pollen tube growth completely, but did not change its diameter. DIDS (20-80 microM) caused pollen tube swelling and bursting, suggesting that DIDS-sensitive channels take part in the regulation of pollen tube osmotic balance. The osmotic effect of low DIDS concentration (20 (Mkappa)M) was not accompanied by changes in the tube growth rate. The mapping of membrane potential on the pollen tube plasmalemma using Di-4-ANEPPS revealed the involvement of NPPB-sensitive but not DIDS-sensitive anion channels in the maintenance of the longitudinal membrane potential gradient along the tube surface. The study of isolated pollen mitochondria showed that DIDS increased their capacity to take up potential-dependent dye DiOC5(3), i. e. caused hyperpolarization of mitochondrial membranes. At the same time DIDS influenced on intramitochondrial ROS content and excretion of ROS from mitochondria. Thus, NPPB and DIDS differently influenced on transmembrane potential distribution along pollen tube plasmalemma, on its osmotic balance, and on mitochondria functioning. This set of data suggests that pollen tube growth is dependent on activity of anion channels that differ in localization and functions. PMID- 20540346 TI - [The involvement of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione and glutoxim on Na+ transport in frog skin]. AB - Using voltage-clamp technique, the role of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione (GSSG) and its pharmacological analogue, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincubation of the skin with tyrosine kinase inhibitor genistein or with two structurally distinct phosphatidylinositol kinase inhibitors, wortmannin and LY294002, significantly decreased the stimulatory effect of GSSG or glutoxim on Na+ transport. The data suggest that GSSG and glutoxim might transactivate insulin receptor in the basolateral membrane of epithelial cells and trigger the signaling cascade, involving tyrosine kinases and phosphatidylinositol kinases, which lead to Na+ transport stimulation in frog skin. PMID- 20540347 TI - [An intergral method for quantitative cell DNA content measurements by digital microphotography]. AB - Quantitative nuclei DNA content measurement based on Feulgen reaction and the analysis of CCD images was tested. The measurements were performed in monochorome CCD option (650 X 514 pixels) with the wavelength 551 nm. The linear dependence of photomatrix elements signals on the falling light was shown with the use of multigraded light absorption filter. The optimal microscope and camera setting and an approach for elimination of the optic blur were found. We have shown that the proper Feulgen fluorescence does not affect our measurements. Densitometric DNA content measurements of blood cells of four vertebrate species (Gallus domesticus, Danio rerio, Homo sapiens and Rana arvalis) showed good consistence to the literature data (http://www.genomesize.com). The precision of our approach is comparable to the other known methods. Current improvement of CCD technical parameters and wide usage of CCD cameras in biological applications gives perspectives for the suggested approach. PMID- 20540348 TI - [Diagnostic and pathogenetic implications of the site specificity of antibody proteases in multiple sclerosis]. AB - Disseminated sclerosis is currently regarded as a CNS autoimmune disease. One of the mechanisms behind this pathology is antibody (AB) formation. In this context, recent data on AB with proteolytic activity are of importance because they participate in selective proteolysis of myelin proteins in patients with disseminated sclerosis. This paper focuses on AB-proteases associated with disseminated sclerosis and site-specificity of antibody-mediated proteolysis of myelin basic protein. Protocol of serodiagnostic algorithm to be used in clinical practice is described. PMID- 20540349 TI - [Genetic aspects of atopic diseases in children]. AB - Atopic diseases is a group of pathologic conditions with polygenic inheritance the development of which is governed by familial predetermination to allergy. This review summarizes results of research on pathogenetic mechanisms of atopic diseases and their clinical features. Analysis includes the structure of hereditary predetermination to allergic reactions and diseases, risk of their development in subsequent generations, the role of age, sex, and ethnic background in pathogenesis of atopic diseases and formation of allergic constitution governed by genotype and environment. Polymorphisms of candidate genes responsible for atopic diseases are considered along with their response to basal pharmacotherapy. PMID- 20540350 TI - [The role of prostaglandins in platelet aggregation in metabolic syndrome]. AB - The role of metabolic products of arachidonic acid and thromboxans in metabolic syndrome was evaluated in 42 patients and 16 healthy subjects. The levels of arachidonic acid and thromboxane were shown to be elevated in patients with metabolic syndrome which accounted for enhanced platelet aggregation in response to ADP, adrenaline, and collagen. It is concluded that that decreased level of cyclic nucleotides (cAMP) and prostacyclin in combination with a rise in the content of Willebrand factor in patients with metabolic syndrome is a major contributor to the development of platelet activity. PMID- 20540351 TI - [Techniques for detection and role of extracellular neutrophil traps in antimicrobial protection]. AB - New methods are proposed for the measurement of the number of extracellular neutrophil traps in peripheral blood and mucosal secretion. Effect of microbial factors on the ability ofgranulocytes to release nuclear DNA into extracellular space and form extracellular traps is evaluated. Normal microflora species are shown to more actively stimulate build-up of extracellular network. Formation of extracellular neutrophil traps may be a major efficacious mechanism for mucosal antimicrobial protection. PMID- 20540352 TI - [Modeling osteoporosis]. AB - The authors propose a method for simulation of systemic osteoporosis by means of bilateral ovariectomy and administration of proton pump inhibitors. The model is applicable to the development of new technologies for the treatment of osteoporosis. PMID- 20540353 TI - [Non-metastatic clear cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics]. AB - Non-metastatic clear-cell renal cancer: dependence of the tumour stage on clinico anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics Sankt Peterburg Pathology Bureau, Sankt Peterburg It was shown based on multivariate regression analysis that pT1a3bN0MO stages of non metastatic clear-cell renal cancer significantly correlate not only with the tumor size and invasion into the fatty tissue and/or renal vein but also with the invasion into the renal capsule and with the mean maximum diameter and mean nucleus area of tumor cells. There was no correlation of clear-cell renal cancer stages with tumor proliferative activity, gene p53 mutation, oncosuppressor gene PTEN expression, fraction of tumour clear-cell component, and such clinical characteristics as patients' sex, age, and body mass index. Taking into account statistically significant differences between the patients' survival rates, the regression equations developed in this work may be used for the prediction of disease outcome. PMID- 20540354 TI - [Use of terahertz electromagnetic radiation at nitric oxide frequencies for the correction of thyroid functional state during stress]. AB - The influence of terahertz electromagnetic radiation at nitric oxide frequencies (150.176-150.664 Ghz) on the functional activity of rat thyroid gland subjected to acute immobilization stress has been studied. It is shown that terahertz radiation totally normalizes thyroid activity in stressed animals within 30 min after application. PMID- 20540355 TI - [Effects of afobasol in the reperfusion arrhythmia model]. AB - Afobasol caused insignificant dose-related decrease of main parameters of cardiac activity in narcotized animals and was similar to pulse-decelerating calcium antagonists in terms of hemodynamic effects. Reperfusion after acute regional myocardial ischemia induced malignant cardiac rhythm disorders and progressive impairment of cardiac pump function. These changes combined with increased peripheral resistance created conditions for the development of cardiac insufficiency. Afobasol administered 5 min before the onset of reperfusion significantly reduced the frequency and intensity of cardiac rhythm disturbances and thereby prevented cardiac insufficiency. It is conjectured that cardioprotectice action of afobasol in these conditions was due to its ability to activate sigma-1 receptors in cardiomyocytes and thereby protected heart cells from excessive accumulation of Ca2+ ions. PMID- 20540356 TI - [Afobasol antifibrillation activity in animals with the intact and denervated myocardium]. AB - The influence of afobasol on threshold electrical fibrillation of the heart was studied in experiments on narcotized cats. It significantly elevated the cardiac fibrillation threshold in animals with intact myocardium and resembled class 1B anti-arrhythmic drug lidocaine in terms of this activity. Similar results were obtained using cats with denervated myocardium. These observations indicate that in the model of electrical fibrillation of the heart afobasol has marked antifibrillation action mediated through cardiomyocytes. This inference was confirmed by the studies of afobasol effects on cardiac rhythm variability in rats with acute myocardial ischemia. It is supposed that afobasol prevents cardiac fibrillation acting as an agonist of cytosolic sigma-1 receptors in cardiomyocytes PMID- 20540357 TI - [Afobasol efficacy in a model of vagotonic atrial fibrillation]. AB - The new anxiolytic agent afobasol (Russia) was introduced into clinical practice by V. V. Zakusov Research Institute of Pharmacology. When administered to cats with vagotonic atrial fibrillation afobasol (7.5 mg/kg v/v) exhibited anti arrhythmic activity at least as high as that of class 1 and III anti-arrhythmic agents (etacisin and cardiocyclide respectively) (Vaughan Williams classification). However, duration of its action was much smaller. These experimental findings were confirmed in clinical studies involving patients with severe psychosomatic pathology associated with paroxysmal flutter. It is supposed that afobasol activates cytosolic sigma-1 receptors in cardiomyocytes and may be used to manage psychoasthenic conditions accompanied by cardioneuroses and/or cardiophobias with disturbed rhythmic activity of the heart. PMID- 20540358 TI - [Molecular characteristic of methicillin-resistant Staphylococcus aureus strains isolated in Moscow clinics]. AB - OBJECTIVES; Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen of nosocomial infection. The goal of this work was to evaluate the clonality of hospital-acquired MRSA (HA-MRSA) circulating in Russian Federation and to compare different multiplex PCR techniques with SNP-based approach for MRSA typing. METHODS: Epidemiologically unrelated MRSA isolates (n = 62) from Moscow hospitals were selected for typing. Genomic DNA from clinical isolates was purified using the DNA express kit (Lytech Ltd, Russia). Staphylococcus chromosomal cassette mec (SCCmec) typing was performed by PCR using the previously described methods. Seven loci from five housekeeping genes (arcC162, arcC210, aroE132, gmk123, tpi241, tpi243 and yqiL333) were used for SNP-typing. Detection of particular nucleotides in selected loci was carried out in the thermocyclic primer extension reaction, followed by mass spectrometry of the products. Standard MLST procedure was performed as reference method. RESULTS: The majority of the MRSA isolates (93.6%) belong to world-wide disseminated clonal complex (CC) 8. Three isolates (4.8%) belong to CC 1. All ST 239 isolates were found to carry SCCmec type III; ST 8 isolates, SCCmec type IV. CONCLUSION: Among Russian MRSA CC 8 isolates carrying SCCmec IV type are predominant. SNP-typing is powerful toll for studies of molecular epidemiology of MRSA. PMID- 20540359 TI - [Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators]. AB - Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation. PMID- 20540360 TI - [A study of the single nucleotide polymorphism in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer]. AB - Using the RT-PCR method for allele discrimination, we examined nine known SNPs in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer (PC). For Russian population data on genotype distribution in studied SNPs was obtained. It was revealed that six of nine analyzed sites in examined locus were polymorphic. Distributions of alleles and genotypes frequency of polymorphic site 1388 T/C (Leu463Pro) in gene FMN1 (rs2306277) were distinguished between patients and control groups (delta = 0.019; chi2 = 7.884). In particular, correlation of OO genotype with increased risk of PC was observed (OR = 2.1591 95% CI 1.2055-3.8726). Moreover, the analysis of the polymorphic site 2911G/A (Glu917Arg) in gene IRS1 (rs1801278) revealed the accumulation of allele A in cancer group in comparison with control group (chi2 = 4.038; p = 0.044). Thus, the obtained data indicate the possibility of participation of polymorphism in genes FMN1 and IRS1 in formation of predisposition to PC. PMID- 20540361 TI - [Assessment of a patient with optic neuropathy]. AB - Optic neuropathy (ON) is defined as the reduction of vision due to inflammatory lesion of the optic nerve. The patient with ON has to be evaluated clinically but also with complex techniques (magnetic resonance imaging, visual evoked potentials, cerebrospinal fluid examination) because ON could be the presenting symptom in multiple sclerosis patients. Corticosteroids should be administrated intravenous and the patient should be followed by the neurologist in order to signal the appearance of new neurological signs. PMID- 20540362 TI - [Acoustic microcavitation]. PMID- 20540363 TI - [Electroretinography in monitoring glaucoma patients]. AB - Ocular electrophysiology investigations come back in actuality with new elements; current functional tests involve bias (VF) and require the use of investigations with a high degree of objectivism: full field ERG, pattern ERG, for early detection and monitoring of certain ophthalmic diseases. PMID- 20540364 TI - [Torsional infinity--ideal for cataract surgery in coaxial system]. PMID- 20540365 TI - [Epstein Barr and cytomegaloviruses in ocular pathology]. AB - Epstein-Barr virus (EBV) and Citomegalovirus (CMV) are Herpesviridae family representative and presents a real danger for human. A very high infect risk of population farther the danger The ocular pathology induced by them can affect all media and tunics of optic analyzer. An etiologic differentiation is necessary for the mentioned viruses induced diseases. The etiologic differentiation has like purpose the enforcement of an effective and optimal antiviral and immunomodulating therapy. PMID- 20540366 TI - [HLA B 27 uveitis in ankylosing spondylitis and reactive arthritis]. AB - Clinical features of uveitis HLA B27 in patients with uveitis associated with ankylosing spondylitis and reactive arthritis. The study was made on 64 patients with uveitis treated in the municipal hospital between 2005-2008. The diagnosis was established after a complex ophthalmologic investigation. Histocompatibility HLA-B27 was determined in all groups of patients. Each patient was consulted by the rheumatologist. In the study were included 50 (78%) men and 14 (22%) women. The frequency of HLA B27+ was 72%. At HLA B27+ associated with ankylosing spondylitis and reactive arthritis is present in the anterior form in 85%, unilateral affection in 92%. Their evolution is chronic in 17% and has a tendency for recidivism in 11% of patients. HLA B27 is a genetic factor of uveitis associated with spondylarthropathies in 72%. The study determined the disease in 78% of men, 72% were acute, 85% were anterior and 92% were unilateral. The study of HLA B27 in patients with uveitis is one of the shortest ways for the earlier diagnosis of ankylosing spondylitis. PMID- 20540367 TI - [Postoperative endophthalmitis after non-pentrating deep sclerectomy]. AB - This is a case report concerning a patient that was subject to non-penetrating deep sclerectomy (with intraoperative Mytomicin C) for the management of advanced open angle glaucoma in the only functional eye. The surgery was uneventful, the visual acuity was preserved and the intraocular pressure was reduced. After 2 months the patient presented with symptoms of postoperative bleb-related endophthalmitis. The treatment of this condition (including pars plana vitrectomy) did not succeed in preventing a severe retinal necrosis that resulted in the loss of visual acuity This is, to our knowledge, the first published case of endophthalmitis after non-penetrating deep sclerectomy. PMID- 20540368 TI - [Multiple optic disc--myth or reality]. AB - OBJECTIVE: To study the clinical aspects of multiple optic papilla. CLINICAL OBSERVATION: We present 2 cases with multiple optic papilla. First case, with an aspect of duplicated double papilla, where at the supranumerary papilla we noticed a cilioretinal artery. The second case, with pseudo-double papilla, in context of a medium myopia, with visualization of the choroidal circulation. DISCUSSIONS AND CONCLUSIONS: The diagnosis of multiple optic papilla is difficult. Its support requires the presence of multiple conditions: double papillary margins, central vascularization with separate emergence, synchronous vascular pulsation, imagistic and morphopathologic arguments. So far no clinical case with those required conditions was ever published. PMID- 20540370 TI - [Complicated recurrent herpetic keratitis in an young patient]. AB - Herpetic keratitis is an increasingly frequent pathology, especially among the adult population. Untreated, it can lead to ocular complications difficult to treat and even to visual disabilities. Also, recurrent episodes should be diagnosed and treated appropriately in order not to leave room for the complicated forms, which often lead to a slow and incomplete visual recovery. PMID- 20540369 TI - [Giant cell arteritis with eye involvment--color Doppler imaging or retrobulabar vessels findings]. AB - BACKGROUND: Giant cell arteritis (temporal arteritis) is a primary vasculitis, that affects large arteries, especially branches of the external carotid artery (ECA). PURPOSE: To assess the role of CDI of retrobulbar vessels in the study of two patients with giant cell arteritis with eye involvement. METHODS: We have used a sonographer with 8-15 MHz linear probe. RESULTS: Both patients presented malaise, temporal headache, tender temporal arteries and signs of inflammation. The first patient had a central retinal artery obstruction of the right eye, and the second had anterior ischaemic optic neuropathy of the left eye. Temporal artery histology was positive in both cases. Ultrasound investigation was performed within the first 10 days of corticosteroid treatment. CDI of retrobulbar vessels detected low blood velocities, especially end-diastolic velocities and high resistance index in all retrobulbar vessels, in both orbits. Typical sonographic features in temporal arteritis were "halo", associated with stenoses or occlusions of branches of ECA. CONCLUSIONS: Ultrasound investigation is a valuable diagnostic tool to investigate giant cell arteritis. PMID- 20540371 TI - [Atrophy of retinal pigment epithelium after macular hole surgery]. AB - We present three cases of macular hole. After macular surgery we observed good anatomical results (closed macular holes) but poor functional results. We try to identified the element who produced atrophy of retinal pigment epithelium. PMID- 20540372 TI - [Ocular siderosis]. AB - We show a clinical case of siderosis bulbi with absolute secondary glaucoma. The initial diagnosis was primary open angle glaucoma in both eyes, and the patient was treated with eye drops for 4 years. After reassessment of anamnesis, clinical and paraclinical investigations we find that one eye is normal and the real diagnosis in the involved eye. PMID- 20540373 TI - [Modern therapy in blepharospasm]. AB - PURPOSE: Pharmaceutical presentation of botulin A toxin (BAT) and its therapeutical use in ophthalmology in essential blepharospasm, as well. This work analyses the results and the disadvantages of the cure. MATERIAL & METHODS: During the last 3 years 21 patients suffering of essential blepharospasm have been cured. The cure with botulin A toxin administrated in efficient doses is followed by a 3-4 months period of pause. RESULTS: At all the patients cured with Dysport, the symptoms have improved or weakened. The cure should be done at least twice a year (from 6 to 6 months) due to the "sprouting" axonal phenomenon. CONCLUSIONS: The treatment of essential blepharospasm with botulin A toxin is a reliable and efficient method, with results relatively quickly installed. In treating this disease, it should be chosen from the very beginning. PMID- 20540374 TI - [Non-pentrating deep sclerectomy--between safety and efficacy]. AB - PURPOSE: To find the indications that would benefit the most from non penetrating deep sclerectomy (NPDS) major advantages. METHOD: Retrospective study that included 40 eyes with open angle glaucoma (primary or pseudoexfoliative) which were subject to NPDS as ambulatory surgery without an implant, but with intraoperative application of mitomycin C. We have determined the LOP C/D ratio, visual acuity and the number of antiglaucoma drugs preoperatively and at 3 months postoperatively. We have analyzed the intraoperative and postoperative complications of NPDS and also the profile of the patients selected for this surgery. RESULTS: Global success (LOP < 21 mmHg + C/D ratio that remained unchanged postoperatively + visual acuity that remained unchanged postoperatively) was obtained in 90% of cases; the number of antiglaucoma drugs was significantly decreased (from 2.72 +/- 0.73 preoperatively to 0.26 +/- 0.21 postoperatively, p < 0.00002). Complete success (LOP < 21 mmHg without antiglaucoma medication) was achieved in 80% of cases. The rate of qualified success (LOP < 21 mmHg with antiglaucoma medication) was 95%; 50% of eyes have LOP < 15 mmHg at 3 months. Intraoperative complications were rare (4 cases) and minor. Postoperative complications were: ocular hypotony (1 case), bleb fibrosis (2 cases), bleb-related endophthalmitis (1 case). The best candidates for NPDS were patients over 70 years with important extraocular comorbidities, advanced open angle glaucoma with preserved visual acuity or monophthalmic patients. CONCLUSIONS: NPDS with intraoperative application of Mitomycin C as ambulatory surgery provides significant LOP reduction while preserving visual acuity and has a low rate of complications in elderly patients with advanced open angle glaucoma or monophthalmic patients. PMID- 20540375 TI - [Stellaris platform--personal experience after the first 100 cases]. PMID- 20540376 TI - Modified endoscopic DCR without stenting and laser assisted. AB - To evaluate the outcomes of endoscopic LASER assisted dacryocystorhinostomy without stenting, a total of 39 patients (41 eyes) with complains of epiphora and diagnosed with nasolacrimal duct obstruction were included in a prospective study. All the patients had the same preoperative assessment, including radiological and ophthalmologic evaluation, with repeated lacrimal washouts, to confirm the postsacal obstruction. The surgical technique's goal was to create a wide opening of the medial wall of the sac, using drilling of the frontal process of the maxillary bone and some of the lacrimal bone, incision of the lacrimal sac and the radial vaporisation of the incision margins performed with Diode LASER, in order to create a 0.7 - 1 cm opening in the medial wall of the sac. Patients were examined endoscopically, at postoperative intervals of 1 month, 3 month, 6 and 9 month minimum (follow-up period ranged between 9 to 21 months, average 11, 8 months). We obtained a good permeability of the opening of the lacrimal sac in 87.8% of our cases (36 eyes). 5 patients (12.2%) required re-evaluation of the medial sac wall area and re-intervention using different methods. The success criteria were considered the patient's relief of symptoms and the endoscopic visualization of a patent stoma. In conclusions, in the hands of an experienced surgeon, endoscopic LASER assisted dacryocystorhinostomy without stenting compares favourably with other techniques. PMID- 20540377 TI - [Avastin in age related macular degeneration]. AB - OBJECTIVE: The purpose of the study is to evaluate the preliminary results of the treatment with Bevacizumab (Avastin) in the neovascular (wet) form of Age-Related Macular Degeneration (AMD). MATERIAL METHOD: The study is retrospective and includes 20 consecutive patients (27 eyes) who had received Avastin intravitreally, hospitalized in the Ophthalmology Clinic from Cluj-Napoca, between September 2007-March 2009, for wet AMD. Every patient had received 3 Avastin injections, approximately one month apart. Each dosis consisted of 0.05 ml (1.25 mg) Avastin. The therapeutical effect has been evaluated by: the value of the visual acuity (VA), the foveolar thickness (FT) and the total macular volume (TMV), before and after the treatment. In order to measure the VA, the classical optotipe has been used and the FT and the TMV have been evaluated by Time Domain (TD)-OCT. The follow-up period has varied between 4-10 months. The statistical interpretation of the results has been performed by the use of the Student t test, a p value < 0.05 being considered statistically sirgnificant. RESULTS: Of the 27 treated eyes, 8 (30%) had a favorable evolution of the VA, 15 (55%)--a stationary one and 4 eyes (15%) had an unfavorable outcome. The FT decreased (favorable evolution) in 18 eyes (66.66%) and increased (unfavorable evolution) in 9 eyes (33.33%). The TMV had a favorable evolution (decrease) in 21 eyes (77.77%) and an unfavorable one (increase), in 6 eyes (22.22%). CONCLUSIONS: The quantitative evolution of the VA has been predominantly stationary (55% of the eyes). Most patients described an improvement in the quality of vision, even if the VA has remained unchanged. The evolution of the FT and of the TMV has been predominantly favorable: 66.66%, 77.77% respectively. We noted the direct correlation between the evolution of the VA and of the morphological parameters evaluated by OCT, only in 33.33% of the treated eyes. PMID- 20540378 TI - [Triamcinolone acetonide bevacizumab performance in treatment and idiopathic macular spider veins]. AB - This article evaluated the efficacy of intravitrean injection of anti VEGF agents and triamcinolon in the treatment of macular telangiectasis. The patients were followed six months. We practiced fluorescein angiography, optical coherence tomography. We measured the thickening of macular edema and best corrected of visual acuity. PMID- 20540379 TI - [Retinopathy of prematurity--screening results]. AB - OBJECTIVE: Analysis of the results of screening for retinopathy of prematurity (ROP) in a sample of prematurely born babies evaluated in the Institute for Mother and Child Care, between September 2002 - 31st December 2007. MATERIALS AND METHOD: A data base of premies screened for retinopathy of prematurity in our clinic and also those referred sporadically from different neonatal units from other towns (1783 babies) was set up, and this was used to analyze aspects referring to the ROP incidence, as well as outcomes of laser treatment. RESULTS: A total of 1783 preterm babies were examined, overall incidence of ROP was 55%. Gestational age (GA) and birth weight (BW) are important factors associated with an increased risk of ROP). Of the 981 premies with various stages of ROF 124 (12.6%) had GA 32 - 34 weeks and 264/981 (26,1%) had BW 1500 - 2000g. 272/1783 (15.2%) had severe ROP which required laser photocoagulation. Favourable outcomes of laser photocoagulation was obtained in 86.7% of the total sample, with significant differences between those with zone II ROP vs those with zone I ROP (93.3% vs 76.9%, p = 0.002). CONCLUSIONS: ROP incidence in Romania is, for the time being, much higher than that reported in the developed countries. We believe that, at present, in our country the ROP inclusion screening criteria should be extended to GA < or = 34 weeks and/or BW < or = 2000g. Short term results of laser photocoagulation are similar to those reported in developed countries. In order to achieve a significant reduction in childhood blindness determined by ROP the current screening and treatment programme needs to be extended to the entire country. PMID- 20540380 TI - [Chondrocutaneous graft in the reconstruction of the inferior palpebra]. AB - PURPOSE: The aim of this study is to evaluate the value of a composite chondrocutaneous auricular graft in the functional reconstruction of the eyelids, and to assess and compare the morphostructural changes between an autologus auricular flap consisting of both cartilage and skin and an autologous cartilage graft, used for eyelid reconstruction in rabbits. MATERIAL AND METHODS: The clinical study follows a series of 12 clinical cases, in which the composite cutaneo-cartilaginous graft was used for the reconstruction of the posterior lamellae of the lower eyelid. The posterior lamellae of lower eyelids from 12 rabbits were reconstructed by using in the left eyelid, the composite cutaneo cartilaginous graft, whereas the right eyelids were reconstructed using only cartilage grafts. The grafts were histologically analyzed in the second, fourth and sixth week. RESULTS: Clinically the graft were well integrated in all patients. The data obtained from the histological analysis describes different manners of conjunctival epithelization in the two types of graft: migration of the peripheral conjunctiva onto the graft surface in the cartilage graft versus metaplasia from pavimentous epithelium to conjunctival epithelium in the composite graft. CONCLUSIONS: The study demonstrates clinically and experimentally the importance of the cutaneocartilaginous graft in reconstruction of the posterior eyelid lamellae. PMID- 20540381 TI - [What sustainable development?]. PMID- 20540382 TI - [Nurses coping with conjugal violence]. PMID- 20540383 TI - [Arduous nature of nursing work and retirement]. PMID- 20540384 TI - [A singular crisis for nursing employment]. PMID- 20540385 TI - [Diabetes and depression, from screening to intervention]. PMID- 20540386 TI - [Somatic nursing in psychiatry. A problem of management]. PMID- 20540387 TI - [Psychiatric disorders and somatic pathologies]. AB - Over recent decades significant advances have been made in the treatment of patients with serious psychiatric illnesses such as schizophrenia or mood disorders. These advances result from the use of new molecules and especially biopsychosocial treatments drawing on multidisciplinarity and networking. Supporting the somatic treatment of patients is one of the major challenges for improving psychiatric care. PMID- 20540388 TI - [The difficulties in assessing pain in mental health]. AB - Understand pain in mental health a model which integrates biological, psychological and socio-cultural factors is called for. Due to the psychiatric dimension, the perception of pain in patients, in particular for those suffering from schizophrenia, is complex. The assessment of pain is imperative. In order to take into account pain in patients suffering from psychiatric disorders, improvement in the initial training of healthcare workers is essential. PMID- 20540389 TI - [The prevalence of metabolic syndrome]. AB - Numerous studies of comorbidity have shown excess mortality and excess morbidity in people suffering from mental disorders. Monitoring of the waist circumference is an essential indicator for screening for metabolic syndrome. PMID- 20540390 TI - [Dermatological diseases in psychiatry]. AB - From Ekbom's syndrome to neurotic acne, from seborrheic dermatitis to psoriasis or rosacea, without forgetting atopic dermatitis in children, these dermatological illnesses all have a direct or indirect link with psychiatric pathology In the field of dermatological infections, treatment must be provided by both the dermatologist and psychiatrist. The skin is an interface, attacked by external factors, as well as expressing psychic conflicts. In this context, there is a real place for psychodermatology. PMID- 20540391 TI - [Pedicures and podiatry in psychiatry and social insecurity]. AB - Practicing pedicures and podiatry in a psychiatric environment is a particular speciality. This specificity arises not only from the disorders and complications encountered, but also from the connection established between the patient and the healthcare worker during treatment. PMID- 20540392 TI - [Psychic disorders and somatic suffering]. AB - To what extent should somatic treatment be taken into account when psychic suffering dominates? How can this care be anticipated when healthcare workers and carers are confronted with patients who do not express what they want? Greatest attention must be paid to somatic care by anticipating body function and relying on the support of the families and the skills of the professionals. PMID- 20540393 TI - [Access to somatic care for patients undergoing psychiatric treatment]. AB - In France, there is no across-the-board formal connection between psychiatric and somatic treatment and the somatic care of patients undergoing psychiatric treatment remains very heterogeneous and inadequate. Despite some attempts at providing structure, it is the place of the physician which must be examined and optimised. PMID- 20540394 TI - [Paranoia, schizophrenia, delusions of persecution and dangerousness]. AB - Unfounded feelings of prejudice and persecution are frequent delusional themes. They are common to people suffering from paranoia and schizophrenia. If they arm the intrafamilial psychotic homicidal acting-out, their criminogenic dimension is much wider. Many more people other than family members can be victims. PMID- 20540395 TI - [Medical-psychologic centers and crisis centers]. PMID- 20540396 TI - [Alternative training and evolution of practices]. PMID- 20540397 TI - [Diagnosis and treatment of colorectal carcinoma in inflammatory bowel disease. Report of the American Gastroenterological Association]. PMID- 20540398 TI - [Acute decompensation of heart failure in the elderly frail patient: an innovative model of care]. AB - Heart failure is a major and growing public health problem that affects close to 10 million European and 5 million North Americans. Substitutive hospital-at-home care, defined as"a service that provides active treatment by health care professionals, in the patient's home, of a condition that otherwise would require acute hospital in-patient care", may be a safe and efficacious alternative to traditional hospital care for elderly patients with an acutely decompensated heart failure. Data discussed in this paper suggest that hospital-at-home management of selected elderly patients with acute decompensation of chronic heart failure may be associated with delayed additional admissions, improvements in quality of life and alleviation of depressive symptoms without adverse effects in regard to mortality. PMID- 20540399 TI - [Omega-3 fatty acids and astaxanthin in health and disease. Recent knowledges]. AB - At present, medicine is aimed to the treatment of lesions. Instead, it would be right to develop the maintenance of normal health. A number of authorities have recently recommended increases in intake of omega-3 fatty acids and astaxanthin for the health of general population. Omega-3 are necessary to provide the optimal function of cellular membrane in health and in disease states. It is well known how at least two servings of fish a week, or dietary supplementation of fatty acids omega-3, should be taken to obtain the health benefits of this essential nutrient. Astaxanthin is a powerful biological antioxidant. This property has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. For the recent evidence of the contemporary presence of omega-3 and astaxanthin in oil of Wild Pacific Salmon Sockeye, a review has been effected for the evaluation of a possible role of such association for the health promotion. PMID- 20540400 TI - [Celiac disease and myelodysplastic syndrome. A case report]. AB - Celiac disease is an immune-mediated disorder induced by the intake of gluten proteins involving primarily the gastrointestinal tract. Myelodysplastic syndromes are clonal hematologic disorders, expanded from myeloid stem cells of uncertain pathogenesis. Anaemia is a common finding in patients with celiac disease. Frequently it is secondary to malabsorption of iron, folic acid or vitamin B12 and usually disappears completely with a strict adherence to a gluten free diet and supplement of deficient factors. To the best of our knowledge, in medical literature only two cases of myelodysplastic syndrome associated with celiac disease have been described. Here we describe the case of a patient affected by adult celiac disease who went into remission following a gluten free diet. Later a macrocytic anaemia without vitamin B12 or folate deficiency appeared. Hematologic tests showed findings consistent with refractory anemia with ring sideroblasts. The association of celiac disease with myelodysplastic syndromes seems not to be casual. It raises the hypothesis of a primitive immunological disorder in both diseases. PMID- 20540401 TI - [Celiac disease and malocclusion]. AB - Celiac disease is an autoimmune disease, caused by a permanent intolerance to gluten, that occurs in genetically predisposed individuals. It causes enteropathy. In these individuals a prolonged exposure to gluten increases the risk of developing other pathologies, which may affect both developing dentition and oral mucosa. Clinical presentations are various and atypical. Celiac patients may have enamel hypoplasia, higher prevalence of dental caries, delayed eruption of teeth and lower jaw growth. These factors predispose to malocclusion. PMID- 20540402 TI - [Atrial fibrillation and heart failure]. AB - Atrial fibrillation (AF) and heart failure (HF) are two conditions widespread on the population, especially in elderly people. When AF and HF coexist in the same patient, as frequently happens, they trigger a vicious circle of mutual influence, who dramatically hesitates in lower quality of life and in increased mortality. The relationship between AF and HF is long and vigorously investigated: it is an ever-changing field of knowledge because alongside well known and proven results, especiallythe pathophysiological ones, there are new horizons of research since many aspects are still obscure. Hence, this limit is reflected in the complexity of the combined management of AF and HF in clinical practice. It also explains an ominous prognosis despite significant therapeutic advances. In this review we go over again the well-established knowledge about the pathophysiology binder HF and AF; we provide some epidemiological, clinical and therapeutic informations, we also highlight the new acquisitions, the new research areas and, finally, the still unresolved questions. PMID- 20540403 TI - [Obesity, diabetes, cancer and cardiovascular risk: a trans-generational network]. AB - The prevalence of obesity has reached epidemic proportions, predisposing to the development of type 2 diabetes, cardiovascular disease and cancer. Lifestyle and genetic heritability are causes of this phenomenon, together with the nutritional environment during intra-uterine life and birth weight. We examine the above mentioned relationships in the family tree of a patient with diabetes, central obesity and cardiovascular disease. PMID- 20540404 TI - Joint Commission expands access to e-App. PMID- 20540405 TI - Correction: Misplaced requirements for disease-specific care. PMID- 20540406 TI - Top 10 standards compliance issues in 2009. Challenging requirements identified. PMID- 20540407 TI - Approved: Suspension of "automatic" sentinel event adverse decision. PMID- 20540408 TI - Clarification: How the National Patient Safety Goal on falls applies to home care services. PMID- 20540409 TI - 2010 Franklin Award presented to Tucson Medical Center Case Management. PMID- 20540410 TI - Inflammatory information. PMID- 20540411 TI - What is your diagnosis? Segmental vitiligo and en coup de sabre. PMID- 20540412 TI - What's eating you? Cat flea (Ctenocephalides felis), Part 1: Clinical features and role as a disease vector. PMID- 20540413 TI - Transverse melanonychia after radiation therapy. PMID- 20540414 TI - Hairpin-induced alopecia: case reports and a review of the literature. AB - Traumatic hair loss is a scalp injury that can cause secondary scarring alopecia. It can result from different types of physical and chemical injury. Hair loss induced by certain hair-styling techniques has been discussed, but we describe a preceding ulcerative process. We describe 3 black adolescent girls with hairpin induced alopecia that started with an ulcer and ended with a scar. We also review the dermatologic literature. PMID- 20540415 TI - Acrodermatitis chronica atrophicans: a case report and review of the literature. AB - Acrodermatitis chronica atrophicans (ACA) is a rare tertiary manifestation of Lyme borreliosis, manifesting as inflammatory and atrophic lesions on acral skin. Although ACA rarely has been reported in the United States, it may be seen in approximately 10% of European cases of Lyme borreliosis, most commonly associated with the genospecies Borrelia afzelii. We report a presumptive case of ACA involving an American woman from Pennsylvania with convincing clinical, histopathologic, and serologic findings. We also provide an overview of the history, epidemiology, pathogenesis, clinical and histopathologic presentation, and treatment of ACA. PMID- 20540416 TI - Desmoplastic trichoepithelioma, infiltrative/morpheaform BCC, and microcystic adnexal carcinoma: differentiation by immunohistochemistry and determining the need for Mohs micrographic surgery. AB - Several important cutaneous neoplasms present with basaloid cells in the dermis. Desmoplastic trichoepithelioma (DTE), infiltrative/morpheaform basal cell carcinoma (BCC), and microcystic adnexal carcinoma (MAC) are tumors in this category that may be difficult to differentiate, especially when evaluating thin biopsy specimens. An accurate diagnosis has important clinical implications. While DTE is a benign neoplasm with indolent behavior, infiltrative/morpheaform BCC and MAC can be highly aggressive, leading to substantial local destruction and potential metastasis. We present a patient with an unusual tumor demonstrating basaloid cells in the dermis and discuss the diagnostic approach for these lesions, emphasizing the potential role of cytokeratin 20 (CK20) in determining the need for Mohs micrographic surgery. PMID- 20540417 TI - A review of bioactive materials and chronic wounds. AB - An increasing number of bioactive materials are indicated for the treatment of chronic lower extremity ulcers. They are promising adjuncts to standard therapy. When used in conjunction with standard therapy for venous leg ulcers and diabetic foot ulcers, bioactive materials may increase the likelihood and rate of healing. This review compares commonly available bioactive materials indicated for chronic wound healing and provides an overview of the relevant Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes for these products. PMID- 20540418 TI - Fluorouracil cream 0.5% for actinic keratoses on multiple body sites: an 18-month open-label study. AB - This prospective 18-month, open-label, multicenter study assessed the long-term safety and efficacy of fluorouracil cream 0.5% in 277 participants with multiple actinic keratoses (AKs) on the face/anterior scalp and other body sites. Two treatment/observation cycles were separated by 12 months. During treatment cycle 1 (TC1), all participants were treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Twelve months later, all participants were assessed for treatment cycle 2 (TC2); participants with face/anterior scalp AKs (N = 98) were re-treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Only 4 participants (7.4%) experienced a treatment-related adverse event (AE) that was not an application site reaction or eye irritation. No unexpected AEs were reported; most were mild or moderate. After TC1 (week 8), the number of AK lesions was significantly reduced on the face/anterior scalp and all other treated body sites (P < .0001). Clearance rates were 30.5% (hands), 39.8% (face/anterior scalp), and 79.1% (lips). After TC2 (week 60), face/anterior scalp AKs were significantly reduced (P < .0001) and the clearance rate was 33.3%. This study indicates that fluorouracil cream 0.5% with a patented microsponge delivery system was well-tolerated and effective in treating and preventing recurrence of AK lesions up to 18 months after initial treatment. PMID- 20540419 TI - Effect of corrosion of steel elements on the treatment of dairy wastewater in a UASB reactor. AB - Experiments were performed in parallel using two laboratory upflow anaerobic sludge blanket (UASB) reactors. One of the two reactors was packed with spiral elements made of steel wire with 48% iron content in order to examine the influence of the steel elements on the chemical oxygen demand (COD) and efficiency of phosphorus removal from synthetically prepared dairy wastewater. A strong relationship was found between anaerobic corrosion and efficiency of phosphorus removal. Phosphorus removal in the reactor packed with steel elements was between 16.4% and 64.4% higher than without the steel elements present. The anaerobic corrosion process improved COD removal efficiency by 1.0-3.1%, which was statistically significant. When steel elements were present the methane content of the biogas was increased by 6.7%. Increasing the organic loading rate had a strong effect on the anaerobic efficiency of the dairy wastewater treatment. PMID- 20540420 TI - UASB reactor hydrodynamics: residence time distribution and proposed modelling tools. AB - The hydrodynamic behaviour of UASB (Up Flow Anaerobic Sludge Blanket) reactors based on residence time distribution curves allows the implementation of global models, including the kinetic aspects of biological reactions. The most relevant hydrodynamic models proposed in the literature are discussed and compared with the extended tanks in series (ETIS) model. Although derived from the tanks in series model, the ETIS model's parameter is not an integer. The ETIS model can be easily solved in the Laplace domain and applied to a two-stage anaerobic digestion linear model. Experimental data from a 250 m3 UASB reactor treating malting wastewater are used to calibrate and validate the proposed model. PMID- 20540421 TI - Municipal wastewater phosphorus removal by coagulation. AB - This study investigated the chemical removal of phosphorus from wastewater by means of adsorption and precipitation. Using secondary effluent from municipal wastewater treatment plants as the model wastewater, phosphorus precipitation was tested with four commonly used metal salt coagulants, and phosphorus adsorption was explored by column experiments with goethite-coated silica sand as porous media. It was concluded that adsorption played a more important role than precipitation in phosphorus removal. As demonstrated by the column experiments (integration of the breakthrough curve), around 65% of phosphorus can be retained through adsorption by goethite-coated silica sand. PMID- 20540422 TI - Agaricus bisporus as a source of tyrosinase for phenol detection for future biosensor development. AB - Phenols are toxic compounds that are present in several industrial wastewaters, so their quantification has great environmental importance. In order to permit an analytical methodology for in situ monitoring, this work aims to study the application of Agaricus bisporus tissue as a source of tyrosinase and the optimum reaction conditions for the development of a phenol biosensor. Such an enzyme is a polyphenol oxidase that transforms many different phenolic compounds into quinones. Experiments with fungi tissue were performed to evaluate different sizes of tissue (0.5, 1.0 and 1.5 cm), different temperatures (23.5 degrees C to 60 degrees C), and different pH values (6, 7 and 8) to quantify analytically phenol content. Amongst the tested conditions, those that had presented larger efficiency in phenol oxidation were attained with the fungal tissue size of 1 cm, at pH 8.0, in the temperature range from 35 degrees C to 45 degrees C. PMID- 20540423 TI - Nitrogen reduction in wastewater treatment using different anox-circulation flow rates and ethanol as a carbon source. AB - We studied the optimization of nitrogen reduction from municipal wastewater in a laboratory-scale modified Ludzack-Ettinger activated sludge wastewater treatment plant (WWTP). The unit consisted of primary denitrification, secondary nitrification, a sludge clarifier and a post-denitrification unit. The process simulates the Kuopio WWTP, which provided the influent utilized. We describe the effect of varying anox-circulation schemes on the nitrogen removal efficiency. We further compare the denitrification efficiencies of ethanol and methanol applied in the post-denitrification unit, and compare the properties and costs of these chemicals as carbon sources. Maximum efficiency of total nitrogen removal (70.8%) was obtained with 256% anox-circulation. The process was, however, not very sensitive, as a wide range of 150-400% of anox-circulations gave good results for nitrogen reduction. The unit achieved high BOD, and COD reductions of wastewater also when nitrogen reduction was moderate. The addition of 40 mg/L/day of ethanol to the post-denitrification tank meant that the nitrate-levels of effluent could be controlled to below 10 mg/L of nitrate nitrogen. Methanol and ethanol were equally effective for denitrification. The use of ethanol instead of methanol could reduce treatment costs by 30% to 0.02 E/m3 of treated wastewater according to 2008 market prices. PMID- 20540424 TI - [Detoxification of textile industry effluents by photocatalytic treatment]. AB - In Morocco the textile industry, representing 31% of all Moroccan industries, is accompanied by high water consumption and important wastewater discharges rejected without any treatment. The focus of this study was to characterize the effluent from the textile industry, to test separately the effect of UV light and TiO2 catalyst and to determine the optimum conditions (pH, concentration and reaction time) in photocatalytic treatment to reduce chemical oxygen demand (COD) and colour. The biodegradability of the effluent was also studied using a toxicity test before and after treatment. After 90 min of reaction time at pH 4 and with 1.5 g F' of TiO2 catalyst, the photocatalytic treatment reached a global removal rate of 53% for COD and 89% for discoloration of the effluent. The relation BOD5/COD increased from around 0 to 0.3. The effluent became accessible to a biological treatment. The toxicity was studied by the Daphnia magna test over 24 hours. The results have shown the important toxicity of these effluents, which are rich in organic matter and other chemical compounds. After treatment by photocatalytic oxidation, the CI50 24 increased from 3.8% to 22.8%. This reduction of toxicity is related to the reduction of COD (53%) and colour (89%). Photocatalytic treatment has been shown to have an environmental benefit and, in combination with a secondary biological treatment, can be important for a significant reduction in the pollution of textile effluents. PMID- 20540425 TI - Application of ADM1 model to a full-scale anaerobic digester under dynamic organic loading conditions. AB - The IWA Anaerobic Digestion Model No. 1 (ADM1) was used to simulate the full scale anaerobic sludge digester of Ankara Central Wastewater Treatment Plant. The digester is a completely mixed, once through continuous flow type which is being fed with a primary and secondary sludge mixture. The variability and unpredicted nature of the primary sludge composition was expected to challenge the model. A one-year dynamic data set from the digester was used for model calibration and validation in the study. The standard ADM1 model was corrected in the study with regard to nitrogen and carbon mass balances. A good correlation between the measured and simulated data was obtained for biogas yield, total volatile fatty acids and pH after heuristically calibrating stoichiometric and kinetic parameters of the ADM1 model. The simulation is sensitive to influent composition. PMID- 20540426 TI - NH4+-NH3 removal from simulated wastewater using UV-TiO2 photocatalysis: effect of co-pollutants and pH. AB - The main objective of the present study was to investigate the efficiency of titanium dioxide (TiO2) assisted photocatalytic degradation (PCD) process for the removal of ammonium-ammonia (NH4(+)-NH3) from the aqueous phase and in the presence of co-pollutants thiosulfate (S2O3(2-)) and p-cresol (C6H4CH3OH) under varying mixed conditions. For the NH4(+)-NH3 only PCD experiments, results showed higher NH4 -NH3 removal at pH 12 compared to pH 7 and 10. For the binary NH4(+) NH3/S2O3(2-) studies the respective results indicated a significant lowering in NH4(+)-NH3 PCD in the presence of S2O32- at pH 7/12 whereas at pH 10 a marked increase in NH4(+)-NH3 removal transpired. A similar trend was noted for the p cresol/NH4(+)-NH3 binary system. Comparing findings from the binary (NH4(+) NH3/S2O3(2-) and p-cresol/NH4(+)-NH3) and tertiary (NH4(+)-NH3/S2O3(2-)/p-cresol) systems, at pH 10, showed fastest NH4(+)-NH3 removal transpiring for the tertiary system as compared to the binary systems, whereas both the binary systems indicated comparable NH4(+)-NH3 removal trends. The respective details have been discussed. PMID- 20540427 TI - Redistribution of residual Pb, Zn, and Cd in soil remediated with EDTA leaching and exposed to earthworms (Eisenia fetida). AB - After soil remediation with ethylenediamine tetraacetate (EDTA) leaching/washing, the residual Pb, Zn, and Cd species are left in the soil in non-labile forms. The effect of earthworms as main soil biotic factors on the residual Pb, Zn, and Cd fraction lability (mobility, bioavailability to plants, and oral-availability) was investigated. Contaminated soil from a smelter site was treated with increasing EDTA concentrations (2.5 to 4-times 40 mmol kg(-1) to gradually reduce the heavy metal content and lability. Leached soils were processed by Eiseniafetida and heavy metal lability and fractionation determined in casts and earthworm-processed soils. In general E. fetida increased heavy metal accessibility/mobility, but the induced changes diminished with the intensity of soil EDTA treatment. Fractionation results indicate the possibility of a time dependent complexation of heavy metals to carbonates favoured by earthworms' gut processes. The transition of residual heavy metals in time (ageing) should be considered. PMID- 20540428 TI - Temperature effects on nitrification in polishing biological aerated filters (BAFs). AB - The effects of temperature on nitrification in a polishing biological aerated filter (BAF) were investigated using a 75-mm diameter pilot-scale BAF with a gravel media size of 5 mm and a depth of 1.7 m. Influent soluble chemical oxygen demand (sCOD) and ammonia-nitrogen (NH3-N) concentrations were approximately 50 mg/L and 25 mg/L simulating the effluent from an aerated lagoon system. For an influent wastewater temperature of 6.5 degrees C, approximately 95% of NH3-N was nitrified at a hydraulic retention time (HRT) of 2 hours. By recirculating 200% of the effluent back into the BAF for a HRT of 1 hour and at 6.5 degrees C, NH3-N percentage removal improved from 54% to 92%. For NH3-N loading larger than 0.9 kg NH3-N/m3-day at 24 degrees C, the mass of NH3-N removed in kg NH3-N/ m3-day reached an asymptotic value of 0.63 kg NH3-N/m3-day. The NH3-N concentrations within the column at different temperatures were modelled using zero-order biotransformation rate kinetics. The results showed that gravel BAF operating at an HRT of 1 hour with 100% or 200% recirculation can be used as an add-on technology for nitrification for cold weather conditions. PMID- 20540429 TI - Nutrient removal as a function of benzene supply within vertical-flow constructed wetlands. AB - The role of benzene, macrophytes and temperature in terms of nutrient removal within constructed wetlands is unknown. Therefore, a research study over approximately 30 months was conducted to assess the potential of vertical-flow constructed wetlands to treat nutrients and to examine the effect of benzene concentration, presence of Phragmites australis (Cav.) Trin. ex Steud (common reed), and temperature control on nutrient removal. Experimental wetlands removed between 72% and 90% of benzene at an influent concentration of 1000 mg L(-1). A statistical analysis indicated that benzene is linked to increased effluent chemical oxygen demand and biochemical oxygen demand concentrations. However, there was no significant relationship between benzene treatment and both nitrogen and phosphorus removal. Phragmites australis played a negligible role in organic matter (chemical oxygen demand, biochemical oxygen demand, nitrogen and phosphorus) removal. Control of temperature favoured biochemical oxygen demand removal. However, no significant difference in chemical oxygen demand, and nitrogen and phosphorus removal was detected. Only the combination of the benzene and temperature variables had a significant impact on biochemical oxygen demand removal. The effluent biochemical oxygen demand concentrations in temperature controlled benzene treatment wetlands were much lower than those located in the natural environment. However, any other combination between benzene, P. australis and the environmental control variables had no significant effect on biochemical oxygen demand, chemical oxygen demand, or nitrogen and phosphorus removal. PMID- 20540430 TI - Influence of nitrate, sulfate and operational parameters on the bioreduction of perchlorate using an up-flow packed bed reactor at high salinity. AB - In this study we have investigated whether electron acceptors, such as nitrate or sulphate ions, competitively inhibit the reduction of perchlorate in brine in continuous up-flow packed bed bioreactors. The effect of pH and hydraulic retention time (HRT) on the reduction of perchlorate at high salinity has also been examined. Reduction of perchlorate was found to be only moderately influenced by nitrate (under 163 mg N L-'), implying that there was no significant microbial competition for electron acceptors. As a result of microbial diversity, there were few differences between microbial communities fed with a variety of media, suggesting that most nitrate-reducing bacteria are able to reduce perchlorate at high salinity. Reduction of perchlorate was almost complete at relatively high sulfate levels (1000 mg L(-1)), neutral pH (6-8) and relatively long HRTs (> 10 h). PMID- 20540431 TI - [Management of adrenal incidentaloma: the position statement of the Croatian referral center for adrenal gland disorders]. AB - Adrenal incidentalomas are tumours of adrenal glands discovered during diagnostic workup for other clinical condition unrelated to adrenal glands. Improvement in imaging techniques and their widespread use in everyday practice have increased detection of adrenal incidentalomas making their management one of the most important challenges of modern endocrinology. Based on the relevant medical literature and guidelines of other international societies a panel of Croatian leading experts in adrenal gland disorders provide practical recommendations for the diagnostics and treatment of adrenal incidentaloma. PMID- 20540432 TI - [The influence of the economic recession on health care labor market in Croatia]. AB - Trends in the labor market, as a result of global economic recession, are characterized by reduction of manpower activity, decreased number of employed and increased number of unemployed persons. As the result of economic recession more then million workplaces are expected to be lost in the European Union. The aim of this study was to analyze the influence of economic recession on labor market in general and healthcare labor market in Croatia. In Q1/2009, the number of employed persons in the European Union declined by -1.2% compared to the same quarter of 2008, while in Croatia the number of employed persons declined by 0.4%. The comparison of quarterly employment rate in Croatia and the European Union in the period from Q2/2008 to Q1/2009 was not significantly different (p = 0.169, df = 6, t = 1.564, Student t test). Average unemployment rate in Q1/2009 in the European Union was 8.1% +/- 0.3 and it was increased by 9.4% compared to Q4/2008, while in Croatia the average unemployment rate in Q1/2009 was 8.4% +/- 0.1 and it was increased by 3.3% compared to Q4/2008. Monthly changes of unemployment rates compared between the European Union and Croatia in the six month period (Q4/2008 and Q1/2009) was significantly different (p = 0.001, df = 10, t = 4.425, Student t test). In Croatian health care system in Q1/2009 the number of employed person increased by 0.7% compared to Q1/2008, while the number of unemployed persons in the same period was reduced by -1.0%. Trends in the labor market in Croatia follow the global trends in the labor market in times of economic recession, although the increase in unemployment in Croatia was slower than in the countries of the European Union. As a result of Croatian healthcare system organization, system of financing, supply and demand on healthcare labor market, healthcare workforce in Croatia was less affected by recession than workforce in Croatia in general. PMID- 20540433 TI - [Are there counterfeit medicines in Croatia?]. AB - Counterfeit medicines are a growing problem in the world, for their use may endanger patient's health and therefore they pose an enormous public health risk. The manufacture of counterfeit medicines usually involves organised crime groups which place the counterfeit medicines on the market for reasons of profit. Detection and prevention of trade in counterfeit medicines requires close cooperation between medicine regulatory authorities, police, customs, judiciary and pharmaceutical industry. To this day, there have been no recorded cases of counterfeit medicines in the legal supply chain in Croatia. However, medicines without marketing authorisation in Croatia, originating from different countries, could be found on the illegal market. Most frequently, this includes medicines for the treatment of erectile dysfunction such as: sildenafil, tadalafil, vardenafil. In this study, 26 medicines for the treatment of erectile dysfunction, seized in illegal supply chain, were tested. High performance liquid chromatography (HPLC) was used for identification and quantification of active substances in the tested samples. It was determined that 13 out of 26 samples did not comply with declared composition of medicine and quality specification. Furthermore, two samples did not contain declared active substance vardenafil and that may indicate that these medicines are counterfeit. PMID- 20540434 TI - [Fournier's gangrene--our experience with 17 patients]. AB - Fournier's gangrene (FG) is a rare form of the skin and subcutaneous tissue bacterial infection characterized clinically by rapid progression and significant mortality, patohistologically by extensive necrosis of supeficial and deep facial planes and epidemiologically by predilection to patients with diabetes, immunosupression, malignant diseases or other debilitating state. In our retrospective study, we analyze 17 patients with FG hospitalised in our hospital in the 16-year period. Mean age of the patients was 58.9, and female-to-male ratio was 1:16. Among the predisposing factors diabetes mellitus (41.2%) and malignant diseases (29.4%) were the most common. Average length of hospital stay was 36 days (2-81) with lethality of 41.2% (7 patients). We assessed no statistical significance of the analysed prognostic parameters. In conclusion, we emphasize that FG is a surgical emergency and we express our impression that lack of physicians' experience is the main factor leading to delay in diagnosis and treatment of this rare, but life threatening disease. PMID- 20540435 TI - [Low doses of sulphonyluria as a successful replacement for insulin therapy in a patient with neonatal diabetes due to a mutation of KCNJ11 gene encoding Kir6.2]. AB - Neonatal diabetes mellitus is a rare metabolic disorder with an estimated incidence of 1:300.000 to 400.000 newborns, and less than 50% of the neonates have permanent neonatal diabetes mellitus (PNDM). Recently, activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of the adenosin triphosphate-sensitive potassium (K(ATP)) channel has been described as the most frequent cause of PNDM. Under physiological circumstances K(ATP) channel closure plays a central role in glucose-stimulated insulin secretion from pancreatic beta cells. Sulphonylurea drugs stimulate insulin secretion by binding to and closing K(ATP) channels and thus bypassing beta cell metabolism stimulate the same chain of reactions as glucose. We describe a boy diagnosed with PNDM at the age of 3 months when insulin therapy was started, and at the age of 4.5 years KCNJ11 gene was sequenced and found that the boy carried a de novo activating R201H mutation. Insulin therapy was successfully switched to low doses of oral glibenclamide. Accordingly, it is important to emphasize that every person diagnosed with diabetes before six months of life, however old they actually are, should be tested for K(ATP) mutations which is offered via the website www.diabetesgenes.org. PMID- 20540436 TI - [Fixed combinations of antihypertensive medications--new opportunity in treatment of hypertension]. AB - Arterial hypertension is one of the major public health problems. Early recognition and treatment, based on total cardiovascular risk assessment, is crucial for cardiovascular and renal protection. The choice of initial drug is often futile because most of hypertensive patients will need more than one medication for achieving blood pressure control. Initiation of treatment wih combination of antihypertensive drugs is reasonable choice especially in high or very high risk patients where it is important to achieve prompt and intensive blood pressure control in order to reduce cardiovascular complications. Fixed combination of two antihypertensive drugs can simplify treatment and favour compliance. The last, 2007 ESH/ESC guidelines, and several studies published in the meantime, favour use of ACE inhibitors or angiotensin receptor blockers with calcium channel blockers or diuretics as the combination of choice. Fixed combination of ramipril and felodipine is in agreement with guidelines recomendations with proven benefit on cardiovascular protection and non-diabetic kidney disease in patients with essential hypertension. PMID- 20540437 TI - [Can introduction of guidelines for use of an intrauterine device reduce changes in microbial flora of female genital system in IUD-users?]. AB - The intrauterine device (IUD), one of the most effective and most common methods of reversible contraception, is used by millions of women worldwide. Although various studies indicate the benefits of its use as a contraceptive method, the greatest concern regarding IUDs is the potential risk for infection. The presence of the IUD gives a solid surface for bacterial attachment and biofilm formation. Infections due to biofilm formation are chronic and difficult to resolve. However, women should be screened and treated for asymptomatic vaginal or cervical infections before IUD insertion. Based on the data in the literature and the data in study conducted in Croatia, it can be concluded that IUD users are at increased risk for development of infection. Treatment strategies in Croatia should take into consideration that Escherichia coli and Ureaplasma urealyticum are dominant causative agents. We conclude that guidelines for the use of IUD in Croatia are a necessity. PMID- 20540438 TI - [Synovial chondromatosis]. AB - Synovial chondromatosis is an uncommon benign disorder of the synovial membrane ofjoints, tendon sheaths, or bursae characterized by the formation of multiple cartilaginous nodules or osseus loose bodies. It is usually a monoarticular disease, and 33 different localizations have been described until now. The aim of this review article is to present the newest knowledge on the etiology, diagnosis, differential diagnosis, and management of synovial chondromatosis. Malignant transformation to chondrosarcoma is an unusual but possible complication. It is closely connected with recurrence rate and usually occurs many years after surgical treatment. More specific details related to surgical treatment of most often affected joints, i.e. shoulder, elbow, hip, knee, and ankle are reported as well at the end of this review article. PMID- 20540439 TI - [Stiff person syndrome (Moersch-Woltman)]. AB - The prime goal of this paper is to offer an overview of main scientific points in epidemiology, genetics, pathogenesis, clinical course and therapeutic strategies in stiff person syndrome (SPS). This syndrome is characterized by progressive muscle rigidity and painful muscle spasms. Three major forms of SPS are described, according to the pathophysiologic basis, autoimmune, paraneoplastic and idiopathic SPS. In autoimmune form of SPS the antibodies are specific for an enzyme (glutamic acid decarboxylase, GAD). If the paraneoplastic form takes place, the antibodies may be specific for presynaptic (amphyphysin) or the postsynaptic protein (gephyrin). The SPS diagnosis should be based on clinical, laboratory and electromyoneurographic criteria, according to Gordon and Lorish. The therapeutic approaches are focused on symptomatic therapy managing the muscle spasm and on possible immunomodulatory procedures to attenuate an autoimmune reaction. Two cases of SPS are reported in the Republic Croatia since 2005. Although it is a rare medical condition, SPS is of clinical importance, especially because it may be the first sign of an underlying undiagnosed malignant disease or if the anesthesia is necessary in SPS patient. PMID- 20540440 TI - [Errors in the historiography of the Civic Hospital in Split: on the occasion of placing a memorial tablet on the former hospital building]. AB - The building of the Civic Hospital in Split was an important event in the life of this city. Although it primarily served as an institution for the care of the poor, its development shows the evolution of the public health care in this territory. In spite of the recent thorough review of the older historiography on this history, incorrect data are permanently published in the literature and lately even in the content of the memorial plaque. This creates the erroneus picture and credibility of Croatian medical heritage, history and historiography. PMID- 20540441 TI - [How do we treat cancer pain in patients with advanced lung cancer?]. PMID- 20540442 TI - [Medical expulsive therapy for ureteral calculi]. PMID- 20540443 TI - Extending submarine crew survival by reducing CO2 production with quickly reversible sedation. AB - INTRODUCTION: CO2 accumulation may limit crew survival in a disabled submarine. Reversible sedation using diazepam and flumazenil was proposed to reduce CO2 production. METHODS: Two groups of three resting subjects were studied during a 48-h placebo phase with diazepam and flumazenil placebos, followed by a 48-h drug phase with oral diazepam to induce sedation and intranasal flumazenil to reverse it. CO2 exchange was measured every 2.5 h; twice a day, cognitive testing and meals were preceded by placebo or flumazenil. Return to sedated state was produced with either placebo or diazepam. In the drug phase, initial diazepam doses (10 to 40 mg) were followed by maintenance doses to achieve sedation corresponding to Alertness Scores of 3 or 4. RESULTS: In the drug phase, subjects received a total of 360-495 mg of diazepam (with doses of 5-40 mg), average alertness score was 3.75, and mean Vco2 was 14% less than in the placebo phase (0.212 vs. 0.248 L x min(-)). Subjects were 21-36% less active when sedated with diazepam. The mean flumazenil dose to restore full alertness was 0.36 mg, with subjects being conversant and oriented within 5 min, performing cognitive tasks at 86-97% of their baseline. Subjects could follow instructions and ambulate independently, though unsteadily 6 h after final flumazenil dose; at 72 h they exhibited normal cognitive and physical functions. DISCUSSION: Reversible sedation to lower crew metabolism in a disabled submarine may be effective, safe, and practical. PMID- 20540444 TI - Spleen contraction during 20 min normobaric hypoxia and 2 min apnea in humans. AB - INTRODUCTION: Spleen contraction occurs in humans during exercise, apnea, and simulated altitude, resulting in ejection of stored red blood cells into circulation. The mechanisms responsible for initiating the contraction are not fully known: hypoxia is likely involved, but other, unknown factors may also contribute. To reveal the initiating factors, we studied its occurrence in two different situations involving similar reductions in arterial oxygen saturation (SaO2). We hypothesized that similar spleen responses would result if the level of hypoxia is the main factor involved. METHODS: Five female and four male healthy volunteers performed two different trials on separate days: (1) 20 min of normobaric hypoxic breathing (14.2% oxygen); and II) 2 min of apnea after a deep inspiration of air. Both trials started and ended with 10 min of sitting eupneic rest. Spleen diameter was intermittently measured via ultrasonic imaging in three dimensions to calculate volume. SaO2 and heart rate (HR) were recorded continuously with a pulse oximeter. RESULTS: Exposures resulted in similar nadir SaO2: 87% after normobaric hypoxia and 89% after apnea. During normobaric hypoxia, spleen volume was reduced by 16% and during apnea by 34%. HR increased by 7% during normobaric hypoxia, but fell by 25% during apnea. DISCUSSION: Both normobaric hypoxia and apnea induced spleen contraction, but despite similar levels of SaO2 apnea evoked a significantly stronger response, possibly due to hypercapnia, faster desaturation, or the apneic stimulus in itself. Spleen contraction may facilitate adaptation to altitude and to apneic diving by elevating blood gas storage capacity. PMID- 20540445 TI - Oxygen consumption during walking and running under fractional weight bearing conditions. AB - INTRODUCTION: Knowledge of changes in oxygen consumption during reduced body weight loading at different speed levels is important, in particular in astronauts who may lose aerobic fitness as well as in clinical patients (e.g., in obese individuals at walking speeds or in injured athletes at running speeds). Therefore, the aim of this study was to analyze oxygen consumption during unloaded walking and running. METHODS: Oxygen consumption (Vo2), heart rate (HR), and Borg rating of perceived exertion (Borg RPE) were quantified in 10 healthy young female and male volunteers at 3 body weight (BW) conditions (100%, 66%, and 33% BW) and 4 treadmill speeds (slow walking at 0.4 m x s(-1), comfortable walking at 1.3 m x s(-1), slow running at 2.2 m x s(-1), and moderately fast running at 3.1 m x s(-1)). Unloading was achieved in a waist-high chamber with increased pressure called Lower Body Positive Pressure (LBPP). RESULTS: All parameters (Vo2, HR, and Borg RPE) decreased during unloaded walking and running. Interestingly, our findings confirm a specific linear relationship between each parameter and treadmill speed for each BW condition with smaller slope angles at higher levels of unloading (e.g., for Vo2, the slope angle decreased from 11.9 at 100% BW to 4.4 at 33% BW). DISCUSSION: Oxygen consumption, heart rate, and Borg rating of perceived exertion are reduced during unloaded exercise with a relatively greater decline at higher treadmill speeds. That is, the higher the treadmill's speed in unloaded conditions, the relatively "easier" it is to exercise. PMID- 20540446 TI - Intravenous perfluorocarbon after onset of decompression sickness decreases mortality in 20-kg swine. AB - INTRODUCTION: Decompression sickness (DCS) occurs when bubbles form due to pressure decreases with severity ranging from trivial to fatal. Standard treatment requires a hyperbaric chamber, not likely to be available at remote sites or during a disabled submarine escape or rescue. Alternative (non recompressive) treatments are needed. Intravenous administration of emulsified perfluorocarbons (PFCs) enhances oxygen delivery to, and inert gas removal from, tissues. Swine studies show PFCs administered with supplemental oxygen before symptom onset can decrease DCS incidence. We used a swine model to test whether PFC plus supplemental oxygen could improve outcome when infused after DCS symptom onset. METHODS: After rapid decompression from 31 min at 200 fsw (7.06 ATA) animals were observed for signs of DCS. Upon DCS onset animals received 100% 02 and were randomized to receive either saline or PFC. Oxygen administration was continued for 1 h and the primary outcomes of mortality and/or abnormal gait were noted 24 h after surfacing. RESULTS: PFC significantly improved survival, with 18/25 (72%) PFC treated animals and 13/29 (45%) saline treated animals alive at 24 h post-exposure. Objective measures of stance/gait trended toward improvement; spinal cord lesions correlated with severity of stance/gait abnormalities. CONCLUSION: PFC administered after DCS onset improved survival in this 20-kg swine model. Further study into the mechanisms of benefit and delayed DCS therapy are warranted. PMID- 20540447 TI - Pressure regulating ear plug testing in a pressure chamber. AB - INTRODUCTION: Middle ear barotrauma is a condition frequently associated with flying. It is usually caused by Eustachian tube (ET) dysfunction. Pressure regulating earplugs (PREP) should improve complaints due to pressure equalization problems. METHODS: There were 21 patients with a history of pressure equalization problems while flying who were examined. ET function was measured with exploratory tests and in a pressure chamber. In a double-blind study, PREP were examined using continuous impedance measurement in the pressure chamber. Eardrum deflection and pressure-equalizing maneuvers were also examined. During pressure exposure the subjective state of patients with and without PREP was compared. RESULTS: Evidence of ET dysfunction was found in twice as many patients with the impedance method in a pressure chamber compared to tympanometry or the Valsalva test. Use of PREP reduced the rate of pressure changes in the external auditory canal. Maximum pressure was reached with a delay of about 7 min. The number of pressure-equalizing maneuvers did not differ significantly. Using PREP the patients reported a significantly better subjective state on the VAS scale of 2.19 +/- 1.50 compared to 3.38 +/- 2.33 without PREP. CONCLUSIONS: Continuous impedance measurements in the pressure chamber identified ET dysfunction more often than the exploratory ET function tests commonly used in routine diagnostics. This novel finding requires further validation. Although use of PREP showed no signs of improving ET function, it did significantly improve individual subjective state during sudden pressure changes. PMID- 20540448 TI - Risk of herniated nucleus pulposus among U.S. astronauts. AB - INTRODUCTION: Astronauts have complained of back pain occurring during spaceflight, presumably due to the elongation of the spine from the lack of gravity. Herniated nucleus pulposus (HNP) is known to occur in aviators exposed to high Gz and has been diagnosed in several astronauts in the immediate post spaceflight period. It is unknown whether astronauts exposed to microgravity are at added risk for developing HNP in the post-spaceflight period due to possible in-flight intervertebral disc changes. METHODS: For a preset study period, incidence rates of HNP were compared between the U.S. astronaut population and a matched control population not involved in spaceflight using the Longitudinal Study of Astronaut Health database. Using a Weibull survival model, time trends of the risk of HNP prior to and after spaceflight were compared within the astronaut group. HNP incidences in other populations that have previously been reported in the literature were also compared with results in this study. RESULTS: The incidence of HNP was 4.3 times higher in the U.S. astronaut population (N=321) compared to matched controls (N=983) not involved in spaceflight. For astronauts, there was relatively more HNP in the cervical region of the spine (18 of 44) than for controls (3 of 35); however, there was no clear increase of HNP incidence in those astronauts who were high performance jet aircraft pilots. There was evidence suggesting that the risk is increased immediately after spaceflight. CONCLUSIONS: Astronauts are at higher risk of incurring HNP, especially immediately following spaceflight. PMID- 20540449 TI - Smokeless tobacco use among military flight personnel: a survey of 543 aviators. AB - INTRODUCTION: Although there has been a steady decline in smoking rates among adults in the United States in recent years, the consumption of smokeless tobacco (ST) continues to increase. Moreover, ST use in the U.S. military is far higher than in the general population. This study was designed to determine the extent of ST use in a military aviation population and measure users' attitudes toward elements of a proposed cessation program. METHODS: A study was conducted at two naval aviation training wings in western Florida. The target population (N=2233) included flight instructors, students, and staff/support personnel who were rated aviators or flight officers. A total of 543 usable questionnaires were returned, yielding a response rate of 24.3%. RESULTS: There were 71 respondents who reported using ST in the last 30 d (13.1%). This group responded favorably to questions regarding the involvement of both medical and dental health professionals as critical components of an effective ST cessation program. DISCUSSION: This survey provides evidence for a rate of ST use among military aviators that is much higher than the U.S. national civilian average of 3.5%. Drawing upon the background of previous dental health-based studies, we propose augmenting existing tobacco cessation resources by creating separate ST cessation programs to reduce ST use among U.S. military aviators. PMID- 20540450 TI - Considerations for the use of salivary IgA for monitoring mucosal immune function. AB - INTRODUCTION: We aimed to make recommendations concerning the use of total IgA in saliva (s-IgA) as an aid for monitoring athletic and military training. METHODS: Unstimulated whole saliva was collected from 16 subjects (11 women and 5 men ages 18-57) during nonconsecutive days of fasting and non-fasting. Seven samples were collected from each subject at 0700, 0900, 1200, 1400, 1600, 1800, and 2030 on each day and a further three samples were collected 30 min after three meals on the non-fasting day (at 0730, 1230, and 1830). Strenuous activity was avoided and subjects did not drink caffeine or alcohol-containing beverages. Albumin and s IgA were measured by commercial nephelometric immunoassays with intra-analytical coefficient of variance (CVA) of 1.8% and 2.9%, respectively. Individual and group variations were determined. Diurnal variation was determined by use of repeated-measures analysis of variance. RESULTS: CV-individual (CV(I)) was 48% for s-IgA concentration and 43% for s-IgA secretion and s-IgA:albumin. CV-group (CVG) for these same measures was 68%, 75%, and 68%, respectively. When measurements were adjusted for saliva flow rates there was no evidence that s-IgA is subject to diurnal variation. There was strong evidence for a postprandial decrease in s-IgA for all measures. CONCLUSION: The high degree of individuality in s-IgA precludes the use of population reference ranges for identifying individual abnormal results. For the purpose of monitoring individuals we recommend using the individual's calculated biological variance (determined from previous serial measurements over a period of days to weeks). Individual abnormal results can then be identified. PMID- 20540451 TI - Activation of platelets and fibrinolysis induced by saturated air dives. AB - INTRODUCTION: The Doppler technique is currently the usual method for detection of bubbles in the circulation following decompression. However, cases of decompression sickness (DCS) frequently occur in the absence of detectable bubbles, so that other markers for increasing risk of DCS would be welcome. This study assessed the hemostatic effects of compressed-air saturation dives that conformed to the "safe" limits of accepted decompression tables. METHODS: We measured coagulation times, thrombin generation, platelets, and fibrinolysis in 21 male divers who were subjected to saturated hyperbaric exposures to 0.28-0.3 MPa (corresponds to 18-20 msw). Each diver did one dive. RESULTS: Pooled before- and after-dive data for all exposures showed after decompression, statistically significant changes included decrease of the mean platelet count after, increased induced platelet aggregation and number of platelet aggregates, increased number of P-selectin (CD62P) positive platelets and CD62P density on platelets, increase of platelet derived microparticles in the blood of the divers, decrease of factor XII, X, and fibrinogen concentrations, and marked increase of plasmin-antiplasmin complex concentration. Thrombin activation markers and coagulation times did not change significantly. CONCLUSIONS: Saturated hyperbaric exposures followed by nominally safe decompression led to activation of platelets and the fibrinolytic system. The probable mechanism for the activation of platelets and fibrinolysis is contact with the surface of evolved bubbles in the divers' circulation. PMID- 20540452 TI - Panic disorder in military aviators: a retrospective study of prevalence. AB - INTRODUCTION: The occurrence of panic disorder (PD) among military pilots and navigators poses questions with respect to medical care and waiver policy, but the prevalence of such disorders is unclear. We studied the epidemiology of PD in a USAF aircrew population. METHODS: Occurrence of PD during the period 2001-2008 was determined using the USAF Aeromedical Information Management Waiver Tracking System, a database containing medical disqualifications and waivers for the entire population of both qualified and disqualified (grounded) USAF aviators. RESULTS: The mean annual USAF pilot and navigator population averaged 17,727 during the study period. The database yielded nine cases labeled as PD. After records review by two experienced aeromedical psychiatrists, only three of the nine cases met diagnostic criteria for PD. Estimated annual PD prevalence was 0.002% (2/100,000) in USAF pilots and navigators. Annual prevalence of PD was 2.7% in the general U.S. population 18 yrS. of age and older and 2.4% in a group of manager/professionals. Odds ratios were 1228 (55/27,269) and 1089 (49/24,175) for the general population and manager/professionals, respectively. DISCUSSION: One of three individuals with PD received a waiver to resume flying after successful treatment. Five of the six cases not meeting criteria for PD (but suffering from varying degrees of situational and/or stress related anxiety) were flying with waivers. The negligible annual PD prevalence in USAF pilots and navigators likely reflects lower aircrew vulnerability to PD because of selection and training processes and does not pose a disease burden upon force strength. PMID- 20540453 TI - Ventricular fibrillation diagnosed during electrophysiological study for non sustained tachycardia. AB - Ventricular fibrillation diagnoses such as Brugada syndrome pose a risk of sudden incapacitation or death in aircrew. This case report presents a 44-yr-old male fighter pilot who unexpectedly developed ventricular fibrillation (VF) during an electrophysiological study (EPS) prior to therapy for non-sustained ventricular tachycardia (nsVT). The initial aeromedical disposition for this case was "qualified for flying duties". with the restriction that he must fly with another pilot due to repeatedly observed nsVT. This pilot wanted to return to flight duty in single-seat aircraft without any restrictions. Therefore, this patient decided to undergo catheter therapy for nsVT. Unexpectedly, not VT but VF was induced by catheter manipulation during EPS. Pilsicainide-induced coved-type ST wave elevation consistent with Brugada syndrome was noted in this patient's electrocardiogram. He was ultimately disqualified due to the diagnosis of VF. This report suggests EPS on rare occasions may uncover another severe disease similar to this case report. PMID- 20540454 TI - Frequent premature ventricular contractions in an orbital spaceflight participant. AB - BACKGROUND: Commercial spaceflight participants on orbital flights typically are older than career astronauts and they often have medical conditions that have not been studied at high g or in microgravity. This is a case report of a 56-yr-old orbital spaceflight participant with essential tremor and frequent premature ventricular contractions that occurred at rates up to 7000 per day. Before training and spaceflight, he was required to complete extensive clinical investigations to demonstrate normal cardiac structures and the absence of cardiac pathology. The evaluation included signal averaged ECG, transthoracic stress echocardiography, exercise tolerance tests, electrophysiological studies, cardiac MRI, electron beam CT, Holter monitoring, and overnight oximetry. While no cardiac pathology was demonstrated, the Russian medical team required that the PVCs be treated prior to training and spaceflight. For the initial flight, a selective beta-1 receptor beta blocker was used and for the second a calcium channel blocker was used in combination with a nonselective beta blocker for tremor control. Analogue environment testing assured that this combination of medications was compatible. CONCLUSION: The spaceflight participant's PVCs were incompletely suppressed with a low-dose selective beta-1 blocker, but were well suppressed by a calcium channel blocker. He tolerated in-flight periodic use of a nonselective beta blocker in combination with a calcium channel blocker. In flight ECG and blood pressure monitoring results were normal, and an ECG obtained midmission and on landing day showed successful PVC suppression. He did not have any cardiac difficulty with launch, on-orbit operations, entry, or recovery PMID- 20540455 TI - Handheld directed energy sensor for environmental monitoring and clinician safety. AB - INTRODUCTION: Directed energy (DE) research and development is generating more powerful portable devices designed to support operational, environmental, clinical, point detection, and remote-sensing applications. These same DE devices present potential for injury, thereby impacting medical operations. The environmental surveillance and clinical communities require handheld sensor platforms that afford preemptive detection and monitoring of potentially hazardous exposures to DE and other electromagnetic (EM) frequencies. METHODS: A personal digital assistant (PDA) was interfaced with a wavelength sensor board via a multifunction data acquisition card to passively detect wavelengths in the 480-950 nm range. A 9V DC battery coupled to a voltage up-converter with a manual ON/OFF switch powered the sensor board. The sensor board was integrated with a standard operating system-based PDA. Graphical programming software integrated the data acquisition card with the PDA. RESULTS: The DE wavelength sensor/PDA platform detected and relayed laser radiation information from 480 to 950 nm ranges, with graphical data output to the PDA screen. DISCUSSION: This project demonstrated the technical ability to detect anthropogenic DE frequency signatures using a handheld, battery-driven DE sensor platform. Laboratory and field assessment studies are underway to validate operational applications. This DE-sensing prototype is designed explicitly for DE medical measurement and signatures intelligence (MED MASINT) to meet the protection needs of environmental and clinical operators. PMID- 20540456 TI - Systems biology in aerospace medical research. PMID- 20540457 TI - You're the flight surgeon. Osteochondritis dissecans. PMID- 20540458 TI - Classics in space medicine. Resume of present knowledge of man's ability to meet the space environment. 1964. PMID- 20540459 TI - Online learning to improve hand hygiene knowledge and compliance among health care workers. AB - BACKGROUND: The Centers for Disease Control and Prevention published a hand hygiene guideline for health care workers. The emergence of online learning approaches has introduced new opportunities for providing continuing education regarding hand hygiene. METHODS: This study assessed the effectiveness of an online continuing education program in increasing health care workers' knowledge of hand hygiene practices and guidelines and promoting behavioral change as measured by self-assessment of adherence to guidelines. A total of 256 health care workers at two hospitals completed all three sessions of the online continuing education program. RESULTS: Health care workers reported a significant improvement in hand hygiene knowledge and self-assessed compliance with hand hygiene behaviors. Most (97%) of the participating health care workers reported that the program was effective in improving clinical compliance behaviors. CONCLUSION: The results of this study indicated that individual health care workers can and will use self-assessment to prompt improvement in hand hygiene. PMID- 20540460 TI - Enhancing the knowledge, attitudes, and skills of preceptors: an Australian perspective. AB - Within the context of nursing education in Australia, the registered nurse (RN) preceptor plays an invaluable role with nursing students; however, many are not specifically trained for this role. This study explored the perceptions of practicing preceptors from one health care facility after completion of a specially designed preceptor program. Results indicated that the participants perceived that the program had increased their knowledge of teaching and learning and increased their skills as preceptors. Further results suggested that when the RN preceptor's knowledge of the teaching and learning process increased, it led to an increase in the RN preceptor's generic preceptor skills. This increased the RN preceptor's confidence, leading to a more positive attitude toward student nurses and a positive effect on preceptor functioning, enhancing the preceptor's ability to include students more in daily nursing tasks. PMID- 20540461 TI - Deterrents to nurses' participation in continuing professional development: an integrative literature review. AB - BACKGROUND: Continuing education (CE) helps nurses keep their practice safe and current. Although the literature provides information about motivating strategies, learning styles and settings, and reinforcement of the need to update skills, little research has focused on barriers to nurses' CE program attendance. This literature review describes factors that deter nurses' CE attendance. METHODS: Ten research studies published between 1990 and 2008 addressing barriers to nurses' CE participation were located. RESULTS: The most frequent deterrents found were the cost of attending CE, inability to get time off from work to attend CE, and child care and home responsibilities. CONCLUSION: Leaders supporting CE must understand factors that motivate and prevent nurses from participating in CE. Implications from this study can assist educators to develop CE offerings to better meet staff needs and increase participation. PMID- 20540462 TI - Developing a nursing personnel policy to address body art using an evidence-based model. AB - BACKGROUND: An increase in the prevalence of body art as a form of self expression has motivated health care organizations to develop policies addressing nursing personnel's body art. METHODS: A systematic review of literature on body art was completed and a telephone survey of 15 hospitals was conducted to query existing policy statements addressing nursing personnel's body art. RESULTS: The literature established no prevalence of body art among nurses or effect of nurses' body art. Of the 13 hospitals (86%) that shared their policy on body art, none provided a rationale or references to support their existing policies. CONCLUSION: A lack of published evidence identifying the effect of body art among nurses shifts the burden of determining care outcomes to the leadership of individual hospitals. Further research on patients' perception of nursing personnel with visible body art, using an evidence-based model, is recommended. PMID- 20540463 TI - Empowering nurses to participate in ethical decision-making at the bedside. AB - Nurses at the bedside have widely varied educational backgrounds. Most bedside nurses have insufficient knowledge in the area of ethical decision-making to feel confident in their ability to participate in ethical decision-making along with the health care team. Continuing education programs for staff nurses should focus on ethical decision-making to empower bedside nurses to participate. The effect of a successful continuing education program in ethics could lead to improved relationships among health care professionals, improved communication with patients and families, and reduced stress-related burnout caused by ethical dilemmas. This article describes a successful continuing education program designed to improve knowledge of ethics and confidence in ethical decision-making that can be adapted for any nursing specialty. PMID- 20540464 TI - Intimate partner violence: screening and intervention in the health care setting. AB - BACKGROUND: The prevalence of intimate partner violence (IPV) has been documented in numerous populations and cultures. IPV is a universal social problem that affects individuals, families, and communities throughout the world. Research supports the idea that victims of IPV view health care providers as a source of help. However, nurses report feelings of inadequacy in their ability to screen for IPV. METHODS: This quality improvement project was undertaken to increase awareness of IPV by educating nursing staff working in the health care setting. The educational program was evaluated through pretests and posttests. A universal IPV screening question was added to the hospital admission intake procedure. Through retrospective chart reviews before and after the educational session, screening for IPV by the nursing staff was evaluated by examination of disclosure rates and referral data. Populations served or affected include nurses and ultimately victims of IPV. RESULTS: The findings support the idea that an educational program can increase nurses' confidence and competency in screening for IPV. The results of chart review will determine whether there is a significant change in behavior relative to the increase in knowledge. CONCLUSION: Additional measures may be needed to enhance nurses' screening and interventional work with patients regarding IPV victimization. PMID- 20540465 TI - Managers' perspectives of new graduates of accelerated nursing programs: how do they compare with other graduates? AB - Nurse managers in focus groups reported that new graduates of all types of prelicensure programs were not prepared clinically for beginning practice. Graduates of accelerated programs had similar knowledge and skills as other new nurses but also brought work experience and maturity to the clinical setting, which fostered their transition to the nursing role. Nurse managers reported generational differences among graduates beyond their educational preparation and explained how those differences affected their learning of new technologies. Educational implications are discussed. PMID- 20540466 TI - Unintended epithelium-only flap creation using a femtosecond laser during LASIK. AB - PURPOSE: to present a patient in whom, during LASIK with the IntraLase femtosecond laser (Abbott Medical Optics), unintended epithelial (instead of anterior stromal) flaps were created in both eyes. METHODS: a 28-year-old man underwent bilateral LASIK using the IntraLase femtosecond laser programmed to create 100-microm flaps. Flap creation was performed uneventfully in both eyes but flap thickness was thinner than attempted. The flaps were easily torn during flap lift because they appeared to consist of epithelium only. Therefore, the procedure was immediately converted to photorefractive keratectomy with the use of mitomycin C. RESULTS: re-epithelialization occurred 3 days after the procedure in both eyes. Three months after treatment, uncorrected distance visual acuity was 20/25 in the right eye and 20/20 in the left eye with no signs of corneal haze on slit-lamp examination. CONCLUSIONS: despite the advantages of the IntraLase femtosecond laser in the creation of a LASIK flap, complications in terms of flap thickness may occur. PMID- 20540467 TI - Is excimer laser corneal surgery appropriate after resolution of corneal edema in fuchs dystrophy by descemet membrane endothelial keratoplasty? AB - PURPOSE: To report a case of apparent central corneal thinning diagnosed after treatment of Fuchs dystrophy by Descemet membrane endothelial keratoplasty (DMEK) and to discuss treatment options with laser refractive surgery. METHODS: A pseudophakic patient with Fuchs dystrophy underwent DMEK, with removal of dysfunctional recipient endothelium and replacement with bare endothelium and Descemet membrane from a donor cornea. Subsequently, a standard preoperative evaluation for LASIK, including refraction, topography, Pentacam (Oculus Optikgerate GmbH), and slit-lamp examination was performed. RESULTS: After DMEK, refraction was +0.75 +2.50 * 115. Corneal topography did not show evidence of corneal ectasia or suspicion of keratoconus. Simulated keratometry was 43.03*40.49. Central corneal thickness was 481 MUm by ultrasonic pachymetry. Pentacam evaluation of the anterior and posterior surfaces showed normal contours relative to a best-fit sphere on the anterior surface, but central elevation of 25 MUm on the posterior surface. The typical increased central corneal thickness of Fuchs dystrophy could have masked a latent forme fruste keratoconus that became evident after the edema resolved with DMEK, or the central edema could have led to loss of stromal thickness causing the forward displacement of the posterior corneal surface. CONCLUSIONS: It is uncertain whether this eye is safe for LASIK or PRK correction of the residual refractive error. This finding of posterior surface forward displacement would be difficult to impossible to detect in an eye after Descemet stripping endothelial keratoplasty due to the addition of stromal tissue on the graft. PMID- 20540468 TI - Successful treatment of recurrent epithelial ingrowth associated with interface fluid syndrome, flap necrosis, and epithelial defects following LASIK. AB - PURPOSE: to report the successful treatment of two patients who developed flap necrosis preceded by recurrent epithelial ingrowth and interface fluid syndrome after LASIK. METHODS: patient 1 was treated with epithelial debridement and flap suturing. Patient 2 was initially treated with epithelial debridement and flap suturing, but developed recurrent epithelial ingrowth in the right eye and 2 weeks later in the left eye. RESULTS: patient 1 developed diffuse interface fluid accumulation in the left eye after epithelial debridement and flap suturing and was treated with timolol meleate 0.5% solution and methazolamide. The interface fluid resolved and the cornea and flap became clear. Slit-lamp examination identified a small area of epithelial ingrowth recurrence, which has remained stable for 3 years. Patient 2 was successfully retreated with epithelial debridement followed by fibrin tissue adhesive application. Five months after debridement and fibrin tissue adhesive, no recurrence of epithelial ingrowth or interface fluid accumulation was noted. CONCLUSIONS: epithelial ingrowth and interface fluid syndrome may be associated with secondary flap necrosis following LASIK, which can be effectively treated with debridement and flap suturing or fibrin tissue adhesive application. PMID- 20540469 TI - Initial resident refractive surgical experience: outcomes of PRK and LASIK for myopia. AB - PURPOSE: To evaluate and compare the outcome of initial resident surgical experience with photorefractive keratectomy (PRK) and LASIK. METHODS: Retrospective review of all cases performed with the VISX Star S4 platform (Abbott Medical Optics) between July 1, 2003 and June 30, 2007. Inclusion criteria were spherical equivalent of -0.50 to -10.00 diopters (D), refractive astigmatic error of <=3.00 D, intention to provide full distance correction, and minimum 3-month postoperative follow-up after initial ablation or retreatment (if performed). RESULTS: A total of 153 cases performed by 20 different residents met the inclusion criteria; 38 eyes underwent PRK and 115 eyes had LASIK. After initial treatment, mean Snellen uncorrected distance visual acuity (UDVA) after PRK was 20/17.3 and after LASIK was 20/19.5. Photorefractive keratectomy was associated with a significantly better approximation between preoperative corrected distance visual acuity (CDVA) and postoperative UDVA (DeltalogMAR 0.009 vs 0.091; P=.004) and a greater percentage of eyes that achieved UDVA of 20/20 or better (94.7% vs 78.3%; P=.02) or 20/30 or better (100% vs 87.8%; P=.02). There was a higher prevalence of retreatment in eyes that underwent LASIK (7.0% vs 0%; P=.20). One (0.9%) eye lost 2 lines of CDVA after LASIK. CONCLUSIONS: Supervised refractive surgery residents can achieve excellent visual outcomes in patients operated during their initial refractive experience. Photorefractive keratectomy was associated with better visual outcome than LASIK. PMID- 20540470 TI - Bilateral explantation of Visian Implantable Collamer Lenses secondary to bilateral acute angle closure resulting from a non-pupillary block mechanism. AB - PURPOSE: To report a case of bilateral non-pupillary block angle closure glaucoma after Visian Implantable Collamer Lens (ICL, STAAR Surgical) surgery. METHODS: A 35-year-old woman with high myopia, white-to-white measurements of 11.8 mm in the right eye and 11.9 mm in the left eye, and anterior chamber depths >3 mm in both eyes underwent simultaneous bilateral ICL implantation with 13.2-mm lenses. RESULTS: Persistent, bilateral acute angle closure developed despite multiple patent peripheral iridotomies and iridectomies. Visante anterior segment optical coherence tomography (AS-OCT, Carl Zeiss Meditec) revealed profound vaulting of the ICLs and angle closure. Both ICLs were explanted. After explantation, ultrasound biomicroscopy demonstrated a sulcus-to-sulcus diameter of 10.8 mm in the right eye and 11.2 mm in the left eye. CONCLUSIONS: The correlation between white-to-white and sulcus-to-sulcus measurements were poor in this patient, resulting in extreme vaulting of the ICL and angle closure from a non-pupillary block mechanism. Proper identification of the mechanism of angle closure is aided by AS-OCT. For non-pupillary block mechanisms, ICL extraction is necessary. PMID- 20540471 TI - Refractive outcome of keratoconus treated by combined femtosecond laser and big bubble deep anterior lamellar keratoplasty. AB - PURPOSE: To report 1-year follow-up in 11 of 13 eyes with keratoconus treated by deep anterior lamellar keratoplasty with a combined femtosecond laser lamellar resection followed by a big-bubble dissection. METHODS: Thirteen eyes with keratoconus were treated. Recipient and donor were prepared with the 60-kHz IntraLase femtosecond laser (Abbott Medical Optics). In the recipient, the femtosecond laser, after performing a lamellar cut 100 MUm above the thinnest corneal point (measured by Pentacam [Oculus Optikgerate GmbH]), was used to make a mushroom-shaped resection (anterior diameter, 9 mm; posterior diameter, 8 mm) from the same depth. In the donor, the mushroom lamellar thickness was calculated according to an original model based on the recipient preoperative corneal thickness. Upon removal of the recipient lamella, air was injected into the residual stroma to achieve a big bubble. The keratectomy was continued up to Descemet membrane. The donor was fit into place and sutured using interrupted sutures, which were removed by 8 months postoperative. Corrected distance visual acuity (CDVA) and refractive astigmatism were calculated by manifest refraction, whereas topographic astigmatism and corneal thickness were measured by Pentacam. RESULTS: A big bubble was successfully achieved in 11 eyes. Twelve months after surgery, mean CDVA was 0.52+/-1.2 (decimal), and refractive sphere and cylinder were -1.50+/-1.70 diopters (D) and 2.00+/-2.60 D, respectively. Three (27%) of 11 eyes at 1 year had a manifest refraction spherical equivalent within 1.00 D of emmetropia. Topographic astigmatism was 2.90+/-1.60 D. The thinnest corneal point was 519+/-27 MUm. CONCLUSIONS: This combination of a femtosecond laser lamellar dissection with a big-bubble technique can improve the standardization of deep anterior lamellar keratoplasty for keratoconus. PMID- 20540472 TI - 2010--a banner year for nursing education. PMID- 20540473 TI - Purpose of the systematic physical assessment in everyday practice: critique of a "sacred cow". AB - Although considered an essential nursing skill, systematic physical assessment is rarely visible in everyday practice. Some nurses question whether systematic physical assessment is relevant to nursing, and others complain that they do not see it used in practice. Why is this, when these skills are considered so integral to nursing? This article challenges nurse educators to reflect on the purpose of the systematic physical assessment within nursing by analyzing the underlying assumptions of this apparent "sacred cow." PMID- 20540474 TI - Innovative learning activity. Education theory and classroom games: increasing knowledge and fun in the classroom. PMID- 20540475 TI - Let's treat obesity seriously. PMID- 20540476 TI - Hypocupremia in patients after gastric bypass surgery. PMID- 20540477 TI - Diagnosing von Willebrand disease. PMID- 20540480 TI - Screening for skin cancer. PMID- 20540482 TI - Treatment of allergic rhinitis. AB - Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy. PMID- 20540483 TI - Office-based strategies for the management of obesity. AB - Roughly two thirds of U.S. adults are overweight or obese. Obesity increases the risk of hypertension, type 2 diabetes mellitus, hyperlipidemia, heart disease, pulmonary disease, hepatobiliary disease, cancer, and a number of psychosocial complications. Physicians often feel unprepared to handle this important problem. Practical office-based strategies include: (1) making recommendations for assisted self-management, including guidance on popular diets, (2) advising patients about commercial weight-loss programs, (3) advising patients about and prescribing medications, (4) recommending bariatric surgery, and (5) supplementing these strategies with counseling about lifestyle changes using a systematic approach. Family physicians should provide basic information about the effectiveness and safety of popular diets and commercial weight-loss programs, and refer patients to appropriate information sources. Sibutramine and orlistat, the only medications currently approved for the long-term treatment of obesity, should only be prescribed in combination with lifestyle changes. Bariatric surgery is an option for adults with a body mass index of 40 kg per m2 or higher, or for those with a body mass index of 35 kg per m2 or higher who have obesity related comorbidities such as type 2 diabetes. The five A's behavioral counseling paradigm (ask, advise, assess, assist, and arrange) can be used as the basis for a systematic, practical approach to the management of obesity that incorporates evidence for managing common obesity-related behaviors. PMID- 20540484 TI - Weight loss: practical tips. PMID- 20540485 TI - Evaluation of anemia in children. AB - Anemia is defined as a hemoglobin level of less than the 5th percentile for age. Causes vary by age. Most children with anemia are asymptomatic, and the condition is detected on screening laboratory evaluation. Screening is recommended only for high-risk children. Anemia is classified as microcytic, normocytic, or macrocytic, based on the mean corpuscular volume. Mild microcytic anemia may be treated presumptively with oral iron therapy in children six to 36 months of age who have risk factors for iron deficiency anemia. If the anemia is severe or is unresponsive to iron therapy, the patient should be evaluated for gastrointestinal blood loss. Other tests used in the evaluation of microcytic anemia include serum iron studies, lead levels, and hemoglobin electrophoresis. Normocytic anemia may be caused by chronic disease, hemolysis, or bone marrow disorders. Workup of normocytic anemia is based on bone marrow function as determined by the reticulocyte count. If the reticulocyte count is elevated, the patient should be evaluated for blood loss or hemolysis. A low reticulocyte count suggests aplasia or a bone marrow disorder. Common tests used in the evaluation of macrocytic anemias include vitamin B12 and folate levels, and thyroid function testing. A peripheral smear can provide additional information in patients with anemia of any morphology. PMID- 20540487 TI - Photo quiz. Cyanosis in an older woman. Diffuse acute limb ischemia. PMID- 20540489 TI - Preparation and characterization of polymer-inorganic nanocomposites by in situ melt polycondensation of L-lactic acid and surface-hydroxylated MgO. AB - Compared with pristine polymers, bionanocomposites derived from biopolymers and inorganic nanoparticles have significantly improved electrical/magnetic properties, mechanical properties, thermal stability, gas barrier properties, and fire retardance. In this study, poly(lactic acid) (PLA) nanocomposites were prepared by in situ melt polycondensation of L-lactic acid with different loading ratios of surface-hydroxylated magnesium oxide (MgO) nanocrystals. Molecular weight, structure, morphology, and thermal properties of the nanocomposites were characterized. PLA-grafted MgO (PLA-g-MgO) was isolated from free PLA for the nanocomposite with 3% MgO via repeated dispersion/centrifugation processes and characterized. The weight-average molecular weight of the PLA-0.01%MgO nanocomposite was 55500, which was 30% higher than that of pure PLA. Discoloration of PLA was obviously depressed in the presence of MgO nanocrystals. Formation of hydrogen bonding between PLA chains and surface -OH groups from MgO was detected by Fourier transform infrared spectroscopy. Morphological images showed uniform dispersion of MgO nanocrystals in the PLA matrix and demonstrated a strong interfacial interaction between the PLA matrix and MgO nanocrystals. PLA MgO nanocomposites exhibited improved thermal stability compared with pure PLA. Calculations based on thermogravimetric analysis revealed that more than 42.5% PLA was successfully grafted into PLA-g-MgO. PMID- 20540490 TI - Kinetic model for biological nitrogen removal using shortcut nitrification denitrification process in sequencing batch reactor. AB - A kinetic model for shortcut nitrification-denitrification process with sequencing batch reactor (SBR) was developed. To test this model, the kinetic parameters of the model including maximum specific rates and half-maximum rate concentrations for shortcut nitrification and denitrification were estimated from the results obtained from a laboratory-scale SBR fed with a soybean curd processing wastewater (400-800 mg COD L(-1), 50-65 mg NH(4)(+)-N L(-1)) at 26 degrees C. In the nitrification step, two DO levels (0.5 and 3.5 mg L(-1)) were tested and the predicated nitrification rates under different NH(4)(+)-N concentrations using this model fit well with correlation coefficient R = 0.9902. In the denitrification step, the process of nitrite removal was close to a zero order reaction if the concentration of electron donor was not so low (COD > 100 mg L(-1)), and concentrations of nitrite and organic matter (as COD) had limited effect on denitrification rate. The model can be used to predict nitrogen removal performance with different influent NH(4)(+)-N and COD concentrations and under various DO concentrations. PMID- 20540491 TI - Red sky at night: long-wavelength photochemistry in the atmosphere. PMID- 20540492 TI - Mechanism and engineering of polyketide chain initiation in fredericamycin biosynthesis. AB - The ability to incorporate atypical primer units through the use of dedicated initiation polyketide synthase (PKS) modules offers opportunities to expand the molecular diversity of polyketide natural products. Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties. We also exploit this PKS module for the design and in vivo biosynthesis of unusually primed analogues of a representative polyketide product, thereby emphasizing its utility to the metabolic engineer. PMID- 20540493 TI - Deactivation of pressure-induced amorphization in silicalite SiO2 by insertion of guest species. AB - The incorporation of carbon dioxide or argon stabilizes the structure of the microporous silica polymorph silicalite well beyond the stability range of tetrahedrally coordinated SiO(2) and, in fact, beyond even the metastability range of low-pressure silica polymorphs such as quartz and cristobalite at room temperature. The bulk modulus of silicalite strongly increases as a result of the incorporation of CO(2) or Ar and is equivalent to that of quartz. The insertion of these species deactivates the normal compression and pressure-induced amorphization mechanisms in this material, impeding the softening of low-energy vibrations, amorphization, and the eventual increase in silicon coordination up to at least 25 GPa. PMID- 20540494 TI - Look and see if it is time to induce protein expression in Escherichia coli cultures. AB - It is shown that Methyl Red can be used as an indicator dye that changes color in Escherichia coli culture as a result of time- and cell density-dependent bleaching by azoreductase produced by the bacteria. For cell cultures that are being used to express a recombinant protein, this phenomenon can be exploited to provide a simple visual cue that cell cultures have reached an appropriate growth phase for addition of an agent to induce protein expression, such as isopropyl thiogalactoside. PMID- 20540495 TI - 1H NMR study of the influence of mutation on the interaction of the C-terminus with the active site in heme oxygenase from Neisseria meningitidis: implications for product release. AB - The HO from the pathogenic bacterium Neisseria meningitidis, NmHO, possesses C terminal His207, Arg208, and His209 residues that are undetected in crystal structures. NMR found the C-terminus ordered and interacting with the active site and shown to undergo a spontaneous cleavage of the C-terminal Arg208-His209 bond that affects the product off rate. A preliminary model for the interaction based on the wild-type (WT) NmHO complexes has been presented [Liu, Y., Ma, L.-H., Satterlee, J. D., Zhang, X., Yoshida, T., and La Mar, G. N. (2006) Biochemistry 45, 3875-3886]. Two-dimensional (1)H NMR data of resting-state, azide-inhibited substrate complexes of the three C-terminal truncation mutants (Des-His209-, Des Arg208His209-, and Des-His207Arg208His209-NmHO) confirm the previous proposed roles for His207 and Arg208 and reveal important additional salt bridges involving the His209 carboxylate and the side chains of both Lys126 and Arg208. Deletion of His209 leads to a qualitatively retained C-terminal geometry, but with increased separation between the C-terminus and active site. Moreover, replacing vinyls with methyls on the substrate leads to a decrease in the separation between the C-terminus and the active site. The expanded model for the C-terminus reveals a less stable His207-Arg208 cis peptide bond, providing a rationalization for its spontaneous cleavage. The rate of this spontaneous cleavage is shown to correlate with the proximity of the C-terminus to the active site, suggesting that the closer interaction leads to increased strain on the already weak His207-Arg208 peptide bond. The relevance of the C-terminus structure for in vitro studies, and the physiological function of product release, is discussed. PMID- 20540496 TI - Model-based thermodynamic analysis of reversible unfolding processes. AB - Folding and unfolding of many biological macromolecules can be characterized thermodynamically, yielding a wealth of information about the stability of various conformations and the interactions that hold them together. The relevant thermodynamic parameters are usually obtained by employing spectroscopic and/or calorimetric techniques and fitting an appropriate thermodynamic model to the experimental data. In this work, we compare the traditional approach of fitting the thermodynamic model to experimental data obtained from each experiment individually and the global approach of simultaneously fitting the model to all available data from different experiments. On the basis of several specific examples of DNA and protein unfolding, we demonstrate that piece-by-piece verification of the proposed thermodynamic model using individual fits is frequently inappropriate and can result in an incorrect mechanism and thermodynamics of the studied unfolding process. We find that while the two approaches are complementary in some aspects of analysis global fitting is essential for the appropriate selection and critical evaluation of the model mechanism. Only a good global fit thus gives us confidence that the obtained thermodynamic parameters of unfolding have real physical meaning. PMID- 20540497 TI - Biscrown-annulated TTFAQ-dianthracene hybrid: synthesis, structure, and metal ion sensing. AB - A new fluorescence chemosensor (3) made up of a biscrown-annulated TTFAQ receptor and two anthracene fluorophores was designed and synthesized. Its solid-state structure was disclosed by X-ray crystallographic analysis, while fluorescence titrations indicated a high sensitivity for large hard metal cations such as Ba(2+). PMID- 20540499 TI - Solute-solvent intermolecular interactions in supercritical Xe, SF6, CO2, and CHF3 investigated by Raman spectroscopy: greatest attractive energy observed in supercritical Xe. AB - Vibrational Raman spectra of the C=C stretching modes of cis- and trans-1,2 dichloroethylene (C(2)H(2)Cl(2)) were measured in supercritical Xe, SF(6), CO(2), and CHF(3). The spectra were collected over a wide range of densities of supercritical fluids at a fixed solute mole fraction and isotherm of T(r) = T/T(c) = 1.02. In all fluids, as the density increased, the peak frequencies of the C=C stretching modes shifted toward the low-energy side. By analyzing these density dependencies using the perturbed hard-sphere theory, the shifted amounts were characterized into attractive and repulsive components. The attractive shifts of both isomers were almost equivalent in supercritical CHF(3), CO(2), and SF(6), whereas they were significantly larger in supercritical Xe. The attractive shifts obtained experimentally were compared with the ones calculated on the basis of dispersion, dipole-dipole, dipole-induced-dipole, and dipole-quadrupole interactions between solute and solvent molecules. The experimental attractive shifts in supercritical Xe were 2-3 times greater than the calculated shifts. The large attractive shifts were ascribed to both an anisotropic solvation structure and to a strong interaction (charge transfer) between Xe and C(2)H(2)Cl(2) molecules. PMID- 20540498 TI - Role of heme in the unfolding and assembly of myoglobin. AB - The unfolding of wild-type holomyoglobin in the ferric state (metMb) appears to be a simple two-state process, even though hemichrome spectra are often observed and apoMb denaturation involves an intermediate. To resolve these discrepancies, we measured GuHCl-induced, equilibrium unfolding of five sperm whale metMb variants, which were selected to examine the relative importance of apoglobin stability and hemin affinity. Combined analysis of CD, Trp fluorescence, and Soret absorbance titration curves for all the variants requires a six-state mechanism containing native (N), intermediate (I), and unfolded (U) states of apoMb and their hemin-bound counterparts, NH (holoMb), IH, and UH, respectively. The unfolding parameters for the apoMbs were obtained in independent experiments and then fixed in the analysis of the holoprotein data, where only the affinities of the apoglobin states for hemin were allowed to vary. This cofactor binding analysis applies generally to all globins and led to three specific conclusions. (1) The stability of holo-metMb is determined primarily by the high affinity (K(d) approximately 10(-13) M) of native apoMb (N) for hemin. (2) The partially unfolded intermediate with hemin bound (IH) has a hemichrome spectrum indicative of a bis-histidyl axial coordination and is seen clearly when the stability of the N state or its affinity for hemin is reduced. (3) Although the affinity of the intermediate for hemin (K(d) approximately 10(-11) M) is approximately 100 fold lower than that for the native state, free hemin can bind to it and promote the assembly of the holoprotein. PMID- 20540500 TI - Unusual isomers of disilacyclopropenylidene (Si2CH2). AB - Nine electronic singlet state structures of Si(2)CH(2) have been systematically investigated by high level theoretical methods. This research employed coupled cluster (CC) methods with single and double excitations (CCSD) and CCSD with perturbative triple excitations [CCSD(T)] using the correlation-consistent polarized valence cc-pVXZ/cc-pV(X+d)Z (X = D, T, and Q) basis sets. Full valence complete active space self-consistent-field (CASSCF) wave functions were used for the interpretation of geometries and physical properties. Among the nine singlet stationary points, six structures (1S-6S) are found to be minima, two structures (7S and 8S) are transition states, and one structure (9S) is a second-order saddle point. The existence of the two peculiar hydrogen bridged isomers, 1S (Si...H...Si) and 4S (agostic CH...Si) is established. Extensive focal point analyses are used to obtain complete basis set (CBS) limit energies. For the six lowest-lying singlet minima, after focal point analyses, the energy ordering and energy differences (in kcal mol(-1), with the zero-point vibrational energy corrected values in parentheses) are predicted to be 1S [0.0 (0.0)] < 3S [14.7 (14.5)] < 4S [25.1 (25.3)] < 5S [28.2 (26.0)] < 6S [45.0 (45.4)] < 2S [73.8 (72.0)]. Their relative energies are strikingly different from those for the isovalent parent C(3)H(2) molecule. Geometries, dipole moments, harmonic vibrational frequencies, and associated infrared (IR) intensities are reported for all equilibrium structures. PMID- 20540501 TI - Mutational analysis of substrate interactions with the active site of dialkylglycine decarboxylase. AB - Pyridoxal phosphate (PLP)-dependent enzymes catalyze many different types of reactions at the alpha-, beta-, and gamma-carbons of amine and amino acid substrates. Dialkylglycine decarboxylase (DGD) is an unusual PLP-dependent enzyme that catalyzes two reaction types, decarboxylation and transamination, in the same active site. A structurally based, functional model has been proposed for the DGD active site, which maintains that R406 is important in determining substrate specificity through interactions with the substrate carboxylate while W138 provides specificity for short-chain alkyl groups. The mechanistic roles of R406 and W138 were investigated using site-directed mutagenesis, alternate substrates, and analysis of steady-state and half-reaction kinetics. Experiments with the R406M and R406K mutants confirm the importance of R406 in substrate binding. Surprisingly, this work also shows that the positive charge of R406 facilitates catalysis of decarboxylation. The W138F mutant demonstrates that W138 indeed acts to limit the size of the subsite C binding pocket, determining specificity for 2,2-dialkylglycines with small side chains as predicted by the model. Finally, work with the double mutant W138F/M141R shows that these mutations expand substrate specificity to include l-glutamate and lead to an increase in specificity for l-glutamate over 2-aminoisobutyrate of approximately 8 orders of magnitude compared to that of wild-type DGD. PMID- 20540502 TI - Accounting for polarization cost when using fixed charge force fields. II. Method and application for computing effect of polarization cost on free energy of hydration. AB - Polarization cost is the energy needed to distort the wave function of a molecule from one appropriate to the gas phase to one appropriate for some condensed phase. Although it is not currently standard practice, polarization cost should be considered when deriving improved fixed charge force fields based on fits to certain types of experimental data and when using such force fields to compute observables that involve changes in molecular polarization. Building on earlier work, we present mathematical expressions and a method to estimate the effect of polarization cost on free energy and enthalpy implied by a charge model meant to represent a solvated state. The charge model can be any combination of point charges, higher-order multipoles, or even distributed charge densities, as long as they do not change in response to environment. The method is illustrated by computing the effect of polarization cost on free energies of hydration for the neutral amino acid side chain analogues as predicted using two popular fixed charge force fields and one based on electron densities computed using quantum chemistry techniques that employ an implicit model to represent aqueous solvent. From comparison of the computed and experimental hydration free energies, we find that two commonly used force fields are too underpolarized in their description of the solute-water interaction. On the other hand, a charge model based on the charge density from a hybrid density functional calculation that used an implicit model for aqueous solvent performs well for hydration free energies of these molecules after the correction for dipole polarization is applied. As such, an improved description of the density (e.g., B3LYP, MP2) in conjunction with an implicit solvent (e.g., PCM) or explicit solvent (e.g., QM/MM) approach may offer promise as a starting point for the development of improved fixed charge models for force fields. PMID- 20540503 TI - Accounting for polarization cost when using fixed charge force fields. I. Method for computing energy. AB - Although it is not currently standard practice, the cost to change the electronic polarization from one appropriate for the gas phase to that implied by the charge model should be considered when deriving force fields based on fits to certain types of experimental data and for using force fields to compute observables that involve changes in molecular polarization. We present mathematical expressions and a method to estimate this polarization cost implied by a fixed charge model force field, where the fixed charge model can be any combination of point charges, higher-order multipoles, or even distributed charge densities, as long as they do not change in response to environment. These expressions illuminate the relationship between polarization costs associated with fixed charge models, self-polarization energies of polarizable models, and quantum chemical based approaches that use continuum representations of the solvent, such as the self consistent reaction field and polarizable continuum models. The technique takes account of the tensorial nature of the polarizabilities and includes quadrupole as well as dipole polarization. The consistency of this approach to one that estimates polarization cost using an implicit solvent quantum chemistry method (PCM) is demonstrated. PMID- 20540504 TI - Electrochemical immunosensors for antibodies to peanut allergen ara h2 using gold nanoparticle-peptide films. AB - Life-threatening allergies to peanuts and tree nuts can be revealed by detecting antibodies (IgEs) to their allergens in patient serum. Herein, we compare several immunosensor-like methodologies for sensitive detection of antibodies to a peptide sequence from the major peanut allergen, Arachis hypogaea 2 (Ara h2). The sensors feature a synthetic peptide layer of the major IgE-binding epitope from Ara h2 attached to a dense gold nanoparticle (AuNP) film on a pyrolytic graphite (PG) electrode. The AuNP-peptide sensor was used to determine model chicken antipeanut antibodies (IgY) in serum. Faradaic and nonfaradaic impedance strategies were compared to amperometric detection. Measurements employed goat antichicken secondary antibodies (Ab(2)) labeled with horseradish peroxidase (HRP) to bind to IgY on the sensor and provide amplified signals. The best impedimetric sensor configuration featured HPR-catalyzed precipitation of the enzyme product onto the sensor measured by nonfaradaic impedance. This sensor configuration had the best detection limit (DL) of 5 pg mL(-1) and the best linear range of over 5 orders of magnitude (from 5 pg mL(-1) to 1 microg mL(-1)) for IgY antibody in undiluted calf serum. This DL was 100-fold lower than label free impedimetric immunosensors (0.5 ng mL(-1)) and 60-fold lower than when using HRP-Ab(2) in amperometric immunosensors (0.3 ng mL(-1)). PMID- 20540505 TI - Optimized method for computing (18)O/(16)O ratios of differentially stable isotope labeled peptides in the context of postdigestion (18)O exchange/labeling. AB - Differential (18)O/(16)O stable isotope labeling of peptides that relies on enzyme-catalyzed oxygen exchange at their carboxyl termini in the presence of H(2)(18)O has been widely used for relative quantitation of peptides/proteins. The role of tryptic proteolysis in bottom-up shotgun proteomics and low reagent costs have made trypsin-catalyzed (18)O postdigestion exchange a convenient and affordable stable isotope labeling approach. However, it is known that trypsin catalyzed (18)O exchange at the carboxyl terminus is in many instances inhomogeneous/incomplete. The extent of the (18)O exchange/incorporation fluctuates from peptide to peptide mostly due to variable enzyme-substrate affinity. Thus, accurate calculation and interpretation of peptide ratios are analytically complicated and in some regard deficient. Therefore, a computational approach capable of improved measurement of actual (18)O incorporation for each differentially labeled peptide pair is needed. In this regard, we have developed an algorithmic method that relies on the trapezoidal rule to integrate peak intensities of all detected isotopic species across a particular peptide ion over the retention time, which fits the isotopic manifold to Poisson distributions. Optimal values for manifold fitting were calculated and then (18)O/(16)O ratios derived via evolutionary programming. The algorithm is tested using trypsin catalyzed (18)O postdigestion exchange to differentially label bovine serum albumin (BSA) at a priori determined ratios. Both accuracy and precision are improved utilizing this rigorous mathematical approach. We further demonstrate the effectiveness of this method to accurately calculate (18)O/(16)O ratios in a large scale proteomic quantitation of detergent resistant membrane microdomains (DRMMs) isolated from cells expressing wild-type HIV-1 Gag and its nonmyristylated mutant. PMID- 20540506 TI - Microfluidic cell culture and metabolism detection with electrospray ionization quadrupole time-of-flight mass spectrometer. AB - A novel method for the characterization of drug metabolites was developed by integrating chip-based solid-phase extraction (SPE) with an online electrospray ionization quadrupole time-of-fight mass spectrometer (ESI-Q-TOF-MS). The integrated microfluidic device was composed of circular chambers for cell culture and straight microchannels with shrink ends to pack the solid-phase material for sample cleanup and concentration prior to mass analysis. By connecting the two separated microchannels with polyethylene tubes, drug metabolism studies related to functional units, including cell culture, metabolism generation, sample pretreatment, and detection, were all integrated into the microfluidic device. To verify the feasibility of a drug metabolism study on the microfluidic device, the metabolism of vitamin E in human lung epithelial A549 cells was studied. The metabolites were successfully detected by online ESI-Q-TOF-MS with high sensitivity and short analysis time (8 min). By integrating several parallel channels, the desalting and concentration process could be simultaneously achieved. The total sample pretreatment time only needed about 15 min, and solvent consumption could be reduced to less than 100 microL. All this demonstrated that the developed microfluidic device could be a potential useful tool for cellular drug metabolism research. PMID- 20540507 TI - Wet catalyst-support films for production of vertically aligned carbon nanotubes. AB - A procedure for vertically aligned carbon nanotube (VA-CNT) production has been developed through liquid-phase deposition of alumoxanes (aluminum oxide hydroxides, boehmite) as a catalyst support. Through a simple spin-coating of alumoxane nanoparticles, uniform centimer-square thin film surfaces were coated and used as supports for subsequent deposition of metal catalyst. Uniform VA-CNTs are observed to grow from this film following deposition of both conventional evaporated Fe catalyst, as well as premade Fe nanoparticles drop-dried from the liquid phase. The quality and uniformity of the VA-CNTs are comparable to growth from conventional evaporated layers of Al(2)O(3). The combined use of alumoxane and Fe nanoparticles to coat surfaces represents an inexpensive and scalable approach to large-scale VA-CNT production that makes chemical vapor deposition significantly more competitive when compared to other CNT production techniques. PMID- 20540508 TI - Egg yolk peptides up-regulate glutathione synthesis and antioxidant enzyme activities in a porcine model of intestinal oxidative stress. AB - Long-term oxidative stress in the gastrointestinal tract can lead to the development of chronic intestinal disorders. Many food-derived antioxidants are effective in vitro, but the variable reports of in vivo efficacy and the pro oxidant nature of some antioxidants necessitate alternative strategies for the reduction of in vivo oxidative stress. Compounds that up-regulate the production of endogenous antioxidants such as glutathione (GSH) and antioxidant enzymes provide novel approaches for the restoration of redox homeostatis. Egg yolk peptides (EYP) prepared from Alcalase and protease N digestion of delipidated egg yolk proteins were found to exhibit antioxidative stress properties. The effect of EYP supplementation was examined in a hydrogen peroxide-induced human colon cell line and in an animal model of intestinal oxidative stress. EYP significantly reduced the pro-inflammatory cytokine, IL-8, in Caco-2 cells. In piglets given intraperitoneal infusions of hydrogen peroxide, EYP treatment increased GSH and gamma-glutamylcysteine synthetase mRNA expression and activity, significantly increased antioxidant enzyme activities, in particular catalase and glutathione S-transferase activities, and reduced protein and lipid oxidation in the duodenum, jejunum, ileum, and colon. Furthermore, EYP boosted the systemic antioxidant status in blood by increasing the GSH concentration in red blood cells. These results suggest that EYP supplementation is a novel strategy for the reduction of intestinal oxidative stress. PMID- 20540509 TI - Iridium-catalyzed anti-diastereo- and enantioselective carbonyl (trimethylsilyl)allylation from the alcohol or aldehyde oxidation level. AB - Using the ortho-cyclometalated pi-allyl iridium precatalyst (R)-I derived from [Ir(cod)Cl](2), 4-cyano-3-nitrobenzoic acid, (R)-SEGPHOS, and allyl acetate, enantioselective transfer hydrogenation of alpha-(trimethylsilyl)allyl acetate in the presence of aldehydes 2a-i mediated by 2-propanol delivers products of (trimethylsilyl)allylation 4a-i in good isolated yields and with exceptional levels of anti-diastereoselectivity and enantioselectivity (90-99% ee). In the absence of 2-propanol, but under otherwise identical reaction conditions, carbonyl (trimethylsilyl)allylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts 4a-i with roughly equivalent isolated yields and stereoselectivities. To evaluate the synthetic utility of the reaction products 4a-i, adduct 4g was converted to the 1,4-ene diol 5g via dioxirane-mediated oxidative desilylation with allylic transposition, the allylic alcohol 6g via protodesilylation with allylic transposition, and the gamma-lactam 7g via chlorosulfonyl isocyanate-mediated cycloaddition. PMID- 20540510 TI - Bivalent diketopiperazine-based tropomysin receptor kinase C (TrkC) antagonists. AB - Bivalent molecules containing two beta-turn mimics with side chains that correspond to hot-spots on the neurotrophin NT-3 were prepared. Binding assays showed the mimetics to be selective TrkC ligands, and biological assays showed one mimetic to be an antagonist of the TrkC receptor. PMID- 20540512 TI - One-electron pseudopotential investigation of CsAr van der Waals system including the spin-orbit interaction. AB - The potential energy curves of the ground state and many excited states of the CsAr van der Waals system have been determined using [Cs(+)] and [Ar] core pseudopotentials and by considering core polarization operators on both atoms. This has permitted to reduce the number of active electrons of the CsAr system to only one electron, i.e., the valence electron, which led to use of large basis sets for Cs and Ar atoms. In this context, the potential energy curves of the ground state and many excited states are performed at the self consistent field (SCF) level. Spin-orbit interaction is also considered within a semiempirical scheme for the states dissociating into Cs(6p) and Cs(5d). The core-core interactions for Cs(+)Ar is included using the coupled cluster simple and double excitation (CCSD) accurate potential of Hickling et al. (Hickling, H.; Viehland, L.; Shepherd, D.; Soldan, P.; Lee, E.; Wright, T. Phys. Chem. Chem. Phys. 2004, 6, 4233). In addition, the spectroscopic constants of these states are derived and compared with the available theoretical and experimental works. Such comparison has shown a very good agreement for the ground and the first excited states. However, the spectroscopic data for the higher excited states are presented for the first time. PMID- 20540511 TI - The effect of structure on nitroxide EPR spectral linewidth. AB - Nitroxides with narrow linewidths are essential for low-frequency EPR spectroscopy and in vivo EPR imaging. In developing a framework for designing narrow-line nitroxides, we sought to understand the unexpectedly narrow line width of 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxyl (5). Computational modeling revealed that the carbonyl double bond in the 4-position allows conformational diversity that results in the observed narrowing of the EPR spectral line. In view of this finding, we synthesized two new nitroxides bearing an exocyclic double bond: 4-methoxycarbonylmethylidene-2,2,6,6-tetramethyl-1-piperidinyloxyl (7) and 4-acetoxymethoxycarbonylmethylidene-2,2,6,6-tetramethyl-1-piperidinyloxyl (9). These nitroxides, like nitroxide 5, exhibited narrow linewidths-consistent with the results of modeling. Nitroxide 8 (4-carboxymethylidene-2,2,6,6 tetramethyl-1-piperidinyloxyl), as a prototype, allows for a variety of structural diversity, such as nitroxide 9,that can, for instance, target tissue compartments for in vivo EPR imaging. PMID- 20540513 TI - Low entropic barrier to the hydrophobic collapse of the prion protein: effects of intermediate states and conformational flexibility. AB - A simple kinetic model is applied to study the folding reaction of the C-terminal domain of the murine prion protein, mPrP(121-231). The model provides an equation linking a protein's folding rate with its native topology and the conformational entropic cost of folding. The model predicts that the average conformational entropic cost per residue associated with the folding transition of mPrP(121-231) is smaller than the average for a broad sample of two-state folding proteins. The results are consistent with the native state of mPrP(121-231) being more flexible than the average protein, but the behavior could also arise from the presence of early intermediate states. The findings are in agreement with experimental and theoretical results on the prion protein conformational flexibility. The model is fully analytical and provides a simple way to obtain a quantitative measure of conformational flexibility in two-state proteins from kinetic and structural experimental data. PMID- 20540514 TI - Selective addition of organolithium reagents to BF2-chelates of beta-ketoesters. AB - A short, mild, and highly chemoselective addition of organolithium reagents to a BF(2) complex of 3-oxopropanoates has been developed. The methodology allows straightforward preparation of various 1,3-dioxa-BF(2) complexes and subsequently leads to the formation of 1,3-diketones starting from the corresponding 3 oxopropanoates. PMID- 20540515 TI - Concise approach to pupukeanane skeleton: synthetic study of chloropupukeananin. AB - A concise synthesis of a highly functionalized chloropupukeananin (1) skeleton via a reverse electron-demand Diels-Alder reaction and intramolecular carbonyl ene reaction sequence based on our proposed biosynthetic pathway is described. PMID- 20540516 TI - Aiming for the ideal synthesis. AB - The field of total synthesis has a rich history and a vibrant future. Landmark advances and revolutionary strides in the logic of synthesis have put the practicing chemist in the enviable position of being able to create nearly any molecule with enough time and effort. The stage is now set for organic chemists to aim for "ideality" in the way molecules are synthesized. This perspective presents a simple and informative definition of "ideality" and demonstrates its use during the self-evaluation of several syntheses from our laboratory. PMID- 20540518 TI - In silico prediction of the 3D structure of trimeric asialoglycoprotein receptor bound to triantennary oligosaccharide. AB - In this study, we present a general-purpose methodology for deriving the three dimensional (3D) arrangement of multivalent transmembrane complexes in the presence of their ligands. Specifically, we predict the most likely families of structures of the experimentally intractable trimeric asialoglycoprotein receptor (ASGP-R), which consists of human hepatic subunits (two subunits of H1 and one subunit of H2), bound to a triantennary oligosaccharide (TA). Because of the complex nature of this multivalent type-II transmembrane hetero-oligomeric receptor, structural studies have to date been unable to provide the 3D arrangement of these subunits. Our approach is based on using the three-pronged ligand of ASGP-R as a computational probe to derive the 3D conformation of the complex and then using this information to predict the relative arrangement of the protein subunits on the cell surface. Because of interprotein subunit clashes, only a few families of TA conformers are compatible with the trimeric structure of ASGP-R. We find that TA displays significant flexibility, matching that detected previously in FRET experiments, and that the predicted complexes derived from the viable TA structures are asymmetric. Significant variation exists with respect to TA presentation to the receptor complex. In summary, this study provides detailed information about TA-ASGP-R interactions and the symmetry of the complex. PMID- 20540517 TI - Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. AB - Virtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false positives. Prioritizing molecules that are both predicted by docking and are HTS active yields well-behaved molecules, relatively unobscured by the false positives to which both techniques are individually prone. PMID- 20540520 TI - Complexes of Gilman reagents with C-S and C-N double bonds: sigma or pi bonding? AB - Upon rapid injection, a variety of thiocarbonyl compounds react with the Gilman reagent Me(2)CuLi at -100 degrees C inside the probe of an NMR spectrometer to give high yields of complexes. Typical examples of substrates include carbon disulfide, methyl dithioacetate, methyl dithiobenzoate, thiobenzophenone, ethylene trithiocarbonate, and phenyl isothiocyanate. Evidence suggesting the formal oxidation state of copper in these complexes to be Cu(III) is presented. The last example was particularly interesting, since it involved a transient intermediate that was identified as a complex with a C-N double bond. Methyl isothiocyanate gave a stable C-N double-bond complex. PMID- 20540519 TI - Development of pH-responsive fluorescent false neurotransmitters. AB - We introduce pH-responsive fluorescent false neurotransmitters (pH-responsive FFNs) as novel probes that act as vesicular monoamine transporter (VMAT) substrates and ratiometric fluorescent pH sensors. The development of these agents was achieved by systematic molecular design that integrated several structural elements, including the aminoethyl group (VMAT recognition), halogenated hydroxy-coumarin core (ratiometric optical pH sensing in the desired pH range), and N- or C-alkylation (modulation of lipophilicity). Of 14 compounds that were synthesized, the probe Mini202 was selected based on the highest uptake in VMAT2-transfected HEK cells and desirable optical properties. Using Mini202, we measured the pH of catecholamine secretory vesicles in PC-12 cells (pH approximately 5.9) via two-photon fluorescence microscopy. Incubation with methamphetamine led to an increase in vesicular pH (pH approximately 6.4), consistent with a proposed mechanism of action of this psychostimulant, and eventually to redistribution of vesicular content (including Mini202) from vesicles to cytoplasm. Mini202 is sufficiently bright, photostable, and suitable for two-photon microscopy. This probe will enable fundamental neuroscience and neuroendocrine research as well as drug screening efforts. PMID- 20540521 TI - Phosphine-free synthesis of p-type copper(I) selenide nanocrystals in hot coordinating solvents. AB - We report a phosphine-free synthesis of p-type copper(I) selenide nanocrystals by a colloidal approach in a mixture of oleylamine and 1-octadecene. The nanocrystals had a cuboctahedral shape and cubic berzelianite phase. Films of these nonstoichiometric copper-deficient Cu(2-x)Se nanocrystals were highly conductive and showed high absorption coefficient in the near-infrared region. These nanocrystals could be used as hole-injection layers in optoelectronic devices. PMID- 20540522 TI - Carboxylation of C-H bonds using N-heterocyclic carbene gold(I) complexes. AB - A highly efficient [(NHC)Au(I)]-based (NHC = N-heterocyclic carbene) catalytic system for the carboxylation of aromatic and heteroaromatic C-H bonds was developed. The significant base strength of the Au-OH species is at the origin of the activation process and permits the facile functionalization of C-H bonds without the use of other organometallic reagents. PMID- 20540523 TI - Nanosecond dynamics of photoexcited lyotropic liquid crystal structures. AB - Home-based soft X-ray time-resolved diffraction (TR-SXD) experiments with nanosecond time resolution (10 ns) and nanometer spatial resolution were carried out at a tabletop soft X-ray plasma source (2.7-5.9 nm). The investigated system was the lyotropic liquid crystal C(16)E(7)/paraffin/glycerol/formamide/IR 5. Usually, major changes in physical, chemical, and/or optical properties of the sample result from structural changes and shrinking morphology. Here, these effects occur as a consequence of the energy absorption in the sample upon optical laser excitation in the IR regime. The variations observed are integral intensity modulations and displacement in the Bragg diffraction angle. To follow the diffracted integral intensity changes, Patterson analysis was used, and the lattice parameter d variations have been followed by applying the Bragg diffraction law. The experimental intensity modulations occur on the nanosecond time scale, and they are assigned to photoinduced diffusion processes within the liquid crystalline phase. The structural response after photoexcitation is experimentally observed as an increase of the lattice constant by 0.5-1 A and is interpreted as a decrease of order in the liquid crystalline phase. This coincides with a reorientation to a photocreated liquid crystal lattice in the surface plane and with respect to the E-field vector of the laser light. The present studies emphasize the possibility of using TR-SXD techniques for studying the transient mechanical dynamics of nanosystems at the submicrosecond time scale. PMID- 20540525 TI - Iridium compounds with kappa-P,P,Si (biPSi) pincer ligands: favoring reactive structures in unsaturated complexes. AB - The structure, coordination properties, insertion processes, and dynamic behavior in solution of the five-coordinate complexes [IrXH(biPSi)] (biPSi = kappa-P,P,Si Si(Me){(CH(2))(3)PPh(2)}(2); X = Cl (1), Br (2), or I (3)) have been investigated. The compounds are formed as mixtures of two isomers, anti and syn, in slow equilibrium in solution. The equilibrium position depends on the halogen and the solvent. Both isomers display distorted square-based pyramidal structures in which the vacant position sits trans to silicon. The equatorial plane of the syn isomer is closer to the T structure due to distortions of steric origin. The small structural differences between the isomers trigger remarkable differences in reactivity. The syn isomers form six-coordinate adducts with chlorinated solvents, CO, P(OMe)(3), or NCMe, always after ligand coordination trans to silicon. The anti isomers do not form detectable adducts with chlorinated solvents and coordinate CO or P(OMe)(3) either trans to silicon (kinetic) or trans to hydride (thermodynamic). NCMe coordinates the anti isomers exclusively at the position trans to hydride. Qualitative and quantitative details (equilibrium constants, enthalpies, entropies, etc.) on these coordination processes are given and discussed. As a result of the different coordination properties, insertion reagents such as acetylene, diphenylacetylene, or the alkylidene resulting from the decomposition of ethyl diazoacetate selectively insert into the Ir-H bond of 1-syn, not into that of 1-anti. These reactions give five-coordinate syn alkenyl or alkyl compounds in which the vacancy also sits trans to silicon. Acetylene is polymerized in the coordination sphere of 1. The nonreactive isomer 1-anti also evolves into the syn insertion products via anti<- >syn isomerizations, the rates of which are notably dependent on the nature of the insertion reactants. H(2) renders anti<-->syn isomerization rates of the same order as the NMR time scale. The reactions are second order (k(obs) = k(anti<- >syn)[H(2)]) and do not involve H(2)/IrH hydrogen atom scrambling. A possible isomerization mechanism, supported by MP2 calculations and compatible with the various experimental observations, is described. It involves Ir(V) intermediates and a key sigma Ir-(eta(2)-SiH) agostic transition state. A similar transition state could also explain the anti<-->syn isomerizations in the absence of oxidative addition reactants, although at the expense of high kinetic barriers strongly dependent on the presence of potential ligands and their nature. PMID- 20540524 TI - Unexpected hormonal activity of a catechol equine estrogen metabolite reveals reversible glutathione conjugation. AB - 4-Hydroxyequilenin (4-OHEN) is a major phase I metabolite of the equine estrogens present in widely prescribed hormone replacement formulations. 4-OHEN is autoxidized to an electrophilic o-quinone that has been shown to redox cycle, generating ROS, and to covalently modify proteins and DNA and thus potentially to act as a chemical carcinogen. To establish the ability of 4-OHEN to act as a hormonal carcinogen at the estrogen receptor (ER), estrogen responsive gene expression and proliferation were studied in ER(+) breast cancer cells. Recruitment by 4-OHEN of ER to estrogen responsive elements (ERE) of DNA in MCF-7 cells was also studied and observed. 4-OHEN was a potent estrogen, with additional weak activity associated with binding to the arylhydrocarbon receptor (AhR). The potency of 4-OHEN toward classical ERalpha mediated activity was unexpected given the reported rapid autoxidation and trapping of the resultant quinone by GSH. Addition of thiols to cell cultures did not attenuate the estrogenic activity of 4-OHEN, and preformed thiol conjugates added to cell incubations only marginally reduced ERE-luciferase induction. On reaction of the 4OHEN-GSH conjugate with NADPH, 4-OHEN was observed to be regenerated at a rate dependent upon NADPH concentration, indicating that intracellular nonenzymatic and enzymatic regeneration of 4-OHEN accounts for the observed estrogenic activity of 4-OHEN. 4-OHEN is therefore capable of inducing chemical and hormonal pathways that may contribute to estrogen-dependent carcinogenesis, and trapping by cellular thiols does not provide a mechanism of termination of these pathways. PMID- 20540526 TI - Cyclosporin A-loaded poly(ethylene glycol)-b-poly(d,l-lactic acid) micelles: preparation, in vitro and in vivo characterization and transport mechanism across the intestinal barrier. AB - To improve the oral bioavailability of poorly water-soluble cyclosporin A (CyA), polymeric micelles based on monomethoxy poly(ethylene glycol)-b-poly(d,l-lactic acid) (mPEG-PLA) were prepared. In vitro release test showed that the cumulative release percentage, about 85%, of CyA from polymeric micelles within 24 h was comparable to that from Sandimmun Neoral, the currently available oral formulation of CyA. A relative oral bioavailability of 137% in rats compared with Sandimmun Neoral was demonstrated for CyA-loaded polymeric micelles. The other aim of the current work was to study the transport mechanism of mPEG-PLA micelles across the intestinal barrier. It was found that polymeric micelles could significantly increase the permeability of CyA across Caco-2 monolayers without significantly affecting transepithelial electrical resistance values, and the apparent permeation coefficient (P(app)) of CyA was significantly higher in the AP-BL direction compared to that in the BL-AP direction, suggesting that polymeric micelles might undergo an active AP to BL transport that probably involved endocytosis which was confirmed by confocal microscope observation. The permeation of CyA through Caco-2 monolayers showed that the P(app) was significantly increased when CyA was formulated with the copolymer below its critical association concentration (CAC) and no significant difference was found above its CAC, implying that mPEG-PLA monomers affected the intestinal P-gp efflux pumps. Therefore, the mPEG-PLA micelles seemed to be a good candidate for oral delivery of poorly soluble drugs. PMID- 20540529 TI - Unexpected tolerance of glycosylation by UDP-GalNAc:polypeptide alpha-N acetylgalactosaminyltransferase revealed by electron capture dissociation mass spectrometry: carbohydrate as potential protective groups. AB - UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs, EC 2.4.1.41), a family of key enzymes that initiate posttranslational modification with O-glycans in mucin synthesis by introduction of alpha-GalNAc residues, are structurally composed of a catalytic domain and a lectin domain. It has been known that multiple Ser/Thr residues are assigned in common mucin glycoproteins as potential O-glycosylation sites and more than 20 distinct isoforms of this enzyme family contribute to produce densely O-glycosylated mucin glycoproteins. However, it seems that the functional role of the lectin domain of ppGalNAcTs remains unclear. We considered that electron capture dissociation mass spectrometry (ECD-MS), a promising method for highly selective fragmentation at peptide linkages of glycopeptides to generate unique c and z series of ions, should allow for precise structural characterization to uncover the mechanism in O-glycosylation of mucin peptides by ppGalNAcTs. In the present study, it was demonstrated that a system composed of an electrospray source, a linear RFQ ion trap that isolates precursor ions, the ECD device, and a TOF mass spectrometer is a nice tool to identify the preferential O-glycosylation sites without any decomposition of the carbohydrate moiety. It should be noted that electrons used for ECD are accelerated within a range from 1.75 to 9.75 eV depending on the structures of glycopeptides of interest. We revealed for the first time that additional installation of a alpha-GalNAc residue at potential glycosylation sites by ppGalNAcT2 proceeds smoothly in various unnatural glycopeptides having alpha-Man, alpha-Fuc, and beta-Gal residues as well as alpha-GalNAc residues. The results may suggest that ppGalNAcT2 did not differentiate totally presubstituted sugar residues in terms of configuration of functional groups, d-, l configuration, and even alpha-, beta-stereochemistry at an anomeric carbon atom when relatively short synthetic peptides were employed for the acceptor substrates. Unexpected characteristics of ppGalNAcT2 motivated us to challenge site-directed installation of alpha-GalNAc residues at desired position(s) by protecting some hydroxyl groups of Thr/Ser residues with selectively removable sugars, notably a novel concept as "carbohydrate as protective groups", toward a goal of the systematic chemical and enzymatic synthesis of biologically important mucin glycopeptides. PMID- 20540528 TI - Study of the multidrug membrane transporter of single living Pseudomonas aeruginosa cells using size-dependent plasmonic nanoparticle optical probes. AB - Multidrug membrane transporters (efflux pumps) in both prokaryotes and eukaryotes are responsible for impossible treatments of a wide variety of diseases, including infections and cancer, underscoring the importance of better understanding of their structures and functions for the design of effective therapies. In this study, we designed and synthesized two silver nanoparticles (Ag NPs) with average diameters of 13.1 +/- 2.5 nm (8.1-38.6 nm) and 91.0 +/- 9.3 nm (56-120 nm) and used the size-dependent plasmonic spectra of single NPs to probe the size-dependent transport kinetics of MexAB-OprM (multidrug transporter) in Pseudomonas aeruginosa in real time at nanometer resolution. We found that the level of accumulation of intracellular NPs in wild-type (WT) cells was higher than in nalB1 (overexpression of MexAB-OprM) but lower than in DeltaABM (deletion of MexAB-OprM). In the presence of proton ionophores (CCCP, inhibitor of proton motive force), we found that intracellular NPs in nalB1 were nearly doubled. These results suggest that MexAB-OprM is responsible for the extrusion of NPs out of cells and NPs (orders of magnitude larger than conventional antibiotics) are the substrates of the transporter, which indicates that the substrates may trigger the assembly of the efflux pump optimized for the extrusion of the encountered substrates. We found that the smaller NPs stayed inside the cells longer than larger NPs, suggesting the size-dependent efflux kinetics of the cells. This study shows that multisized NPs can be used to mimic various sizes of antibiotics for probing the size-dependent efflux kinetics of multidrug membrane transporters in single living cells. PMID- 20540527 TI - Silencing heat shock protein 27 decreases metastatic behavior of human head and neck squamous cell cancer cells in vitro. AB - The small heat shock protein 27 (Hsp27) is a molecular chaperone that is involved in a variety of cellular functions in cancer cells. The purpose of this research is to study Hsp27 in vitro metastatic behaviors of head and neck squamous cell carcinoma cells (HNSCC). The expression of Hsp27 in primary and metastatic cell lines derived from the primary HNSCC and a synchronous lymph node metastasis in the same patient was determined using real-time PCR and Western blotting. Proliferation of the primary and metastatic HNSCC cell lines was evaluated using the MTS proliferation assay. Metastatic behavior was assessed using migration and invasion assays. SiRNA knockdown of Hsp27 was performed in the highly migratory metastatic HNSCC cell line. MTS assays showed that the primary (UM-SCC-22A) and metastatic (UM-SCC-22B) HNSCC have similar proliferation rates. However, UM-SCC 22B derived from the metastasis showed 2.3- to 3.6-fold higher migration ability and 2-fold higher invasion ability than UM-SCC-22A. Real-time PCR demonstrated that Hsp27 mRNA is 22.4-fold higher in metastatic UM-SCC-22B than primary UM-SCC 22A. Similarly, Western blotting showed that Hsp27 is rarely detectable in UM-SCC 22A whereas UM-SCC-22B expresses a 25-fold higher level of Hsp27 protein. SiRNA mediated knockdown of Hsp27 in UM-SCC-22B reduced Hsp27 mRNA expression by nearly 6-fold and protein expression by 23-fold. Furthermore, siRNA knockdown of Hsp27 decreased metastatic behaviors of UM-SCC-22B by 3- to 4-fold in migration and 2 fold in cell invasion reducing cell invasion and migration to levels similar to the primary HNSCC UM-SCC-22A. These data indicate that Hsp27 may regulate metastatic potential of HNSCC cancer cells. Targeting Hsp27 may decrease metastasis in head and neck squamous cell cancer cells. PMID- 20540530 TI - Uses and biases of volunteer water quality data. AB - State water quality monitoring has been augmented by volunteer monitoring programs throughout the United States. Although a significant effort has been put forth by volunteers, questions remain as to whether volunteer data are accurate and can be used by regulators. In this study, typical volunteer water quality measurements from laboratory and environmental samples in Iowa were analyzed for error and bias. Volunteer measurements of nitrate+nitrite were significantly lower (about 2-fold) than concentrations determined via standard methods in both laboratory-prepared and environmental samples. Total reactive phosphorus concentrations analyzed by volunteers were similar to measurements determined via standard methods in laboratory-prepared samples and environmental samples, but were statistically lower than the actual concentration in four of the five laboratory-prepared samples. Volunteer water quality measurements were successful in identifying and classifying most of the waters which violate United States Environmental Protection Agency recommended water quality criteria for total nitrogen (66%) and for total phosphorus (52%) with the accuracy improving when accounting for error and biases in the volunteer data. An understanding of the error and bias in volunteer water quality measurements can allow regulators to incorporate volunteer water quality data into total maximum daily load planning or state water quality reporting. PMID- 20540531 TI - Nitrate in groundwater of the United States, 1991-2003. AB - An assessment of nitrate concentrations in groundwater in the United States indicates that concentrations are highest in shallow, oxic groundwater beneath areas with high N inputs. During 1991-2003, 5101 wells were sampled in 51 study areas throughout the U.S. as part of the U.S. Geological Survey National Water Quality Assessment (NAWQA) program. The well networks reflect the existing used resource represented by domestic wells in major aquifers (major aquifer studies), and recently recharged groundwater beneath dominant land-surface activities (land use studies). Nitrate concentrations were highest in shallow groundwater beneath agricultural land use in areas with well-drained soils and oxic geochemical conditions. Nitrate concentrations were lowest in deep groundwater where groundwater is reduced, or where groundwater is older and hence concentrations reflect historically low N application rates. Classification and regression tree analysis was used to identify the relative importance of N inputs, biogeochemical processes, and physical aquifer properties in explaining nitrate concentrations in groundwater. Factors ranked by reduction in sum of squares indicate that dissolved iron concentrations explained most of the variation in groundwater nitrate concentration, followed by manganese, calcium, farm N fertilizer inputs, percent well-drained soils, and dissolved oxygen. Overall, nitrate concentrations in groundwater are most significantly affected by redox conditions, followed by nonpoint-source N inputs. Other water-quality indicators and physical variables had a secondary influence on nitrate concentrations. PMID- 20540532 TI - Polybrominated diphenyl ether (PBDE) levels in peregrine falcon (Falco peregrinus) eggs from California correlate with diet and human population density. AB - Peregrine falcons are now considered a conservation success story due in part to the phasing out of harmful contaminants that adversely affected reproduction. Recent studies have shown that peregrine eggs collected from California cities, however, have high levels of the higher-brominated polybrominated diphenyl ethers (SigmaPBDE(183-209)), a class of industrial flame retardants, in comparison to published data for other wildlife. Sources of these high PBDE levels and unusual PBDE profiles are unknown. Here we analyzed the stable carbon (delta(13)C), hydrogen (deltaD), and nitrogen (delta(15)N) isotope composition of peregrine eggs collected from urban and nonurban habitats. We found that delta(13)C values were significantly higher in urban versus nonurban eggs, suggesting that urban peregrines indirectly receive anthropogenic subsidies via their consumption of prey reliant on corn-based anthropogenic foods. delta(15)N and deltaD values were significantly lower in urban versus nonurban eggs, reflecting differences in dietary diversity and food/water sources available to peregrines in each habitat. These patterns suggest a link between an anthropogenic diet and high levels of SigmaPBDE(183-209) in California peregrines, and identify anthropogenic food as a potentially important PBDE exposure pathway for urban wildlife. If diet is an important PBDE exposure pathway for peregrines, continued high body burdens of SigmaPBDE(183-209) may be a potential risk to ongoing peregrine conservation efforts in California. PMID- 20540533 TI - Investigation of thermodynamic parameters in the thermal decomposition of plastic waste-waste lube oil compounds. AB - Thermal decomposition properties of plastic waste-waste lube oil compounds were investigated under nonisothermal conditions. Polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) were selected as representative household plastic wastes. A plastic waste mixture (PWM) and waste lube oil (WLO) were mixed with mixing ratios of 33, 50, and 67 (w/w) % on a PWM weight basis, and thermogravimetric (TG) experiments were performed from 25 to 600 degrees C. The Flynn-Wall method and the Ozawa-Flynn-Wall method were used for analyses of thermodynamic parameters. In this study, activation energies of PWM/WLO compounds ranged from 73.4 to 229.6 kJ/mol between 0.2 and 0.8 of normalized mass conversions, and the 50% PWM/WLO compound had lower activation energies and enthalpies among the PWM/WLO samples at each mass conversion. At the point of maximum differential mass conversion, the analyzed activation energies, enthalpies, entropies, and Gibbs free energies indicated that mixing PWM and WLO has advantages in reducing energy to decrease the degree of disorder. However, no difference in overall energy that would require overcoming both thermal decomposition reactions and degree of disorder was observed among PWM/WLO compounds under these experimental conditions. PMID- 20540534 TI - Noncovalent interactions of long-chain perfluoroalkyl acids with serum albumin. AB - Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios. PMID- 20540535 TI - Triterpene saponins from Clematis chinensis and their potential anti-inflammatory activity. AB - Seven new triterpene saponins, clematochinenosides A-G (1-7), together with 17 known saponins (8-24), were isolated from the roots and rhizomes of Clematis chinensis. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Compounds 1, 3-7, and 20-24 showed inhibitory activities against COX-1 and COX-2 enzymes. PMID- 20540536 TI - Long-range electron transfer reactions between hemes of MauG and different forms of tryptophan tryptophylquinone of methylamine dehydrogenase. AB - The diheme enzyme MauG catalyzes the post-translational modification of a precursor protein of methylamine dehydrogenase (preMADH) to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. This six-electron oxidation of preMADH requires long-range electron transfer (ET) as the structure of the MauG-preMADH complex reveals that the shortest distance between the modified residues of preMADH and the nearest heme of MauG is 14.0 A [Jensen, L. M. R., Sanishvili, R., Davidson, V. L., and Wilmot, C. M. (2010) Science 327, 1392-1394]. The kinetics of two ET reactions between MADH and MauG have been analyzed. Interprotein ET from quinol MADH to the high-valent bis Fe(IV) form of MauG exhibits a K(d) of 11.2 microM and a rate constant of 20 s( 1). ET from diferrous MauG to oxidized TTQ of MADH exhibits a K(d) of 10.1 microM and a rate constant of 0.07 s(-1). These similar K(d) values are much greater than that for the MauG-preMADH complex, indicating that the extent of TTQ maturity rather than its redox state influences complex formation. The difference in rate constants is consistent with a larger driving force for the faster reaction. Analysis of the structure of the MauG-preMADH complex in the context of ET theory and these results suggests that direct electron tunneling between the residues that form TTQ and the five-coordinate oxygen-binding heme is not possible, and that ET requires electron hopping via the six-coordinate heme. PMID- 20540538 TI - Measurements of 13C/12C methane from anaerobic digesters: comparison of optical spectrometry with continuous-flow isotope ratio mass spectrometry. AB - Methane production by anaerobic digestion of biomass has recently become more attractive because of its potential for renewable energy production. Analytical tools are needed to study and optimize the ongoing processes in biogas reactors. It is considered that optical methods providing continuous measurements at high temporal resolution of carbon isotope ratios of methane (delta(13)C(CH4)) might be of great help for this purpose. In this study we have tested near-infrared laser optical spectrometry and compared it with conventional continuous-flow isotope ratio mass spectrometry (CF-IRMS) using several methane carbon isotope standards and a large number of biogas samples from batch anaerobic reactors. Results from measurements on these samples were used to determine and compare the precision of the two techniques and to quantify for systematic offsets. With pure standards analytical precision of measurements for delta(13)C(CH4) was found to be in the range of 0.33 and 0.48 per thousand, and 0.09 and 0.27 per thousand for the optical method and CF-IRMS, respectively. Biogas samples showed an average mean deviation of delta(13)C(CH4) of 0.38 per thousand and 0.08 per thousand for the optical method and CF-IRMS, respectively. Although the tested laser optical spectrometer showed a dependence of delta(13)C(CH4) on CH(4) mixing ratio in the range of 500 to 8000 ppm this could be easily corrected. After correction, the delta(13)C(CH4) values usually varied within 0.7 per thousand from those measured by conventional CF-IRMS and thus results from both methods agreed within the given analytical uncertainties. Although the precision of the conventional CF IRMS is higher than the tested optical system, both instruments were well within the acceptable delta(13)C(CH4) precision required for biogas methane measurements. The advantages of the optical system are its simplicity of operation, speed of analysis, good precision, reduced costs in comparison to IRMS, and the potential for field applications. PMID- 20540537 TI - (18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer. AB - Radiolabeled RGD (Arg-Gly-Asp) and bombesin (BBN) radiotracers that specifically target integrin alpha(v)beta(3) and gastrin releasing peptide receptor (GRPR) are both promising radiopharmaceuticals for tumor imaging. We recently designed and synthesized a RGD-BBN heterodimeric peptide with both RGD and BBN motifs in one single molecule. The (18)F-labeled RGD-BBN heterodimer exhibited dual integrin alpha(v)beta(3) and GRPR targeting in a PC-3 prostate cancer model. In this study we investigated whether radiolabeled RGD-BBN tracers can be used to detect breast cancer by using microPET. Cell binding assay demonstrated that the high GRPR expressing breast cancer cells typically express low to moderate level of integrin alpha(v)beta(3), while high integrin alpha(v)beta(3) expressing breast cancer cells have negligible level of GRPR. We labeled RGD-BBN heterodimer with three positron emitting radionuclides (18)F, (64)Cu, and (68)Ga and investigated the corresponding PET radiotracers in both orthotopic T47D (GRPR(+)/low integrin alpha(v)beta(3)) and MDA-MB-435 (GRPR(-)/integrin alpha(v)beta(3)(+)) breast cancer models. The three radiotracers all possessed in vitro dual integrin alpha(v)beta(3) and GRPR binding affinity. The advantages of the RGD-BBN radiotracers over the corresponding BBN analogues are obvious for imaging MDA-MB 435 (GRPR(-)/integrin alpha(v)beta(3)(+)) tumor. (18)F-FB-PEG(3)-RGD-BBN showed lower tumor uptake than (64)Cu-NOTA-RGD-BBN and (68)Ga-NOTA-RGD-BBN but was able to visualize breast cancer tumors with high contrast. Synthesis of (64)Cu-NOTA RGD-BBN and (68)Ga-NOTA-RGD-BBN is much faster and easier than (18)F-FB-PEG(3) RGD-BBN. (64)Cu-NOTA-RGD-BBN showed prolonged tumor uptake but also higher liver retention and kidney uptake than (68)Ga-NOTA-RGD-BBN and (18)F-FB-PEG(3)-RGD-BBN. (68)Ga-NOTA-RGD-BBN possessed high tumor signals but also relatively high background uptake compared with the other two radiotracers. In summary, the prosthetic labeling groups, chelators, and isotopes all have a profound effect on the tumor targeting efficacy and in vivo kinetics of the RGD-BBN tracers for dual integrin and GRPR recognition. Further development of suitably labeled RGD-BBN tracers for PET imaging of cancer is warranted. PMID- 20540539 TI - Comparative human cell toxicogenomic analysis of monohaloacetic acid drinking water disinfection byproducts. AB - The monohaloacetic acids (monoHAAs), iodoacetic, bromoacetic and chloroacetic acids are toxic disinfection byproducts. In vitro toxicological end points were integrated with DNA damage and repair pathway-focused toxicogenomic analyses to evaluate monoHAA-induced alterations of gene expression in normal nontransformed human cells. When compared to concurrent control transcriptome profiles, metabolic pathways involved in the cellular responses to toxic agents were identified and provided insight into the biological mechanisms of toxicity. Using the Database for Annotation, Visualization and Integrated Discovery to analyze the gene array data, the majority of the altered transcriptome profiles were associated with genes responding to DNA damage or those regulating cell cycle or apoptosis. The major pathways involved with altered gene expression were ATM, MAPK, p53, BRCA1, BRCA2, and ATR. These latter pathways highlight the involvement of DNA repair, especially the repair of double strand DNA breaks. All of the resolved pathways are involved in human cell stress response to DNA damage and regulate different stages in cell cycle progression or apoptosis. PMID- 20540540 TI - Electrochemical wastewater treatment directly powered by photovoltaic panels: electrooxidation of a dye-containing wastewater. AB - Electrochemical technologies have proved to be useful for the treatment of wastewater, but to enhance their green characteristics it seems interesting to use a green electric energy such as that provided by photovoltaic (PV) cells, which are actually under active research to decrease the economic cost of solar kW. The aim of this work is to demonstrate the feasibility and utility of using an electrooxidation system directly powered by a photovoltaic array for the treatment of a wastewater. The experimental system used was an industrial electrochemical filter press reactor and a 40-module PV array. The influence on the degradation of a dye-containing solution (Remazol RB 133) of different experimental parameters such as the PV array and electrochemical reactor configurations has been studied. It has been demonstrated that the electrical configuration of the PV array has a strong influence on the optimal use of the electric energy generated. The optimum PV array configuration changes with the intensity of the solar irradiation, the conductivity of the solution, and the concentration of pollutant in the wastewater. A useful and effective methodology to adjust the EO-PV system operation conditions to the wastewater treatment is proposed. PMID- 20540541 TI - Significantly higher polybrominated diphenyl ether levels in young U.S. children than in their mothers. AB - While young children are rarely included in biomonitoring studies, they are presumed to be at greater risk of ingesting environmental contaminants particularly those that accumulate in foods or shed from consumer products. The widely used fire retardants polybrominated diphenyl ethers (PBDEs) are ubiquitous contaminants in the indoor environment and are widely detected at higher levels in Americans than in individuals from other countries. However, there are only three studies of PBDEs in U.S. children. We hypothesized that PBDEs are present in higher concentrations in young children than their mothers. PBDEs were assessed in blood samples collected concurrently from 20 mothers and their children, ages 1.5 to 4 years. The chemical analyses were performed by GC/MS applying selected ion monitoring. The samples were analyzed for 20 PBDE congeners; 11 were detected. SigmaPBDEs for children were typically 2.8 times higher than for mothers, with median child:mother ratios varying from 2 to 4 for individual congeners. In 19 of 20 families studied, children had higher SigmaPBDE concentrations than their mothers with significant (p < 0.01) concentration differences for five of the PBDE congeners. Decabromodiphenyl ether (BDE-209) was quantitated in 13 children and 9 mothers. Other studies indicate PBDEs are not elevated at birth, suggesting that early life is an intense period of PBDE intake. Children's increased hand-to-mouth activity, dietary preferences, and exposures from breast milk may result in greater ingestion of PBDEs than adults. These findings suggest that measurements from adults likely do not reflect exposures to young children despite sharing homes and similar diets. PMID- 20540542 TI - Correlating transport behavior with cell properties for eight porcine Escherichia coli isolates. AB - In this study we investigate how growth stage and depositional environment affect variability of cell properties and transport behavior of eight porcine E. coli isolates. We compared the surface properties for cells harvested during exponential and stationary growth phase and their transport behavior through columns packed with either uncoated or Fe-coated quartz sand. We then investigated correlations between measured cell properties and fitted bacterial attachment efficiencies. For both growth stages we found that bacterial attachment efficiencies in the uncoated quartz sand varied among the eight different isolates by over an order of magnitude whereas attachment efficiencies in the Fe-coated sands varied by a factor of less than two. With the exception of one isolate, growth condition had minimal impact on attachment efficiencies to the uncoated sands. A strong and statistically significant inverse relationship was observed between bacterial attachment efficiencies in the uncoated quartz sand columns and log-transformed zeta potential, whereas a mild yet statistically significant relationship between bacterial attachment efficiencies in the Fe coated sands and cell width was observed. For the experimental conditions used in our study, we found that variability in E. coli transport was more dependent on the depositional environment than on growth conditions. PMID- 20540543 TI - Microbial community- and metabolite dynamics of an anoxic dechlorinating bioreactor. AB - Monitoring and quantification of organohalide respiring bacteria is essential for optimization of on-site bioremediation of anoxic subsurface sites contaminated with chloroethenes. Molecular monitoring and model simulations were applied to determine degradation performance of an in situ dechlorinating bioreactor and its influence on the contamination plume. Dehalococcoides was the dominant dechlorinating microorganism as revealed by qPCR targeting 16S rRNA- and chloroethene reductive dehalogenase-encoding genes (tceA, vcrA, bvcA). The presence of all three reductive dehalogenases genes indicated coexistence of several distinct organohalide respiring bacterial populations in the bioreactor and groundwater. Mass balancing revealed that main dechlorinating activities were reduction of cis-dichloroethene and vinyl chloride. Analysis of growth kinetics showed that when performance of the bioreactor improved due to especially the addition of molasses, dechlorinating microorganisms were growing close to their maximum growth rate. Once near-complete dehalogenation was achieved, Dehalococcoides only grew slowly and population density did not further increase. The bioreactor influenced dechlorinating populations in the plume with subsequent decrease in chlorinated compound concentrations over time. In the present study, a combination of molecular diagnostics with mass-balancing and kinetic modeling improved insight into organohalide respiring bacteria and metabolite dynamics in an in situ dechlorinating bioreactor and showed its utility in monitoring bioremediation. PMID- 20540544 TI - Patterns of development and abnormalities among tadpoles in a constructed wetland receiving treated wastewater. AB - Constructed wetlands are promoted for effectiveness at treating wastewater and potential value as wildlife habitat; however, wildlife performance studies in treated wastewater wetlands are limited. We used repeated surveys of larval amphibians along three wetland systems and four reference sites to test the hypothesis that bullfrog tadpoles exposed to direct inputs of treated wastewater develop slower, show a higher frequency of abnormalities, and are smaller at metamorphosis compared to tadpoles from reference ponds. Bullfrog tadpoles from wastewater wetlands were similar in size at metamorphosis compared to tadpoles from reference sites; however, they did show a much higher frequency of abnormalities including severe edema, scoliosis, and extreme calcinosis of soft tissues. Calcinosis was novel to the literature on amphibian abnormalities, the most frequent abnormality, and restricted exclusively to treatment wetlands. Within the constructed wetlands, tadpole development was slower and the frequency of scoliosis and calcinosis was higher in those cells receiving direct inputs of treated wastewater. Our results suggest that portions of constructed wetlands that directly receive treated wastewater may be poor amphibian habitat. PMID- 20540545 TI - Probing the lifetimes of internally excited amyl nitrite cations. AB - The photoelectron spectrum shows that multiphoton ionization of amyl nitrite, C(5)H(11)ONO, using ultrafast laser pulses deposits up to 3.7 eV of energy into internal degrees of freedom. As a result, the molecules fragment to produce various daughter ions of masses 87, 71, 60, 57, 41, 30, 29, and 27. Absorption of an additional photon with 3 eV of energy by the ions yields transients with picosecond decay times, revealing the time scale of the decomposition dynamics of the initially prepared parent ion. Each mass peak has a distinct time constant, in the range of 1.2 to 7.9 ps, emphasizing the dependence of the fragmentation mechanism on the ion internal energy. PMID- 20540546 TI - Theoretical investigation on the stability of negatively charged formic acid clusters. AB - Recent experimental results on negatively charged formic acid clusters generated by the impact of (252)Cf fission fragments on icy formic acid target are compared to quantum mechanical calculations. Structures for the clusters series, (HCOOH)nOH(-), where 2 < or = n < or = 4, are proposed based on ab initio electronic structure methods. The results show that cluster growth does not have a regular pattern of nucleation. A stability analysis was performed considering the commonly defined stability function. Temporal behavior of the clusters was evaluated by Born-Oppenheimer molecular dynamics to check the mechanism that provides cluster stability. The evaluated temporal profiles indicate the importance of hydrogen atom migration between the formic acid moieties in maintaining the stability of the structures and the water formation due to hydrogen abstraction by the hydroxyl approach. PMID- 20540547 TI - The ground state estimation by global optimization of an effective potential. Application to binary para-H(2)/ortho-D(2) molecular clusters. AB - It is demonstrated how the problem of ground state estimation of an n-body system can be recast as the less demanding problem of finding the global minimum of an effective potential in the 3n-dimensional coordinate space. The latter emerges when the solution of the imaginary-time Schrodinger equation is approximated by a variational Gaussian wavepacket (VGW). The VGW becomes stationary in the infinite imaginary-time limit. Such a stationary solution is not only exact for a harmonic potential, but it also provides a good approximation for a quantum state that is still localized in one of the basins of attraction, when, for example, the harmonic approximation may fail. The landscape of the effective potential is favorable for its global optimization, and is particularly suitable for optimization by GMIN, an open source program designed for global optimization using the basin-hopping algorithm. Consequently, the methodology is applied within GMIN to estimate the ground state structures of several binary para H(2)/ortho-D(2) molecular clusters. The results are generally consistent with the previous observations for homogeneous para-H(2) and ortho-D(2) clusters, as well as for smaller binary clusters. PMID- 20540548 TI - Spatiotemporal dynamics of mixed Landolt systems in open gel reactors: effect of diffusive feed. AB - In this report we present an experimental study on the spatiotemporal dynamics of the iodate-sulfite-ferrocyanide and the iodate-sulfite-thiourea systems. Both systems are capable of producing nontrivial reaction-diffusion patterns when they are operated in a one-side-fed open spatial reactor. An important parameter of these types of reactors is the time scale of the diffusive feed, which is determined by the "thickness" of the gel and diffusion coefficients of the chemicals. A conical shape gel is used to study the effect of the thickness gradient on the dynamics. We show that spatiotemporal oscillations stop below a critical thickness. It is demonstrated that the period of the oscillations is determined by the time scale of the inhibitory kinetics and the time scale of the diffusive feed together. In the case of the iodate-sulfite-thiourea system we observed the appearance of a stationary iodine front in the presence of the oscillating pH front. An experimentally supported kinetic explanation is given to account this phenomena. PMID- 20540549 TI - The molecular structure of hexamethyldigermane determined by gas-phase electron diffraction with theoretical calculations for (CH3)3M-M(CH3)3 where M = C, Si, and Ge. AB - Gas-phase electron diffraction (GED) data together with results from ab initio molecular orbital calculations (HF and MP2/6-311+G(d,p)) have been used to determine the structure of hexamethyldigermane ((CH(3))(3)Ge-Ge(CH(3))(3)). The equilibrium symmetry is D(3d), but the molecule has a very low-frequency, large amplitude, torsional mode (phiCGeGeC) that lowers the thermal average symmetry. The effect of this large-amplitude mode on the interatomic distances was described by a dynamic model which consisted of a set of pseudoconformers spaced at even intervals. The amount of each pseudoconformer was obtained from the ab initio calculations (HF/6-311+G(d,p)). The results for the principal distances (r(a)) and angles (angle(h1)) obtained from the combined GED/ab initio (with estimated 1sigma uncertainties) are r(Ge-Ge) = 2.417(2) A, r(Ge-C) = 1.956(1) A, r(C-H) = 1.097(5) A, angleGeGeC = 110.5(2) degrees, and angleGeCH = 108.8(6) degrees. Theoretical calculations were performed for the related molecules ((CH(3))(3)Si-Si(CH(3))(3) and (CH(3))(3)C-C(CH(3))(3)). PMID- 20540550 TI - EOMCC, MRPT, and TDDFT studies of charge transfer processes in mixed-valence compounds: application to the spiro molecule. AB - The proper description of electron transfer (ET) processes in mixed-valence compounds poses a significant challenge for commonly used theoretical approaches. In this paper we analyze the 1(2)A(2) and 2(2)A(2) potential energy surfaces of the Spiro cation (5,5'(4H,4H')-spirobi[cyclopenta[c]pyrrole]2,2',6,6'-tetrahydro cation) which is a frequently used model to study ET processes. We compare and contrast the results obtained with three different methods: multireference perturbation theory, equation-of-motion coupled cluster theory, time-dependent density functional theory. We demonstrate that the proper inclusion of dynamical correlation effects plays a crucial role in the description of an avoided crossing between potential energy surfaces. We also find that proper balancing of the ground- and excited-state correlation effects is especially challenging in the vicinity of the 1(2)A(2) and 2(2)A(2) avoided crossing region. PMID- 20540551 TI - Probing in vitro interactions between Lactococcus lactis and mucins using AFM. AB - This work was devoted to the first AFM investigation of the adhesion force to pig gastric mucin (PGM) using Lactococcus lactis as the model for lactic acid bacteria. The PGM coating on polystyrene was characterized using a complementary set of multiscale analytical methods, including AFM (HarmoniX mode), XPS, and the sessile drop method. The PGM layer, which was mainly composed of C-O, C-N, COOH, CONH, and sulfur-related species (protein core and oligosaccharide side chains), was quite homogeneous and hydrophilic, with an estimated thickness of 3.4 nm. L. lactis cells were immobilized on the AFM tip (lacto probe) and used as a force probe to measure the interaction forces between bacteria and PGM-coated polystyrene on the nanoscale. After mucin adsorption, adhesion force levels were lower because of the interplay of electrostatic, hydrophilic, and steric repulsions. For example, the adhesion forces of the lacto probe to bare and PGM coated polymer were 0.74 +/- 0.10 and 0.12 +/- 0.06 nN, respectively. The shape analysis of retraction force-distance curves highlighted the contribution of both nonspecific and specific forces (ligand/receptor bonding). The lacto probe concept and the associated AFM measurements may now provide a powerful framework for understanding interaction mechanisms between mucins and lactic acid bacteria. PMID- 20540552 TI - Formation of bandgap and subbands in graphene nanomeshes with sub-10 nm ribbon width fabricated via nanoimprint lithography. AB - We fabricated hexagonal graphene nanomeshes (GNMs) with sub-10 nm ribbon width. The fabrication combines nanoimprint lithography, block-copolymer self-assembly for high-resolution nanoimprint template patterning, and electrostatic printing of graphene. Graphene field-effect transistors (GFETs) made from GNMs exhibit very different electronic characteristics in comparison with unpatterned GFETs even at room temperature. We observed multiplateaus in the drain current-gate voltage dependence as well as an enhancement of ON/OFF current ratio with reduction of the average ribbon width of GNMs. These effects are attributed to the formation of electronic subbands and a bandgap in GNMs. Such mesoscopic graphene structures and the nanofabrication methods could be employed to construct future electronic devices based on graphene superlattices. PMID- 20540553 TI - Bulk heterojunction polymer memory devices with reduced graphene oxide as electrodes. AB - A unique device structure with a configuration of reduced graphene oxide (rGO) /P3HT:PCBM/Al has been designed for the polymer nonvolatile memory device. The current-voltage (I-V) characteristics of the fabricated device showed the electrical bistability with a write-once-read-many-times (WORM) memory effect. The memory device exhibits a high ON/OFF ratio (10(4)-10(5)) and low switching threshold voltage (0.5-1.2 V), which are dependent on the sheet resistance of rGO electrode. Our experimental results confirm that the carrier transport mechanisms in the OFF and ON states are dominated by the thermionic emission current and ohmic current, respectively. The polarization of PCBM domains and the localized internal electrical field formed among the adjacent domains are proposed to explain the electrical transition of the memory device. PMID- 20540554 TI - Reduced N-alkyl substituted bis(imino)pyridine cobalt complexes: molecular and electronic structures for compounds varying by three oxidation states. AB - The stepwise 1-3 electron reduction of the N-alkyl substituted bis(imino)pyridine cobalt dichloride complexes, ((R)APDI)CoCl(2), was studied where (R)APDI = 2,6 (RN=CMe)(2)C(5)H(3)N, R = C(6)H(11) (Cy), CHMe(2) ((i)Pr). One electron reduction with either zinc metal or NaBEt(3)H furnished the bis(imino)pyridine cobalt monochloride compounds, ((R)APDI)CoCl. X-ray diffraction on the ((iPr)APDI)CoCl derivative established a distortion from square planar geometry where the chloride ligand is lifted out of the idealized cobalt-chelate plane. Superconducting Quantum Interference Device (SQUID) magnetometry on both compounds established spin crossover behavior with an S = 1 state being predominant at room temperature. Computational studies, in combination with experimental results, establish that the triplet spin isomer arises from a high spin Co(II) center (S(Co) = 3/2) antiferromagnetically coupled to a bis(imino)pyridine chelate radical anion, [PDI](-) (S(PDI) = 1/2). At lower temperatures, the Co(II) ion undergoes a spin transition to the low spin form (S(Co) = 1/2) and antiferromagnetic coupling gives rise to the observed diamagnetic ground state. Replacing the chloride ligand with a methyl group, namely ((R)APDI)CoCH(3), also yielded distorted compounds, albeit less pronounced, that are diamagnetic at room temperature. Two electron reduction of the ((R)APDI)CoCl(2) derivatives with excess 0.5% sodium amalgam or 2 equiv of NaBEt(3)H furnished the bis(chelate)cobalt complexes, ((R)APDI)(2)Co, while three electron reduction with 3 equiv of sodium naphthalenide yielded the cobalt dinitrogen anions, [Na(solv)(3)][((R)APDI)CoN(2)] (solv = THF, Et(2)O). Both bis(chelate) compounds were crystallographically characterized and determined to have S = 3/2 ground states by SQUID magnetometry and electron paramagnetic resonance (EPR) spectroscopy. Computational studies, in combination with metrical parameters determined from X-ray diffraction, establish a high spin (S(Co) = 3/2) cobalt(II) center with two bis(imino)pyridine chelate radical anions. Antiferromagnetic coupling between the two chelate centered radicals is mediated by a doubly occupied t(2g) cobalt orbital and gives rise to the observed overall quartet ground state. PMID- 20540555 TI - Changing stations in single bistable rotaxane molecules under electrochemical control. AB - We have directly observed electrochemically driven single-molecule station changes within bistable rotaxane molecules anchored laterally on gold surfaces. These observations were achieved by employing molecular designs that significantly reduced the mobility and enhanced the assembly of molecules in orientations conducive to direct measurement using scanning tunneling microscopy. The results reveal molecular-level details of the station changes of surface bound bistable rotaxane molecules, correlated with their different redox states. The mechanical motions within these mechanically interlocked molecules are influenced by their interactions with the surface and with neighboring molecules, as well as by the conformations of the dumbbell component. PMID- 20540556 TI - Synthesis and photophysics of platinum(II) 6-phenyl-4-(9,9-dihexylfluoren-2-yl) 2,2'-bipyridine complexes with phenothiazinyl acetylide ligand. AB - Two platinum 6-phenyl-4-(9,9-dihexylfluoren-2-yl)-2,2'-bipyridine complexes (4 and 5) with phenothiazinyl acetylide ligand were synthesized and characterized. Their UV-vis absorption and emission characteristics in solution and in Langmuir Blodgett (LB) film were systematically investigated. The triplet transient difference absorption and nonlinear absorption properties were also studied for these complexes. Both complexes exhibit a broad metal-to-ligand charge transfer/intraligand charge transfer/ligand-to-ligand charge transfer ((1)MLCT/(1)ILCT/(1)LLCT) absorption band between 400 and 500 nm and a (3)MLCT/(3)ILCT/(3)pi,pi* emission band at approximately 594 nm at room temperature, which blue shifts at 77 K. Both UV-vis absorption and emission spectra show negative solvatochromic effect. The triplet excited-state lifetime at room temperature for complex 4 is approximately 1.2 micros, which is longer than that for complex 5 (approximately 600 ns). The emission quantum yield of complex 4 in toluene is 0.18 and 0.053 for complex 5. Both of the complexes also exhibit broad and moderately strong triplet transient absorption from the near-UV to the near-IR spectral region. However, 5 exhibits stronger reverse-saturable absorption than complex 4 does at 532 nm for nanosecond laser pulses. This is attributed to the weaker ground-state absorption but stronger triplet excited state absorption at 532 nm for 5 than for 4, which leads to a larger ratio of excited-state absorption cross section to ground-state absorption for 5 than 4. In addition, LB films of 4 and 5 were prepared and characterized by AFM technique. The UV-vis absorption and emission spectra of the LB films of 4 and 5 were also investigated and compared with those obtained in solution. PMID- 20540557 TI - Surface actuation of smart nanoshutters. AB - Patterned polymer brush surfaces have been fabricated using the molecular scratchcard lithography technique, where a functional top nanolayer (acting also as a resist) is selectively removed using a scanning probe tip to expose underlying atom-transfer radical polymerization (ATRP) initiator sites. The lateral spreading of grafted polymer brush patterns across the adjacent functional resist surface can be reversibly actuated via solvent exposure. Effectively, this methodology provides a means for hiding/unveiling functional surfaces on the nanoscale. PMID- 20540558 TI - Synthesis of galabiose-chitosan conjugate as potent inhibitor of Streptococcus suis adhesion. AB - The aim of this work is to construct a safe and effective drug candidate against Streptococcus suis infection. A panel of chitosan-based polymer conjugates with branched galabiose (Galalpha1-4Gal) side chains was synthesized as inhibitors of S. suis adhesion. The synthesis was achieved by using an aldehyde-functionalized galabiose derivative to graft it onto chitosan amino groups. Structural compositions of the conjugates were verified by 1H NMR spectroscopy and CHN elemental analyses. Potent inhibitory activities of the conjugates against S. suis adhesion to human erythrocytes were determined at low nanomolar concentration by HAI assay. An SPR study revealed a high affinity binding (Kd=39.6 nM) of the conjugate with BSI-B4 lectin. By using biocompatible chitosan as the scaffold for presenting S. suis -specific galabiose units, as well as the concise route tailored for the conjugate syntheses, the present study provides a practical way for explorations of new anti- S. suis therapies. PMID- 20540559 TI - Structures and properties of metalloid Al and Ga clusters open our eyes to the diversity and complexity of fundamental chemical and physical processes during formation and dissolution of metals. PMID- 20540560 TI - Fluoride ion complexation and sensing using organoboron compounds. PMID- 20540561 TI - Evaluation of metalloendopeptidase Lys-N protease performance under different sample handling conditions. AB - Trypsin, the most widely used enzyme in proteomics, has a few caveats as it does not perform well under certain harsh sample handling conditions and creates relatively short peptides less amenable to, for instance, electron transfer dissociation. There is, thus, room for improvement using alternative proteases. Here, we evaluate the performance of such an alternative protease, the metalloendopeptidase Lys-N, in sample preparation for proteomic analyses under various experimental conditions. The experimental parameters we evaluated were protein-to-protease ratio, incubation time, temperature, and several concentrations of denaturing modifiers often used in proteomics sample handling. Our data reveal that Lys-N is still very efficient under some very harsh (denaturing) conditions (e.g., 8 M urea, 80% acetonitrile) and at temperatures as low as 4 degrees C and up to 80 degrees C but severely hampered by guanidine hydrochloride and methanol. These rather unique features make Lys-N a good candidate for a variety of applications, such as membrane proteomics and possibly H/D exchange mass spectrometry. Additionally, we show that Lys-N is capable of, in contrast to trypsin or Lys-C, cleaving adjacent to mono- and dimethylated lysines, making it a good candidate for targeted epigenetic analysis of for instance histones. PMID- 20540562 TI - Tissue-specific defense and thermo-adaptive mechanisms of soybean seedlings under heat stress revealed by proteomic approach. AB - A comparative proteomic approach was employed to explore tissue-specific protein expression patterns in soybean seedlings under heat stress. The changes in the protein expression profiles of soybean seedling leaves, stems, and roots were analyzed after exposure to high temperatures. A total of 54, 35, and 61 differentially expressed proteins were identified from heat-treated leaves, stems, and roots, respectively. Differentially expressed heat shock proteins (HSPs) and proteins involved in antioxidant defense were mostly up-regulated, whereas proteins associated with photosynthesis, secondary metabolism, and amino acid and protein biosynthesis were down-regulated in response to heat stress. A group of proteins, specifically low molecular weight HSPs and HSP70, were up regulated and expressed in a similar manner in all tissues. Proteomic analysis indicated that the responses of HSP70, CPN-60 beta, and ChsHSP were tissue specific, and this observation was validated by immunoblot analysis. The heat responsive sHSPs were not induced by other stresses such as cold and hydrogen peroxide. Taken together, these results suggest that to cope with heat stress soybean seedlings operate tissue-specific defenses and adaptive mechanisms, whereas a common defense mechanism associated with the induction of several HSPs was employed in all three tissues. In addition, tissue-specific proteins may play a crucial role in defending each type of tissues against thermal stress. PMID- 20540564 TI - Molecular fluorescence, phosphorescence, and chemiluminescence spectrometry. PMID- 20540563 TI - Profiling the proteome of the venom from the social wasp Polybia paulista: a clue to understand the envenoming mechanism. AB - The study reported here is a classical bottom-up proteomic approach where proteins from wasp venom were extracted and separated by 2-DE; the individual protein spots were proteolytically digested and subsequently identified by using tandem mass spectrometry and database query with the protein search engine MASCOT. Eighty-four venom proteins belonging to 12 different molecular functions were identified. These proteins were classified into three groups; the first is constituted of typical venom proteins: antigens-5, hyaluronidases, phospholipases, heat shock proteins, metalloproteinases, metalloproteinase desintegrin like proteins, serine proteinases, proteinase inhibitors, vascular endothelial growth factor-related protein, arginine kinases, Sol i-II and -II like proteins, alpha-glucosidase, and superoxide dismutases. The second contained proteins structurally related to the muscles that involves the venom reservoir. The third group, associated with the housekeeping of cells from venom glands, was composed of enzymes, membrane proteins of different types, and transcriptional factors. The composition of P. paulista venom permits us to hypothesize about a general envenoming mechanism based on five actions: (i) diffusion of venom through the tissues and to the blood, (ii) tissue, (iii) hemolysis, (iv) inflammation, and (v) allergy-played by antigen-5, PLA1, hyaluronidase, HSP 60, HSP 90, and arginine kinases. PMID- 20540565 TI - Cr(III)-Cr(III) interactions in two alkoxo-bridged heterometallic Zn2Cr2 complexes self-assembled from zinc oxide, Reinecke's salt, and diethanolamine. AB - Two new tetranuclear complexes, [Zn(2)Cr(2)(NCS)(4)(Dea)(2)(HDea)(2)].4DMSO (1; DMSO = dimethyl sulfoxide) and [Zn(2)Cr(2)(NCS)(4)(Dea)(2)(HDea)(2)].2CH(3)CN (2), were prepared from zinc oxide, Reinecke's salt, NH(4)[Cr(NCS)(4)(NH(3))(2)].H(2)O, ammonium thiocyanate, and a nonaqueous solution of diethanolamine (H(2)Dea) in a reaction carried out under open air. Both compounds have similar centrosymmetric crystal structures based on a tetranuclear {Zn(2)Cr(2)(mu(3)-O)(2)(mu-O)(4)} core. Variable-temperature magnetic susceptibility measurements of 1 and 2 show weak antiferromagnetic coupling between chromium centers. The magnetic data and high-field, high frequency electron paramagnetic resonance spectra were analyzed in terms of the spin Hamiltonian H = JS(1).S(2) - j(S(1).S(2) + mu(B)B{g(1)}S(1) + D(Cr){S(z1)(2) - S(1)(S(1) + 1)/3} + E(Cr)(S(x1)(2) - S(y1)(2)) + mu(B)B{g(2)}S(2) + D(Cr){S(z2)(2) - S(2)(S(2) + 1)/3} + E(Cr)(S(x2)(2) - S(y2)(2)) + D(12){S(z1)S(z2) - S(1).S(2)/3} + E(12)(S(x1)S(x2) - S(y1)S(y2)) with J = 13.7 cm(-1), j = 1.1 cm(-1), D(Cr) = 0.3864 cm(-1), E(Cr) = -0.1104 cm(-1), D(12) = 0.1873 cm(-1), and E(12) = -0.0155 cm(-1) for 1 and J = 9.4 cm(-1), j = 0.8 cm( 1), D(Cr) = 0.3564 cm(-1), E(Cr) = -0.0647 cm(-1), D(12) = -0.1850 cm(-1), and E(12) = -0.0112 cm(-1) for 2. Density functional theory (DFT) calculations were employed to calculate the zero-field splitting on Cr(3+) ions. Calculations of the exchange integrals J were attempted by using the "broken-symmetry" DFT method. PMID- 20540566 TI - Study of the coordination abilities of stibine ligands to gold(I). AB - The reaction of [AuCl(tht)] (tht = tetrahydrothiophene) with SbMes(n)Ph(3-n) (n = 3 (1), 2 (2), 1 (3)) produces the 1:1 adducts [AuCl(SbMes(n)Ph(3-n))] (n = 3 (4), 2 (5), 1 (6)), with a Sb-Au-Cl environment, regardless of the molar ratio used (1:1 to 1:4). Addition of the same stibines to [Au(tht)(2)]ClO(4) (molar ratio 1:1 to 1:4) results in isolation of the 1:2 adducts [Au(SbMes(n)Ph(3 n))(2)]ClO(4) (n = 3 (7), 2 (10)), containing linear Sb-Au-Sb fragments, or the 1:3 adduct [Au(SbMesPh(2))(3)]ClO(4) (11), with a quasi trigonal planar AuSb(3) core. The same 1:2 cations are produced when [Au(tht)(2)]CF(3)SO(3) is reacted with 1 or following a rearrangement process when 4 is treated with AgSbF(6), that is, [Au(SbMes(3))(2)]X (X = CF(3)SO(3) (8), SbF(6) (9)). The compounds were characterized by spectroscopic methods, and the molecular structures of 2-4, 7, 8.2CDCl(3), 9, and 11 were established by single-crystal X-ray diffraction. Theoretical calculations were carried out on model systems of type ER(3) and [Au(ER(3))(n)](+) (E = P or Sb; R = Ph or Mes; n = 2, 3, or 4) to gain insight into the bonding nature of SbR(3) ligands in homoleptic gold-stibine adducts, in comparison with phosphine-gold(I) compounds. Steric effects govern the coordination of stibines with mesityl substituents. A preference for higher coordination numbers is observed for SbPh(3) when compared with PPh(3) and experimentally observed C-Sb-C and Sb-C structural distortions of stibines upon coordination are reproduced theoretically. PMID- 20540567 TI - Synthesis, characterization, and crystallographic study of the PbO-Bi2O3-V2O5 system: Pb(3-x)Bi(2x/3)V2O8 (0.20 < or = x < or = 0.50). AB - A new solid solution Pb(3-x)Bi(2x/3)V(2)O(8) (0.20 < or = x < or = 0.50), stabilizing the high-temperature gamma form of Pb(3)V(2)O(8), has been isolated in the system Pb(3)V(2)O(8)-BiVO(4). The single-crystal structure of the composition x = 0.50 (Pb(2.5)Bi(1/3)V(2)O(8)) was solved using single-crystal X ray diffraction (XRD) technique. The compound crystallizes in the trigonal crystal system R3m (No. 166) with a palmierite structural type with a = 5.7463(3) A, c = 20.3047(12) A, V = 580.64(5) A(3), and Z = 3. The final R1 value of 0.0406 was achieved for 217 independent reflections during the structure refinement. The variable-temperature powder XRD shows the absence of any phase transition for all of the members of the solid solution in the limit of 398-80 K. The new solid solution has been characterized by neutron powder diffraction, solid-state UV-vis diffuse-reflectance spectra, scanning electron microscopy, and X-ray photoelectron spectroscopy (XPS). Alternating-current impedance studies indicate conductivity on the order of 10(-4) Omega(-1) cm(-1) for Pb(2.5)Bi(1/3)V(2)O(8). The change in color of the samples from brown to yellow at high temperature was explained by XPS studies, which indicate the plausible formation of the ppm level of Bi(2)O(3) at such elevated temperature ranges. PMID- 20540568 TI - Comparative proteomic analysis of early-stage soybean seedlings responses to flooding by using gel and gel-free techniques. AB - Gel-based and gel-free proteomics techniques were used to investigate early responses to flooding stress in the roots and hypocotyls of soybean seedlings. Proteins from 2-day-old soybean seedlings flooded for 12 h were extracted and analyzed. Two mass-spectroscopy-based proteomics analyses, two-dimensional fluorescence difference gel electrophoresis, and nanoliquid chromatography identified 32 from 17 spots and 81 proteins, respectively, as responsive to flooding stress. On the basis of the number and function of proteins identified, glycolysis and fermentation enzymes and inducers of heat shock proteins were key elements in the early responses to flooding stress. Analysis of enzyme activities and carbohydrate contents in flooded seedlings showed that glucose degradation and sucrose accumulation accelerated during flooding due to activation of glycolysis and down-regulation of sucrose degrading enzymes. Additionally, the methylglyoxal pathway, which is detoxification system linked to glycolysis, was up-regulated. Furthermore, two-dimensional polyacrylamide gel electrophoresis based phosphoproteomics analysis showed that proteins involved in protein folding and synthesis were dephosphorylated under flooding conditions. These results suggest that translational and post-translational control during flooding possibly induces an imbalance in the expression of proteins involved in several metabolic pathways including carbohydrate metabolism that might cause flooding injury of soybean seedlings. PMID- 20540569 TI - Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse. AB - Alcohol-induced liver disease (ALD) is a leading cause of nonaccident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively nonspecific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study, the metabolic changes associated with ALD were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-beta-d glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of a metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID- 20540570 TI - Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex. AB - We reported previously the feasibility to radiolabel peptides with fluorine-18 ((18)F) using a rapid one-pot method that first mixes (18)F(-) with Al(3+) and then binds the (Al(18)F)(2+) complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al(18)F NOTA complexes were stable in vitro in human serum, and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100 degrees C, and the peptides could be labeled in as little as 5 min. The IMP467 peptide could be labeled up to 115 GBq/micromol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID- 20540571 TI - Microbially enhanced carbon capture and storage by mineral-trapping and solubility-trapping. AB - The potential of microorganisms for enhancing carbon capture and storage (CCS) via mineral-trapping (where dissolved CO(2) is precipitated in carbonate minerals) and solubility trapping (as dissolved carbonate species in solution) was investigated. The bacterial hydrolysis of urea (ureolysis) was investigated in microcosms including synthetic brine (SB) mimicking a prospective deep subsurface CCS site with variable headspace pressures [p(CO(2))] of (13)C-CO(2). Dissolved Ca(2+) in the SB was completely precipitated as calcite during microbially induced hydrolysis of 5-20 g L(-1) urea. The incorporation of carbonate ions from (13)C-CO(2) ((13)C-CO(3)(2-)) into calcite increased with increasing p((13)CO(2)) and increasing urea concentrations: from 8.3% of total carbon in CaCO(3) at 1 g L(-1) to 31% at 5 g L(-1), and 37% at 20 g L(-1). This demonstrated that ureolysis was effective at precipitating initially gaseous [CO(2)(g)] originating from the headspace over the brine. Modeling the change in brine chemistry and carbonate precipitation after equilibration with the initial p(CO(2)) demonstrated that no net precipitation of CO(2)(g) via mineral-trapping occurred, since urea hydrolysis results in the production of dissolved inorganic carbon. However, the pH increase induced by bacterial ureolysis generated a net flux of CO(2)(g) into the brine. This reduced the headspace concentration of CO(2) by up to 32 mM per 100 mM urea hydrolyzed because the capacity of the brine for carbonate ions was increased, thus enhancing the solubility-trapping capacity of the brine. Together with the previously demonstrated permeability reduction of rock cores at high pressure by microbial biofilms and resilience of biofilms to supercritical CO(2), this suggests that engineered biomineralizing biofilms may enhance CCS via solubility-trapping, mineral formation, and CO(2)(g) leakage reduction. PMID- 20540572 TI - Least-squares analysis of phosphorus soil sorption data with weighting from variance function estimation: a statistical case for the Freundlich isotherm. AB - Phosphorus soil sorption data are typically fitted to simple isotherms for the purpose of compactly summarizing experimental results and extrapolating beyond the range of measurements. Here, the question of which of the commonly preferred models-Langmuir and Freundlich-is better, is addressed using weighted least squares, with weights obtained by variance function analysis of replicate data. Proper weighting in this case requires attention to a special problem-that the dependent variable S is not measured, rather is calculated from the measured equilibrium concentration C. The latter is commonly taken as the independent variable but is subject to experimental error, violating a fundamental least squares assumption. This problem is handled through an effective variance treatment. When the data are fitted to the Langmuir, Freundlich, and Temkin isotherms, only the Freundlich model yields a statistically adequate chi(2) value, and then only when S is taken to include labile residual P (S(0)) estimated from isotope-exchange experiments. The Freundlich model also yields good estimates of S(0) when this is treated as an adjustable parameter rather than a known quantity-of relevance to studies in which S(0) is not measured. By contrast, neglect of weights and labile P can lead to a mistaken preference for the Langmuir model. PMID- 20540573 TI - A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States. AB - We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment. PMID- 20540574 TI - Nonhydrolyzable ubiquitin-isopeptide isosteres as deubiquitinating enzyme probes. AB - We demonstrate that oxime ligation is an efficient, straightforward, and generally applicable strategy for generating nonhydrolyzable ubiquitin (Ub) isopeptide isosteres. We synthesized nonhydrolyzable K48- and K63-linked Ub isopeptide isosteres to investigate the selectivity of deubiquitinating enzymes for specific linkages employing surface plasmon resonance spectroscopy. The results indicate that deubiquitinating enzymes specifically recognize the local peptide sequence flanking Ub-branched lysine residues in target proteins. The described strategy allows the systematic investigation of sequence requirements for substrate selectivity of deubiquitinating enzymes. PMID- 20540575 TI - Lead detoxification activity and ADMET hepatotoxicity of N-(alpha-L-arabino furanos-1-yl)-L-cysteine. AB - N-(alpha-L-Arabinofuranos-1-yl)-L-cysteine was stereoselectively prepared from L arabinose and l-cysteine. Its in vivo detoxification action was evaluated on lead loaded mice at the doses of 0.1, 0.2, and 0.4 mmol/kg. The results show that lead accumulation in the livers, kidneys, brains, and femurs of the treated mice could be efficiently decreased by N-(alpha-L-arabinofuranos-1-yl)-L-cysteine, even at the dose of 0.1 mmol/kg. Compared with the lead detoxification efficacy, 0.4 mmol/kg of N-(alpha-L-arabinofuranos-1-yl)-L-cysteine did not affect the essential metals in the treated mice, such as Fe, Cu, Zn, and Ca. In the apparent permeability coefficient test, the values of P(app)(A-->B), P(app)(B-->A), and P(app)(A-->B)/P(app)(B-->A) indicated that N-(alpha-L-arabinofuranos-1-yl)-L cysteine was transported actively across the Caco-2 cell monolayer. Silico molecular modeling results predicted that N-(alpha-L-arabinofuranos-1-yl)-L cysteine had no hepatotoxicity. PMID- 20540576 TI - Enantioselective preparation of 8-oxabicyclo[3.2.1]octane derivatives via asymmetric [3+2]-cycloaddition of platinum-containing carbonyl ylides with vinyl ethers. AB - A catalytic asymmetric synthesis of 8-oxabicyclo[3.2.1]octane derivatives was achieved through the [3+2]-cycloaddition of the platinum-containing carbonyl ylides generated from acyclic gamma,delta-ynones on treatment with 10 mol % of PtCl(2)-Walphos and AgSbF(6). Synthetically useful 8-oxabicyclo[3.2.1]octane derivatives were obtained in good yields and mostly in over 90% ee's. PMID- 20540577 TI - When is chemical similarity significant? The statistical distribution of chemical similarity scores and its extreme values. AB - As repositories of chemical molecules continue to expand and become more open, it becomes increasingly important to develop tools to search them efficiently and assess the statistical significance of chemical similarity scores. Here, we develop a general framework for understanding, modeling, predicting, and approximating the distribution of chemical similarity scores and its extreme values in large databases. The framework can be applied to different chemical representations and similarity measures but is demonstrated here using the most common binary fingerprints with the Tanimoto similarity measure. After introducing several probabilistic models of fingerprints, including the Conditional Gaussian Uniform model, we show that the distribution of Tanimoto scores can be approximated by the distribution of the ratio of two correlated Normal random variables associated with the corresponding unions and intersections. This remains true also when the distribution of similarity scores is conditioned on the size of the query molecules to derive more fine-grained results and improve chemical retrieval. The corresponding extreme value distributions for the maximum scores are approximated by Weibull distributions. From these various distributions and their analytical forms, Z-scores, E-values, and p-values are derived to assess the significance of similarity scores. In addition, the framework also allows one to predict the value of standard chemical retrieval metrics, such as sensitivity and specificity at fixed thresholds, or receiver operating characteristic (ROC) curves at multiple thresholds, and to detect outliers in the form of atypical molecules. Numerous and diverse experiments that have been performed, in part with large sets of molecules from the ChemDB, show remarkable agreement between theory and empirical results. PMID- 20540578 TI - Role of low flow and backward flow zones on colloid transport in pore structures derived from real porous media. AB - To examine the relevance of low flow zones and flow vortices to colloid transport in real porous media, lattice-Boltzmann (LB) simulations were combined with X-ray microtomography (XMT) to simulate flow fields in glass beads and quartz sand. Backward flow zones were demonstrated to be widely present in both porous media, with a greater volume fraction in the former relative to the latter porous media. Glass beads in the XMT images were approximated as spheres and their coordinates and radii were extracted to allow reconstruction of pore structures. LB simulations were again performed and the simulated flow fields in the reconstructed pore structures were coupled to a three-dimensional particle tracking algorithm. Particle tracking simulations demonstrated that significant amounts of colloids stayed in the simulated domains for long periods (up to 50 pore volumes). The percentages of colloids with long residence time increased as the depth of the secondary energy minimum increased. The majority of the colloids with long residence time were translated to low flow zones while being associated with grain surfaces via secondary minima. A small fraction of colloids entered low flow zones without being associated with the grains surfaces. Backward flow zones were also found to trap a small fraction of colloids for significantly long time (up to 10 pore volumes). In overall, however, backward flow zones trapped fewer colloids for shorter durations than low flow zones. In summary, this work demonstrates the importance of temporary trapping of colloids by the low flow and backward flow zones in real porous media. This trapping process can explain a number of intriguing experimental observations. PMID- 20540579 TI - An efficient nickel catalyst for the reduction of carbon dioxide with a borane. AB - Nickel hydride with a diphosphinite-based ligand catalyzes the highly efficient reduction of CO(2) with catecholborane, and the hydrolysis of the resulting methoxyboryl species produces CH(3)OH in good yield. The mechanism involves a nickel formate, formaldehyde, and a nickel methoxide as different reduced stages for CO(2). The reaction may also be catalyzed by an air-stable nickel formate. PMID- 20540580 TI - Synthesis and solution self-assembly of side-chain cobaltocenium-containing block copolymers. AB - The synthesis of side-chain cobaltocenium-containing block copolymers and their self-assembly in solution was studied. Highly pure monocarboxycobaltocenium was prepared and subsequently attached to side chains of poly(tert-butyl acrylate) block-poly(2-hydroxyethyl acrylate), yielding poly(tert-butyl acrylate)-block poly(2-acryloyloxyethyl cobaltoceniumcarboxylate). The cobaltocenium block copolymers exhibited vesicle morphology in the mixture of acetone and water, while micelles of nanotubes were formed in the mixture of acetone and chloroform. PMID- 20540581 TI - Copper-catalyzed intramolecular C-H oxidation/acylation of formyl-N arylformamides leading to indoline-2,3-diones. AB - A new, efficient Cu-catalyzed intramolecular C-H oxidation/acylation method has been developed for the synthesis of substituted indoline-2,3-diones (isatins). In the presence of CuCl(2) and O(2), a variety of formyl-N-arylformamides underwent the tandem reaction to afford the corresponding indoline-2,3-diones in moderate to good yields. It is noteworthy that the reaction serves as the first example of transition-metal-catalyzed transformation for the preparation of indoline-2,3 diones. PMID- 20540582 TI - 1,8,1',8'-Tetrakis(dimethylamino)-2,2'-dinaphthylmethanols: double in/out proton sponges with low-barrier hydrogen-bond switching. AB - Previously unknown bis[1,8-bis(dimethylamino)naphth-2-yl]phenylmethanol (5) and bis[1,8-bis(dimethylamino)naphth-2-yl]methanol (6) have been obtained and studied by combination of X-ray, NMR, and IR techniques at variable temperature. It has been established that both proton sponge units in the solid tertiary alcohol 5 exist in nonconventional in/out form, one of which is fixed by intramolecular O H...N hydrogen bonding. In solution, a fast interconversion of two isoenergetic hydrogen chelates occurs which can be frozen below 183 K. Unlike this, the secondary alcohol 6 in the solid at 100 K adopts the in/out-in/in conformation and at 293 K demonstrates a kind of dynamic behavior which can be described as temperature-driven dimer-induced rechelation. In solution under ambient conditions 6 exists as an equilibrating mixture of chelated and unchelated monomeric forms in a approximately 1:1.8 molar ratio. PMID- 20540583 TI - Impact of distant charge reversals within a robust beta-barrel protein pore. AB - Among all beta-barrel pores, staphylococcal alpha-hemolysin (alphaHL), a heptameric transmembrane protein of known high-resolution crystal structure, features a high stability in planar lipid bilayers under a wide range of harsh experimental conditions. Here, we employed single-channel electrical recordings and standard protein engineering to explore the impact of two distant charge reversals within the interior of the beta-barrel part of the pore. The charge reversals were replacements of lysines with aspartic acids. A charge reversal within the structurally stiff region of the beta barrel near the pore constriction reduced the open-state current of the pore, but produced a quiet pore, showing current fluctuation-free channel behavior. In contrast, a charge reversal on the trans entrance, within the structurally flexible glycine-rich turn of the beta barrel, increased the open-state current and produced gating activity of the pore in the form of large-amplitude and frequent current fluctuations. Remarkably, cumulative insertion of the two distant charge reversals resulted in a large-amplitude permanent blockade of the beta barrel, as judged by both single-channel and macroscopic current measurements. The results from this work suggest that these distant charge reversals are energetically coupled, producing different impacts on the ionic transport, the unitary conductance and the open-state probability of the pore. PMID- 20540584 TI - Emission red shift and unusual band narrowing of Mn2+ in NaCaPO4 phosphor. AB - Concentration dependence of Mn(2+) luminescence in NaCaPO(4)/Mn(2+) is investigated by structural analyses and optical and laser excitation spectroscopies in the temperature range 19-300 K. NaCaPO(4)/Mn(2+) forms solid solution over the Mn(2+) concentration range 1.0-22 mol %. We observe the red shift and unusual band narrowing of Mn(2+) emission by increasing Mn(2+) concentration in NaCaPO(4). The lifetime of Mn(2+) emission lengthens unexpectedly for higher Mn(2+) concentration. The results are discussed in relation with crystal structure, photon reabsorption, exchange interaction, and energy transfer and energy migration in NaCaPO(4)/Mn(2+). PMID- 20540585 TI - Analysis of vibrational Raman optical activity signatures of the (TG)(N) and (GG)(N) conformations of isotactic polypropylene chains in terms of localized modes. AB - In a previous study [Lamparska, E.; Liegeois, V.; Quinet, O.; Champagne, B. ChemPhysChem 2006, 7, 2366-2376], signatures associated to the helical structure of a small oligomer of a polypropylene chain were highlighted in the vibrational Raman optical activity (VROA) spectra. Nevertheless, it was difficult to pursue the analysis of longer chains. Indeed, the number of normal modes is becoming large and they are delocalized over the whole chain, increasing the complexity of their analysis. With a new tool developed to analyze the vibrational spectra [Jacob, Ch. R.; Reiher, M. J. Chem. Phys. 2009, 130, 084106], one can understand the normal modes, the VROA intensity of the bands, and the band shapes of long polymer chains by investigating the vibrational coupling matrices and the intensity coupling matrices. The VROA couplet at around 1100 cm(-1) (previously evidenced as a signature of the (TG)(N) helical pitch) can now be thoroughly analyzed and compared to the corresponding signature in the (GG)(N) conformer. The mode localization approach shows that for both conformations this couplet arises from a phase difference within the localized modes of both peaks, leading to the inversion of the sign of the total VROA intensity. Comparing the (TG)(N) and (GG)(N) conformers, the vibrational and intensity coupling matrices completely change with the modification of the structure. This leads for the (TG)(19) conformer to a negative-positive couplet, whereas for the (GG)(19) conformation, a characteristic positive-negative-positive pattern is found. PMID- 20540586 TI - Acyclic cucurbit[n]uril congeners are high affinity hosts. AB - We present the design, synthesis via methylene bridged glycoluril tetramer building blocks, and charaterization of acyclic cucurbit[n]uril congeners that function as hosts for a wide variety of ammonium ions in water. The X-ray crystallographic characterization of the free host and its complexes with p xylylenediamine and spermine establish the flexibility of the methylene bridged backbone of the acyclic cucurbit[n]uril congeners that allow them to adapt to the structural features of the guest. We find that the acyclic cucurbit[n]uril congeners-with their four contiguous methylene bridged glycoluril units and two aromatic o-xylylene walls bearing CO(2)H substituents-bind to ammonium ions in buffered water with values of K(a) ranging from approximately 10(5) M(-1) to greater than 10(9) M(-1). Similar to the cucurbit[n]uril family of hosts, we find that increasing the concentration of metal cations in the buffer reduces the affinity of the acyclic cucurbit[n]uril congener toward guests by competitive binding at the ureidyl C horizontal lineO portals. Although the acyclic cucurbit[n]uril congeners retain the ability to bind to ammonium ions with high affinity, they do so with lower selectivity than cucurbit[n]urils presumably do to the structural flexibility of the hosts. A methylene bridged glycoluril tetramer model compound that lacks the substituted o-xylylene walls is a much lower affinity host, which establishes the importance of these rings on the overall recognition behavior of the acyclic cucurbit[n]uril congeners. Overall, the results in this paper establish that acyclic cucurbit[n]uril receptors that contain four or more contiguous methylene bridged glycoluril units retain many of the excellent recognition properties of the cucurbit[n]uril family. PMID- 20540587 TI - Dynamic behaviors of interactions: application of normal coordinates of internal vibrations to AIM dual functional analysis. AB - A method to evaluate the dynamic nature of interactions is proposed based on the AIM dual functional analysis. Normal coordinates of internal vibrations (NIV) are employed to generate the perturbed structures necessary for the analysis. H(b)(r(c)) are plotted versus H(b)(r(c))-V(b)(r(c))/2 [= (variant Planck's over 2pi(2)/8m)nabla(2)rho(b)(r(c))] at bond critical points for the purpose. The plots are represented by the polar (R, theta) coordinate. Each plot for an interaction shows a specific curve, which is expressed by (theta(p), kappa(p)): theta(p) corresponds to the tangent line for the plot from the y-direction, and kappa(p) is the curvature. Although (R, theta) values correspond to the static nature of interactions, (theta(p), kappa(p)) values show the dynamic nature. The applicability of NIV is examined exemplified by the charge-transfer interactions as the first step to analyze the dynamic behaviors of interactions with NIV. The (theta(p), kappa(p)) values evaluated with NIV are very close to those obtained by the partial-optimization method (POM), where the distances or angles in question are fixed suitably, if the internal vibrations are substantially located on the interactions in question. The magnitudes of differences in theta(p) and kappa(p) between those evaluated with NIV and POM are < or = 2 degrees and < or = 2 au(-1), respectively, for usual interactions. The treatment is demonstrated to be applicable to a wide range of interactions. PMID- 20540588 TI - Attractive interactions between side chains of histidine-histidine and histidine arginine-based cationic dipeptides in water. AB - Molecular dynamics simulations of histidine-based dipeptides in water show that a protonated histidine side chain group has a propensity for forming like-charged contact pairs with another protonated histidine or with arginine. This effect is of similar strength to that in previously observed arginine-arginine pairing. Even stronger contact pairs are formed in singly protonated or deprotonated dihistidine, where stacking of aromatic rings is not weakened by Coulomb repulsion between the side chains. Similar pairing behavior is also observed in a mixed solution of imidazole and imidazolium chloride. PMID- 20540589 TI - Monte Carlo simulations of mixtures involving ketones and aldehydes by a direct bubble pressure calculation. AB - Ketone and aldehyde molecules are involved in a large variety of industrial applications. Because they are mainly present mixed with other compounds, the prediction of phase equilibrium of mixtures involving these classes of molecules is of first interest particularly to design and optimize separation processes. The main goal of this work is to propose a transferable force field for ketones and aldehydes that allows accurate molecular simulations of not only pure compounds but also complex mixtures. The proposed force field is based on the anisotropic united-atoms AUA4 potential developed for hydrocarbons, and it introduces only one new atom, the carbonyl oxygen. The Lennard-Jones parameters of this oxygen atom have been adjusted on saturated thermodynamic properties of both acetone and acetaldehyde. To simulate mixtures, Monte Carlo simulations are carried out in a specific pseudoensemble which allows a direct calculation of the bubble pressure. For polar mixtures involved in this study, we show that this approach is an interesting alternative to classical calculations in the isothermal-isobaric Gibbs ensemble. The pressure-composition diagrams of polar + polar and polar + nonpolar binary mixtures are well reproduced. Mutual solubilities as well as azeotrope location, if present, are accurately predicted without any empirical binary interaction parameters or readjustment. Such result highlights the transferability of the proposed force field, which is an essential feature toward the simulation of complex oxygenated mixtures of industrial interest. PMID- 20540590 TI - Ghost writers, vested interest and funding disclosures. PMID- 20540591 TI - On the need to clarify and disseminate contemporary knowledge of hormone therapy initiated near menopause. AB - The dramatic change in opinion on postmenopausal hormone therapy (HT) following initial reports from the Women's Health Initiative (WHI) came about as the 'baby boom' generation of women created the largest population of newly menopausal women in history. That trial of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) focused on outcomes in women starting HT a decade or more after menopause. Yet clinical practice has focused on initiation near menopause. Recent findings in the limited numbers of younger menopausal women in the WHI CEE + MPA trial, and findings in the CEE-only trial, suggest that age at initiating HT strongly influences outcomes, and that benefits greatly exceed risk for most women who start within 10 years of menopause. Findings in other cohorts support this view. Benefits are both short (vasomotor, dyspareunia) and long term (bone health, possible coronary risk reduction). Not all postmenopausal women have indications for HT, but, even if the fraction is one third, the numbers affected are staggering. Low-dose and non-oral regimens, and other compounds, were introduced in the wake of the WHI. Emerging evidence suggests that these may further reduce risk in some population subgroups. The demonizing of HT may already have caused a burden of chronic disease that could have been mitigated or delayed. It is time for action to re-establish appropriate clinical context based on this emerging evidence, to reverse the inappropriate broad generalization of the WHI findings to younger menopausal women, and to support outcomes studies of current regimens in younger menopausal women. PMID- 20540592 TI - DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence. AB - The marked age-related decline in serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) has suggested that a deficiency of these steroids may be causally related to the development of a series of diseases that are generally associated with aging. Postulated consequences of low DHEA levels include insulin resistance, obesity, cardiovascular disease, cancer, reduction of the immune defence system as well as psychosocial problems such as depression and a general deterioration in the sensation of well-being and cognitive function. Clinically, the spectrum of women that would benefit from DHEA therapy is not clearly defined and nor is the dosage of hormone treatment. Whether DHEA therapy could be prescribed as a general anti-aging therapy or could be an alternative treatment for women suffering from androgen deficiency syndrome remains uncertain across studies. The lack of definitive evidence for biological mechanisms and the presence of only a few studies that address these emerging issues of DHEA therapy in postmenopausal women might encourage a new critical analysis of the available literature, evidencing current limits and incongruities. PMID- 20540594 TI - Vertebral artery-posterior inferior cerebellar artery bypass using a radial artery graft for hemorrhagic dissecting vertebral artery aneurysms: surgical technique and report of 2 cases. AB - Endovascular occlusion of hemorrhagic dissecting aneurysms of the vertebral artery (VA) is not possible when the posterior inferior cerebellar artery (PICA) originates from the dissecting aneurysm or when the contralateral VA provides inadequate collateral blood flow to the distal basilar circulation. The authors introduce a VA-PICA bypass with radial artery interposition graft and aneurysm trapping as an alternative approach and describe 2 cases in which this bypass was used to treat hemorrhagic dissecting VA aneurysms. The VA-PICA bypass is performed via a standard far lateral approach. An end-to-side anastomosis between the radial artery graft and the PICA at the level of the caudal loop is performed first, and an end-to-side anastomosis is performed between the V(3) segment and the proximal end of the radial artery graft. A 56-year-old woman harbored a hemorrhagic dissecting VA aneurysm incorporating the origin of the PICA. Endovascular treatment failed, with aneurysm refilling on follow-up angiography. A 65-year-old man had a hemorrhagic dissecting VA aneurysm and a hypoplastic contralateral VA. Both patients were treated with the VA-PICA bypass and aneurysm trapping, with adequate filling of the PICA territory in the first patient and both the PICA territory and the basilar circulation in the second patient. Vertebral artery-PICA bypass with radial artery interposition graft and subsequent trapping of the dissected VA segment is an alternative to occipital artery-PICA and PICA-PICA bypass for the treatment of hemorrhagic dissecting VA aneurysms that are not suitable for endovascular occlusion. PMID- 20540595 TI - Radiosurgery for pituitary adenomas. PMID- 20540596 TI - Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes. AB - OBJECT: Gamma Knife surgery (GKS) is a common treatment for recurrent or residual pituitary adenomas. This study evaluates a large cohort of patients with a pituitary adenoma to characterize factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency. METHODS: A total of 418 patients who underwent GKS with a minimum follow-up of 6 months (median 31 months) and for whom there was complete follow-up were evaluated. Statistical analysis was performed to evaluate for significant factors (p < 0.05) related to treatment outcomes. RESULTS: In patients with a secretory pituitary adenoma, the median time to endocrine remission was 48.9 months. The tumor margin radiation dose was inversely correlated with time to endocrine remission. Smaller adenoma volume correlated with improved endocrine remission in those with secretory adenomas. Cessation of pituitary suppressive medications at the time of GKS had a trend toward statistical significance in regard to influencing endocrine remission. In 90.3% of patients there was tumor control. A higher margin radiation dose significantly affected control of adenoma growth. New onset of a pituitary hormone deficiency following GKS was seen in 24.4% of patients. Treatment with pituitary hormone suppressive medication at the time of GKS, a prior craniotomy, and larger adenoma volume at the time of radiosurgery were significantly related to loss of pituitary function. CONCLUSIONS: Smaller adenoma volume improves the probability of endocrine remission and lowers the risk of new pituitary hormone deficiency with GKS. A higher margin dose offers a greater chance of endocrine remission and control of tumor growth. PMID- 20540597 TI - Spontaneous intracranial hypotension. PMID- 20540598 TI - Cranial arteriovenous fistulas and myelopathy. PMID- 20540599 TI - Sexual intercourse and cerebral aneurysmal rupture: potential mechanisms and precipitants. AB - Aneurysmal subarachnoid hemorrhage (SAH) is a significant cause of death in young and middle-aged individuals and causes tremendous morbidity in affected patients. Despite the identification of various risk factors, the series of events leading to the formation, growth, and rupture of intracranial aneurysms is poorly understood. Cerebral aneurysm rupture has been associated with sexual intercourse and other forms of physical exercise. In fact, multiple case series reported that coitus was the immediate preceding activity in 3.8-14.5% of patients suffering from aneurysmal SAH. This may be related to the large elevations in mean arterial blood pressure that occur in both males and females during sexual intercourse (130-175 and 125-160 mm Hg, respectively). While coitus and physical exercise share important physiological similarities, each may differentially affect the probability that a preformed aneurysm will rupture. In this literature review and synthesis, the authors analyze the physiological human response to sexual intercourse in an effort to delineate those factors that may precipitate aneurysmal rupture. The authors' analysis is based on the original data collected by Masters and Johnson. To the authors' knowledge, this is the first review to address the link between sexual intercourse and intracranial aneurysmal rupture. While actual measurements of the physiological variables relevant to SAH were not performed in this article, the authors make reasonable assumptions based on the available data to help elucidate the mechanism of sexually induced aneurysmal rupture. PMID- 20540600 TI - Trigeminal neuralgia resulting from auditory brainstem implant cable compression. AB - The authors report a case of neurofibromatosis Type 2 presenting with symptoms of trigeminal neuralgia refractory to medical management following placement of an auditory brainstem implant (ABI). Physical examination and history revealed trigeminal neuralgia. A 3D FIESTA (fast imaging employing steady-state acquisition) MR imaging study demonstrated compression of the trigeminal nerve by an ABI cable. After maximal medical therapy, a retrosigmoid microscopic decompression of the trigeminal nerve achieved complete symptom resolution. This is the first report of an ABI cable becoming displaced, resulting in neurovascular compression. This case demonstrates that trigeminal neuralgia can result from nonvascular compression of the trigeminal nerve. PMID- 20540601 TI - Myelopathy due to intracranial dural arteriovenous fistula: a potential diagnostic pitfall. Case report. AB - Intracranial dural arteriovenous fistula (DAVF) is rare and potentially life threatening disease often presenting as vascular myelopathy. The early and proper diagnosis is challenging because the clinical manifestations are related to the distribution of the draining vein, not the fistula site, and imaging findings are similar to demyelinating disease of the spinal cord. The authors present the case of a 45-year-old man who developed acute progressive quadriplegia and respiratory difficulty with an enhancing, longitudinally extensive cervical cord lesion. These symptoms were highly suspicious for transverse myelitis but were caused by an intracranial DAVF. Intracranial DAVF with venous reflux to the brainstem and spinal cord is a rare but important differential diagnosis of progressive worsening myelopathy that is treatment resistant and gives the diagnostic impression of transverse myelitis. PMID- 20540602 TI - Significance of dsRNA Genetic Elements in Plant Pathogenic Fungi. PMID- 20540604 TI - Systematic position of Histomonas meleagridis based on four protein genes. AB - Phylogenetic trees based on parabasalid sequences of the small subunit rRNA placed Histomonas meleagridis in close proximity to Dientamoeba fragilis, Tritrichomonas foetus, and Monocercomonas sp. In this study, we sequenced partial genes of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), enolase, and alpha tubulin from 2 strains of H. meleagridis. We found 5 different GAPDH sequences, 6 different enolase sequences, and 3 alpha-tubulin sequences. Phylogenetic trees based on the obtained sequences showed a close relationship of H. meleagridis with T. foetus and, to some extent, Monocercomonas sp. In conclusion, our findings further corroborate the ssu rRNA-based tree. Consequently, our study also supports the hypothesis that H. meleagridis secondarily lost cytoskeletal structures. PMID- 20540605 TI - Did trypanosomatid parasites contain a eukaryotic alga-derived plastid in their evolutionary past? AB - The Trypanosomatidae is closely related to euglenids that harbor plastids acquired from a green alga via secondary endosymbiosis. This discovery led to the idea that trypanosomatid parasites contained a green alga-derived plastid in their evolutionary past, an evolutionary scenario that was criticized based on the rarity of plant/plastid/cyanobacterium-like genes in the completely sequenced genomes of Trypanosoma and Leishmania species. Because it is difficult to identify such genes, however, their apparent rarity does not preclude a previous plastid endosymbiosis in the Trypanosomatidae. The genome of the plastid-less apicomplexan Cryptosporidium parvum preserves only a handful of plant/plastid/cyanobacterium-like genes, suggesting massive loss of plastid genes after elimination of its plastid. Additional support for such wholesale gene loss comes from fucoxanthin-containing dinoflagellates. Trypanosomatid nuclear genomes contain cyanobacterium-, green plant-, and haptophyte alga-derived genes, suggesting that they could have possessed a plastid in their evolutionary past; however, these genes also could represent examples of more typical horizontal gene transfer that did not accompany a plastid endosymbiosis. Thus, the presence of host cell genes that were adapted for use in the plastid would be much stronger evidence for a past plastid endosymbiosis in the Trypanosomatidae. Good examples of such genes are those encoding superoxide dismutases (SODs). Trypanosomatid parasites possess 4 iron-containing SODs, with 2 of them, SODA and SODC, targeted to the mitochondrion. In contrast with SODAs with classical single domain mitochondrial targeting signals, SODCs carry bipartite pre-sequences composed of a signal peptide, followed by a transit peptide. Interestingly, these N-terminal extensions show striking similarities in length, hydropathy profiles, amino acid composition, and targeting properties to pre-sequences of proteins targeted to eukaryotic alga-derived plastids of euglenids and dinoflagellates. In turn, phylogenetic analyses indicate that SODCs originated from a mitochondrion targeted SOD via gene duplication and were inherited vertically in the trypanosomatid lineage. These data represent a new kind of evidence for a past plastid endosymbiosis in the Trypanosomatidae, but the nature of this plastid remains unclear. It is usually assumed that the trypanosomatid plastid shared a common origin with that of euglenids, but Delta 4 desaturase phylogenies suggest that it could have originated via an independent, tertiary endosymbiosis involving a haptophyte alga. It is also possible that ancestors of the Trypanosomatidae initially possessed a primary plastid that later was replaced by a secondary or tertiary plastid. PMID- 20540606 TI - Overexpression of SERCA1a in the mdx diaphragm reduces susceptibility to contraction-induced damage. AB - Although the precise pathophysiological mechanism of muscle damage in dystrophin deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne muscular dystrophy patients and mouse models of dystrophin deficiency exhibit extensive abnormalities of calcium homeostasis, which we hypothesized would be mitigated by increased expression of the sarcoplasmic reticulum calcium pump. Neonatal adeno-associated virus gene transfer of sarcoplasmic reticulum ATPase 1a to the mdx diaphragm decreased centrally located nuclei and resulted in reduced susceptibility to eccentric contraction-induced damage at 6 months of age. As the diaphragm is the mouse muscle most representative of human disease, these results provide impetus for further investigation of therapeutic strategies aimed at enhanced cytosolic calcium removal. PMID- 20540607 TI - The potential of mycoparasites for biological control of plant diseases*. PMID- 20540608 TI - Long-distance dispersion of rust pathogens. PMID- 20540609 TI - Modeling food webs: exploring unexplained structure using latent traits. AB - Several stochastic models have tried to capture the architecture of food webs. This approach is interesting, but it is limited by the fact that different assumptions can yield similar results. To overcome this limitation, we develop a purely statistical approach. Body size in terms of an optimal ratio between prey and predator is used as explanatory variable. In 12 observed food webs, this model predicts, on average, 20% of interactions. To analyze the unexplained part, we introduce a latent term: each species is described by two latent traits, foraging and vulnerability, that represent nonmeasured characteristics of species once the optimal body size has been accounted for. The model now correctly predicts an average of 73% of links. The key features of our approach are that latent traits quantify the structure that is left unexplained by the explanatory variable and that this quantification allows a test of whether independent biological information, such as microhabitat use, camouflage, or phylogeny, explains this structure. We illustrate this method with phylogeny and find that it is linked to one or both latent traits in nine of 12 food webs. Our approach opens the door to the formulation of more complex models that can be applied to any kind of biological network. PMID- 20540610 TI - Dietary supplementation with carotenoids improves immunity without increasing its cost in a crustacean. AB - Costs of immunity include self-harming autoreactivity through the production of cytotoxic chemicals. While carotenoids stimulate immunity and reduce oxidative stress during immune activity in vertebrates, their involvement in invertebrate immunity is unclear. Recently, a positive correlation between immune defenses and concentration of carotenoids in the hemolymph was demonstrated in the crustacean Gammarus pulex, suggesting an important role of carotenoids in invertebrate immunity. We tested the causality of this relationship by using a dietary supplementation with carotenoids and measuring several immune parameters. We found that dietary carotenoids had a broad immunostimulating effect, enhancing phenoloxidase activity and resistance to a bacterial infection. When immune challenged, gammarids fed with carotenoids did not pay an additional survival cost because of autoreactivity, despite their intensified immune activity. Therefore, dietary carotenoids improved gammarids' immunity without inducing additional self-harming. This underlines the importance of carotenoids in both the regulation and the evolution of immunity in G. pulex. PMID- 20540611 TI - Differential var gene expression in children with malaria and antidromic effects on host gene expression. AB - Among 62 children with mild malaria, cerebral malaria, or severe malarial anemia, we analyzed the transcription of different var gene types. There was no difference in parasitemia level or body temperature between groups. However, a significantly different expression pattern was observed in children with cerebral malaria, compared with that in patients in the other 2 groups: children with cerebral malaria had lower expression of the upsA subtype but higher expression of the upsB and upsC subtypes. Furthermore, expression of human genes responsive to tumor necrosis factor and hypoxia correlated with distinct ups types. PMID- 20540612 TI - The need to problematize interprofessional education and practice activities. PMID- 20540613 TI - Measures of interprofessional education and collaboration. AB - Healthcare and social services professionals are being called to engage in interprofessional education (IPE) and interprofessional collaboration (IPC) in order to provide efficient and effective care to clients and patients. As such, it is important to conduct research that contributes to evaluation of collaborative practice. A necessary component to any strong quantitative research methodology is the type of instruments used for data collection. However, identifying valid and reliable instruments to use in this area of research can be a daunting task. The purpose of this paper is to review the quantitative measures (i.e., surveys and questionnaires) described in the interprofessional literature. Twenty-three instruments were identified and analyzed for validity and reliability statistics, sample size, ease of access to items on measure, and applicability of measure to diverse professional populations. The two primary measures reviewed are the Readiness for Interprofessional Learning Scale (Parsell & Bligh, 1998 ) and the Interdisciplinary Education Perception Scale (Luecht, Madsen, Taugher, & Petterson, 1990 ). Limited information existed for the remaining measures. Despite the number of measures available for assessing and evaluating IPE and IPC, most lack sufficient theoretical and psychometric development. Several issues that impact the development of sound measures are discussed and implications for future IPC are proposed. PMID- 20540614 TI - An intervention to improve interprofessional collaboration and communications: a comparative qualitative study. AB - Interprofessional communication and collaboration are promoted by policymakers as fundamental building blocks for improving patient safety and meeting the demands of increasingly complex care. This paper reports qualitative findings of an interprofessional intervention designed to improve communication and collaboration between different professions in general internal medicine (GIM) hospital wards in Canada. The intervention promoted self-introduction by role and profession to a collaborating colleague in relation to the shared patient, a question or communication regarding the patient, to be followed by an explicit request for feedback from the partner professional. Implementation and uptake of the intervention were evaluated using qualitative methods, including 90 hours of ethnographic observations and interviews collected in both intervention and comparison wards. Documentary data were also collected and analysed. Fieldnotes and interviews were transcribed and analysed thematically. Our findings suggested that the intervention did not produce the anticipated changes in communication and collaboration between health professionals, and allowed us to identify barriers to the implementation of effective collaboration interventions. Despite initially offering verbal support, senior physicians, nurses, and allied health professionals minimally explained the intervention to their junior colleagues and rarely role-modelled or reiterated support for it. Professional resistances as well as the fast paced, interruptive environment reduced opportunities or incentive to enhance restrictive interprofessional relationships. In a healthcare setting where face-to-face spontaneous interprofessional communication is not hostile but is rare and impersonal, the perceived benefits of improvement are insufficient to implement simple and potentially beneficial communication changes, in the face of habit, and absence of continued senior clinician and management support. PMID- 20540615 TI - Evaluation of a multidisciplinary faculty to support learning in surgical practice. AB - The Theatre Faculty Project was a programme of education seminars, personal study and workplace educational activities for surgeons, operating theatre staff and surgical trainees at a hospital in north-west England. Its aim was to create a multidisciplinary faculty with an understanding of implicit aspects of surgical practice, of how these enter clinical thinking and professional judgement and are used to enhance the learning, teaching and assessment of surgeons. A qualitative evaluation of the faculty project showed improved educational understanding and multidisciplinary awareness among its participants. Refinements of the programme were identified to help those (surgeons in particular) having difficulty conceptually or practically with clinical reflective writing and with portfolio building. However, the support of Trust management at the host hospital will be vital in extending the programme beyond its initial group of volunteers and in integrating the multidisciplinary faculty into its organizational structures. PMID- 20540618 TI - Diagnostic strategy for blood culture-negative endocarditis. PMID- 20540619 TI - Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. AB - BACKGROUND. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. METHODS. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. RESULTS. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. CONCLUSIONS. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available. PMID- 20540620 TI - Characterization of norovirus-associated traveler's diarrhea. AB - BACKGROUND: Traveler's diarrhea is the most common medical complaint of international visitors to developing regions. Previous findings suggested that noroviruses (NoVs) are an underappreciated cause of traveler's diarrhea. METHODS. In the present study, we sought to define the presence of NoVs in 320 acute diarrheic stool samples collected from 299 US students who traveled to Guadalajara, Cuernavaca, or Puerto Vallarta, Mexico, during the period from 2007 through 2008. Conventional and quantitative real-time polymerase chain reaction assays were used to detect and determine NoV loads in stool samples. NoV strains were characterized by purification of viral RNA followed by sequencing of the viral capsid protein 1 gene. Sequences were compared using multiple sequence alignment, and phylogenetic trees were generated to evaluate the evolutionary relatedness of the viral strains associated with cases of traveler's diarrhea. RESULTS: NoV RNA was detected in 30 (9.4%) of 320 samples. Twelve strains belonged to genogroup I, and 18 strains belonged to genogroup II. NoV prevalence was higher in the winter season than in the summer season (23% vs 7%, respectively; P = .001). The cDNA viral loads of genogroup I viruses were found to be 500-fold higher than those of genogroup II strains. Phylogenetic analysis revealed a diverse population of NoV strains over different locations and years. CONCLUSIONS: NoV strains are important causes of traveler's diarrhea in Mexico, especially during the wintertime, and US students in Mexico may represent a suitable group for future NoV vaccine efficacy trials. PMID- 20540621 TI - High prevalence of macrolide resistance in Mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in China. AB - The resistance rate of 67 Mycoplasma pneumoniae isolates from 356 ambulatory adult patients with respiratory tract infection was 69% (46 of 67). All 46 macrolide-resistant strains harbored point mutations in the 23S ribosomal RNA gene. Patients infected with macrolide-resistant M. pneumoniae required significantly longer durations of antibiotic therapy and had longer time to resolution of fever. PMID- 20540622 TI - Options for incorporating children's inhaled dose into human health risk assessment. AB - Increasing attention has been placed on inhalation dosimetry in children because of children's greater air intake rate and unique windows of vulnerability for various toxicants and health outcomes. However, risk assessments have not incorporated this information because dosimetric adjustments have focused upon extrapolation across species rather than across age groups within the human population. The objectives of this study were to synthesize information regarding child/adult intake and dosimetry differences for particles and gases for potential application to risk assessment. Data and models gathered at a 2006 workshop and more recent studies were reviewed to better understand lung development and inhaled dose in children. The results show that child/adult differences exist both on a chemical intake basis and on a deposited or systemic dose basis. These differences can persist for several years and are not captured by standard intraspecies uncertainty factors or by USEPA's reference concentration (RfC) methodology. Options for incorporating children's inhalation exposures into human risk assessments include (1) 3-fold default air intake adjustment for the first 3 years of life with a reduced factor for older children; (2) superseding this default via simplified dosimetry models akin to USEPA's RfC methodology modified for children; (3) utilizing more sophisticated models with better anatomical and air flow descriptions; (4) running these models with input distributions to reflect interchild variability; (5) developing more advanced approaches involving imaging techniques and computational fluid dynamic (CFD) models. These options will enable children's inhaled dose to have a quantitative role in risk assessment that has been lacking and will establish a basis for ongoing research. PMID- 20540624 TI - Variation in echocardiographic and cardiac hemodynamic effects of PM and ozone inhalation exposure in strains related to Nppa and Npr1 gene knock-out mice. AB - Elevated levels of ambient co-pollutants are associated with adverse cardiovascular outcomes shown by epidemiology studies. The role of particulate matter (PM) and ozone (O3) as co-pollutants in this association is unclear. We hypothesize that cardiac function following PM and O3 exposure is variably affected by genetic determinants (Nppa and Npr1 genes) and age. Heart function was measured before and after 2 days each of the following exposure sequence; (1) 2-h filtered air (FA) and 3-h carbon black (CB; 0.5 microg/m(3)); (2) 2-h O3 (0.6 ppm) and 3-h FA; (3) 5-h FA; and, (4) 2-h O3 and 3-h CB. Two age groups (5 and 18 months old (mo)) were tested in C57Bl/6J (B6) and 129S1/SvImJ (129) mice using echocardiographic (echo) and in vivo hemodynamic (IVH) measurements. With echo, posterior wall thickness was significantly (P < 0.01) greater in 129 relative to B6 mice at baseline. With CB exposure, young B6 and older 129 mice show significant (P < 0.01) reductions in fractional shortening (FS) compared to FA. With O3 exposure, FS was significantly (P < 0.01) diminished in young 129, which was attributable to significant increases in end-systolic left ventricular diameter. With O3 and CB combined, notable (P < 0.01) declines in heart rate and end-systolic posterior wall thickness occurred in young 129 mice. The IVH measurements showed striking (P < 0.05) compromises in cardiac function after CB and O3 exposure; however, strain differences were undetectable. These results suggest that PM and O3 exposures, alone and combined, lead to different cardiac functional changes, and these unique changes are age-specific and dependent on Nppa and Npr1 genes. PMID- 20540623 TI - Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge. AB - Ozone and lipopolysaccharide (LPS) are environmental pollutants with adverse health effects noted in both healthy and asthmatic individuals. The authors and others have shown that inhalation of ozone and LPS both induce airway neutrophilia. Based on these similarities, the authors tested the hypothesis that common biological factors determine response to these two different agents. Fifteen healthy, nonasthmatic volunteers underwent a 0.4 part per million ozone exposure for 2 h while performing intermittent moderate exercise. These same subjects underwent an inhaled LPS challenge with 20,000 LPS units of Clinical Center Reference LPS, with a minimum of 1 month separating these two challenge sessions. Induced sputum was obtained 24 h before and 4-6 h after each exposure session. Sputum was assessed for total and differential cell counts and expression of cell surface proteins as measured by flow cytometry. Sputum supernatants were assayed for cytokine concentration. Both ozone and LPS challenge augmented sputum neutrophils and subjects' responses were significantly correlated (R = .73) with each other. Ozone had greater overall influence on cell surface proteins by modifying both monocytes (CD14, human leukocyte antigen [HLA] DR, CD11b) and macrophages (CD11b, HLA-DR) versus LPS where CD14 and HLA-DR were modified only on monocytes. However, LPS significantly increased interleukin (IL) 1beta, IL-6, and tumor necrosis factor (TNF)-alpha, with no significant increases seen after ozone challenge. Ozone and LPS exposure in healthy volunteers induce similar neutrophil responses in the airways; however, downstream activation of innate immune responses differ, suggesting that oxidant versus bacterial air pollutants may be mediated by different mechanisms. PMID- 20540625 TI - Falls are a fact of life for some patients after discharge from a rehabilitation programme. AB - PURPOSE: This paper reports on a 3-month post-discharge falls profile of a cohort of patients discharged home from an acute rehabilitation setting. METHODS: A consecutively-sampled cohort of consenting patients was prospectively followed for 3 months after discharge from a large Australian metropolitan acute rehabilitation facility. Patients were diagnostically classified by the reason for admission. All patients completed a monthly falls diary. Each month, falls were described by severity, location, frequency and outcome. Patients also completed the World Health Organisation's quality of life (QoL-BREF) at Months 1 and 3. RESULTS: Almost a third of the study participants fell during the study [105 fallers of 342 total (31%)]. Of these, 21 fell more than once (20%). There were significant differences in falls reported per diagnostic group, including frequency, impact, severity and ability to get up. Irrespective of diagnostic group, fallers had lower QoL scores compared to non-fallers. Both the neurological and orthopaedic trauma groups were most at risk of falling in Months 1 and 3, whereas in Month 2, only the neurological group was most at risk of falling. CONCLUSION: Falls are a fact of life for some patients during their community rehabilitation phase. Patients from different diagnostic groups have different over-time risk profiles for falling. Thus, there is no 'one-size fits all' solution for falls prevention. This study provides useful data to assist in formulating appropriate falls prevention strategies for recently ill people. PMID- 20540626 TI - One woman's story about her everyday life after a spinal cord injury. AB - PURPOSE: The aim was to describe and offer an explanation for how one woman viewed her everyday life after a spinal cord injury (SCI). METHOD: Data were collected by conducting three interviews with one woman with a SCI. Open-ended questions were used with the intention of capturing the woman's own story. The narrative approach inspired by Polkinghorne was used to describe the woman's experiences of her everyday life after the SCI. RESULTS: The analysis revealed that, events influenced her everyday life after a SCI and these events influenced her identity, habits and participation in activities. Further, how she has gone from a state of hopelessness in the early days to a reconstructed identity, associated with a new insight during the 2 years after the accident through a complex and dynamic process of change. In our interpretation we have attempted to provide an explanation of why this outcome came about. CONCLUSIONS: When using narratives, professionals within health-care could focus on the individual instead of the diagnosis or disability. Further, according to a client-centred perspective it is important to attain the client's experiences and knowledge to gain a more complete picture in order to obtain a profound understanding of the client. PMID- 20540627 TI - Integration of in silico and in vitro platforms for pharmacokinetic pharmacodynamic modeling. AB - IMPORTANCE OF THE FIELD: Pharmacokinetic-pharmacodynamic (PK-PD) modeling enables quantitative prediction of the dose-response relationship. Recent advances in microscale technology enabled researchers to create in vitro systems that mimic biological systems more closely. Combination of mathematical modeling and microscale technology offers the possibility of faster, cheaper and more accurate prediction of the drug's effect with a reduced need for animal or human subjects. AREAS COVERED IN THIS REVIEW: This article discusses combining in vitro microscale systems and PK-PD models for improved prediction of drug's efficacy and toxicity. First, we describe the concept of PK-PD modeling and its applications. Different classes of PK-PD models are described. Microscale technology offers an opportunity for building physical systems that mimic PK-PD models. Recent progress in this approach during the last decade is summarized. WHAT THE READER WILL GAIN: This article is intended to review how microscale technology combined with cell cultures, also known as 'cells-on-a-chip', can confer a novel aspect to current PK-PD modeling. Readers will gain a comprehensive knowledge of PK-PD modeling and 'cells-on-a-chip' technology, with the prospect of how they may be combined for synergistic effect. TAKE HOME MESSAGE: The combination of microscale technology and PK-PD modeling should contribute to the development of a novel in vitro/in silico platform for more physiologically-realistic drug screening. PMID- 20540628 TI - Endoscopic treatment of distal choroidal artery aneurysm. AB - Distal choroidal artery aneurysms stemming from the lateral wall of the ventricles are rare and are mostly associated with moyamoya disease. The treatment of these aneurysms is difficult because of their deep location. The authors report the case of a 50-year-old woman followed for moyamoya disease presenting with 2 intraventricular hemorrhages. Cerebral angiography showed an aneurysm located on the left distal choroidal artery. Magnetic resonance imaging also demonstrated that the lesion protruded from the lateral wall of the trigone of the left lateral ventricle. Using MR imaging-guided stereotactic localization, the aneurysm was accurately reached endoscopically and successfully resected from the parent artery. The patient was discharged neurologically intact. To the best of the authors' knowledge, this is the first report of a successfully endoscopically treated distal anterior choroidal artery aneurysm. Endoscopic surgery may be added to the armamentarium of procedures used to treat intraventricular aneurysms. PMID- 20540630 TI - Lipoprotein-A and carotid intima media thickness as cardiovascular risk factors in patients of chronic kidney disease. AB - Patients in all stages of chronic kidney disease (CKD) are considered in the "high-risk group" for development of cardiovascular disease (CVD). The study was undertaken in 60 adult patients of chronic renal failure. The patients were divided into three groups: Group I had subjects with CKD (stages 1 and 2); Group II had subjects with CKD (stages 3 and 4) on conservative therapy for 3 months; and Group III had subjects with CKD (stage 5) on regular hemodialysis for at least 3-4 weeks. Carotid sonography was done in all patients at the time of inclusion in the study. The patients in all the groups were then followed for 6 months and the relevant investigations were carried out, initially at the time of presentation, and then at third- and sixth-month interval. The patients were monitored for various renal parameters along with serum lipoprotein-A [Lp (A)]. The value of carotid intima media thickness (CA-IMT) was increased in group II and III as compared to group I. The calcification of carotids was higher in patients of group III. The maximum number of patients having plaques and stenosis in the carotids were seen in group III (50%), followed by group II (20%). Patients in group III had 5-10 times higher levels of Lp (A) as compared to patients in group I. The comparison of Lp (A) levels between group I and group II was also highly statistically significant. PMID- 20540631 TI - Commencing peritoneal dialysis with 1.1% amino acid solution does not influence biochemical nutritional parameters in incident CAPD patients. AB - OBJECTIVE: To evaluate the influence of 1.1% amino acid dialysis solutions on nutritional parameters in incident continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: The effect of daily use of 1.1% amino acid solution was studied retrospectively in 32 incident CAPD patients (14 women and 18 men, mean age 54 +/- 13 years) who began CAPD at our tertiary university hospital between July 2005 and February 2009 (amino acid solution (AAS) group). Serum total protein, albumin, and creatinine were assessed for all patients prior to dialysis and at the end of the study period. Thirty-two control patients (12 women and 20 men, mean age 52 +/- 14 years) who started peritoneal dialysis with a standard CAPD program were also investigated and grouped as the dextrose solution (DS) group. RESULTS: Baseline serum albumin levels were significantly lower in the AAS group compared to the DS group (3.4 +/- 0.4 g/dL vs. 3.7 +/- 0.5 g/dL, p = 0.011). At the end of the 12-month follow-up period, mean serum albumin levels had decreased from 3.4 to 3.3 g/dL in the AAS group (p = 0.218) and increased from 3.7 to 3.8 g/dL in the DS group (p = 0.360). Overall, no significant changes were observed in serum total protein, creatinine, or albumin in either group. CONCLUSIONS: Amino acid solutions conferred no demonstrable benefit on biochemical parameters in incident CAPD patients. The effects of AAS may be different when added to the CAPD regimen of patients undergoing prior CAPD treatment. PMID- 20540632 TI - Microalbuminuria is not associated with endothelial dysfunction and coronary atherosclerosis in patients with acute coronary syndromes. AB - BACKGROUND: Microalbuminuria is associated with atherosclerosis and it is a strong and independent predictor of increased risk for cardiovascular morbidity and mortality. However, the underlying mechanisms of the association of albuminuria and cardiovascular disease are not well understood. We examined the association of endothelial dysfunction with microalbuminuria in non-diabetic and non-hypertensive patients with acute coronary syndromes (ACS). METHODS: We compared endothelial function by flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN) and angiographic properties among 27 microalbuminuric and 106 normoalbuminuric patients. Severity of coronary arteriosclerosis was evaluated using the Gensini score and number of diseased vessels. RESULTS: We evaluated 133 patients (106 males; mean age 59 +/- 11 years). Microalbuminuria was present in 27 (20.3%) subjects. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics. FMD and GTN responses were not different in microalbuminuric patients compared with normoalbuminuric patients (FMD 8.2 +/- 5.3 vs. 7.9 +/- 6.5%, p = 0.54 and GTN 9.3 +/- 5.4 vs. 10.2 +/- 6.9%, p = 0.82). Microalbuminuria was not associated with endothelial dysfunction (p = 0.49). Morphological properties of coronary lesion were not different. CONCLUSION: The presence of microalbuminuria is not associated with endothelial dysfunction and severity of angiographic coronary atherosclerosis in non-diabetic and non-hypertensive patients with ACS. PMID- 20540633 TI - Lack of association between transient receptor potential cation channel 6 polymorphisms and primary membranous glomerulonephritis. AB - Membranous glomerulonephritis (MGN) is one common cause of idiopathic nephrotic syndrome. Transient receptor potential cation channel 6 (TRPC6) has been identified as causing a familial form of progressive focal and segmental glomerulosclerosis. The objective was to clarify the relationship between TRPC6 polymorphisms and MGN. We recruited a cohort of 134 biopsy-diagnosed MGN patients and 265 healthy subjects. Genotyping of TRPC6 polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analyzed associations between TRPC6 gene polymorphisms and clinical manifestations and pathogenesis of MGN. There was no statistically significant difference of TRPC6 gene rs3824935 C/T, rs17096918 C/T, and rs4326755 A/G polymorphisms between controls and patients with MGN. There was no statistical significance of allele frequencies in these two groups. The characteristics of clinical parameters in TRPC6 gene (rs3284935) C/T polymorphism revealed no difference except proteinuria (p < 0.0005) between CC and non-CC genotype in MGN patients. Besides, no apparent statistically significant differences of rs17096918 C/T (TT and non-TT) and rs4326755 A/G (AA and non-AA) polymorphisms between genotypes were found in the clinical parameters. There is no different genotype distribution between normal controls and patients with MGN of TRPC6 gene. The data also show that TRPC6 gene may not be associated with disease clinical course of MGN. PMID- 20540634 TI - Mannitol is an independent risk factor of acute kidney injury after cerebral trauma: a case-control study. AB - We retrospectively studied a random cohort of patients with cerebral trauma to investigate the risk factors of acute kidney injury (AKI) following cerebral trauma. AKI was determined using the RIFLE (risk, injury, failure, loss, or end stage kidney) staging criteria. About 171 patients were chosen in the study, with 53 patients in AKI group and 118 patients without AKI in non-AKI group. By logistic regression analysis, univariate analysis revealed that age, hypertension, emergent surgery, systemic inflammatory response syndrome (SIRS), Glasgow coma score (GCS), sequential organ failure assessment (SOFA) score, the respiration, coagulation, and cardiovascular components of the SOFA score, mechanical ventilation time, red blood cell transfusion, plasma transfusion, and the accumulative doses of furosemide, torsemide, and mannitol were significantly related to AKI after cerebral trauma. Logistic multivariate regression analysis showed that SOFA score [odds ratio (OR) = 1.516, 95% confidence interval (CI) 1.222-1.881, p < 0.001], the accumulative doses of torsemide (OR = 0.016, 95% CI 1.002-1.031, p = 0.016), and the accumulative doses of mannitol (OR = 2.687, 95% CI 1.062-6.800, p = 0.037) were independent risk factors of AKI. This model had a good discrimination for AKI with an area under the receiver operating characteristic (ROC) curve of 0.901 (p < 0.001). The accumulative doses of mannitol as a risk factor of AKI were identified by propensity score match (PSM) method. We concluded that AKI was a common complication in patients with cerebral trauma. SOFA score and the accumulative doses of torsemide and mannitol were independent risk factors of AKI following cerebral trauma. PMID- 20540635 TI - Effects of atorvastatin versus probucol on low-density lipoprotein subtype distribution and renal function in hyperlipidemic patients with nondiabetic nephropathy. AB - OBJECTIVES: Small dense low-density lipoprotein (LDL) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL. However, few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy. METHODS: This study was a randomized crossover trial comparing the effects of atorvastatin (10 mg/day) and probucol (500 mg/day) administered for 24 weeks in 31 patients (urinary albumin excretion 0.3-2.0 g/day and creatinine clearance >30 mL/min/1.73 m (2) ). Lipid parameters, mean LDL particle diameter, creatinine clearance, and urinary albumin to creatinine excretion ratio were measured before and during treatment periods. MAIN FINDINGS: Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations. When stratified by mean baseline LDL particle size at 25.5 nm, atorvastatin increased (p < 0.05) LDL particle size from 24.6 +/- 0.5 to 25.2 +/- 0.9 nm only in the <25.5 nm (pattern B) group, whereas probucol decreased (p < 0.05) LDL size from 24.8 +/- 0.9 to 24.2 +/- 0.9 nm in the pattern B group and from 25.9 +/- 0.5 to 24.6 +/- 0.8 nm in the >or=25.5 nm (pattern A) group. No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment. CONCLUSIONS: Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy, although both agents exhibited no renoprotective action, suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection. PMID- 20540636 TI - Renal tubular acidosis in renal transplantation recipients. AB - AIM: We aimed to investigate the prevalence, type, and possible risk factors of renal tubular acidosis (RTA) in Turkish patients with renal transplantation. PATIENTS AND METHOD: The study included 66 adult renal transplantation recipients. We recorded the parameters of venous blood gas analysis including serum pH value, serum bicarbonate (HCO(3)) concentration, presence of metabolic acidosis, which was defined as low HCO(3) (<22 mEq/L), and serum pH value (<7.35) together, and base excess and urine pH at the last follow-up. Creatinine clearance was determined from 24-hour collected urine samples. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. RESULTS: Mean age of 66 patients was 37.0 +/- 10.4 years; 48 of 66 patients were male. RTA was found in 14 (21.2%) patients. Considering for differential diagnosis of RTA, 4 patients had type 2 RTA and 10 had type 1 RTA. On the contrary, type 4 RTA was observed in no patients. Creatinine clearance was meaningfully lower in acidosis group than in those of the nonacidosis group (55.16 +/- 23.27 vs. 71.06 +/- 28.14 mL/min; p = 0.028). HCO(3) was correlated with hemoglobin level (r = 0.423, p = 0.001) and creatinine clearance (r = 0.262, p = 0.034). It was inversely correlated with cyclosporine A (CsA) level (r = 0.499, p = 0.035). CONCLUSION: RTA is a common complication after kidney transplantation. It is related with low creatinine clearance, low hemoglobin level, and high CsA level. Particularly, the value of creatinine clearance is lower and the possibility of RTA is higher. PMID- 20540637 TI - Analyses of renal outcome following transplantation adjusting for informative right censoring and demographic factors: A longitudinal study. AB - Demographic factors such as race, vital status, gender, and age could affect the final renal outcome of patients who undergo renal transplantation. These demographic factors could be assessed at the recipient and donor levels. Repeated measures for blood urea nitrogen (BUN) are typically recorded for each patient following renal transplantation, as a biomarker to assess renal progress. However, once a patient develops renal failure due to graft rejection, no measurement of BUN can be registered and the patient goes back to dialysis. This causes loss of follow-up and incomplete data on BUN measurements, a problem referred to as informative right censoring. If this problem is ignored, inaccurate, and biased estimates will be generated. In this study, unbiased estimates for the rate of change of BUN levels over time adjusted for informative right censoring and demographic factors were acquired using a sophisticated model of analysis. Our results demonstrated that BUN levels for Caucasians were decreasing at a greater rate than African Americans (p < 0.0001). When donors are deceased, African American recipients showed an increase instead of a decrease in their BUN levels following transplantation. Moreover, African Americans showed a decrease in their BUN levels when the donors were African Americans compared with when donors were Caucasians (p = 0.03). Our results also showed that BUN levels were decreasing at a greater rate when donors and recipients were of different gender than when they were of the same gender (p = 0.009). These results suggest that the success of renal transplantation is impacted by the donor/recipient demographic factors. PMID- 20540638 TI - Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. AB - Acute kidney injury (AKI) is a common disorder associated with high morbidity and mortality rates. Ischemia is the leading cause of AKI. This is a pilot study investigating the ability of multiple urinary cytokines to predict renal functional outcome and mortality in patients with ischemic AKI. Urine samples were obtained from 45 subjects with ischemic AKI on the day of renal consultation and 3 days later. The urinary concentrations of interleukin (IL)-1beta, IL-6, IL 8, monocyte chemotactic protein (MCP)-1, interferon-inducible protein (IP)-10, regulated on activation, normal T-expressed and secreted (RANTES), transforming growth factor (TGF)-alpha, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were measured simultaneously using a microsphere based immunofluorescence assay. Urinary cytokine levels (pg/mg urine creatinine), which predict renal functional recovery or no recovery the next day and 7 days and 3 months later, were identified. Increased urinary IP-10 and IL-8 predicted no renal functional recovery the next day. Increased urinary IP-10 and VEGF predicted no renal recovery by 7 days. Increased urinary IP-10 and VEGF predicted no renal recovery by 4 days, whereas increased urinary EGF predicted renal functional recovery at that time. Increased urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF predicted patient's death within 3 months. Our findings suggest that urinary IP-10, IL-8, VEGF, TGF-alpha, and EGF may predict renal functional outcome at various times along the course of ischemic AKI and that urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF may predict mortality of the patients within 3 months. PMID- 20540639 TI - Improved plasma amino acids pattern following 12 months of supplemented low protein diet in peritoneal dialysis patients. AB - BACKGROUND: Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. METHODS: This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. RESULTS: Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. CONCLUSIONS: A low protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients. PMID- 20540640 TI - Immune response after a single vaccination against 2009 influenza A H1N1 in hemodialysis patients. AB - BACKGROUND: Influenza infection is a significant cause of morbidity and mortality in general population. Hemodialysis patients are considered at high risk of influenza infection given their altered immune status. Pandemic influenza virus is new for human beings, so it is hard to predict the response to infection or vaccination. We aimed to evaluate the response to pandemic H1N1 vaccination in hemodialysis patients. METHODS: A total of 70 patients on chronic hemodialysis and 20 controls who had been vaccinated against the pandemic influenza virus 5 weeks before the time of blood sampling were included into this study. The anti H1N1 immunoglobulin G (IgG) antibodies of the patients were studied with enzyme immune assay (EIA) method. Our cut-off optical density (OD) value was 1.503. If the patient's OD value was equal or higher than this value, it was considered as positive. If it was lower, it was considered as negative. RESULTS: The mean OD value was 2.22 +/- 0.42 in the patient group and 1.99 +/- 0.34 in the control group (p < 0.05). Two of 70 patients and 1 of the controls had negative OD values and they were considered as nonresponsive to vaccination. There was also a negative correlation between the age and OD values in the patient group (r = 0.277, p < 0.05). CONCLUSION: H1N1 vaccine can be performed safely and cost effectively with a single dose to the risk groups especially to the hemodialysis patients. Evaluation of H1N1 IgG antibody with enzyme-linked immunosorbent assay (ELISA) may be a safe, easy, and cost-effective assay. PMID- 20540641 TI - Improved detection of hepatitis C virus infection by transcription-mediated amplification technology in dialysis population. AB - BACKGROUND: Hepatitis C virus (HCV) infection remains common among patients undergoing maintenance dialysis and plays an adverse effect on survival in this population. Accurate detection of HCV viremia (HCV RNA) in dialysis patients requires a sensitive and specific diagnostic test. METHODS: The Versant HCV RNA Qualitative Assay, based on transcription-mediated amplification (TMA) technique, was prospectively evaluated in 112 dialysis patients. Performance characteristics of the Versant HCV TMA Assay were evaluated in comparison to the Amplicor((R)) 2.0 HCV test based on polymerase chain reaction (PCR) technique. In addition, anti-HCV serologic tests including third-generation enzyme immunoassay and Recombinant Immunoblot Assay were performed. RESULTS: Of the 112 specimens tested, 29 were reactive by Versant HCV TMA Assay, yielding an overall prevalence of HCV viremia of 25.9%. The concordance between TMA and PCR techniques was excellent [91% (101/112)]. Eleven specimens (10%) were invalid or equivocal by PCR due to interference phenomena; all 11 specimens had valid TMA results (2 patients being TMA reactive and 9 nonreactive). Four specimens [3.6% (4/112)] that tested PCR-negative and HCV TMA nonreactive were anti-HCV seropositive, consistent with resolved HCV infection. In the group of seronegative samples, one was reactive by TMA Assay [1.25% (1/80)]. CONCLUSIONS: The HCV TMA technology seems a highly sensitive tool for detecting HCV RNA in the dialysis population, with no evidence of specimen interference. One EIA-negative but HCV-RNA-positive patient by Versant HCV TMA Assay was identified. Prospective clinical trials are under way to assess the clinical impact related to the use of HCV TMA technology in dialysis population. PMID- 20540642 TI - Interaction of endothelin-1 and nitric oxide pathways in human tubular epithelial cells under the influence of cyclosporine-A. AB - BACKGROUND: The exact mechanism of cyclosporine (CsA) nephrotoxicity has not been clarified. In this study, we investigated the effect of pharmacological doses of CsA on the production of nitric oxide synthases (NOSs) and endothelin (ET) receptors (ETR-A, ETR-B), in human tubular cells [human kidney (HK)-2], to identify any implication of these pathways in CsA nephrotoxicity. METHODS: Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at various concentrations (0-1000 ng/mL). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine mRNA synthesis of NOSs (eNOS, iNOS) and ET receptors (ETR-A, ETR-B) and western blot analysis for the subsequent proteins. RESULTS: A dose-dependent induction of synthesis of NO synthases eNOS and iNOS and ET receptors ETR-A and ETR-B was observed, even at therapeutic doses of CsA. An interaction between NO and ET-1 systems under the influence of CsA was also observed. Blockage of NO production was followed by down-regulation of ETR-B whereas blockade of ET pathway with ET receptor antagonists was followed by down regulation of eNOS expression. CONCLUSION: CsA induces NOSs as well as ET receptor mRNA and protein synthesis in tubular epithelial cells. The up regulation of NO and ET-1 pathways is probably implicated in the nephrotoxic action of CsA, whereas an interplay between ETR-B and eNOS seems to be involved. PMID- 20540643 TI - Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats. AB - OBJECTIVES: To investigate the effect of silymarin and milk thistle extract on the progression of diabetic nephropathy (DN) in rats. METHODS: Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg). Silymarin (100 mg/kg/d) or the extract (1.2 g/kg/d) was gavaged for 4 weeks. Blood glucose (BS), serum urea (S(u)), serum creatinine (S(cr)), and 24-h urine protein (Up) were measured and glomerular filtration rate (GFR) was calculated. Concentration of thiobarbituric acid reactive species (TBARS) and activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the renal tissue. RESULTS: Data were expressed as mean +/- SEM. Silymarin or the extract had no significant effect on BS, S(cr), and GFR. Both milk thistle extract and silymarin, respectively, decreased S(u) (mg/dL) (87.1 +/- 7.78, p < 0.001; 84.5 +/- 7.15, p < 0.001), Up (mg) (5.22 +/- 1.56, p = 0.014; 5.67 +/- 0.86, p = 0.034), and tissue TBARS (nmol/mg protein) (0.67 +/- 0.04, p < 0.001; 0.63 +/- 0.07, p < 0.001) in diabetic rats, compared to diabetic control (DC) (S(u): 131.0 +/- 4.55, Up: 8.3 +/- 0.84, TBARS: 0.94 +/- 0.06). Both the extract and silymarin could increase the activity of CAT (IU/mg protein) (25.5 +/- 4.0, p = 0.005; 20 +/- 1.8, p = 0.16) and GPx (IU/mg protein) (0.86 +/- 0.05, p = 0.005; 0.74 +/- 0.04, p = 0.10), respectively, in diabetic rats compared to DC (CAT = 14.4 +/- 2.0, GPx = 0.57 +/- 0.02). CONCLUSION: Milk thistle extract, to a lesser extent silymarin, can attenuate DN in rats possibly by increasing kidney CAT and GPx activity and decreasing lipid peroxidation in renal tissue. PMID- 20540644 TI - The association between neopterin and acetaminophen-induced nephrotoxicity. AB - INTRODUCTION: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP induced nephrotoxicity. MATERIALS AND METHODS: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. RESULTS: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). CONCLUSIONS: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury. PMID- 20540645 TI - An unusual manifestation of brucellosis infection: acute renal failure. AB - Brucellosis is a disease of multisystem organ involvement and resembles many other diseases. Rare involvements of the disease include musculoskeletal, gastrointestinal, cardiovascular, and central nervous systems, while renal involvement is exceedingly rare. Herein, we present a case of acute renal failure (ARF) due to brucellosis infection manifesting with progressively elevated urea and creatinine levels. To our knowledge, this is the first case report to reveal an association between brucellosis infection and (ARF) in the literature. We wish to present this unusual manifestation of brucellosis infection in the hope that it will be a nice contribution to the pathogenesis of the disease and to the literature. PMID- 20540646 TI - Lethal Strongyloides stercoralis superinfection in an immunocompromised patient. AB - In this article, we describe the case of a 49-year-old male gypsy on hemodialysis that was referred to our center due to high fever, breathlessness, and productive cough with bloody sputum. Forty-five days before hospitalization, he was treated for vasculitis with prednisolone and intravenous cyclophosphamide. Soon after admission he was resuscitated and intubated after a cardiac arrest. A large worm load of Strongyloides stercoralis larvae was identified in the sputum. The patient was treated with thiopental 25 mg/kgBW/12 h through a Levine tube and died 24 h later. PMID- 20540647 TI - Triggering of atypical hemolytic uremic syndrome by influenza A (H1N1). AB - We report a case of atypical hemolytic uremic syndrome (aHUS) triggered by influenza A (H1N1) in a 17-year-old boy with a mutation in the gene (CD46) encoding the transmembrane complement regulator membrane cofactor protein. The patient recovered completely following treatment with oseltamivir, plasma exchange, and hemodialysis. We describe the case and discuss this unusual association of diseases. PMID- 20540650 TI - Insulin micropiles comprising biodegradable polymers for production of a long term hypoglycemic effect. AB - As a percutaneous sustained-release preparation, insulin micropiles (MPs) were prepared with biodegradable polymers poly(lactic acid) (PLA), poly(epsilon caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA) as the base. The obtained PLA, PCL, and PLGA MPs of which the insulin:polymer ratio was 1:2 were administered to rat skin at 40 IU/kg and hypoglycemic effects measured for 6 days. The order of the hypoglycemic effect was PLA>PCL>PLGA. PLA MP showed the strongest hypoglycemic effect (2 days). The hypoglycemic effect of insulin PLA MP was dependent on the formulation; the order was insulin:PLA (2:1)>insulin:PLA (1:1)>insulin:PLA (1:2). As the ratio of insulin to the polymer base increased, the hypoglycemic effect increased. The area above the plasma glucose levels vs. time curves for 6 days from insulin:PLA (2:1) MPs, 10, 20, 30, and 40 IU/ kg, were 249 +/- 108, 2003 +/- 379, 3960 +/- 794, and 6311 +/- 726%.h. A dose dependent hypoglycemic effect was obtained at 10-40 IU/kg and pharmacological availabilities were 11.1%, 44.5%, 58.6%, and 70%, respectively. Insulin:PLA (2:1) MP showed high plasma insulin level, 86.9-134.7 IU/mL, for 3 days. There was no damage to rat skin. These results suggest the usefulness of insulin:PLA (2:1) MP as a sustained-release percutaneous delivery system for insulin. PMID- 20540648 TI - Molecular pathways in the induction of interleukin-27-driven regulatory type 1 cells. AB - Type 1 regulatory (Tr1) cells have emerged as key players in the prevention of autoimmunity. They produce high levels of the immunosuppressive cytokine interleukin (IL)-10 and confer protection against a wide panel of autoimmune diseases. However, the molecular pathways leading to their generation have long remained elusive. We have recently identified IL-27, a member of the IL-12 cytokine family, as a novel cytokine that induces Tr1 cells. Further analysis of IL-27-driven Tr1 cells have identified a critical role of the transcription factor avian musculoaponeurotic fibrosarcoma v-maf and of IL-21 in the generation of IL-27-induced Tr1 cells. Importantly, IL-27 also induces Tr1 cells in humans, suggesting that IL-27 administration may dampen tissue inflammation in humans as well. Here, we review the role of IL-27 in the generation of Tr1 cells and discuss its potential to alleviate autoimmune diseases. PMID- 20540651 TI - Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis. AB - The mannosylated gelatin nanoparticles (Mn-GNPs) were prepared for the selective delivery of an antitubercular drug, isoniazid (INH), to the alveolar macrophages. The gelatin nanoparticles (GNPs) were prepared by using a two-step desolvation method and efficiently conjugated with mannose. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency, in vitro drug release, macrophage uptake, in vivo biodistribution, antitubercular activity and hepatotoxicity of plain and Mn-GNPs were determined. The size of nanoparticles (both plain and Mn-GNPs) was found to be in range of 260-380 nm, and maximum drug payload was found to be 40-55%. Average particle size of Mn-GNPs was more, whereas drug entrapment was lesser compared to plain GNPs. The organ distribution studies demonstrated the efficiency of Mn-GNPs for spatial delivery of INH to alveolar tissues. Intravenous administration of INH loaded Mn-GNPs (I Mn-GNPs) resulted in significant reduction in bacterial counts in the lungs and spleen of tuberculosis-infected (TB-infected) mice and also reduction in the hepatotoxicity of the drug. This study revealed that mannose conjugated GNPs may be explored as potential carrier for safer and efficient management of TB through targeted delivery of INH when compared to plain GNPs and free drug. PMID- 20540652 TI - Clinical effectiveness and safety evaluation of long-term pioglitazone treatment for erythropoietin responsiveness and insulin resistance in type 2 diabetic patients on hemodialysis. AB - BACKGROUND: We aimed to assess the effect of long-term pioglitazone treatment on erythropoietin responsiveness and insulin resistance in type 2 diabetic patients on hemodialysis. METHODS: We conducted a prospective, open-label, parallel-group, controlled study of 63 type 2 diabetic hemodialysis patients who were randomly assigned to two groups: pioglitazone group (P-group; 15-30 mg/day pioglitazone plus conventional oral hypoglycemic agents) and control group (C-group; conventional oral hypoglycemic agents alone). We determined the efficacy of pioglitazone by monitoring anemia, glycemic control, insulin resistance, and levels of inflammatory cytokines and high-molecular-weight (HMW) adiponectin for 96 weeks. RESULTS: Pioglitazone effectively reduced erythropoietin dose and maintained the target hemoglobin levels by improving insulin resistance up to the end of the study. In the P-group, hemoglobin A(1c), glycated albumin, and triglycerides significantly decreased compared with the C-group. There was a significant reduction in homeostasis model assessment for insulin resistance and the level of high-sensitivity C-reactive protein, and a significant increase in HMW adiponectin level in the P-group; these changes were significantly different compared with values for the C-group. No serious adverse effects such as hypoglycemia, liver impairment, or heart failure were observed in any of the patients. CONCLUSION: Pioglitazone treatment resulted in better glycemic control, improved lipid levels, an increase in insulin sensitivity and adiponectin levels, and a decrease in inflammatory markers, thus improving the risk factors of cardiovascular disease. Erythropoietin responsiveness improved with a reduction in erythropoietin dose and may be associated with the improvement in insulin resistance due to long-term pioglitazone treatment. PMID- 20540653 TI - Dapoxetine for premature ejaculation. AB - IMPORTANCE OF THE FIELD: Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological factors. Drug treatment of PE with an off-label antidepressant selective serotonin reuptake inhibitor (SSRI) drug is common. The lack of an approved drug and total reliance on off-label treatment represents a substantial unmet treatment need. AREAS COVERED IN THIS REVIEW: Medline and the proceedings of major international and regional scientific meetings during the period 1994 2010 were searched for publications or abstracts using the word 'dapoxetine' in the title, abstract or keywords. This search was then manually cross-referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III efficacy and safety studies and drug interaction studies. Dapoxetine is a potent SSRI, which is administered on demand 1-3 h before planned sexual contact. Dapoxetine is rapidly absorbed and eliminated, resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing. Dapoxetine 30 and 60 mg has been evaluated in five randomized, double-blind, placebo-controlled studies in 6,081 men aged > or = 18 years. Outcome measures included stopwatch measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (p < 0.001 for all). The most common adverse events included nausea, dizziness and headache, and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. WHAT THE READER WILL GAIN: Readers will gain insight into the epidemiology, pathophysiology and contemporary drug treatment of premature ejaculation. TAKE HOME MESSAGE: Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine. PMID- 20540654 TI - Memantine ER, a once-daily formulation for the treatment of Alzheimer's disease. AB - IMPORTANCE OF THE FIELD: Alzheimer's disease is a progressive, degenerative brain disease. As the disease progresses, patients and caregivers face increasing problems with medication adherence. Given its relentlessly progressive nature, newer and more effective therapies for Alzheimer's disease are needed. Memantine 10 mg twice daily is the FDA-approved regimen for the treatment of moderate to severe Alzheimer's disease. AREAS COVERED IN THIS REVIEW: The goal of this article is to review the once-daily memantine ER 28 mg formulation for the treatment of Alzheimer's disease, which, by simplifying the dosage regimen, decreases the problems of medication adherence. A new extended-release formulation has been developed to improve adherence and possibly efficacy without compromising an excellent tolerability and safety profile. There is also a possibility of dose-dependent improvement/superiority in cognitive, global and behavioral measures as well as in verbal fluency with higher-dose (28 mg/day) memantine. WHAT THE READER WILL GAIN: Readers will become knowledgeable about this new dose and preparation of memantine. However, these advantages remain provisional and more research is needed to evaluate patient adherence, outcomes and caregiver burden related to twice-daily versus once-daily administration in patients with moderate to severe Alzheimer's disease. TAKE HOME MESSAGE: A new, once-daily, higher-dose preparation of memantine seems to be well tolerated and may provide additional benefits for selected patients with Alzheimer's disease. PMID- 20540655 TI - Comparison of vaginal and transabdominal collection of amniotic fluid for fetal lung maturity tests. AB - BACKGROUNDS: The lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) are two tests that can be used to estimate the probability of the occurrence of respiratory distress syndrome (RDS). Our objective was to compare the prognostic capacity of the L/S ratio and the LBC in the prediction of RDS from amniotic fluid that was obtained either transabdominally or vaginally. METHODS: Consecutive women undergoing amniotic fluid sampling for determination of fetal lung maturity were included. In case the membranes were ruptured, amniotic fluid was obtained vaginally. Otherwise, amniotic fluid was obtained by transabdominal amniocentesis. In each specimen, an L/S ratio and a LBC were measured. The predictive capacity of specimens that were obtained vaginally and transabdominally were compared by calculating the area under the receiver operating-characteristic curve (AUC) analysis. RESULTS: In 260 patients amniotic fluid was collected transabdominally, whereas in the other 67 patients there were ruptured membranes, and fluid was collected vaginally. RDS occurred in 25% of the patients without ruptured membranes, and in 34% of the patients with ruptured membranes. For the L/S ratio, the AUC was 0.56 (SE 0.09) for the vaginally collected specimens, and 0.93 (SE 0.02) in the specimens that were collected abdominally. For the LBC, the AUCs were 0.52 (SE 0.08) and 0.84 (SE 0.03), respectively. CONCLUSIONS: Fetal lung maturity tests that are performed in vaginally obtained specimens in patients with ruptured membranes are of no use in the prediction of RDS. PMID- 20540656 TI - Maternal and neonatal characteristics of an immigrant population in an Italian hospital. AB - OBJECTIVE: The objective of this study was to evaluate clinical and epidemiological characteristics of the maternal and neonatal immigrant population and to compare it with the Italian population in the Agostino Gemelli Hospital (Rome). METHODS: This study was a prospective population-based study. We compared 595 newborns from immigrant mothers with 2413 newborns from Italian mothers. Neonatal characteristics included in this study were sex, gestational age, birth weight, Apgar score, transfer to pathology units, minor pathologies, and type of breastfeeding at discharge. Maternal characteristics included nationality, age, parity, type of delivery, twin birth, and pathology during the pregnancy. RESULTS: Immigrant newborns comprised 20% of the total births included in the study. No statistically significant differences were found between immigrant and Italian newborns in gestational age, birth weight, or Apgar score. Immigrant newborns were transferred to the Paediatric Infectious Disease Unit more frequently than Italian newborns, had a significantly higher incidence of hyperbilirubinemia and a higher rate of exclusive and prevalent breastfeeding at discharge. Immigrant mothers came predominantly from Eastern Europe, were younger and had caesarean sections less frequently than Italian mothers. CONCLUSION: No significant differences in biological and clinical characteristics or in medical practice were found between groups, except for a higher frequency of neonatal hyperbilirubinemia and an inclination among immigrant mothers toward breastfeeding. PMID- 20540657 TI - The significance of a positive second trimester serum screen for trisomy 18. AB - OBJECTIVES: We designed this study to estimate the proportion of fetuses in pregnancies with positive second trimester serum screens for trisomy 18 who actually have trisomy 18, to estimate the proportion of women with trisomy 18 who have a negative serum screen, and to assess the role of ultrasound in the diagnosis of trisomy 18. METHODS: Retrospective study of two cohorts of pregnant women in 2004 and 2005: (1) those with a second trimester serum screen positive for trisomy 18 and (2) those with fetuses having trisomy 18. RESULTS: There were 93 women with positive serum screens for trisomy 18. Of these, only three had a fetus with trisomy 18. There were five other cases of trisomy 18, three of which had a negative second trimester serum screen for trisomy 18. All fetuses with trisomy 18 had multiple major structural abnormalities detected on targeted genetic sonography. CONCLUSIONS: A positive second trimester serum screen has a poor sensitivity and poor prediction for trisomy 18. Trisomy 18 is highly unlikely if a woman with a positive screen for trisomy 18 has no fetal abnormalities detected on targeted genetic sonography. Women with a positive second trimester serum screen for trisomy 18 should be offered genetic sonography, and the practice of routine amniocentesis for all women with a positive screen should be discouraged when targeted genetic sonography is available. PMID- 20540658 TI - The performance of second trimester long bone ratios for Down syndrome screening is influenced by gestational age. AB - OBJECTIVE: To determine if gestational age (GA) at the time of ultrasound impacts the positive predictive value of shortened femur and humerus lengths (FL, HL) for trisomy 21 (T21). METHODS: Sonograms from 14 to 21 and 6/7 weeks' gestation were collected over a 28 month period. Multiple gestations or fetuses with major structural anomalies were excluded. Biometric data and GA were obtained; the expected HL (or FL): observed HL (or FL) ratios were calculated using two regression formulas (Benacerraf and Nyberg). A HL ratio <0.90 and a FL ratio <0.91 were considered shortened. T21 fetuses were identified through database and chart review. Positive predictive values (PPV) for T21 of the shortened bone ratios were determined, then stratified by GA. RESULTS: Of the 2606 ultrasounds, 8.9% and 18.9% of fetuses had shortened HL and FL ratios, respectively, using the Benacerraf formula. Shortened ratios were noted significantly less commonly (2.3 and 4.4%, respectively, P < 0.001 for each) using the Nyberg formula. With either formula, abnormal bone ratios were more frequently documented with a GA less than 17 weeks (P < 0.001). There were 17 T21 pregnancies. CONCLUSIONS: GA and formula selection influence the performance of long bone ratios as soft markers for T21 in the second trimester. PMID- 20540659 TI - Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy. AB - OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre eclampsia (PET). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET. PMID- 20540660 TI - Should the visceral peritoneum at the bladder flap closed at cesarean sections? A post-partum sonographic and clinical assessment. AB - OBJECTIVE: To compare cesarean section (CS) using open or closed visceral peritoneum of the bladder flap (BF) in relation to fluid collection in vesico uterine space (VUS) by ultrasound (US) and clinical outcome. MATERIAL AND METHODS: A prospective cohort of repeat CS in 474 in advanced first and second stage of labor was studied. All women underwent a Misgav Ladach CS, in local combined anesthesia. These were divided into two groups by surgical management of the BF at the time of CS: Group I (n = 262), with visceral peritoneum left open and Group II (n = 212), with visceral peritoneum closed. An US check for the fluid collections in the VUS was done in the third post-operative day. The two groups were also clinically compared for: intra-operative estimated blood loss, the need for post-CS pain killers, febrile morbidity and duration of hospital stay. RESULTS: Visceral peritoneum (VP) closure resulted in a significant increase blood collections in the VUS (p < 0.05). VP closure resulted in a significantly higher morbidity in all the following parameters. Rate of BFHs, post-operative fever, need for post-operative analgesia, require antibiotic administration and prolonged hospitalisation (p < 0.05). CONCLUSIONS: VP suturing of women requiring CS for dystocia is associated to increased rate of blood collection in the VUS, which could possibly explain the higher rate of puerperal complications in these patients. These data clearly indicate that suturing the VP of the BF in women undergoing CS for dystocia is contraindicated. This data could be probably extrapolated to all cesarean deliveries. PMID- 20540661 TI - Can we use neopterin as marker of viral infections in pregnant women with symptoms of imminent spontaneous abortion? AB - PURPOSE: To find out if determination of neopterin can be used for the detection of viral infections in pregnant women with symptoms of imminent spontaneous abortion. METHODS: Eighty-eight pregnant women with symptoms of imminent spontaneous abortion (investigated group) and 88 healthy pregnant women were evaluated (control group). Neopterin level and IgM and IgG antibodies for eight viruses in the blood were determined. RESULTS: Parvo B19 virus and elevated neopterin values were found in significantly higher number in investigated group than in control. There was no correlation between women with acute ParvoB19 infection and elevated neopterin level. CONCLUSIONS: The determination of neopterin in the sera cannot be used for screening of viral infections in pregnancy. PMID- 20540662 TI - Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby. AB - Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions. PMID- 20540663 TI - Hoechst 33342 induces radiosensitization in malignant glioma cells via increase in mitochondrial reactive oxygen species. AB - Mitochondrial DNA plays an important role in cellular sensitivity to cancer therapeutic agents. Hoechst 33342, a DNA minor groove binding ligand, has shown radiosensitizing effects in different cancer cell lines. In the present study, the possible binding of Hoechst 33342 with mitochondrial DNA, isolated from human cerebral glioma (BMG-1) cells, was investigated and consequences of this binding on excessive reactive oxygen species (ROS) generation in irradiated BMG-1 cells were studied. Alteration in the fluorescence spectroscopic characteristics of Hoechst 33342 suggested binding of Hoechst 33342 with isolated mitochondria and mitochondrial DNA. Persistent increase in level of ROS in the presence of Hoechst 33342 has been observed, which was further enhanced in irradiated cells. Investigations using inhibitors of ETC complex I suggested that mitochondrial bound Hoechst 33342 contributed to increased ROS, which was associated with alteration in DeltaPsim and antioxidant machinery. These factors appeared to contribute in potentiating radiation-induced cell death in BMG-1 cells. The finding from these studies will be useful in designing better anti-cancer strategies. PMID- 20540664 TI - Cumulative clinical pregnancy rates after COH and IUI in subfertile couples. AB - To evaluate the influence of female age and cause of infertility on the outcome of controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI), we studied 2717 COH cycles in 1035 subfertile couples. The cumulative clinical pregnancy rates were 39% and 58% after three and six COH cycles, respectively. The cumulative pregnancy rate significantly decreased with maternal age and differed by cause of infertility. The cumulative pregnancy rate continued to increase with an increase in COH cycle number up to the third, or forth cycle, in patients with mechanical and combined infertility, respectively, and in up to the second cycle in patients aged 40 years or more. These findings provide treatment guidelines for clinicians in determining the likelihood of treatment success and the point at which to proceed to the next treatment strategy. PMID- 20540665 TI - Prevalence of metabolic syndrome in women with polycystic ovary syndrome, using two proposed definitions. AB - AIM: To compare the prevalence rate of metabolic syndrome (MS) in women with polycystic ovary syndrome (PCOS) using the Adult Treatment Panel III (ATP III) criteria, with that using the International Diabetes Federation (IDF) criteria and also to assess the metabolic risk factors for this syndrome. METHODS: This was a cross-sectional study, 198 women with PCOS were studied. MS was diagnosed as per the ATP III and IDF criteria, separately. RESULTS: MS was found in 37.9% cases (ATP III criteria) and 47.5% cases of PCOS (IDF criteria) (p = 0.02). In adolescents, prevalence of MS was more with the IDF criteria (p = 0.009) but in adults, the prevalence rates were similar between the two criteria (p = 0.08). Women with MS had significantly higher body mass index, irrespective of age and the definition used. Dyslipidemia was found more common than elevated fasting glucose abnormality, using either of the criteria. CONCLUSION: Prevalence rate of MS in PCOS depends on the definition used. With IDF criteria, in the whole group, the prevalence was significantly higher. A universally accepted definition of MS, suitable for adolescents and adults, is urgently needed. PMID- 20540666 TI - The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes: Results from two placebo-controlled interventions. AB - Omega-3 (omega3) fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular disease. Despite these benefits, concern remains that omega3 fatty acids may increase lipid peroxidation. It has previously been shown that urinary F(2)-isoprostanes (F(2) IsoPs) were reduced following omega3 fatty acid supplementation in humans. It is now determined whether EPA or DHA supplementation affects plasma F(2)-IsoPs. In two 6-week placebo-controlled interventions, Study A: overweight, dyslipidaemic men; and Study B: treated-hypertensive Type 2 diabetic, patients were randomized to 4 g daily EPA, DHA. Post-intervention plasma F(2)-IsoPs were significantly reduced by EPA (24% in Study A, 19% in Study B) and by DHA (14% in Study A, 23% in Study B) relative to the olive oil group. The fall in plasma F(2)-IsoPs was not altered in analyses that corrected for changes in plasma arachidonic acid, which was reduced with EPA and DHA supplementation. Neither F(3)- nor F(4)-IsoPs were observed in plasma in both studies. These results show that in humans, EPA and DHA reduce in vivo oxidant stress as measured in human plasma and urine. PMID- 20540667 TI - Domains of increased thickness in microvillar membranes of the small intestinal enterocyte. AB - The apical surface of the enterocyte is sculpted into a dense array of cylindrical microvillar protrusions by supporting actin filaments. Membrane microdomains (rafts) enriched in cholesterol and glycosphingolipids comprise roughly 50% of the microvillar membrane and play a vital role in orchestrating absorptive/digestive action of dietary nutrients at this important cellular interface. Increased membrane thickness is believed to be a morphological characteristic of rafts. Thus, we investigated whether the high contents of lipid rafts in the microvillar membrane is reflected in local variations in membrane thickness. We measured membrane thickness directly from electron micrographs of sections of fixed mucosal tissue. Indeed, mapping of the microvillar membrane revealed a biphasic distribution of membrane thickness. As a point of reference the thickness distribution of the basolateral membrane was clearly monophasic. The encountered domains of increased thickness (DITs) occupied 48% of the microvillar membrane and from the data we estimated the area of a single DIT to have a lower limit of 600 nm(2). In other experiments we mapped the organization of biochemically defined lipid rafts by immunogold labeling of alkaline phosphatase, a well documented raft marker. Strikingly, the alkaline phosphatase localized to distinct regions of the membrane in a pattern similar to the observed distribution of DITs. Although we were unable to measure membrane thickness directly on the immunogold labeled specimens, and thereby establish an unequivocal connection between DITs and rafts, we conclude that the brush border membrane of the enterocyte contains microdomains distinguishable both by membrane morphology and protein composition. PMID- 20540669 TI - Impact of female and male obesity on IVF/ICSI: results of 700,000 ART-cycles in Germany. AB - To our knowledge, this is the first analysis in which male and female weights have been combined. The registry dataset covering a 12-year period was analysed for all treatment cycles where an embryo transfer was reported. In all, 706,360 cycles were analysed. Treatments include IVF, ICSI, IVF/ICSI and CPE. The highest success rate in IVF cycles was found in couples, with an obese male partner. In the group of obese women, the pregnancy rate decreased to 27.2%. Similar to IVF treatment, the highest success rate in ICSI cycles was found in couples, where either the male or the female partner was obese. The highest success rate in cycles with a cryopreserved embryo transfer was observed in couples where both partner were obese. The lowest success rate was seen where the female partner was obese. Our data analysis suggests that the combination of an obese male and a normal-weight female is positively related to better implantation rates in IVF as well as ICSI-cycles. This combination is more likely to be found in couples with a higher social status. Therefore, the increased pregnancy rate in this group might as well be related to other lifestyle factors associated with higher social status. PMID- 20540670 TI - Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population. AB - Gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) share common pathophysiological features, including beta-cell dysfunction and insulin resistance. In this study, we investigated the association between GDM and five recently identified T2D susceptibility loci, in a Greek population. We studied 148 women with GDM and 107 non-diabetic unrelated pregnant Greek women, for polymorphisms in the TCF7L2 gene (rs7903146 C/T), the PPARG gene (Pro12Ala), the KCNJ11 gene (E23K), the IRS1 gene (G972R) and in the FOXC2 gene (-512C>T). The T allele of the TCF7L2 rs7903146 (C/T) polymorphism was found to be significantly associated with an increased risk of GDM [p = 0.0003; odds ratio (OR) 2.04 (95%CI 1.38-3.00)]. Additionally, CT and TT genotypes were significantly overrepresented in women with GDM compared to controls (p = 0.0003 and p = 0.0148, respectively). Analysis of the IRS1 G972R polymorphism showed that the R-allele frequency was increased in women with GDM [(p = 0.009; OR 1.67 (95%CI 1.14-2.47)]. The genotypes and allele frequencies of the other polymorphisms studied did not statistically differ between the GDM and the control women. Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women. PMID- 20540668 TI - High plasma membrane lipid order imaged at the immunological synapse periphery in live T cells. AB - Cholesterol- and glycosphingolipid-enriched membrane lipid microdomains, frequently called lipid rafts, are thought to play an important role in the spatial and temporal organization of immunological synapses. Higher ordering of lipid acyl chains was suggested for these entities and imaging of membrane order in living cells during activation can therefore help to understand the mechanisms responsible for the supramolecular organization of molecules involved in the activation of T cells. Here, we employ the phase-sensitive membrane dye di-4 ANEPPDHQ together with a variety of spectrally-resolved microscopy techniques, including 2-channel ratiometric TIRF microscopy and fluorescence lifetime imaging, to characterize membrane order at the T cell immunological synapse at high spatial and temporal resolution in live cells at physiological temperature. We find that higher membrane order resides at the immunological synapse periphery where proximal signalling through the immunoreceptors and accessory proteins in microclusters has previously been shown to take place. The observed spatial patterning of membrane order in the immunological synapse depends on active receptor signalling. PMID- 20540671 TI - Perinatal outcomes in post-thyroidectomy pregnancies. AB - OBJECTIVE: To investigate pregnancy outcome in patients post-total thyroidectomy. METHODS: A retrospective study comparing pregnancy outcome of women post-total thyroidectomy (n = 50), patients with hypothyroidism due to other reasons (n = 1015) and pregnancies without hypothyroidism (n = 200,000) was performed. RESULTS: A significant linear association was documented between the three groups and adverse outcomes such as placental abruption (6.1% in the total thyroidectomy group, 1.0% in hypothyroidism and 0.8% in the no-hypothyroidism group; p = 0.002), and caesarean delivery (33.3% in the total thyroidectomy, 30.4 in hypothyroidism and 14.4% in the no-hypothyroidism group; p < 0.001). Total thyroidectomy was independently associated with placental abruption and fertility treatment in a multivariable model controlling for maternal age. No significant differences were noted between the groups in terms of perinatal outcomes such as low Apgar score (<7) at 1 min (6.1% vs. 4.5% and 4.3%; p = 0.846) and 5 min (3.0% vs. 0.6% and 3.0%; p = 0.198); perinatal mortality (0.0% vs. 0.9% and 0.01%; p = 0.293). CONCLUSIONS: Women post-total thyroidectomy and women with hypothyroidism due to other reasons are at increased risk for adverse obstetric outcomes, while the risk is higher for pregnancies with total thyroidectomy as compared to hypothyroidism due to other reasons. PMID- 20540672 TI - Can serum oestradiol be a predictor of quality of oocytes and embryos, maturation of oocytes and pregnancy rate in ICSI cycles? AB - Our aim was to assess the influence of ratios of oestradiol (E2) to either number of follicles >= 14 mm on the day of human chorionic gonadotropin administration (E2/fol) or the number of oocytes retrieved (E2/o) during oocyte pick up and total serum E2 levels on the day of embryo transfer (ETE2) on the outcome of ICSI cycles. The assessed outcomes were number of oocytes retrieved (NRO), number of mature oocytes (NMO), number of fertilised oocytes (NFO), number of transferred embryos (NTE), qualities of oocytes (OQS), qualities of embryos (EQS) and pregnancy rates (PR). Two hundred and twenty-seven ICSI-ET cycles admitted to our IVF clinic during a 2-year period with normal ovarian reserve receiving long luteal GnRH agonist protocol were included. The E2/fol levels correlated positively with NRO (r = 0.202, p = 0.002), NMO (r = 0.199, p = 0.003) and NFO (r = 0.159, p = 0.018). However, we observed negative correlations between E2/o and NMO (r = -0.329, p <0.001), NFO (r = -0.219, p = 0.001), EQ5 (r = -0.203, p = 0.040). Oocyte quality scores were not affected from either E2/fol or E2/o levels. Implantation, clinical and ongoing PRs were comparable between groups categorised due to E2/fol, E2/o and ETE2. It seems that high E2/fol ratio may have beneficial effects on NRO, NMO and NFO while E2/o may adversely affect these parameters. Neither of the E2 levels is associated with pregnancy rates in women with normal ovarian reserve. PMID- 20540673 TI - Association of serum and follicular fluid SHBG levels and SHBG (TAAAA)n polymorphism with follicle size in women undergoing ovarian stimulation. AB - OBJECTIVE: Sex hormone-binding globulin (SHBG) is the main transport protein of sex steroids. Recently, it has been found to be produced by granulosa lutein cells, suggesting a local role of SHBG in the ovary. The aim of this study was to investigate whether serum and follicular fluid SHBG levels and SHBG (TAAAA)(n) polymorphism are related to follicle size and pregnancy rate in women undergoing in vitro fertilisation. METHODS: The study population consisted of 154 women with tubal and/or male-factor infertility undergoing IVF/ICSI and follicular fluid with oocytes from small (diameter <=12 mm) and large (diameter >=18 mm) follicles were studied. Genotyping of SHBG (TAAAA)(n) polymorphism was performed in peripheral blood samples. Serum and follicular fluids were used for hormones determination. RESULTS: Women with short allele genotypes (with less than 8 TAAAA repeats) had higher number of small follicles compared to women with long allele genotypes (5.6 +/- 3.9 vs. 3.5 +/- 3.2 small follicles, p < 0.003). Follicular fluid SHBG levels correlated positively with serum SHBG levels (p < 0.001) and with the total number of follicles (p < 0.02). Furthermore, small follicles had higher follicular fluid SHBG concentration compared to large follicles (102.9 +/- 35.0 nmol/l vs. 85.85 +/- 34.88 nmol/l, p < 0.028). CONCLUSION: SHBG levels and the SHBG (TAAAA)(n) polymorphism are associated with follicle size. PMID- 20540674 TI - Severe osteoporosis with multiple vertebral fractures after gender reassignment therapy - is it male or female osteoporosis? AB - OBJECTIVE: We report about a 49-years-old patient with severe osteoporosis and multiple vertebral fractures after male-to-female reassignment therapy. The patient had 12 years of hormone replacement therapy (HRT) with very low serum levels of estradiol and testosterone at the time the fractures occurred. The reasons are currently not known. Most likely the patient seems to be non compliant with the HRT intake. RESULTS: Bone mineral density (BMD) measurements showed highly decreased T-Scores between -3.5 and -4.5. All routine laboratory parameters, especially the markers of bone turnover, were within the normal range. MU-CT 3D-structural analysis of the bone biopsy showed a highly reduced trabecular connectivity (Conn.Dens.). Bone mineral density distribution (BMDD), measured by quantitative backscattered electron imaging (qBEI), showed a BMDD within normal range, except heterogeneity index (Ca(WIDTH)) and fraction of highly mineralised bone (Ca(HIGH)), which were increased. CONCLUSIONS: We conclude that our patient has a cross-sex hormonal therapy induced total imbalance of bone homeostasis, because of the long lasting under monitored hormone therapy which led to severe interferences in physiological maturities. Male-to-female transsexuals without an adequate estrogen treatment are at increased risk of developing osteoporosis. PMID- 20540675 TI - Relationship between uric acid and metabolic syndrome according to menopausal status. AB - OBJECTIVE: Uric acid, the levels of which have been shown to increase after menopause, has been associated with metabolic syndrome. The prevalence of metabolic syndrome has also been determined to increase after menopause. Therefore, we surmised that menopausal status-specific analyses for the characterisation of the relationship between uric acid and the metabolic syndrome were warranted. METHODS: We included 1644 patients: 1018 premenopausal women and 626 postmenopausal women, all of whom participated in annual health examinations at Anam Hospital in Seoul, Korea, from January 2008 through December 2008. RESULTS: On the multivariate logistic regression analysis, uric acid was identified as an independent risk factor for metabolic syndrome in both premenopausal and postmenopausal women. Uric acid levels had different relationships with blood pressure based on menopausal status, however, no such relationships with fasting glucose or age were found. CONCLUSIONS: Increased uric acid levels were associated with increased risk for metabolic syndrome in both premenopausal and postmenopausal women. In studies regarding uric acid and metabolic syndrome in women, the effects of menopausal status should be considered. PMID- 20540676 TI - Evaluation of postpartum carbohydrate intolerance and cardiovascular risk factors in women with gestational diabetes. AB - We aimed to evaluate the predictors of subsequent development of postpartum carbohydrate intolerance, metabolic syndrome and cardiovascular risk factors in women with previous GDM. Two hundred fifty-two consecutive women with GDM were enrolled. After exclusion of women who did not attend to the hospital for follow up visits for minimum 1 year, data of 195 patients were evaluated. Seventy-one lean women with negative screening for GDM were included as a control group. The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose and metabolic syndrome was significantly higher in women with previous GDM than healthy controls. Women with previous GDM were more insulin resistant, had an atherogenic lipid profile and increased carotid IMT. The most important predictors of postpartum diabetes were the need for insulin treatment during index pregnancy and glucose values on antepartum OGTT. Among women with previous GDM, the development of postpartum diabetes and metabolic syndrome was associated with increased carotid IMT. Our data show that women with previous GDM are at high risk for developing carbohydrate intolerance, metabolic syndrome and atherosclerosis. Antepartum prediction of high risk subjects for the subsequent development of postpartum carbohydrate intolerance and metabolic syndrome seems to be vital to prevent cardiovascular outcomes. PMID- 20540677 TI - The quantitative insulin sensitivity check index is not able to detect early metabolic alterations in young patients with polycystic ovarian syndrome. AB - OBJECTIVE: To verify whether QUICKY is a suitable method for the identification of metabolic deterioration in normal weight patients affected by polycystic ovarian syndrome (PCOS). DESIGN: Prospective clinical study. PATIENT(S): Seventy nine PCOS normal weight adolescent subjects, 50 eumenorrheic, normal weight, non hirsute controls matched for age and BMI. METHOD(S): Quantitative insulin sensitivity check index (QUICKY) and integrated secretory area under the curve of insulin values (I-AUC) during oral glucose tolerance test were calculated. RESULT(S): Seventy-nine PCOS and 50 controls were studied. Normal insulin sensitivity was defined as upper control 95th percentile by QUICKY values <0.31, I-AUC at 180 min < 16,645. When applying the calculated I-AUC cut-off, 41 PCOS were classified as normoinsulinemic and 38 as hyperinsulinemic, whereas using the calculated QUICKY cut-off, only 19 PCOS could be classified as insulin resistant (IR). Fifteen out of the 60 non-IR PCOS presented hyperinsulinemia; fasting glucose and insulin levels and QUICKY were not sufficient to identify these subjects. Thus, QUICKY displayed a low sensitivity (44%) and specificity (91%) in the diagnosis of the metabolic disorder disclosed by I-AUC. CONCLUSIONS.: In young normal weight patients with PCOS the prevalence of early alterations of insulin metabolism are not detectable by QUICKY studies. PMID- 20540679 TI - Iatrogenic skin injury in the neonatal intensive care unit. AB - Although neonatal care has become more and more meticulous with significant changes in technology in the neonatal intensive care unit (NICU) in the past 50 years, iatrogenic cutaneous injuries continue to occur. Although the incidence of severe injuries is decreasing because the more difficult procedures are being replaced by improved techniques, skin injuries have not yet been completely eliminated. However, the nature and causes of cutaneous injuries have changed, and the injuries are frequent but generally minor. The major risk factors are low birth weight, gestational age, length of stay, a central venous line, mechanical ventilation, and support with continuous positive airway pressure. The rate of iatrogenic events is about 57% at gestational ages of 24-27 weeks, compared with 3% at term. There are no current comprehensive reviews of iatrogenic cutaneous injury. The purpose of this review is to describe the iatrogenic cutaneous injuries that may occur in the newborns as a consequence of perinatal and postnatal medical procedures. With increased survival of extremely-low-birth weight (ELBW) infants and changing modes of management in the NICU, neonatologists must make every effort to recognize injuries and prevent their occurrence in the NICU. PMID- 20540678 TI - Effects of sildenafil and tadalafil on ischemia/reperfusion injury in fetal rat brain. AB - OBJECTIVE: The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, sildenafil and tadalafil, in ischemia/reperfusion (I/R)-induced oxidative injury in fetal rat brain. METHODS: Timed pregnant adult Wistar rats were randomly assigned to the following groups (n = 6 for each group): saline + none I/R (1), saline + I/R (2), sildenafil + none I/R (3); sildenafil + I/R (4), tadalafil + none I/R (5) and tadalafil + I/R (6). Fetal ischemia was induced by clamping the utero-ovarian artery bilaterally. Fetuses were delivered and 268 fetal rats were decapitated. Malondialdehyde (MDA) levels and, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed in fetal brain tissue homogenates by spectrophotometric methods. RESULTS: In saline + I/R group, MDA levels were increased and, SOD and GSH-Px activities were decreased significantly comparing with saline + none I/R group. Both tadalafil and sildenafil treatment decreased the MDA levels significantly in ischemia/reperfusion groups, whereas this effect was significantly more potent with tadalafil. SOD levels were significantly decreased in all groups after I/R. Tadalafil seems to be more effective than sildenafil by means of increasing GSH-Px activity significantly after I/R. CONCLUSION: Our results indicate some beneficial effects of PDE5 inhibitory drugs, especially tadalafil, on oxidative I/R injury in fetal rat brains. PMID- 20540680 TI - Peripartum intensive care. AB - OBJECTIVE: To determine the prevalence rate of intensive care unit (ICU) admissions in Hospital Corporation of America (HCA) hospitals and further delineate indications and outcomes in a retrospective review at one such hospital. STUDY DESIGN: Diagnosis-related group and revenue codes were combined to calculate maternity admissions to the ICU in HCA hospitals. Prospectively logged maternal admissions were retrospectively reviewed for calendar years 2004 2008 at Presbyterian/St. Luke's Medical Center (PSL) using inpatient medical records. RESULTS: The prevalence rate of peripartum ICU admissions in HCA hospitals among 602,488 deliveries was 0.41%. At PSL, a high-acuity maternal fetal service, the occurrence of ICU admissions was 0.62%. Leading indications were hemorrhage and preeclampsia/eclampsia; multiples were over-represented, 20% required hysterectomy and nearly one-third of the patients were ventilated. CONCLUSIONS: The full scope of ICU resources should be available to the obstetric patient as the maternal requirement for such care is not rare. PMID- 20540681 TI - How patients in New Zealand view community treatment orders. AB - BACKGROUND: New Zealand operates a well-embedded community treatment order scheme for patients with serious mental disorders. A similar scheme may be enacted for England and Wales. AIM: To explore the views of patients with recent experience of community treatment orders. METHOD: All patients in one region under an order in the last 2 years, not readmitted to hospital for at least 6 months, were included, subject to their capacity and consent. Forty-two patients out of 84 potential participants were interviewed. RESULTS: The majority of patients were generally supportive of the community treatment order, especially if the alternative was hospital. Many valued the access to services and sense of security obtained, and attributed improvements in their health to treatment under the order. They also experienced reduced choice about medication and restrictions on residence and travel. For a minority this meant they were strongly opposed to the order, but for most the restrictions did not unduly hinder them. The majority of patients viewed the order as a helpful step towards community stability. CONCLUSIONS: The usefulness of community treatment orders is accepted by most patients under them in NZ, as well as by most psychiatrists. Critical factors include the quality of therapeutic relationships and the structure provided for community mental health care. PMID- 20540682 TI - Comparisons between mitochondrial genomes of domestic goat (Capra hircus) reveal the presence of numts and multiple sequencing errors. AB - MATERIALS AND METHODS: In the present study, we amplified and sequenced the complete mitochondrial genome from a Vietnamese domestic goat (Capra hircus). The data were compared with mtDNA sequences available in the nucleotide databases. RESULTS: The results revealed many problems in the goat mitochondrial reference genome (GenBank accession number NC_005044). Firstly, the authors did not sequence the complete genome, simply 44.5% of its total length. Secondly, two fragments (representing 1201 and 2384 nt) contained an unusually high percentage of sequencing errors. Thirdly, a segment of 1881 nt, covering most of nd5 and the 5' part of nd6, was shown to be a nuclear sequence of mitochondrial origin (Numt). Surprisingly, a similar Numt was also detected in four other goat mitochondrial genomes available in GenBank (GU22978-81). Two primers were designed specially to amplify approximately 960 nt of the Numt identified in goat mtDNA genomes. After cloning, two Numts were detected for C. hircus. Several Numts, most of them with stop codon or frameshift mutations, were also found in Hemitragus jemlahicus (Himalayan tahr) and Pseudois nayaur (bharal). Phylogenetic analyses suggest that a nuclear integration occurred in the common ancestor of Ammotragus, Arabitragus, Capra, Hemitragus and Pseudois, followed by several subsequent duplication events. CONCLUSION: As poor-quality sequences can produce misleading interpretations of both phylogeny and molecular evolution, we propose including a new link to each accession number in the nucleotide databases, named "external expertise", which could be openly and continually updated by non anonymous searchers in order to validate good-quality data, or, conversely, to indicate possible problems in the sequence, such as DNA contamination or sequencing errors. This information could prove very useful over time to select good-quality sequences for in silico analyses. PMID- 20540683 TI - Measurement of response of pulmonal tumors in 64-slice MDCT. AB - BACKGROUND: Advances in CT technology from single to multi-detector row CT (MDCT) permit a high resolution and volumetric presentation of pulmonary lesions. This implicates emerging measurement techniques that need to be contrasted with established methods. PURPOSE: To compare bidimensional, unidimensional, and volumetric methods for evaluation of treatment response in patients with lung lesions. MATERIAL AND METHODS: This study comprised 68 patients with pulmonary lesions who underwent a total of 276 64-MDCTs of chest at baseline and follow-up. RECIST and WHO criteria were used for unidimensional and bidimensional methods and region growing (RG) for volumetry. Patients were classified into four response categories. Respectively, two measurement techniques were contrasted and the kappa index was calculated. For intra-observer reproducibility the relative measurement error (RME) and kappa index with regard to agreement of response categories were evaluated. RESULTS: Comparison of WHO und RECIST criteria achieves high correlation with kappa indices of 0.76 and 0.82. In particular, lesions with moderate increase of size in the range of 25-44% for bidimensional and 12-29% for unidimensional measurement result in different response categories when applying WHO and RECIST criteria. WHO criteria delivered PD more often than RECIST. kappa indices of 0.79 and 0.87 were attained in comparison of RECIST and RG, and 0.83 and 0.84 for WHO and RG. RME was 2.82% for RECIST, 7.53% for WHO, and 8.97% for RG. Intra-observer reproducibility was 95% for RECIST, 95% for WHO, and 96% for RG. CONCLUSION: The comparison of all methods resulted in no statistically significant differences. WHO criteria seemed to diverge the most, they declared several lesions prematurely as progression, and showed no benefit in comparison to RECIST. RG showed the best reproducibility, considered irregular lesions, was slightly superior to RECIST, and could be applied uniformly. Unidimensional measurement represents an adequate alternative with the advantage of better clinical work flow. PMID- 20540684 TI - Checkmark: a sign for the detection of iliopsoas pathology on MRI of the hip. AB - BACKGROUND: The iliopsoas compartment can be involved in many different disease processes with a wide variety of symptoms that may simulate avascular necrosis (AVN) of the femoral head. The psoas muscle merges with the iliacus to form a checkmark ( radical) shape in the coronal MRI plane, with normal muscle intensities, on both sides of the spine. PURPOSE: To evaluate whether abnormality of this checkmark shape (obliteration or abnormal intensity), the checkmark sign, can be used as a simple indicator of iliopsoas pathologies on MR examinations performed for suspected AVN of the hip. MATERIAL AND METHODS: A total of 75 hip MRI examinations performed during 2007 for suspected AVN (male:female ratio, 44:31; average age, 41 years) were retrospectively assessed. The iliopsoas compartment was assessed on the coronal T1 and T2 fat saturated sequences for the presence of the checkmark sign by a consensus of two readers. RESULTS: Twenty-six patients had signs of AVN and 49 patients had either other hip findings or normal hips. A normal checkmark shape was observed in all but two examinations. Obliteration of the checkmark shape, a positive checkmark sign, in those two was due to psoas compartment pathology (infection and hematoma of the iliopsoas compartment). CONCLUSION: A positive checkmark sign (abnormal shape or intensity) can serve as a clue for unsuspected iliopsoas pathology when evaluating MRI of the hip in patients with suspected AVN. PMID- 20540685 TI - Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles. AB - The blood-brain barrier is a major barrier in the neurological diseases treatment and precludes the entry of drugs from blood to brain. Here, we developed 29-amino acid peptide derived from rabies virus glycoprotein (RVG29) peptide conjugated itraconazole-loaded albumin nanoparticles (RVG29-ITZ-NPs). The RVG29 peptide was conjugated to the albumin NPs using biotin-binding streptavidin as crosslinker. The NPs were characterized in terms of particle size, zeta potential, drug loading and release behavior in vitro. Cellular uptake of RVG29-ITZ-NPs was investigated by flow cytometry. Pharmacokinetics and brain distribution of RVG29 ITZ-NPs were investigated after intravenous administration of NPs. The particle size of RVG29-ITZ-NPs was 89.3 +/- 1.9 nm as determined by dynamic light scattering. The zeta potential of RVG29-ITZ-NPs was -33.1 +/- 0.9 mV. RVG29-ITZ NPs exhibited a sustained release profile within 24 h. In vitro cellular uptake studies demonstrated that RVG29 significantly facilitated the intracellular delivery of NPs. A significant (P < 0.05) accumulation of ITZ in brain was observed for RVG29-ITZ-NPs as compared with ITZ-NPs and cyclodextrin formulation of ITZ (ITZ-CD). These results suggested that RVG29-ITZ-NPs can be exploited as a potential therapeutic formulation for the intracranial fungal infection. PMID- 20540686 TI - An unusual case of familial ALS and cerebellar ataxia. AB - We report a case of familial amyotrophic lateral sclerosis (FALS) with clinical signs of cerebellar and posterior column involvement. The patient's work-up showed a known mutation (E100K) in the gene for Cu/Zn superoxide dismutase 1 (SOD1). Our case illustrates that extramotor symptoms, such as prominent cerebellar signs, can be seen in patients with FALS. PMID- 20540687 TI - Potential approaches for drug delivery to the brain: past, present, and future. AB - The objective of this article is to provide the reader with an update on some research highlights from the past to the present, as well as future possibilities to achieve improved delivery of drugs across the blood-brain barrier (BBB). In the past, dye studies confirmed the presence of the BBB and blood-cerebrospinal fluid barriers, which seem to play a major role in transporting drug molecules for the treatment of life-threatening diseases such as brain cancer and Alzheimer's. Presently, transportation mechanisms such as simple diffusion, carrier-mediated, absorptive-mediated, and receptor-mediated transcytosis are extensively used for BBB uptake of drug molecules. The spectrum of future neuropharmaceuticals falling into these categories ranges from peptides to nucleotide-based drugs as well as gene and stem cell delivery agents, and is increasing at a rapid rate with promising results. There has also been considerable progress in the development of quantitative methods to examine BBB permeability in humans and animals. Currently, intravenous administration and in situ brain perfusion techniques are the most versatile and sensitive methods to measure transport into the brain. This article also reviews the various methodologies available for assessing the transfer of drug molecules undergoing significant uptake through the BBB in vivo. PMID- 20540688 TI - Gemini amphiphiles: a novel class of nonviral gene delivery vectors. AB - A number of carriers have been developed for the delivery of genes, but the search for a clinically successful ideal carrier is ongoing. Nonviral carriers, especially cationic liposomes, were developed to resolve issues related to the immunogenicity and oncogenicity of viral carriers. Many synthetic cationic amphiphiles have been synthesized and structurally modified to incorporate genes into vesicular carriers to enhance DNA transfection efficiency and to reduce carrier toxicity. Of these carriers, gemini amphiphiles have demonstrated the suitable physiochemical properties needed for promising and novel gene carriers. Moreover, three basic parts (head, spacer, and chain) in the structure of gemini amphiphiles provide ample opportunities to tailor them according to the needs of specific gene delivery. Initial studies have demonstrated the superiority of gemini amphiphiles in gene delivery efficiency over currently used carriers for gene delivery. This article critically reviews these studies and provides a balanced view to fellow scientists to carry out their efforts in filling in the technological gaps. PMID- 20540690 TI - Atypical antipsychotic metabolism and excretion. AB - BACKGROUND: The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored. OBJECTIVE: To analyze the excretion profile of atypical antipsychotic agents and compare the overall magnitude of metabolism (changed vs. unchanged drug) and route of excretion (feces vs. urine). Secondary objectives include providing: 1) dosing information in hepatic and renal impairment, and 2) context of the specific enzymes and pathways involved in each agents' biotransformation. METHODS: Published literature and each manufacturer's radiolabeled drug absorption, distribution, metabolism and excretion data and U.S. prescribing information were reviewed. RESULTS: With the exception of paliperidone, atypical antipsychotics undergo extensive metabolism (i.e., or = 800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (chi(2)(1) (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (chi(2)(16) (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (chi(2)(9) (heterogeneity) = 149.68, p < 0.001). CONCLUSIONS: Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID- 20540728 TI - Mitochondrial heteroplasmy and DNA barcoding in Hawaiian Hylaeus (Nesoprosopis) bees (Hymenoptera: Colletidae). AB - BACKGROUND: The past several years have seen a flurry of papers seeking to clarify the utility and limits of DNA barcoding, particularly in areas such as species discovery and paralogy due to nuclear pseudogenes. Heteroplasmy, the coexistence of multiple mitochondrial haplotypes in a single organism, has been cited as a potentially serious problem for DNA barcoding but its effect on identification accuracy has not been tested. In addition, few studies of barcoding have tested a large group of closely-related species with a well established morphological taxonomy. In this study we examine both of these issues, by densely sampling the Hawaiian Hylaeus bee radiation. RESULTS: Individuals from 21 of the 49 a priori morphologically-defined species exhibited coding sequence heteroplasmy at levels of 1-6% or more. All homoplasmic species were successfully identified by COI using standard methods of analysis, but only 71% of heteroplasmic species. The success rate in identifying heteroplasmic species was increased to 86% by treating polymorphisms as character states rather than ambiguities. Nuclear pseudogenes (numts) were also present in four species, and were distinguishable from heteroplasmic sequences by patterns of nucleotide and amino acid change. CONCLUSIONS: Heteroplasmy significantly decreased the reliability of species identification. In addition, the practical issue of dealing with large numbers of polymorphisms- and resulting increased time and labor required - makes the development of DNA barcode databases considerably more complex than has previously been suggested. The impact of heteroplasmy on the utility of DNA barcoding as a bulk specimen identification tool will depend upon its frequency across populations, which remains unknown. However, DNA barcoding is still likely to remain an important identification tool for those species that are difficult or impossible to identify through morphology, as is the case for the ecologically important solitary bee fauna. PMID- 20540729 TI - Hydrogen sulphide induces micro opioid receptor-dependent analgesia in a rodent model of visceral pain. AB - BACKGROUND: Hydrogen sulphide (H2S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating KATP channels. A body of evidence support the notion that KATP channels interact with endogenous opioids. Whether H2S-induced analgesia involves opioid receptors is unknown. METHODS: The perception of painful sensation induced by colorectal distension (CRD) in conscious rats was measured by assessing the abdominal withdrawal reflex. The contribution of opioid receptors to H2S-induced analgesia was investigated by administering rats with selective mu, kappa and delta opioid receptor antagonists and antisenses. To investigate whether H2S causes mu opioid receptor (MOR) transactivation, the neuronal like cells SKNMCs were challenged with H2S in the presence of MOR agonist (DAMGO) or antagonist (CTAP). MOR activation and phosphorylation, its association to beta arrestin and internalization were measured. RESULTS: H2S exerted a potent analgesic effects on CRD-induced pain. H2S-induced analgesia required the activation of the opioid system. By pharmacological and molecular analyses, a robust inhibition of H2S induced analgesia was observed in response to central administration of CTAP and MOR antisense, while kappa and delta receptors were less involved. H2S caused MOR transactivation and internalization in SKNMCs by a mechanism that required AKT phosphorylation. MOR transactivation was inhibited by LY294002, a PI3K inhibitor, and glibenclamide, a KATP channels blocker. CONCLUSIONS: This study provides pharmacological and molecular evidence that antinociception exerted by H2S in a rodent model of visceral pain is modulated by the transactivation of MOR. This observation provides support for development of new pharmacological approaches to visceral pain. PMID- 20540730 TI - Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary artery pressure: a clinical study. AB - INTRODUCTION: Pulse-pressure variation (PPV) due to increased right ventricular afterload and dysfunction may misleadingly suggest volume responsiveness. We aimed to assess prediction of volume responsiveness with PPV in patients with increased pulmonary artery pressure. METHODS: Fifteen cardiac surgery patients with a history of increased pulmonary artery pressure (mean pressure, 27 +/- 5 mm Hg (mean +/- SD) before fluid challenges) and seven septic shock patients (mean pulmonary artery pressure, 33 +/- 10 mm Hg) were challenged with 200 ml hydroxyethyl starch boli ordered on clinical indication. PPV, right ventricular ejection fraction (EF) and end-diastolic volume (EDV), stroke volume (SV), and intravascular pressures were measured before and after volume challenges. RESULTS: Of 69 fluid challenges, 19 (28%) increased SV > 10%. PPV did not predict volume responsiveness (area under the receiver operating characteristic curve, 0.555; P = 0.485). PPV was >or=13% before 46 (67%) fluid challenges, and SV increased in 13 (28%). Right ventricular EF decreased in none of the fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.0003). EDV increased in 28% of fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.272). CONCLUSIONS: Both early after cardiac surgery and in septic shock, patients with increased pulmonary artery pressure respond poorly to fluid administration. Under these conditions, PPV cannot be used to predict fluid responsiveness. The frequent reduction in right ventricular EF when SV did not increase suggests that right ventricular dysfunction contributed to the poor response to fluids. PMID- 20540731 TI - Chlorhexidine rinse for prevention of urethritis in men linked to oral sex. AB - BACKGROUND: Oral sex among teenagers is on the rise. Similarity between the oral flora and organisms recovered from nongonococcal urethritis and prostatitis, points to retrograde entry of bacteria from oral cavity into the urethra following insertive oral intercourse. PRESENTATION OF THE HYPOTHESIS: Chlorhexidine has a wide spectrum of anti-bactericidal activity encompassing gram positive and negative bacteria. It is also effective against HIV and HBV. It produced large and prolonged reductions in salivary bacterial counts within 7-h of its use. Hence, it would seem logic to postulate that rinsing with chlorhexidine before oral sex will be effective for prevention of retrograde entry of bacteria from oral cavity into the urethra. The recommendation for rinsing will be: 15 ml of a 0.12% or 10 ml of 0.2% chlorhexidine rinse for 30 seconds. Also other drug delivery systems such as chlorhexidine chewing gum or spray can be used. TESTING THE HYPOTHESIS: Men suffering from recurrent nongonococcal urethritis or prostatitis are good subjects for testing the hypothesis. They perform genital safe sex via consistent use of condom. Yet they generally received unprotected insertive oral intercourse. Chlorhexidine can be used for prevention of recurrences of the disease. IMPLICATIONS OF THE HYPOTHESIS: The chlorhexidine will be a new, easy, attractive and effective method for reduction of nongonococcal urethritis, prostatitis and epidydimitis following insertive oral intercourse. It is poorly absorbed from skin, mucosa and gastrointestinal tract indicating systemic safety of chlorhexidine. The agent does not cause any bacterial resistance and supra-infection. PMID- 20540732 TI - A profile of hospital-admitted paediatric burns patients in South Africa. AB - BACKGROUND: Injuries and deaths from burns are a serious, yet preventable health problem globally. This paper describes burns in a cohort of children admitted to the Red Cross Children's Hospital, in Cape Town, South Africa.This six month retrospective case note review looked at a sample of consecutively admitted patients from the 1 st April 2007 to the 30 th September 2007. Information was collected using a project-specific data capture sheet. Descriptive statistics (percentages, medians, means and standard deviations) were calculated, and data was compared between age groups. Spearman's correlation co-efficient was employed to look at the association between the total body surface area and the length of stay in hospital. FINDINGS: During the study period, 294 children were admitted (f= 115 (39.1%), m= 179 (60.9%)). Hot liquids caused 83.0% of the burns and 36.0% of these occurred in children aged two years or younger. Children over the age of five were equally susceptible to hot liquid burns, but the mechanism differed from that which caused burns in the younger child. CONCLUSION: In South Africa, most hospitalised burnt children came from informal settlements where home safety is a low priority. Black babies and toddlers are most at risk for sustaining severe burns when their environment is disorganized with respect to safety. Burns injuries can be prevented by improving the home environment and socio-economic living conditions through the health, social welfare, education and housing departments. PMID- 20540733 TI - In planta gene expression analysis of Xanthomonas oryzae pathovar oryzae, African strain MAI1. AB - BACKGROUND: Bacterial leaf blight causes significant yield losses in rice crops throughout Asia and Africa. Although both the Asian and African strains of the pathogen, Xanthomonas oryzae pv. oryzae (Xoo), induce similar symptoms, they are nevertheless genetically different, with the African strains being more closely related to the Asian X. oryzae pv. oryzicola (Xoc). RESULTS: Changes in gene expression of the African Xoo strain MAI1 in the susceptible rice cultivar Nipponbare were profiled, using an SSH Xoo DNA microarray. Microarray hybridization was performed comparing bacteria recovered from plant tissues at 1, 3, and 6 days after inoculation (dai) with bacteria grown in vitro. A total of 710 bacterial genes were found to be differentially expressed, with 407 up regulated and 303 down-regulated. Expression profiling indicated that less than 20% of the 710 bacterial transcripts were induced in the first 24 h after inoculation, whereas 63% were differentially expressed at 6 dai. The 710 differentially expressed genes were one-end sequenced. 535 sequences were obtained from which 147 non-redundant sequences were identified. Differentially expressed genes were related to metabolism, secretion and transport, pathogen adherence to plant tissues, plant cell-wall degradation, IS elements, and virulence. In addition, various other genes encoding proteins with unknown function or showing no similarity to other proteins were also induced. The Xoo MAI1 non-redundant set of sequences was compared against several X. oryzae genomes, revealing a specific group of genes that was present only in MAI1. Numerous IS elements were also found to be differentially expressed. Quantitative real-time PCR confirmed 86% of the identified profile on a set of 14 genes selected according to the microarray analysis. CONCLUSIONS: This is the first report to compare the expression of Xoo genes in planta across different time points during infection. This work shows that as-yet-unidentified and potentially new virulence factors are appearing in an emerging African pathogen. It also confirms that African Xoo strains do differ from their Asian counterparts, even at the transcriptional level. PMID- 20540735 TI - Algorithmic approaches to aid species' delimitation in multidimensional morphospace. AB - BACKGROUND: The species is a fundamental unit of biological pattern and process, but its delimitation has proven a ready source of argument and disagreement. Here, we discuss four key steps that utilize statistical thresholds to describe the morphological variability within a sample and hence assess whether there is evidence for one or multiple species. Once the initial set of biologically relevant traits on comparable individuals has been identified, there is no need for the investigator to hypothesise how specimens might be divided among groups, nor the traits on which groups might be separated. RESULTS: Principal components are obtained using robust covariance estimates and retained only if they exceed threshold amounts of explanatory power, before model-based clustering is performed on the dimension-reduced space. We apply these steps in an attempt to resolve ongoing debates among taxonomists working on the extinct Eocene planktonic foraminifera Turborotalia, providing statistical evidence for two species shortly before the lineage's extinction near the Eocene/Oligocene boundary. CONCLUSION: By estimating variance robustly (samples containing incipient species are unlikely to be scaled optimally by means and standard deviations) and identifying thresholds relevant to a particular system rather than universal standards, the steps of the framework aim to optimize the chances of delineation without imposing pre-conceived patterns onto estimates of species limits. PMID- 20540734 TI - Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women. AB - INTRODUCTION: The potential association between hypo- and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women. METHODS: In the Malmo Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Cox's proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre- and peri/postmenopausal women separately. RESULTS: Overall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer. CONCLUSIONS: This is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner. PMID- 20540736 TI - In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. AB - BACKGROUND: CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes. METHODS: In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases. RESULTS: ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts. CONCLUSIONS: Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells. PMID- 20540737 TI - Seasonal variations of melatonin in ram seminal plasma are correlated to those of testosterone and antioxidant enzymes. AB - BACKGROUND: Some breeds of sheep are highly seasonal in terms of reproductive capability, and these changes are regulated by photoperiod and melatonin secretion. These changes affect the reproductive performance of rams, impairing semen quality and modifying hormonal profiles. Also, the antioxidant defence systems seem to be modulated by melatonin secretion, and shows seasonal variations. The aim of this study was to investigate the presence of melatonin and testosterone in ram seminal plasma and their variations between the breeding and non-breeding seasons. In addition, we analyzed the possible correlations between these hormones and the antioxidant enzyme defence system activity. METHODS: Seminal plasma from nine Rasa Aragonesa rams were collected for one year, and their levels of melatonin, testosterone, superoxide dismutase (SOD), glutathione reductase (GRD), glutathione peroxidase (GPX) and catalase (CAT) were measured. RESULTS: All samples presented measurable quantities of hormones and antioxidant enzymes. Both hormones showed monthly variations, with a decrease after the winter solstice and a rise after the summer solstice that reached the maximum levels in October-November, and a marked seasonal variation (P < 0.01) with higher levels in the breeding season. The yearly pattern of GRD and catalase was close to that of melatonin, and GRD showed a significant seasonal variation (P < 0.01) with a higher activity during the breeding season. Linear regression analysis between the studied hormones and antioxidant enzymes showed a significant correlation between melatonin and testosterone, GRD, SOD and catalase. CONCLUSIONS: These results show the presence of melatonin and testosterone in ram seminal plasma, and that both hormones have seasonal variations, and support the idea that seasonal variations of fertility in the ram involve interplay between melatonin and the antioxidant defence system. PMID- 20540738 TI - Can follow-up study questions about correct and consistent condom use reduce respondent over-reporting among groups at high risk? An analysis of datasets from six countries. PMID- 20540739 TI - Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors. AB - BACKGROUND: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. METHODS: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of alpha, beta and gamma tubulin was also performed. RESULTS: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. CONCLUSIONS: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001). PMID- 20540740 TI - Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells. AB - BACKGROUND: During cerebellar development, Purkinje cells (PCs) form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT) is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. RESULTS: We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML), the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA) inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain derived neurotrophic factor (BDNF) promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. CONCLUSION: Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo. PMID- 20540741 TI - Molecular genetic analysis of a cattle population to reconstitute the extinct Algarvia breed. AB - BACKGROUND: Decisions to initiate conservation programmes need to account for extant variability, diversity loss and cultural and economic aspects. Molecular markers were used to investigate if putative Algarvia animals could be identified for use as progenitors in a breeding programme to recover this nearly extinct breed. METHODS: 46 individuals phenotypically representative of Algarvia cattle were genotyped for 27 microsatellite loci and compared with 11 Portuguese autochthonous and three imported breeds. Genetic distances and factorial correspondence analyses (FCA) were performed to investigate the relationship among Algarvia and related breeds. Assignment tests were done to identify representative individuals of the breed. Y chromosome and mtDNA analyses were used to further characterize Algarvia animals. Gene- and allelic-based conservation analyses were used to determine breed contributions to overall genetic diversity. RESULTS: Genetic distance and FCA results confirmed the close relationship between Algarvia and southern Portuguese breeds. Assignment tests without breed information classified 17 Algarvia animals in this cluster with a high probability (q > 0.95). With breed information, 30 cows and three bulls were identified (q > 0.95) that could be used to reconstitute the Algarvia breed. Molecular and morphological results were concordant. These animals showed intermediate levels of genetic diversity (MNA = 6.0 +/- 1.6, Rt = 5.7 +/- 1.4, Ho = 0.63 +/- 0.19 and He = 0.69 +/- 0.10) relative to other Portuguese breeds. Evidence of inbreeding was also detected (Fis = 0.083, P < 0.001). The four Algarvia bulls had Y-haplotypes H6Y2 and H11Y2, common in Portuguese cattle. The mtDNA composition showed prevalence of T3 matrilines and presence of the African derived T1a haplogroup. This analysis confirmed the genetic proximity of Algarvia and Garvonesa breeds (Fst = 0.028, P > 0.05). Algarvia cattle provide an intermediate contribution (CB = 6.18, CW = -0.06 and D1 = 0.50) to the overall gene diversity of Portuguese cattle. Algarvia and seven other autochthonous breeds made no contribution to the overall allelic diversity. CONCLUSIONS: Molecular analyses complemented previous morphological findings to identify 33 animals that can be considered remnants of the Algarvia breed. Results of genetic diversity and conservation analyses provide objective information to establish a management program to reconstitute the Algarvia breed. PMID- 20540742 TI - Roles of CUP-5, the Caenorhabditis elegans orthologue of human TRPML1, in lysosome and gut granule biogenesis. AB - BACKGROUND: CUP-5 is a Transient Receptor Potential protein in C. elegans that is the orthologue of mammalian TRPML1. Loss of TRPML1 results in the lysosomal storage disorder Mucolipidosis type IV. Loss of CUP-5 results in embryonic lethality and the accumulation of enlarged yolk granules in developing intestinal cells. The embryonic lethality of cup-5 mutants is rescued by mutations in mrp-4, which is required for gut granule differentiation. Gut granules are intestine specific lysosome-related organelles that accumulate birefringent material. This link between CUP-5 and gut granules led us to determine the roles of CUP-5 in lysosome and gut granule biogenesis in developing intestinal cells. RESULTS: We show that CUP-5 protein localizes to lysosomes, but not to gut granules, in developing intestinal cells. Loss of CUP-5 results in defects in endo-lysosomal transport in developing intestinal cells of C. elegans embryos. This ultimately leads to the appearance of enlarged terminal vacuoles that show defective lysosomal degradation and that have lysosomal and endosomal markers. In contrast, gut granule biogenesis is normal in the absence of CUP-5. Furthermore, loss of CUP-5 does not result in inappropriate fusion or mixing of content between lysosomes and gut granules. CONCLUSIONS: Using an in vivo model of MLIV, we show that there is a defect in lysosomal transport/biogenesis that is earlier than the presumed function of TRPML1 in terminal lysosomes. Our results indicate that CUP 5 is required for the biogenesis of lysosomes but not of gut granules. Thus, cellular phenotypes in Mucolipidosis type IV are likely not due to defects in lysosome-related organelle biogenesis, but due to progressive defects in lysosomal transport that lead to severe lysosomal dysfunction. PMID- 20540743 TI - Immune disease expressed in liver and platelets in an adolescent: a case report. AB - We report a case of a 15-year-old boy with autoimmune hepatitis lacking common serologic markers and normal gammaglobulinemia associated with immune thrombocytopenia and family history of psoriasis. He presented to our department with a 4-year history of a cervical posterior lymphadenopathy and recent petechiae. Previous laboratory results 6 months before already showed hepatocellular injury. After exclusion of other causes, the diagnosis of autoimmune hepatitis was made based on clinical grounds, associated immune disorder and histological features of liver biopsy.The authors alert for this atypical presentation of autoimmune hepatitis and associated immune thrombocytopenia. PMID- 20540744 TI - Bioethics in biomedicine in the context of a global higher education area. AB - The University is tasked with drawing together, transmitting and maintaining knowledge, while creating an area where the ethical "sense" required for working in the field of Biology and Biomedicine can be provided. Although scientific knowledge is present on an overwhelming scale in nature and, therefore, its discovery is unceasing, this does not mean that, as a human being, the researcher has no limitations. It is Bioethics that sets this limit. The successful spreading of knowledge, therefore, which is proclaimed with the creation of a Global Higher Education Area, should also pursue the establishment of the bioethical principles necessary for the credibility of science and its progress so that the society that it promotes and sustains becomes a reality. PMID- 20540745 TI - Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients. AB - BACKGROUND: The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported. METHODS: Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years. RESULTS: In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (P = 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (P > 0.05), but were found between the FEC and NE treatment groups (P < 0.05). Furthermore, no significant differences were found between the TE and NE regimens (P > 0.05). Tamoxifen use was a significant predictor for CIA (P = 0.001), and age was also a significant predictor (P < 0.001). In multivariate analysis, age (P < 0.001), the type of chemotherapy regimens (P = 0.009) and tamoxifen use (P = 0.003) were all significant predictors. CONCLUSIONS: Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen. PMID- 20540746 TI - Glucosylceramide synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and beta-catenin signaling. AB - BACKGROUND: Drug resistance is the outcome of multiple-gene interactions in cancer cells under stress of anticancer agents. MDR1 overexpression is most commonly detected in drug-resistant cancers and accompanied with other gene alterations including enhanced glucosylceramide synthase (GCS). MDR1 encodes for P-glycoprotein that extrudes anticancer drugs. Polymorphisms of MDR1 disrupt the effects of P-glycoprotein antagonists and limit the success of drug resistance reversal in clinical trials. GCS converts ceramide to glucosylceramide, reducing the impact of ceramide-induced apoptosis and increasing glycosphingolipid (GSL) synthesis. Understanding the molecular mechanisms underlying MDR1 overexpression and how it interacts with GCS may find effective approaches to reverse drug resistance. RESULTS: MDR1 and GCS were coincidently overexpressed in drug resistant breast, ovary, cervical and colon cancer cells; silencing GCS using a novel mixed-backbone oligonucleotide (MBO-asGCS) sensitized these four drug resistant cell lines to doxorubicin. This sensitization was correlated with the decreased MDR1 expression and the increased doxorubicin accumulation. Doxorubicin treatment induced GCS and MDR1 expression in tumors, but MBO-asGCS treatment eliminated "in-vivo" growth of drug-resistant tumor (NCI/ADR-RES). MBO-asGCS suppressed the expression of MDR1 with GCS and sensitized NCI/ADR-RES tumor to doxorubicin. The expression of P-glycoprotein and the function of its drug efflux of tumors were decreased by 4 and 8 times after MBO-asGCS treatment, even though this treatment did not have a significant effect on P-glycoprotein in normal small intestine. GCS transient transfection induced MDR1 overexpression and increased P-glycoprotein efflux in dose-dependent fashion in OVCAR-8 cancer cells. GSL profiling, silencing of globotriaosylceramide synthase and assessment of signaling pathway indicated that GCS transfection significantly increased globo series GSLs (globotriaosylceramide Gb3, globotetraosylceramide Gb4) on GSL enriched microdomain (GEM), activated cSrc kinase, decreased beta-catenin phosphorylation, and increased nuclear beta-catenin. These consequently increased MDR1 promoter activation and its expression. Conversely, MBO-asGCS treatments decreased globo series GSLs (Gb3, Gb4), cSrc kinase and nuclear beta-catenin, and suppressed MDR-1 expression in dose-dependent pattern. CONCLUSION: This study demonstrates, for the first time, that GCS upregulates MDR1 expression modulating drug resistance of cancer. GSLs, in particular globo series GSLs mediate gene expression of MDR1 through cSrc and beta-catenin signaling pathway. PMID- 20540747 TI - Reassociation kinetics-based approach for partial genome sequencing of the cattle tick, Rhipicephalus (Boophilus) microplus. AB - BACKGROUND: The size and repetitive nature of the Rhipicephalus microplus genome makes obtaining a full genome sequence fiscally and technically problematic. To selectively obtain gene-enriched regions of this tick's genome, Cot filtration was performed, and Cot-filtered DNA was sequenced via 454 FLX pyrosequencing. RESULTS: The sequenced Cot-filtered genomic DNA was assembled with an EST-based gene index of 14,586 unique entries where each EST served as a potential "seed" for scaffold formation. The new sequence assembly extended the lengths of 3,913 of the 14,586 gene index entries. Over half of the extensions corresponded to extensions of over 30 amino acids. To survey the repetitive elements in the tick genome, the complete sequences of five BAC clones were determined. Both Class I and II transposable elements were found. Comparison of the BAC and Cot filtration data indicates that Cot filtration was highly successful in filtering repetitive DNA out of the genomic DNA used in 454 sequencing. CONCLUSION: Cot filtration is a very useful strategy to incorporate into genome sequencing projects on organisms with large genome sizes and which contain high percentages of repetitive, difficult to assemble, genomic DNA. Combining the Cot selection approach with 454 sequencing and assembly with a pre-existing EST database as seeds resulted in extensions of 27% of the members of the EST database. PMID- 20540748 TI - Unexpectedly high burden of rotavirus gastroenteritis in very young infants. AB - BACKGROUND: The highest incidence of rotavirus gastroenteritis has generally been reported in children 6-24 months of age. Young infants are thought to be partially protected by maternal antibodies acquired transplacentally or via breast milk. The purpose of our study was to assess the age distribution of children with confirmed community-acquired rotavirus gastroenteritis presenting to an urban referral hospital. METHODS: Children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by ELISA (followed by genotyping if ELISA-positive) since the 1994-95 epidemic season. RESULTS: Over the last 12 rotavirus seasons prior to the introduction of the pentavalent rotavirus vaccine in 2006, stool specimens from 1646 patients tested positive for community acquired rotavirus infection. Gender or age was not recorded in 6 and 5 cases, respectively. Overall, 58% of the cases occurred in boys. G1 was the predominant VP7 serotype, accounting for 72% of cases. The median (IQR) age was 11 (5-21) months. A total of 790 (48%) cases occurred in children outside the commonly quoted peak age range, with 27% in infants <6 months of age and 21% in children >24 months of age. A total of 220 (13%) cases occurred during the first 3 months of life, and the highest number of episodes per month of age [97 (6%)] was observed during the second month of life. CONCLUSIONS: The incidence of community acquired rotavirus gastroenteritis monitored over 12 seasons in the prevaccine era at a major university hospital was nearly constant for each month of age during the first year of life, revealing an unexpectedly high incidence of symptomatic rotavirus disease in infants <3 months old. A sizeable fraction of cases occurred in children too young to have been vaccinated according to current recommendations. PMID- 20540749 TI - Cholesterol in human atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability. AB - BACKGROUND: Cholesterol deposition in arterial wall drives atherosclerosis. The key goal of this study was to examine the relationship between plaque cholesterol content and patient characteristics that typically associate with disease state and lesion vulnerability. Quantitative assays for free cholesterol, cholesteryl ester, triglyceride, and protein markers in atherosclerotic plaque were established and applied to plaque samples from multiple patients and arterial beds (Carotid and peripheral arteries; 98 lesions in total). RESULTS: We observed a lower cholesterol level in restenotic than primary peripheral plaque. We observed a trend toward a higher level in symptomatic than asymptomatic carotid plaque. Peripheral plaque from a group of well-managed diabetic patients displayed a weak trend of more free cholesterol deposition than plaque from non diabetic patients. Plaque triglyceride content exhibited less difference in the same comparisons. We also measured cholesterol in multiple segments within one carotid plaque sample, and found that cholesterol content positively correlated with markers of plaque vulnerability, and negatively correlated with stability markers. CONCLUSIONS: Our results offer important biological validation of cholesterol as a key lipid marker for plaque severity. Results also suggest cholesterol is a more sensitive plaque marker than routine histological staining for neutral lipids. PMID- 20540750 TI - Chromosome 16p11.2 deletions: another piece in the genetic puzzle of childhood obesity. AB - Ipercaloric diet and reduced physical activity have driven the rise in the prevalence of childhood obesity over a relatively short time interval. Family and twin studies have led to the conclusion that the strong predictive value of parental body mass index (BMI) mainly stems from genetic rather than environmental factors. Whereas the common polygenic obesity arises when an individual genetic make-up is susceptible to an environment that promotes energy consumption over energy expenditure, monogenic obesity, on the contrary, is the obesity associated with a single gene mutation, which is sufficient by itself to cause weight gain in a food abundant context. Genes involved in the leptin melanocortin pathway are often mutated in these cases. The cumulative prevalence of monogenic obesity among children with severe obesity is about 5%. Recently, deletions in the region p11.2 of the chromosome 16 encompassing the gene SH2B1, which is involved in the leptin and insulin signaling, have been reported in about 0.5% of children with severe early-onset obesity. These patients show extreme hyperphagia, severe insulin resistance and, in some cases, mild developmental delay. PMID- 20540752 TI - The consequences of including non-additive effects on the genetic evaluation of harvest body weight in Coho salmon (Oncorhynchus kisutch). AB - BACKGROUND: In this study, we used different animal models to estimate genetic and environmental variance components on harvest weight in two populations of Oncorhynchus kisutch, forming two classes i.e. odd- and even-year spawners. METHODS: The models used were: additive, with and without inbreeding as a covariable (A + F and A respectively); additive plus common environmental due to full-sib families and inbreeding (A + C + F); additive plus parental dominance and inbreeding (A + D + F); and a full model (A + C + D + F). Genetic parameters and breeding values obtained by different models were compared to evaluate the consequences of including non-additive effects on genetic evaluation. RESULTS: Including inbreeding as a covariable did not affect the estimation of genetic parameters, but heritability was reduced when dominance or common environmental effects were included. A high heritability for harvest weight was estimated in both populations (even = 0.46 and odd = 0.50) when simple additive models (A + F and A) were used. Heritabilities decreased to 0.21 (even) and 0.37 (odd) when the full model was used (A + C + D + F). In this full model, the magnitude of the dominance variance was 0.19 (even) and 0.06 (odd), while the magnitude of the common environmental effect was lower than 0.01 in both populations. The correlation between breeding values estimated with different models was very high in all cases (i.e. higher than 0.98). However, ranking of the 30 best males and the 100 best females per generation changed when a high dominance variance was estimated, as was the case in one of the two populations (even). CONCLUSIONS: Dominance and common environmental variance may be important components of variance in harvest weight in O. kisutch, thus not including them may produce an overestimation of the predicted response; furthermore, genetic evaluation was seen to be partially affected, since the ranking of selected animals changed with the inclusion of non-additive effects in the animal model. PMID- 20540751 TI - Rab-mediated vesicular transport is required for neuronal positioning in the developing Drosophila visual system. AB - BACKGROUND: The establishment of tissue architecture in the nervous system requires the proper migration and positioning of newly born neurons during embryonic development. Defects in nuclear translocation, a key process in neuronal positioning, are associated with brain diseases such as lissencephaly in humans. Accumulated evidence suggests that the molecular mechanisms controlling neuronal movement are conserved throughout evolution. While the initial events of neuronal migration have been extensively studied, less is known about the molecular details underlying the establishment of neuronal architecture after initial migration. RESULTS: In a search for novel players in the control of photoreceptor (R cell) positioning in the developing fly visual system, we found that misexpression of the RabGAP RN-Tre disrupted the apical localization of R cell nuclei. RN-Tre interacts with Rab5 and Rab11 in the fly eye. Genetic analysis shows that Rab5, Shi and Rab11 are required for maintaining apical localization of R-cell nuclei. CONCLUSIONS: We propose that Rab5, Shi and Rab11 function together in a vesicular transport pathway for regulating R-cell positioning in the developing eye. PMID- 20540753 TI - Effects of methods of descending stairs forwards versus backwards on knee joint force in patients with osteoarthritis of the knee: a clinical controlled study. AB - BACKGROUND: The aim of this study was to investigate the kinetic characteristics of compensatory backward descending movement performed by patients with osteoarthritis of the knee. METHODS: Using a three-dimensional motion analysis system, we investigated lower extremity joint angles, joint moments, joint force of the support leg in forward and backward descending movements on stairs, and joint force of the leading leg at landing in 7 female patients with osteoarthritis of the knee. RESULTS: Compared with the forward descending movement, knee joint angle, joint moment and joint force of the support leg all decreased in the backward descending movement. Joint force of the leading leg at landing was also reduced in the backward descending movement. In addition, we confirmed that the center of body mass was mainly controlled by the knee and ankle joints in the forward descending movement, and by the hip joint in the backward descending movement. CONCLUSIONS: Since it has been reported that knee flexion angle and extensor muscle strength are decreased in patients with osteoarthritis of the knee, we believe that backward descending movement is an effective method to use the hip joint to compensate for these functional defects. In addition, due to the decreased knee joint force both in the leading and support legs in backward descending movement, the effectiveness of compensatory motion for pain control and knee joint protection was also suggested. PMID- 20540754 TI - Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle. AB - BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN) regulates several biological functions involving the modulation of cell behaviors via cell cell and cell-matrix interactions. According to its diverse functions, we hypothesized that EMMPRIN may play an important role in endometrial remodeling and establishment of pregnancy in cow. METHODS: In this study, endometrial tissues from the cyclic cows during before ovulation, after ovulation and middle of estrous cycle; and pregnant endometrial tissues from Day 19 to 35 of gestation have been used. Expression of mRNA was analyzed by RT-PCR, qPCR and in situ hybridization whereas protein expression by immunohistochemistry and western blot analysis. RESULTS: EMMPRIN mRNA was expressed in both cyclic and pregnant endometrium and significantly higher in the endometrium at Day 35 of gestation than the cyclic endometrium. In Western blot analysis, an approximately 65 kDa band was detected in the endometrium, and approximately 51 kDa in the cultured bovine epithelial cells and BT-1 cells, respectively. Both in situ hybridization and immunohistochemistry data showed that EMMPRIN was primarily expressed in luminal and glandular epithelium with strong staining on Day 19 conceptus. At Day 19 of gestation, expression of EMMPRIN mRNA on luminal epithelium was decreased than that observed at middle of estrous cycle, however, on Day 30 of gestation, slightly increased expression was found at the site of placentation. Expression of matrix metalloproteinase-2 (MMP-2) and MMP-14 mRNA were mainly detected in stroma and their expression also decreased at Day 19 of gestation however it was also expressed at the site of placentation at Day 30 of gestation as observed for EMMPRIN. Expression of MMP-1 or -9 mRNA was very low and was below the detection limit in the cyclic and pregnant endometrium. CONCLUSION: EMMPRIN from the luminal epithelium may regulate the expression of stromal MMP-2 and -14 suggesting its crucial role in adhesion and fusion of embryo to luminal epithelium by directly itself through physiological tissues remodeling and developmental process, and/or stimulating MMPs to compensate endometrial functions. PMID- 20540755 TI - Characterization of the Taenia spp HDP2 sequence and development of a novel PCR based assay for discrimination of Taenia saginata from Taenia asiatica. AB - A previously described Taenia saginata HDP2 DNA sequence, a 4-kb polymorphic fragment, was previously used as the basis for developing PCR diagnostic protocols for the species-specific discrimination of T. saginata from T. solium and for the differentiation of T. saginata from T. asiatica. The latter was shown subsequently to lack the required specificity, so we undertook genetic studies of the HDP2 sequence from T. saginata and T. asiatica to determine why, and to develop a novel HDP2-PCR protocol for the simultaneous unambiguous identification of human taeniids. Sequencing and further analysis of the HDP2 DNA fragments of 19 Asiatic isolates of T. saginata and T. asiatica indicated that the HDP2 sequences of both species exhibited clear genomic variability, due to polymorphic variable fragments, that could correspond to the non-transcribed region of ribosomal DNA. This newly observed polymorphism allowed us to develop a novel, reproducible and reliable HDP2-PCR protocol which permitted the simultaneous discrimination of all T. saginata and T. asiatica isolates examined. This species specific identification was based on, and facilitated by, the clear size difference in amplicon profiles generated: fragments of 1300 bp, 600 bp and 300 bp were produced for T. asiatica, amplicons of 1300 bp and 300 bp being obtained for T. saginata. Control T. solium samples produced one amplicon of 600 bp with the HDP2-PCR protocol. The assay has the potential to prove useful as a diagnostic tool in areas such as South East Asia where T. saginata, T. asiatica and T. solium coexist. PMID- 20540756 TI - Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies. AB - BACKGROUND: Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder. It is associated with risk for preterm birth and HIV infection. The etiology of the condition has been debated for nearly half a century and the lack of knowledge about its cause and progression has stymied efforts to improve therapy and prevention. Gardnerella vaginalis was originally identified as the causative agent, but subsequent findings that it is commonly isolated from seemingly healthy women cast doubt on this claim. Recent studies shedding light on the virulence properties of G. vaginalis, however, have drawn the species back into the spotlight. RESULTS: In this study, we sequenced the genomes of a strain of G. vaginalis from a healthy woman, and one from a woman with bacterial vaginosis. Comparative analysis of the genomes revealed significant divergence and in vitro studies indicated disparities in the virulence potential of the two strains. The commensal isolate exhibited reduced cytotoxicity and yet the cytolysin proteins encoded by the two strains were nearly identical, differing at a single amino acid, and were transcribed at similar levels. The BV-associated strain encoded a different variant of a biofilm associated protein gene and demonstrated greater adherence, aggregation, and biofilm formation. Using filters with different pore sizes, we found that direct contact between the bacteria and epithelial cells is required for cytotoxicity. CONCLUSIONS: The results indicated that contact is required for cytotoxicity and suggested that reduced cytotoxicity in the commensal isolate could be due to impaired adherence. This study outlines two distinct genotypic variants of G. vaginalis, one apparently commensal and one pathogenic, and presents evidence for disparate virulence potentials. PMID- 20540757 TI - Planning training seminars in palliative care: a cross-sectional survey on the preferences of general practitioners and nurses in Austria. AB - BACKGROUND: Training in palliative care is frequently requested by health care professionals. However, little is known in detail about the subject matters and the educational preferences of physicians and staff or assistant nurses in this field. METHODS: All 897 registered GPs and all 933 registered home care nurses in the district of Steiermark/Austria were sent postal questionnaires. RESULTS: Results from 546 (30%) respondents revealed that GPs prefer evening courses and weekend seminars, whereas staff and assistant nurses prefer one-day courses. Multidisciplinary sessions are preferred by almost 80% of all professional groups. GPs preferred multi disciplinary groups most frequently when addressing psychosocial needs (88.8%) and ethical questions (85.8%). Staff and assistant nurses preferred multidisciplinary groups most frequently in the area of pain management (88%) and opted for multi disciplinary learning to a significantly higher extent than GPs (69%; p < 0.01). Those topics were ranked first which are not only deepening, but supplementing the professional training. On average, GPs were willing to spend a maximum amount of euro 400 per year for training seminars in palliative care, whereas nurses would spend approximately euro 190 for such classes.The results provide a detailed analysis of the preferences of GPs and nurses and offer guidance for the organisation of training seminars in palliative care. CONCLUSIONS: Medical and nursing education programs often pursue separate paths. Yet our findings indicate that in palliative care multidisciplinary training seminars are favoured by both, doctors and nurses. Also, both groups prefer topics that are not only deepening, but supplementing their professional knowledge. PMID- 20540758 TI - Equivalence of multibreed animal models and hierarchical Bayes analysis for maternally influenced traits. AB - BACKGROUND: It has been argued that multibreed animal models should include a heterogeneous covariance structure. However, the estimation of the (co)variance components is not an easy task, because these parameters can not be factored out from the inverse of the additive genetic covariance matrix. An alternative model, based on the decomposition of the genetic covariance matrix by source of variability, provides a much simpler formulation. In this study, we formalize the equivalence between this alternative model and the one derived from the quantitative genetic theory. Further, we extend the model to include maternal effects and, in order to estimate the (co)variance components, we describe a hierarchical Bayes implementation. Finally, we implement the model to weaning weight data from an Angus x Hereford crossbred experiment. METHODS: Our argument is based on redefining the vectors of breeding values by breed origin such that they do not include individuals with null contributions. Next, we define matrices that retrieve the null-row and the null-column pattern and, by means of appropriate algebraic operations, we demonstrate the equivalence. The extension to include maternal effects and the estimation of the (co)variance components through the hierarchical Bayes analysis are then straightforward. A FORTRAN 90 Gibbs sampler was specifically programmed and executed to estimate the (co)variance components of the Angus x Hereford population. RESULTS: In general, genetic (co)variance components showed marginal posterior densities with a high degree of symmetry, except for the segregation components. Angus and Hereford breeds contributed with 50.26% and 41.73% of the total direct additive variance, and with 23.59% and 59.65% of the total maternal additive variance. In turn, the contribution of the segregation variance was not significant in either case, which suggests that the allelic frequencies in the two parental breeds were similar. CONCLUSION: The multibreed maternal animal model introduced in this study simplifies the problem of estimating (co)variance components in the framework of a hierarchical Bayes analysis. Using this approach, we obtained for the first time estimates of the full set of genetic (co)variance components. It would be interesting to assess the performance of the procedure with field data, especially when interbreed information is limited. PMID- 20540759 TI - Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain. AB - BACKGROUND: The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined. RESULTS: We found a significant reduction of intracortical inhibition in the hemisphere contralateral to the lesioned nerve in the neuralgia patients. Intracortical inhibition in the ipsilateral hemisphere of neuralgia patients and in both hemispheres of osteoarthritis patients did not significantly differ from the control group. Disinhibition was significantly more pronounced in neuralgia patients with moderate/severe pain intensity than in patients with mild pain intensity, whereas the relative compound motor action potential as a parameter of nerve injury severity did not correlate with the amount of disinhibition. CONCLUSIONS: Our results suggest a close relationship between motor cortex inhibition and chronic neuropathic pain in the neuralgia patients, which is independent from nerve injury severity. The lack of cortical disinhibition in patients with painful osteoarthritis points at differences in the pathophysiological processes of different chronic pain conditions with respect to the involvement of different brain circuitry. PMID- 20540760 TI - Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase. AB - BACKGROUND: The unique S28 family of proteases is comprised of the carboxypeptidase PRCP and the aminopeptidase DPP7. The structural basis of the different substrate specificities of the two enzymes is not understood nor has the structure of the S28 fold been described. RESULTS: The experimentally phased 2.8 A crystal structure is presented for human PRCP. PRCP contains an alpha/beta hydrolase domain harboring the catalytic Asp-His-Ser triad and a novel helical structural domain that caps the active site. Structural comparisons with prolylendopeptidase and DPP4 identify the S1 proline binding site of PRCP. A structure-based alignment with the previously undescribed structure of DPP7 illuminates the mechanism of orthogonal substrate specificity of PRCP and DPP7. PRCP has an extended active-site cleft that can accommodate proline substrates with multiple N-terminal residues. In contrast, the substrate binding groove of DPP7 is occluded by a short amino-acid insertion unique to DPP7 that creates a truncated active site selective for dipeptidyl proteolysis of N-terminal substrates. CONCLUSION: The results define the structure of the S28 family of proteases, provide the structural basis of PRCP and DPP7 substrate specificity and enable the rational design of selective PRCP modulators. PMID- 20540761 TI - Intricate environment-modulated genetic networks control isoflavone accumulation in soybean seeds. AB - BACKGROUND: Soybean (Glycine max [L] Merr.) seed isoflavones have long been considered a desirable trait to target in selection programs for their contribution to human health and plant defense systems. However, attempts to modify seed isoflavone contents have not always produced the expected results because their genetic basis is polygenic and complex. Undoubtedly, the extreme variability that seed isoflavones display over environments has obscured our understanding of the genetics involved. RESULTS: In this study, a mapping population of RILs with three replicates was analyzed in four different environments (two locations over two years). We found a total of thirty-five main effect genomic regions and many epistatic interactions controlling genistein, daidzein, glycitein and total isoflavone accumulation in seeds. The use of distinct environments permitted detection of a great number of environment modulated and minor-effect QTL. Our findings suggest that isoflavone seed concentration is controlled by a complex network of multiple minor-effect loci interconnected by a dense epistatic map of interactions. The magnitude and significance of the effects of many of the nodes and connections in the network varied depending on the environmental conditions. In an attempt to unravel the genetic architecture underlying the traits studied, we searched on a genome-wide scale for genomic regions homologous to the most important identified isoflavone biosynthetic genes. We identified putative candidate genes for several of the main-effect and epistatic QTL and for QTL reported by other groups. CONCLUSIONS: To better understand the underlying genetics of isoflavone accumulation, we performed a large scale analysis to identify genomic regions associated with isoflavone concentrations. We not only identified a number of such regions, but also found that they can interact with one another and with the environment to form a complex adaptable network controlling seed isoflavone levels. We also found putative candidate genes in several regions and overall we advanced the knowledge of the genetics underlying isoflavone synthesis. PMID- 20540762 TI - A gene frequency model for QTL mapping using Bayesian inference. AB - BACKGROUND: Information for mapping of quantitative trait loci (QTL) comes from two sources: linkage disequilibrium (non-random association of allele states) and cosegregation (non-random association of allele origin). Information from LD can be captured by modeling conditional means and variances at the QTL given marker information. Similarly, information from cosegregation can be captured by modeling conditional covariances. Here, we consider a Bayesian model based on gene frequency (BGF) where both conditional means and variances are modeled as a function of the conditional gene frequencies at the QTL. The parameters in this model include these gene frequencies, additive effect of the QTL, its location, and the residual variance. Bayesian methodology was used to estimate these parameters. The priors used were: logit-normal for gene frequencies, normal for the additive effect, uniform for location, and inverse chi-square for the residual variance. Computer simulation was used to compare the power to detect and accuracy to map QTL by this method with those from least squares analysis using a regression model (LSR). RESULTS: To simplify the analysis, data from unrelated individuals in a purebred population were simulated, where only LD information contributes to map the QTL. LD was simulated in a chromosomal segment of 1 cM with one QTL by random mating in a population of size 500 for 1000 generations and in a population of size 100 for 50 generations. The comparison was studied under a range of conditions, which included SNP density of 0.1, 0.05 or 0.02 cM, sample size of 500 or 1000, and phenotypic variance explained by QTL of 2 or 5%. Both 1 and 2-SNP models were considered. Power to detect the QTL for the BGF, ranged from 0.4 to 0.99, and close or equal to the power of the regression using least squares (LSR). Precision to map QTL position of BGF, quantified by the mean absolute error, ranged from 0.11 to 0.21 cM for BGF, and was better than the precision of LSR, which ranged from 0.12 to 0.25 cM. CONCLUSIONS: In conclusion given a high SNP density, the gene frequency model can be used to map QTL with considerable accuracy even within a 1 cM region. PMID- 20540763 TI - Progesterone reverses the mesenchymal phenotypes of basal phenotype breast cancer cells via a membrane progesterone receptor mediated pathway. AB - INTRODUCTION: Basal phenotype breast cancers (BPBC) are often associated with apparent epithelial to mesenchymal transition (EMT). The role of progesterone (P4) in regulating EMT of BPBC has not been reported. METHODS: The EMT relevant biology was investigated in vitro using human BPBC cell models (MDA-MB468 and MDA MB231) with P4, PR agonist (RU486), and PR antagonist (R5020) treatments. The essential role of membrane progesterone receptor alpha (mPRalpha) in the P4 regulated EMT was demonstrated by knocking down the endogenous gene and/or stably transfecting exogenous mPRalpha gene in the BPBC cell models. RESULTS: The expression of snail and down-stream EMT proteins such as occludin, fibronectin, and E-cadherin was significantly regulated by P4 incubation, which was accompanied by cell morphological reversion from mesenchymal to epithelial phenotypes. In searching for the cell mediator of P4' action in the MDA-MB468 (MB468) cells, it was found that mPRalpha but not the nuclear PR has an essential role in the P4 mediated EMT inhibition. Knocking down the expression of mPRalpha with specific siRNA blocked the P4's effects on expression of the EMT proteins. In another BPBC cell line--MDA-MB231 (MB231), which is mPRalpha negative by Western blotting--P4 treatment did not alter cell proliferation and EMT protein expressions. Introduction of the exogenous mPRalpha cDNA into these cells caused cell proliferation, but not EMT, to become responsive to P4 treatment. In further studies, it was found that activation of the PI3K/Akt pathway is necessary for the P4-induced EMT reversion. To define the potential inter-mediate steps between mPRalpha and PI3K, we demonstrated that mPRalpha, caveolin-1 (Cav-1), and epidermal growth factor receptor (EGFR) are colocalized in the membrane of caveolar vesicle and the P4-repressed EMT in MB468 cells can be blocked by EGFR inhibitor (AG1478) and PI3K inhibitor (wortmannin). CONCLUSIONS: Our data suggest that the signaling cascade of P4 induced mesenchymal repression is mediated through mPRalpha and other caveolae bound signaling molecules namely Cav-1, EGFR, and PI3K. This novel finding may have great impact on fully understanding the pathogenesis of BPBC and provide an essential clue for developing a targeted therapeutic strategy for treatment of BPBC. PMID- 20540764 TI - An in vivo RNA interference screen identifies gene networks controlling Drosophila melanogaster blood cell homeostasis. AB - BACKGROUND: In metazoans, the hematopoietic system plays a key role both in normal development and in defense of the organism. In Drosophila, the cellular immune response involves three types of blood cells: plasmatocytes, crystal cells and lamellocytes. This last cell type is barely present in healthy larvae, but its production is strongly induced upon wasp parasitization or in mutant contexts affecting larval blood cell homeostasis. Notably, several zygotic mutations leading to melanotic mass (or "tumor") formation in larvae have been associated to the deregulated differentiation of lamellocytes. To gain further insights into the gene regulatory network and the mechanisms controlling larval blood cell homeostasis, we conducted a tissue-specific loss of function screen using hemocyte-specific Gal4 drivers and UAS-dsRNA transgenic lines. RESULTS: By targeting around 10% of the Drosophila genes, this in vivo RNA interference screen allowed us to recover 59 melanotic tumor suppressor genes. In line with previous studies, we show that melanotic tumor formation is associated with the precocious differentiation of stem-cell like blood progenitors in the larval hematopoietic organ (the lymph gland) and the spurious differentiation of lamellocytes. We also find that melanotic tumor formation can be elicited by defects either in the fat body, the embryo-derived hemocytes or the lymph gland. In addition, we provide a definitive confirmation that lymph gland is not the only source of lamellocytes as embryo-derived plasmatocytes can differentiate into lamellocytes either upon wasp infection or upon loss of function of the Friend of GATA cofactor U-shaped. CONCLUSIONS: In this study, we identify 55 genes whose function had not been linked to blood cell development or function before in Drosophila. Moreover our analyses reveal an unanticipated plasticity of embryo-derived plasmatocytes, thereby shedding new light on blood cell lineage relationship, and pinpoint the Friend of GATA transcription cofactor U-shaped as a key regulator of the plasmatocyte to lamellocyte transformation. PMID- 20540766 TI - Cost-effectiveness analysis of clinical specialist outreach as compared to referral system in Ethiopia: an economic evaluation. AB - BACKGROUND: In countries with scarce specialized Human resource for health, patients are usually referred. The other alternative has been mobilizing specialists, clinical specialist outreach. This study examines whether clinical specialist outreach is a cost effective way of using scarce health expertise to provide specialist care as compared to provision of such services through referral system in Ethiopia. METHODS: A cross-sectional study on four purposively selected regional hospitals and three central referral hospitals was conducted from Feb 4-24, 2009. The perspective of analysis was societal covering analytic horizon and time frame from 1 April 2007 to 31 Dec 2008. Data were collected using interview of specialists, project focal persons, patients and review of records. To ensure the propriety standards of evaluation, Ethical clearance was obtained from Jimma University. RESULTS: It was found that 532 patients were operated at outreach hospitals in 125 specialist days. The unit cost of surgical procedures was found to be ETB 4,499.43. On the other hand, if the 125 clinical specialist days were spent to serve patients referred from zonal and regional hospitals at central referral hospitals, 438 patients could have been served. And the unit cost of surgical procedures through referral would have been ETB 6,523.27 per patient. This makes clinical specialist outreach 1.45 times more cost effective way of using scarce clinical specialists' time as compared to referral system. CONCLUSION: Clinical specialist outreach is a cost effective and cost saving way of spending clinical specialists' time as compared to provision of similar services through referral system. PMID- 20540765 TI - Analysis of the vp2 gene sequence of a new mutated mink enteritis parvovirus strain in PR China. AB - BACKGROUND: Mink enteritis virus (MEV) causes a highly contagious viral disease of mink with a worldwide distribution. MEV has a linear, single-stranded, negative-sense DNA with a genome length of approximately 5,000 bp. The VP2 protein is the major structural protein of the parvovirus encoded by the vp2 gene. VP2 is highly antigenic and plays important roles in determining viral host ranges and tissue tropisms. This study describes the bionomics and vp2 gene analysis of a mutated strain, MEV-DL, which was isolated recently in China and outlines its homologous relationships with other selected strains registered in Genbank. RESULTS: The MEV-DL strain can infect F81 cells with cytopathic effects. Pig erythrocytes were agglutinated by the MEV-DL strain. The generation of MEV-DL in F81 cells could infect mink within three months and cause a disease that was similar to that caused by wild-type MEV. A comparative analysis of the vp2 gene nucleotide (nt) sequence of MEV-DL showed that this was more than 99% homologous with other mink enteritis parvoviruses in Genbank. However, the nucleotide residues at positions 1,065 and 1,238 in the MEV-DL strain of the vp2 gene differed from those of all the other MEV strains described previously. It is noteworthy that the mutation at the nucleotide residues position 1,238 led to Asp/Gly replacement. This may lead to structural changes. A phylogenetic tree and sequence distance table were obtained, which showed that the MEV-DL and ZYL-1 strains had the closest inheritance distance. CONCLUSIONS: A new variation of the vp2 gene exists in the MEV-DL strain, which may lead to structural changes of the VP2 protein. Phylogenetic analysis showed that MEV-DL may originate from the ZYL 1 strain in DaLian. PMID- 20540767 TI - Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study. AB - BACKGROUND: Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology. METHODS: Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (> or = 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions. RESULTS: Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination. CONCLUSIONS: Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children. TRIAL REGISTRATION: D9614C00097; ClinicalTrials.gov identifier NCT00228527. PMID- 20540768 TI - Quercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73. AB - BACKGROUND: The alkylating agent dacarbazine (DTIC) has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, deltaNp73. METHODS: DB 1 melanoma (p53 wildtype), and SK Mel 28 (p53 mutant) cell lines were treated with TMZ (400 microM) for 48 hrs followed by Qct (75 microM) for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation. RESULTS: After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of ataxia telangiectasia mutated (ATM) and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of deltaNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of deltaNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of deltaNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis. CONCLUSION: This study demonstrates that Qct can sensitize cells to TMZ and that the mechanisms of sensitization involve modulation of p53 family members. PMID- 20540769 TI - 'Imported risk' or 'health transition'? Smoking prevalence among ethnic German immigrants from the Former Soviet Union by duration of stay in Germany - analysis of microcensus data. AB - BACKGROUND: It can be assumed that resettlers (ethnic German immigrants from the Former Soviet Union) show similar smoking patterns as persons in their countries of origin at the time of migration. We analysed how the smoking prevalence among resettlers differs from that among the general population of Germany and whether the prevalence differs between groups with increasing duration of stay. METHODS: To estimate the smoking prevalence we used the scientific-use-file (n = 477,239) of the German 2005 microcensus, an annual census representing 1% of all German households. Participation in the microcensus is obligatory (unit-nonresponse <7%). We stratified the prevalence of smoking among resettlers and the comparison group (population of Germany without resettlers) by age, sex, educational level and duration of stay. In total, 14,373 (3% of the total) persons were identified as resettlers. RESULTS: Female resettlers with short duration of stay had a significantly lower smoking prevalence than women in the comparison group. With increasing duration of stay their smoking prevalence appears to converge to that of the comparison group (e.g.: high educational level, age group 25-44 years: short duration of stay 15%, long duration of stay 24%, comparison group 28%). In contrast, the smoking prevalence among male resettlers with short duration of stay was significantly higher than that among men in the comparison group, but also with a trend towards converging (e.g.: high educational level, age group 25 44 years: short duration of stay 44%, long duration of stay 35%, comparison group 36%). Except for female resettlers with short duration of stay, the participants with low educational level had on average a higher smoking prevalence than those with a high educational level. CONCLUSIONS: This is the first study estimating the smoking prevalence among resettlers by duration of stay. The results support the hypothesis that resettlers brought different smoking habits from their countries of origin shortly after migration. The observed convergence of the smoking habits with increasing duration of stay is in line with the hypothesis of migration as 'health transition'. However, due to the cross-sectional design of the study, further research is needed to confirm these findings. PMID- 20540770 TI - Identification of three single nucleotide polymorphisms in Anopheles gambiae immune signaling genes that are associated with natural Plasmodium falciparum infection. AB - BACKGROUND: Laboratory studies have demonstrated that a variety of immune signaling pathways regulate malaria parasite infection in Anopheles gambiae, the primary vector species in Africa. METHODS: To begin to understand the importance of these associations under natural conditions, an association mapping approach was adopted to determine whether single nucleotide polymorphisms (SNPs) in selected immune signaling genes in A. gambiae collected in Mali were associated with the phenotype of Plasmodium falciparum infection. RESULTS: Three SNPs were identified in field-collected mosquitoes that were associated with parasite infection in molecular form-dependent patterns: two were detected in the Toll5B gene and one was detected in the gene encoding insulin-like peptide 3 precursor. In addition, one infection-associated Toll5B SNP was in linkage disequilibrium with a SNP in sequence encoding a mitogen-activated protein kinase that has been associated with Toll signaling in mammalian cells. Both Toll5B SNPs showed divergence from Hardy-Weinberg equilibrium, suggesting that selection pressure(s) are acting on these loci. CONCLUSIONS: Seven of these eight infection-associated and linked SNPs alter codon frequency or introduce non-synonymous changes that would be predicted to alter protein structure and, hence, function, suggesting that these SNPs could alter immune signaling and responsiveness to parasite infection. PMID- 20540771 TI - The process of recovery of people with mental illness: the perspectives of patients, family members and care providers: part 1. AB - BACKGROUND: It is a qualitative design study that examines points of divergence and convergence in the perspectives on recovery of 36 participants or 12 triads. Each triad comprising a patient, a family member/friend, a care provider and documents the procedural, analytic of triangulating perspectives as a means of understanding the recovery process which is illustrated by four case studies. Variations are considered as they relate to individual characteristics, type of participant (patient, family, member/friend and care provider), and mental illness. This paper which is part of a larger study and is based on a qualitative research design documents the process of recovery of people with mental illness: Developing a Model of Recovery in Mental Health: A middle range theory. METHODS: Data were collected in field notes through semi-structured interviews based on three interview guides (one for patients, one for family members/friends, and one for caregivers). Cross analysis and triangulation methods were used to analyse the areas of convergence and divergence on the recovery process of all triads. RESULTS: In general, with the 36 participants united in 12 triads, two themes emerge from the cross-analysis process or triangulation of data sources (12 triads analysis in 12 cases studies). Two themes emerge from the analysis process of the content of 36 interviews with participants: (1) Revealing dynamic context, situating patients in their dynamic context; and (2) Relationship issues in a recovery process, furthering our understanding of such issues. We provide four case studies examples (among 12 cases studies) to illustrate the variations in the way recovery is perceived, interpreted and expressed in relation to the different contexts of interaction. CONCLUSION: The perspectives of the three participants (patients, family members/friends and care providers) suggest that recovery depends on constructing meaning around mental illness experiences and that the process is based on each person's dynamic context (e.g., social network, relationship), life experiences and other social determinants (e.g., symptoms, environment). The findings of this study add to existing knowledge about the determinants of the recovery of persons suffering with a mental illness and significant other utilizing public mental health services in Montreal, Canada. PMID- 20540772 TI - A surveillance sector review applied to infectious diseases at a country level. AB - BACKGROUND: The new International Health Regulations (IHR) require World Health Organization (WHO) member states to assess their core capacity for surveillance. Such reviews also have the potential to identify important surveillance gaps, improve the organisation of disparate surveillance systems and to focus attention on upstream hazards, determinants and interventions. METHODS: We developed a surveillance sector review method for evaluating all of the surveillance systems and related activities across a sector, in this case those concerned with infectious diseases in New Zealand. The first stage was a systematic description of these surveillance systems using a newly developed framework and classification system. Key informant interviews were conducted to validate the available information on the systems identified. RESULTS: We identified 91 surveillance systems and related activities in the 12 coherent categories of infectious diseases examined. The majority (n = 40 or 44%) of these were disease surveillance systems. They covered all categories, particularly for more severe outcomes including those resulting in death or hospitalisations. Except for some notifiable diseases and influenza, surveillance of less severe, but important infectious diseases occurring in the community was largely absent. There were 31 systems (34%) for surveillance of upstream infectious disease hazards, including risk and protective factors. This area tended to have many potential gaps and lack integration, partly because such systems were operated by a range of different agencies, often outside the health sector. There were fewer surveillance systems for determinants, including population size and characteristics (n = 9), and interventions (n = 11). CONCLUSIONS: It was possible to create and populate a workable framework for describing all the infectious diseases surveillance systems and related activities in a single developed country and to identify potential surveillance sector gaps. This is the first stage in a review process that will lead to identification of priorities for surveillance sector development. PMID- 20540773 TI - The 341C/T polymorphism in the GSTP1 gene is associated with increased risk of oesophageal cancer. AB - BACKGROUND: The Glutathione S-transferases (GSTs) comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study the effects of polymorphisms in these genes on the risk of developing oesophageal squamous cell carcinoma (OSCC) were evaluated in a hospital-based case-control study in two South African population groups. Genetic polymorphisms in GSTs were investigated in 245 patients and 288 controls samples by PCR-RFLP analysis. RESULTS: The GSTP1 341T variant was associated with significantly increased risk of developing OSCC as observed from the odds ratios for the GSTP1 341C/T and GSTP1 341T/T genotypes (OR = 4.98; 95%CI 3.05-8.11 and OR = 10.9; 95%CI 2.43 49.1, respectively) when compared to the homozygous GSTP1 341C/C genotype. The risk for OSCC in the combined GSTP1 341C/T and T/T genotypes was higher in tobacco smokers (OR = 7.51, 95% CI 3.82-14.7), alcohol consumers (OR = 15.3, 95% CI 1.81-12.9) and those using wood or charcoal for cooking and heating (OR = 12.1, 95% CI 3.26-49) when compared to those who did not smoke tobacco, or did not consume alcohol or user other forms of fuel for cooking and heating. Despite the close proximity of the two GSTP1 SNPs (313A>G and 341C>T), they were not in linkage disequilibrium in these two population groups (D':1.0, LOD: 0.52, r2: 0.225). The GSTP1 313A/G polymorphism on the other hand, did not display any association with OSSC. The homozygous GSTT1*0 genotype was associated with increased risk of OSCC (OR = 1.71, 95%CI 1.18-2.46) while the homozygous GSTM1*0 genotype was associated with significantly decreased risk of OSCC in the Mixed Ancestry subjects (OR= 0.39, 95%CI 0.25-0.62). CONCLUSIONS: This study shows that the risk of developing OSCC in the South African population can be partly explained by genetic polymorphisms in GST coding genes and their interaction with environmental factors such as tobacco smoke and alcohol consumption. PMID- 20540774 TI - Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue specific requirement for Dicer1 in adrenal, testis, and ovary. AB - BACKGROUND: The synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking Dicer1 die in early embryogenesis. In this study, we investigated whether Dicer1 is required for development of adrenal, testis, and ovary in mouse embryos. RESULTS: To target Dicer1 deletion specifically in developing adrenals and gonads, we used Steroidogenic factor 1-cre (Sf1/Cre) line in which Cre recombinase is active in the progenitor cells of adrenals and gonads. Lack of Dicer1 in the SF1-positive cells did not affect formation and early differentiation of the adrenals and gonads. However, increasing numbers of apoptotic cells were first detected in the Dicer1 knockout adrenal cortex at 18.5 days post coitum (dpc), followed by apoptosis of somatic cells and germ cells in the testis at postnatal day 0. Affected adrenal and testes underwent complete degeneration 48 hrs after the onset of apoptosis. However, ovaries were not affected at least until postnatal day 5, when the animals died due to adrenal insufficiency. CONCLUSIONS: Dicer1 is dispensable for formation and differentiation of fetal tissues derived from the SF1-positive adrenogonadal primordium. Dicer1 is essential for maintaining cell survival in adrenal and testis; however, development of the ovary from fetal stages to postnatal day 5 does not require the presence of Dicer1. Our results reveal a tissue-specific requirement of Dicer1 and microRNAs. Future research is needed to understand how the tissue-specific role of Dicer1 is established. PMID- 20540775 TI - Healthcare professionals' intentions to use wiki-based reminders to promote best practices in trauma care: a survey protocol. AB - BACKGROUND: Healthcare professionals are increasingly using wikis as collaborative tools to create, synthesize, share, and disseminate knowledge in healthcare. Because wikis depend on collaborators to keep content up-to-date, healthcare professionals who use wikis must adopt behaviors that foster this collaboration. This protocol describes the methods we will use to develop and test the metrological qualities of a questionnaire that will assess healthcare professionals' intentions and the determinants of those intentions to use wiki based reminders that promote best practices in trauma care. METHODS: Using the Theory of Planned Behavior, we will conduct semi-structured interviews of healthcare professionals to identify salient beliefs that may affect their future use of wikis. These beliefs will inform our questionnaire on intended behavior. A test-retest of the survey will verify the questionnaire's stability over time. We will interview 50 healthcare professionals (25 physicians and 25 allied health professionals) working in the emergency departments of three trauma centers in Quebec, Canada. We will analyze the content of the interviews and construct and pilot a questionnaire. We will then test the revised questionnaire with 30 healthcare professionals (15 physicians and 15 allied health professionals) and retest it two weeks later. We will assess the internal consistency of the questionnaire constructs using Cronbach's alpha coefficients and determine their stability with the intra-class correlation (ICC). DISCUSSION: To our knowledge, this study will be the first to develop and test a theory-based survey that measures healthcare professionals' intentions to use a wiki-based intervention. This study will identify professionals' salient beliefs qualitatively and will quantify the psychometric capacities of the questionnaire based on those beliefs. PMID- 20540776 TI - Adenoviral oncoprotein E1B55K mediates colocalization of SSBP2 and PML in response to stress. AB - Transient expression of adenoviral oncoprotein E1B55K in normal cells induces aggresome formation and sequestration of critical host proteins in aggresomes. Our previous studies reported that Sequence Specific Binding Protein 2 (SSBP2), a candidate tumor suppressor is recruited to aggresomes in adenovirally transformed human embryonal kidney 293 (HEK293) cells. To understand the extent and significance of the E1B55K-SSBP2 interactions in these cells, we have examined SSBP2 localization under conditions of stress in HEK293 cells. SSBP2 localizes to PML- Nuclear Bodies (PML-NBs) in response to inhibition of nuclear export, treatment with etoposide, hydroxyurea or gamma irradiation only in HEK293 cells. Furthermore, the PML-NBs grow in size and number in response to radiation over a 24 hour period in HEK293 cells analogous to previous findings for other cell types. Nonetheless, we conclude that E1B55K subverts SSBP2 function in HEK293 cells. These findings demonstrate the limitations in using HEK293 cells to study DNA damage response and other cellular processes since SSBP2 and similar regulatory proteins are aberrantly localized due to constitutive E1B55K expression. PMID- 20540777 TI - Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients. AB - BACKGROUND: We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood. The aim of the present study was to investigate their numbers and function within induced sputum. METHODS: Induced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD56+ cells (NK and NKT-like cells) were used in an LDH release assay to determine cytotoxicity. RESULTS: The proportion of NK cells and NKT-like cells in smokers with COPD (COPD subjects) was significantly higher (12.7% and 3%, respectively) than in healthy smokers (smokers) (5.7%, p < 0.01; 1%, p < 0.001) and non-smoking healthy subjects (HNS) (4.2%, p < 0.001; 0.8%, p < 0.01). The proportions of NK cells and NKT-like cells expressing both perforin and granzyme B were also significantly higher in COPD subjects compared to smokers and HNS. CD56+ cells from COPD subjects were significantly more cytotoxic (1414 biological lytic activity) than those from smokers (142.5; p < 0.01) and HNS (3.8; p < 0.001) and were inversely correlated to FEV1. (r = -0.75; p = 0.0098). CONCLUSION: We have shown an increased proportion of NK and NKT-like cells in the induced sputum of COPD subjects and have demonstrated that these cells are significantly more cytotoxic in COPD subjects than smokers and HNS. PMID- 20540778 TI - Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5). AB - BACKGROUND: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. METHODS: Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. RESULTS: In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable = 4,451) and every 6 weeks (number evaluable = 52,683) respectively. CONCLUSIONS: Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00090233. PMID- 20540779 TI - Introducing W.A.T.E.R.S.: a workflow for the alignment, taxonomy, and ecology of ribosomal sequences. AB - BACKGROUND: For more than two decades microbiologists have used a highly conserved microbial gene as a phylogenetic marker for bacteria and archaea. The small-subunit ribosomal RNA gene, also known as 16 S rRNA, is encoded by ribosomal DNA, 16 S rDNA, and has provided a powerful comparative tool to microbial ecologists. Over time, the microbial ecology field has matured from small-scale studies in a select number of environments to massive collections of sequence data that are paired with dozens of corresponding collection variables. As the complexity of data and tool sets have grown, the need for flexible automation and maintenance of the core processes of 16 S rDNA sequence analysis has increased correspondingly. RESULTS: We present WATERS, an integrated approach for 16 S rDNA analysis that bundles a suite of publicly available 16 S rDNA analysis software tools into a single software package. The "toolkit" includes sequence alignment, chimera removal, OTU determination, taxonomy assignment, phylogentic tree construction as well as a host of ecological analysis and visualization tools. WATERS employs a flexible, collection-oriented 'workflow' approach using the open-source Kepler system as a platform. CONCLUSIONS: By packaging available software tools into a single automated workflow, WATERS simplifies 16 S rDNA analyses, especially for those without specialized bioinformatics, programming expertise. In addition, WATERS, like some of the newer comprehensive rRNA analysis tools, allows researchers to minimize the time dedicated to carrying out tedious informatics steps and to focus their attention instead on the biological interpretation of the results. One advantage of WATERS over other comprehensive tools is that the use of the Kepler workflow system facilitates result interpretation and reproducibility via a data provenance sub system. Furthermore, new "actors" can be added to the workflow as desired and we see WATERS as an initial seed for a sizeable and growing repository of interoperable, easy-to-combine tools for asking increasingly complex microbial ecology questions. PMID- 20540780 TI - Chitosan can stop or postpone the death of the suckling mice challenged with foot and-mouth disease virus. AB - In the study, a method called "hardening in liquid phase" for preparing chitosan granules with glutaraldehyde as crosslinker and Tween 80 as surfactant and paraffin liquid as dispersant was established. The chitosan granules were light yellow and insoluble in water or oil, but they swelled in acid solution and narrowed in neutral or alkaline solution. Furthermore, some of characteristics of the chitosan granules were revealed. (a) Stability: Their shapes were stable at pH 7.0 and pH 8.0 and -30 degrees C-120 degrees C. The shelf life is at least one year in vitro at room temperature. (b) SAFETY: Some experiments of their lethal effect to suckling mice and pathogenicity to mature mice proved the chitosan granules were harmless. (c) Antiviral activity: Some suckling mice injected with chitosan granules were still alive or delayed death compared with control group when they challenged with foot-and-mouth disease virus (FMDV). Such anti-FMDV capacity could maintain 1 week and was the strongest on the third day. PMID- 20540781 TI - Laser microdissection of conifer stem tissues: isolation and analysis of high quality RNA, terpene synthase enzyme activity and terpenoid metabolites from resin ducts and cambial zone tissue of white spruce (Picea glauca). AB - BACKGROUND: Laser microdissection (LMD) has been established for isolation of individual tissue types from herbaceous plants. However, there are few reports of cell- and tissue-specific analysis in woody perennials. While microdissected tissues are commonly analyzed for gene expression, reports of protein, enzyme activity and metabolite analysis are limited due in part to an inability to amplify these molecules. Conifer stem tissues are organized in regular patterns with xylem, phloem and cortex development controlled by the activity of the cambial zone (CZ). Defense responses of conifer stems against insects and pathogens involve increased accumulation of terpenoids in cortical resin ducts (CRDs) and de novo formation of traumatic resin ducts from CZ initials. These tissues are difficult to isolate for tissue-specific molecular and biochemical characterization and are thus good targets for application of LMD. RESULTS: We describe robust methods for isolation of individual tissue-types from white spruce (Picea glauca) stems for analysis of RNA, enzyme activity and metabolites. A tangential cryosectioning approach was important for obtaining large quantities of CRD and CZ tissues using LMD. We report differential expression of genes involved in terpenoid metabolism between CRD and CZ tissues and in response to methyl jasmonate (MeJA). Transcript levels of beta-pinene synthase and levopimaradiene/abietadiene synthase were constitutively higher in CRDs, but induction was stronger in CZ in response to MeJA. 3-Carene synthase was more strongly induced in CRDs compared to CZ. A differential induction pattern was observed for 1-deoxyxyulose-5-phosphate synthase, which was up-regulated in CRDs and down-regulated in CZ. We identified terpene synthase enzyme activity in CZ protein extracts and terpenoid metabolites in both CRD and CZ tissues. CONCLUSIONS: Methods are described that allow for analysis of RNA, enzyme activity and terpenoid metabolites in individual tissues isolated by LMD from woody conifer stems. Patterns of gene expression are demonstrated in specific tissues that may be masked in analysis of heterogeneous samples. Combined analysis of transcripts, proteins and metabolites of individual tissues will facilitate future characterization of complex processes of woody plant development, including periodic stem growth and dormancy, cell specialization, and defense and may be applied widely to other plant species. PMID- 20540782 TI - GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons. AB - BACKGROUND: Gangliosides, sialic acid-containing glycosphingolipids exist in mammalian cell membranes particularly neuronal membranes. The trisialoganglioside (GT1b) is one of the major brain gangliosides and acts as an endogenous regulator in the brain. We previously showed GT1b induces mesencephalic dopaminergic (DA) neuronal death, both in vivo and in vitro. We further investigate the underlying mechanisms of GT1b neurotoxicity. RESULTS: Consistent with earlier findings, GT1b attenuated the DA neuron number and dopamine uptake level in mesencephalic cultures. Morphological evidence revealed GT1b-induced chromatin condensation and nuclear fragmentation as well as an increased number of TUNEL-positive cells, compared to control cultures. Interestingly, while GT1b enhanced caspase-3 activity, DEVD, a caspase-3 inhibitor, failed to rescue DA neuronal death. Immunoblot analysis revealed that GT1b inactivates Akt through dephosphorylation at both Ser473 and Thr308, subsequent dephosphorylation of GSK-3beta, a substrate of Akt, and hyperphosphorylation of tau, downstream of GSK-3beta. Moreover, a GSK 3beta specific inhibitor, L803-mt, attenuated tau phosphorylation and rescued DA neurons from cell death in mesencephalic cultures. CONCLUSION: Our data provide novel evidence that a Akt/GSK-3beta/tau-dependent, but not caspase-3 signaling pathway plays a pivotal role in GT1b-mediated neurotoxic actions on mesencephalic DA neurons. PMID- 20540783 TI - Commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4. AB - BACKGROUND: Major burn is associated with decreased gut barrier function and increased bacterial translocation (BT). This study is to investigate whether commensal microflora induce host defense and decrease BT in burn mice. METHODS: First, we treated Wild type (WT) mice with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in gut. The intestinal permeability, glutathione level, NF-kappaB DNA-binding activity, TLR4 expression of intestinal mucosa, BT to mesenteric lymph nodes (MLNs), and bacterial killing activity of peritoneal cells were measured after thermal injury. Second, lung of animals were harvested for MPO activity and TNFalpha mRNA expression assay. Third, WT animals were treated with oral antibiotics with or without LPS supplement after burn. At 48 hr after burn, TLR4 expression of intestinal mucosa and bacterial killing activity of cells were examined. Finally, bacterial killing activity and BT to MLNs after thermal injury in C3H/HeJ (TLR4 mutant) mice were measured. RESULTS: Burn induced BT to MLNs in WT mice. Commensal depletion decreased TLR4 expression as well as NF-kappaB activation of intestine, myeloperoxidase (MPO) activity as well as TNFalpha expression of lung, and bacterial killing activity of peritoneal cells. Oral LPS supplement markedly reduced 81% of burn-induced BT and increased TLR4 expression, MPO activity of lung, as well as bacterial killing activity of peritoneal cells. LPS supplement did not change BT or bacterial killing activity in C3H/HeJ mice. CONCLUSIONS: Collectively, commensal microflora induce TLR4 expression of intestine and bacterial killing activity of inflammatory cells in burn. TLR4 ligand increases bacterial killing activity and decreases burn-induced BT. Taken together with the abolition of LPS effect in TLR4 mutant mice, we conclude that commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4. PMID- 20540784 TI - The Thai version of the PSS-10: An Investigation of its psychometric properties. AB - BACKGROUND: Among the stress instruments that measure the degree to which life events are perceived as stressful, the Perceived Stress Scale (PSS) is widely used. The goal of this study was to examine the psychometric properties of a Thai version of the PSS-10 (T-PSS-10) with a clinical and non-clinical sample. Internal consistency, test-retest reliability, concurrent validity, and the factorial structure of the scale were tested. METHODS: A total sample of 479 adult participants was recruited for the study: 368 medical students and 111 patients from two hospitals in Northern Thailand. The T-PSS-10 was used along with the Thai version of State Trait Anxiety Inventory (STAI), the Thai Version of the Rosenberg Self-Esteem Scale (RSES), and the Thai Depression Inventory (TDI). RESULTS: Exploratory Factor Analysis (EFA) yielded 2 factors with eigenvalues of 5.05 and 1.60, accounting for 66 percent of variance. Factor 1 consisted of 6 items representing "stress"; whereas Factor 2 consisted of 4 items representing "control". The item loadings ranged from 0.547 to 0.881. Investigation of the fit indices associated with Maximum Likelihood (ML) estimation revealed that the two-factor solution was adequate [chi2 = 35.035 (df = 26, N = 368, p < 0.111)]; Goodness-of-Fit Index (GFI) = 0.981; Root Mean Square Residual (RMR) = 0.022; Standardized Root Mean square Residual (SRMR) = 0.037, Comparative Fit Index (CFI) = 0.989; Normed Fit Index (NFI) = 0.96, Non-Normed Fit Index (NNFI) = 0.981, Root Mean Square Error of Approximation (RMSEA) = 0.031. It was found that the T-PSS-10 had a significant positive correlation with the STAI (r = 0.60, p < 0.0001), and the TDI (r = 0.55, p < 0.0001); and was significantly negatively correlated with the RSES (r = -0.46, p < 0.0001, N = 368). The overall Cronbach's alpha was 0.85. The ICC was 0.82 (95% CI, 0.72 and 0.88) at 4 week-retest reliability. CONCLUSIONS: The Thai version of the PSS-10 demonstrated excellent goodness-of-fit for the two factor solution model, as well as good reliability and validity for estimating the level of stress perception with a Thai population. Limitations of the study are discussed. PMID- 20540785 TI - Compliance with herpes zoster vaccination in young and adult individuals in two regions of Italy. AB - BACKGROUND: The purpose of this work was to explore the knowledge and acceptance of Varicella Zoster Virus (VZV)-Herpes Zoster (HZ) vaccination in the general Italian population, where the HZ vaccine has not yet been distributed, using a prevalence study of subjects from two regions in Italy. METHODS: A group of 3,173 individuals were interviewed using a questionnaire. The youngest age group (or= 41 years) were interviewed by general practitioners in their office. RESULTS: In both regions, the majority of subjects had been infected with varicella, and only 165 (5.2%) subjects reported receiving the VZV vaccination. Regarding HZ, 2,749 (86.6%) individuals stated that they knew of the virus and 2,233 (70%) were willing to be vaccinated against HZ. The majority of people willing to be vaccinated were in the middle and older age groups (36.6% and 44.7%, respectively). CONCLUSION: Compliance versus vaccination results were satisfactory and probably, with the upcoming availability of the HZ vaccine in Italy, adults will be favourably disposed towards vaccination. PMID- 20540787 TI - Preferences for benefit packages for community-based health insurance: an exploratory study in Nigeria. AB - BACKGROUND: It is important that community-based health insurance (CBHI) schemes are designed in such a way as to ensure the relevance of the benefit packages to potential clients. Hence, this paper provides an understanding of the preferred benefit packages by different economic status groups as well as urban and rural dwellers for CBHI in Southeast Nigeria. METHODS: The study took place in rural, urban and semi-urban communities of south-east Nigeria. A questionnaire was used to collect information from 3070 randomly picked household heads. Focus group discussions were used to collect qualitative data. Data was examined for links between preferences for benefit packages with SES and geographic residence of the respondents. RESULTS: Respondents in the rural areas and in the lower SES preferred a comprehensive benefit package which includes all inpatient, outpatient and emergencies services, while those in urban areas as well as those in the higher SES group showed a preference for benefit packages which will cover only basic disease control interventions. CONCLUSION: Equity concerns in preferences for services to be offered by the CBHI scheme should be addressed for CBHI to succeed in different contexts. PMID- 20540786 TI - The association of 18F-deoxyglucose (FDG) uptake of PET with polymorphisms in the glucose transporter gene (SLC2A1) and hypoxia-related genes (HIF1A, VEGFA, APEX1) in non-small cell lung cancer. SLC2A1 polymorphisms and FDG-PET in NSCLC patients. AB - BACKGROUND: Positron emission tomography imaging of lung cancers with 2-[fluorine 18]-fluoro-2-deoxy-D-glucose is a non-invasive diagnostic, and prognostic tool that measures tumor metabolism. We have analyzed the effect of solute carrier family 2 (facilitated glucose transporter), member 1 polymorphisms on 2-[fluorine 18]-fluoro-2-deoxy-D-glucose-uptake with a combination of polymorphisms of hypoxia-inducible factor 1 alpha, apurinic/apyimidinic endonuclease, and vascular endothelial growth factor A in a hypoxia-related pathway. METHODS: We investigated the association between solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T, hypoxia-inducible factor 1 alpha Pro582Ser, Ala588Thr, apurinic/apyimidinic endonuclease Asp148Glu, or vascular endothelial growth factor A +936C>T and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake among 154 patients with non-small-cell lung cancer. RESULTS: The solute carrier family 2 (facilitated glucose transporter), member 1 -2841A>T polymorphism was significantly associated with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-uptake in combination with the apurinic/apyimidinic endonuclease Asp148Glu (T>G) polymorphism in the squamous cell type of non-small-cell lung cancer. The solute carrier family 2 (facilitated glucose transporter), member 1 TT genotype had a higher maximum standardized uptake values than the AA + AT genotype when the apurinic/apyimidinic endonuclease genotype was TT (mean maximum standardized uptake values, 12.47 +/- 1.33 versus 8.46 +/- 2.90, respectively; P = 0.028). The mean maximum standardized uptake values were not statistically different with respect to vascular endothelial growth factor A and hypoxia-inducible factor 1 alpha polymorphisms. CONCLUSION: A glucose transporter gene polymorphism was shown to be statistically associated with glucose-uptake when the apurinic/apyimidinic endonuclease genotype is TT in patients with the squamous cell type of non-small-cell lung cancer. Our findings suggest that a newly developed tracer for positron emission tomography could be affected by genetic polymorphisms. PMID- 20540788 TI - Pearsonema (syn Capillaria) plica associated cystitis in a Fennoscandian arctic fox (Vulpes lagopus: a case report. AB - The bladderworm Pearsonema (syn Capillaria) plica affects domestic dogs and wild carnivores worldwide. A high prevalence in red foxes (Vulpes vulpes) has been reported in many European countries. P. plica inhabits the lower urinary tract and is considered to be of low pathogenic significance in dogs mostly causing asymptomatic infections. However, a higher level of pathogenicity has been reported in foxes. A severe cystitis associated with numerous bladderworms was found in a captive arctic fox (Vulpes lagopus) originating from the endangered Fennoscandian arctic fox population. To our knowledge this is the first description of P. plica infection in an arctic fox. PMID- 20540789 TI - Combined effects of IL-8 and CXCR2 gene polymorphisms on breast cancer susceptibility and aggressiveness. AB - BACKGROUND: Interleukin-8 (IL-8/CXCL-8) is a prototype of the ELR+CXC chemokines that play an important role in the promotion and progression of many human cancers including breast cancer. We have recently showed the implication of polymorphism (-251) T/A of IL-8 gene in the susceptibility and prognosis of breast carcinoma. IL-8 acts through its CXCR1 and CXCR2 receptors. CXCR2, expressed on the endothelial cells, is the receptor involved in mediating the angiogenic effects of ELR+CXC chemokines and in particular IL-8.In the current study, we investigated the susceptibility and prognostic implications of the genetic variation in CXCR2 in breast carcinoma. We also confirmed the implication of IL-8 (-251) T/A polymorphism in a larger cohort. Finally, we combined the IL-8 and CXCR2 variant alleles and analyzed their effects in breast cancer risk and prognosis. METHODS: We used the allele-specific polymerase chain reaction to characterize the variation of IL-8 and CXCR2 for 409 unrelated Tunisian patients with breast carcinoma and 301 healthy control subjects. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for breast cancer. Associations of the genetic marker with the rates of breast carcinoma-specific overall survival and disease-free survival were assessed using univariate and multivariate analyses. RESULTS: A highly significant association was found between the homozygous CXCR2 (+ 1208) TT genotype (adjusted OR = 2.89; P = 0.008) and breast carcinoma. A significantly increased risk of breast carcinoma was associated with IL-8 (-251) A allele (adjusted OR = 1.86; P = 0.001). The presence of two higher risk genotypes (the TA and TT in IL-8, and the TT in CXCR2) significantly increased the risk of developing breast carcinoma (adjusted OR = 4.15; P = 0.0004).The CXCR2 (+ 1208) T allele manifested a significant association with an aggressive phenotype of breast carcinoma as defined by a large tumor size, a high histological grade, and auxiliary's lymph node metastasis. A significant association between the IL-8 (-251) A allele and the aggressive form of breast carcinoma was also found.Moreover, the presence of the IL-8 (-251) A and/or the CXCR2 (+ 1208) T allele showed a significant association with a decreased overall survival and disease-free survival in breast carcinoma patients. CONCLUSION: Our results indicated that the polymorphisms in IL-8 and CXCR2 genes are associated with increased breast cancer risk, as well as disease progress, supporting our hypothesis for IL-8 and ELR+CXC chemokine receptor (CXCR2) involvement in breast cancer pathogenesis. PMID- 20540790 TI - A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a. AB - BACKGROUND: Shigella flexneri is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of S. flexneri have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence related proteins of S. flexneri, we performed differential in-gel electrophoresis (DIGE) analysis to measure changes in the expression profile that are induced by a temperature increase. RESULTS: The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains. CONCLUSION: Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA. PMID- 20540791 TI - Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross species comparative analysis coupled with copy number alterations (CNA) of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species. RESULTS: We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF beta signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation. CONCLUSIONS: The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC. PMID- 20540792 TI - Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads. AB - In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification. PMID- 20540793 TI - Inequities in utilization of maternal health interventions in Namibia: implications for progress towards MDG 5 targets. AB - BACKGROUND: Inequities in the utilization of maternal health services impede progress towards the MDG 5 target of reducing the maternal mortality ratio by three quarters, between 1990 and 2015. In Namibia, despite increasing investments in the health sector, the maternal mortality ratio has increased from 271 per 100,000 live births in the period 1991-2000 to 449 per 100,000 live births in 1998-2007. Monitoring equity in the use of maternal health services is important to target scarce resources to those with more need and expedite the progress towards the MDG 5 target. The objective of this study is to measure socio economic inequalities in access to maternal health services and propose recommendations relevant for policy and planning. METHODS: Data from the Namibia Demographic and Health Survey 2006-07 are analyzed for inequities in the utilization of maternal health. In measuring the inequities, rate-ratios, concentration curves and concentration indices are used. RESULTS: Regions with relatively high human development index have the highest rates of delivery by skilled health service providers. The rate of caesarean section in women with post secondary education is about seven times that of women with no education. Women in urban areas are delivered by skilled providers 30% more than their rural counterparts. The rich use the public health facilities 30% more than the poor for child delivery. CONCLUSION: Most of the indicators such as delivery by trained health providers, delivery by caesarean section and postnatal care show inequities favoring the most educated, urban areas, regions with high human development indices and the wealthy. In the presence of inequities, it is difficult to achieve a significant reduction in the maternal mortality ratio needed to realize the MDG 5 targets so long as a large segment of society has inadequate access to essential maternal health services and other basic social services. Addressing inequities in access to maternal health services should not only be seen as a health systems issue. The social determinants of health have to be tackled through multi-sectoral approaches in line with the principles of Primary Health Care and the recommendations of the Commission on Social Determinants of Health. PMID- 20540794 TI - Gender-related power differences, beliefs and reactions towards people living with HIV/AIDS: an urban study in Nigeria. AB - BACKGROUND: Although there are an increasing number of studies on HIV-related stigma in Nigeria, very little research has focused on how power differences based on gender perpetuate the stigmatization of people living with HIV/AIDS (PLWHA) and how these gender differences affect the care that PLWHA receive in health care institutions. We explore gender-related beliefs and reactions of society, including health care professionals (HCPs), with regard to PLWHA, using Connell's theoretical framework of gender and power (1987). With Connell's structural theory of gender and power (financial inequality, authority and structure of social norms), we can describe gender differences in stigmatization of PLWHA. METHOD: We conducted in-depth semi-structured interviews, lasting 60 to 90 minutes, with 100 persons (40 members of the general public, 40 HCPs and 20 PLWHA) in Port Harcourt, Nigeria. The interviews were tape-recorded and transcribed verbatim. The Nvivo 7 computer package was used to analyze the data. RESULTS: There are similarities and differences between the general public and HCPs towards PLWHA in gender-related beliefs and reactions. For instance, although association with promiscuity and power differences were commonly acknowledged in the different groups, there are differences in how these reactions are shown; such as HCPs asking the female PLWHA to inform their partners to ensure payment of hospital bills. Women with HIV/AIDS in particular are therefore in a disadvantaged position with regard to the care they receive. CONCLUSION: Despite the fact that men and women with HIV/AIDS suffer the same illness, clear disparities are apparent in the negative reaction women and men living with HIV/AIDS experience in society. We show that women's generally low status in society contributes to the extreme negative reactions to which female PLWHA are subject. The government should create policies aimed at reducing the power differences in family, society and health care systems, which would be important to decrease the gender-related differences in stigma experienced by PLWHA. Interventions should be directed at the prevailing societal norms through appropriate legislation and advocacy at grassroots level with the support of men to counter laws that put women in a disadvantaged position. Furthermore, development of a policy that encourages equality in access to health care for all patients with HIV/AIDS by applying the same conditions to both men and women in health care institutions is recommended. There is a need to protect women's rights through implementing support policies, including paying attention to gender in the training of HCPs. PMID- 20540795 TI - Is there an association between PEPFAR funding and improvement in national health indicators in Africa? A retrospective study. AB - BACKGROUND: The US President's Emergency Plan for AIDS Relief (PEPFAR) was reauthorized in June 2008 with a three-fold increase in funds, and a broader, more explicit mandate to improve health in the low- and middle-income countries that it funded. However, the ability of a disease-specific, or vertical, programme to have a spill-over effect and improve health outcomes has been questioned. In this study, we sought to examine associations between being designated as a PEPFAR focus country (and receiving increased PEPFAR funding) and non-HIV-specific health outcomes in the World Health Organization (WHO) Africa Region, the area most affected by the HIV/AIDS epidemic. METHODS: A retrospective analysis of publicly available health outcomes data published by the World Health Organization was performed for all countries in the WHO Africa Region. Fractional changes in health indicators between 2000 and 2006 were calculated, and PEPFAR focus and non-focus countries were then compared. RESULTS: Overall, countries in the WHO Africa Region showed a small worsening in health outcomes status when all indicators were analyzed together and weighted equally. However, more health indicators improved than worsened over this six-year period. A comparison of PEPFAR focus and non-focus countries found no significant difference in the fractional change among 13 of 14 health indicators during the study period. CONCLUSIONS: This study suggests that vertical programmes, even one that is the scale of PEPFAR, may have little or no impact on health outcomes not explicitly targeted. PMID- 20540796 TI - Population genetic structure of the malaria vector Anopheles nili in sub-Saharan Africa. AB - BACKGROUND: Anopheles nili is a widespread efficient vector of human malaria parasites in the humid savannas and forested areas of sub-Saharan Africa. Understanding An. nili population structure and gene flow patterns could be useful for the development of locally-adapted vector control measures. METHODS: Polymorphism at eleven recently developed microsatelitte markers, and sequence variation in four genes within the 28s rDNA subunit (ITS2 and D3) and mtDNA (COII and ND4) were assessed to explore the level of genetic variability and differentiation among nine populations of An. nili from Senegal, Ivory Coast, Burkina Faso, Nigeria, Cameroon and the Democratic Republic of Congo (DRC). RESULTS: All microsatellite loci successfully amplified in all populations, showing high and very similar levels of genetic diversity in populations from West Africa and Cameroon (mean Rs = 8.10-8.88, mean He = 0.805-0.849) and much lower diversity in the Kenge population from DRC (mean Rs = 5.43, mean He = 0.594). Bayesian clustering analysis of microsatellite allelic frequencies revealed two main genetic clusters in the dataset. The first one included only the Kenge population and the second grouped together all other populations. High Fst estimates based on microsatellites (Fst > 0.118, P < 0.001) were observed in all comparisons between Kenge and all other populations. By contrast, low Fst estimates (Fst < 0.022, P < 0.05) were observed between populations within the second cluster. The correlation between genetic and geographic distances was weak and possibly obscured by demographic instability. Sequence variation in mtDNA genes matched these results, whereas low polymorphism in rDNA genes prevented detection of any population substructure at this geographical scale. CONCLUSION: Overall, high genetic homogeneity of the An. nili gene pool was found across its distribution range in West and Central Africa, although demographic events probably resulted in a higher level of genetic isolation in the marginal population of Kenge (DRC). The role of the equatorial forest block as a barrier to gene flow and the implication of such findings for vector control are discussed. PMID- 20540797 TI - Do measures matter? Comparing surface-density-derived and census-tract-derived measures of racial residential segregation. AB - BACKGROUND: Racial residential segregation is hypothesized to affect population health by systematically patterning health-relevant exposures and opportunities according to individuals' race or income. Growing interest into the association between residential segregation and health disparities demands more rigorous appraisal of commonly used measures of segregation. Most current studies rely on census tracts as approximations of the local residential environment when calculating segregation indices of either neighborhoods or metropolitan areas. Because census tracts are arbitrary in size and shape, reliance on this geographic scale limits understanding of place-health associations. More flexible, explicitly spatial derivations of traditional segregation indices have been proposed but have not been compared with tract-derived measures in the context of health disparities studies common to social epidemiology, health demography, or medical geography. We compared segregation measured with tract derived as well as GIS surface-density-derived indices. Measures were compared by region and population size, and segregation measures were linked to birth record to estimate the difference in association between segregation and very preterm birth. Separate analyses focus on metropolitan segregation and on neighborhood segregation. RESULTS: Across 231 metropolitan areas, tract-derived and surface density-derived segregation measures are highly correlated. However overall correlation obscures important differences by region and metropolitan size. In general the discrepancy between measure types is greatest for small metropolitan areas, declining with increasing population size. Discrepancies in measures are greatest in the South, and smallest in Western metropolitan areas. Choice of segregation index changed the magnitude of the measured association between segregation and very preterm birth. For example among black women, the risk ratio for very preterm birth in metropolitan areas changed from 2.12 to 1.68 for the effect of high versus low segregation when using surface-density-derived versus tract-derived segregation indices. Variation in effect size was smaller but still present in analyses of neighborhood racial composition and very preterm birth in Atlanta neighborhoods. CONCLUSION: Census tract-derived measures of segregation are highly correlated with recently introduced spatial segregation measures, but the residual differences among measures are not uniform for all areas. Use of surface-density-derived measures provides researchers with tools to further explore the spatial relationships between segregation and health disparities. PMID- 20540798 TI - Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis. AB - BACKGROUND: The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis. METHODS: Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 +/- 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index > or = 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect. RESULTS: In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index > or = 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index > or = 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27). CONCLUSIONS: The present study demonstrates a sex differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis. PMID- 20540799 TI - Factors influencing knowledge about childhood autism among final year undergraduate Medical, Nursing and Psychology students of University of Nigeria, Enugu State, Nigeria. AB - BACKGROUND: Knowledge and awareness about childhood autism is low among health care workers and the general populace in Nigeria. Poor knowledge about childhood autism among final year medical, nursing and psychology students who would form tomorrow's child health care professionals can compromise early recognition and interventions that are known to improve prognosis in childhood autism. Educational factors that could be influencing knowledge about childhood autism among these future health care professionals are unknown. This study assessed knowledge about childhood autism among final year undergraduate medical, nursing and psychology students in south-eastern Nigeria and determined the factors that could be influencing such knowledge. METHODS: One hundred final year undergraduate students were randomly selected from each of the Departments of Medicine, Nursing Science and Psychology respectively of University of Nigeria, Enugu State, Nigeria making a sample size of three hundred. A socio-demographic questionnaire and knowledge about childhood autism among health workers (KCAHW) questionnaire were administered to the students. RESULTS: The total mean score for the three groups of students on the KCAHW questionnaire was 10.67+/-3.73 out of a possible total score of 19, with medical, nursing and psychology students having total mean scores of 12.24+/-3.24, 10.76+/-3.50 and 9.01+/-3.76 respectively. The mean scores for the three groups showed statistically significant difference for domain 1 (p=0.000), domain 3 (p=0.029), domain 4 (p=0.000) and total score (p=0.000), with medical students more likely to recognise symptoms and signs of autism compared to nursing and psychology students. The mean score in domain 2 did not show statistically significant difference among the three groups (p=0.769). The total score on the KCAHW questionnaire is positively correlated with the number of weeks of posting in psychiatry (r=0.319, p=0.000) and the number of weeks of posting in paediatrics (r=0.372, p=0.000). The total score is also positively correlated with the number of credit hours of lectures in psychiatry/abnormal psychology (r=0.324, p=0.000) and the number of credit hours of lectures in paediatrics (r=0.372, p=0.000). The field of study also influenced knowledge about childhood autism (p=0.000). CONCLUSION: Peculiar situation in this environment as signified by inadequate human resources needed in the area of clinical psychology training often times necessitates employing first degree graduates in psychology into clinical positions. This calls for additional exposure of the undergraduate psychology students to training curriculum aimed at improving their early recognition of symptoms of autism spectrum disorders in this environment. PMID- 20540800 TI - Histological and ultrastructural evaluation of the early healing of the lateral collateral ligament epiligament tissue in a rat knee model. AB - BACKGROUND: In this study, we evaluated the changes which occurred in the epiligament, an enveloping tissue of the ligament, during the ligament healing. We assessed the association of epiligament elements that could be involved in ligament healing. METHODS: Thirty-two 8-month old male Wistar rats were used in this study. In twenty-four of them the lateral collateral ligament of the knee joint was surgically transected and was allowed to heal spontaneously. The evaluation of the epiligament healing included light microscopy and transmission electron microscopy. RESULTS: At the eight, sixteenth and thirtieth day after injury, the animals were sacrificed and the ligaments were examined. Our results revealed that on the eight and sixteenth day post-injury the epiligament tissue is not completely regenerated. Till the thirtieth day after injury the epiligament is similar to normal, but not fully restored. CONCLUSION: Our study offered a more complete description of the epiligament healing process and defined its important role in ligament healing. Thus, we provided a base for new strategies in ligament treatment. PMID- 20540801 TI - High prevalence of minor neurologic deficits in a long-term neurodevelopmental follow-up of children with severe persistent pulmonary hypertension of the newborn: a cohort study. AB - BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a severe condition that determines a profound brain hypoxia. Inhaled nitric oxide was approved for the treatment of PPHN since the end of the 1990s. The debate upon the long term outcome of these children is still open. Our aim was to investigate the incidence of minor long-term neurodevelopmental problems in a cohort of children affected by severe PPHN. METHODS: All neonates with severe PPHN treated with inhaled nitric oxide in our facility between 01.01.02 and 31.12.07 were seen in a follow up visit and evaluated with a neurodevelopmental scale, according to their age at the time of observation. RESULTS: in the study period 31 children were diagnosed with severe PPHN. 29 survived. 27 accepted to come for follow-up. Mean age: 41 months (range 12 - 70 months).26% of the evaluated children had some behavioural problems, while 22% had some language disturbances. CONCLUSIONS: This is the first neurodevelopmental follow-up of neonates with PPHN in which children older than 36 months have been evaluated.There is an unexpected high incidence of minor neurological deficits, mainly regarding the fields of language and behaviour. These deficits seem to be related to the severity of illness rather than to the treatment. Language and behaviour are considered "higher functions" in humans and their integrity can be better defined in older children. PMID- 20540802 TI - Anaemia and thrombocytopenia in patients with prostate cancer and bone metastases. AB - BACKGROUND: The purpose of this study was to determine the incidence, risk factors and prognostic impact of anaemia and thrombocytopenia in patients with bone metastases (BM) from prostate cancer. METHODS: Retrospective cohort study including 51 consecutive patients treated at a community hospital. Twenty-nine patients (57%) received taxotere after diagnosis of BM. RESULTS: Haemoglobin (Hb) < or = 12.0 g/dL at BM detection was associated with shorter overall survival. During follow-up, 25 patients (49%) experienced episodes with Hb < 10 g/dL unrelated to side effects of cancer therapy. Fifteen patients required red blood cell transfusion. Median time from diagnosis of BM to Hb < 10 g/dL was 23 months. Median survival from Hb < 10 g/dL was 5.4 months. There was no factor predicting for Hb < 10 g/dL. Five patients (10%) developed thrombocyte (Trc) count <50 x 10(9)/L. All of these had previously received blood transfusion. Median interval from Hb < 10 g/dL to Trc < 50 x 10(9)/L was 2.5 months. Survival after thrombocytopenia was short (3 weeks to 4 months). Haematuria and subdural haematoma were among the causes of death. CONCLUSIONS: We found high rates of significant bone marrow failure in treatment-refractory patients. Both Hb < 10 g/dL and Trc < 50 x 10(9)/L predict for unfavourable survival. PMID- 20540803 TI - How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania. AB - BACKGROUND: HIV prevention trials conducted among disadvantaged vulnerable at risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. METHODS: A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits. RESULTS: 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. CONCLUSIONS: Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64716212. PMID- 20540804 TI - A novel method for purifying bluetongue virus with high purity by co immunoprecipitation with agarose protein A. AB - BACKGROUND: Bluetongue virus (BTV) is an icosahedral non-enveloped virus within the genus Orbivirus of Reoviridae and exists as 24 distinct serotypes. BTV can infect all ruminant species and causes severe sickness in sheep. Recently, it was reported that BTV can infect some human cancer cells selectively. Because of the important oncolysis of this virus, we developed a novel purifying method for large-scale production. The purifying logic is simple, which is picking out all the components unwanted and the left is what we want. The process can be summarized in 4 steps: centrifugation, pulling down cell debrises and soluble proteins by co-immunoprecipitation with agarose Protein A, dialysis and filtration sterilization after concentration. RESULTS: The result of transmission electron microscope (TEM) observation showed that the sample of purified virus has a very clear background and the virions still kept intact. The result of 50% tissue culture infective dose (TCID(50)) assay showed that the bioactivity of purified virus is relatively high. CONCLUSIONS: This method can purify BTV-10 with high quality and high biological activity on large-scale production. It also can be used for purifying other BTV serotypes. PMID- 20540805 TI - Isolation and antisense suppression of flavonoid 3', 5'-hydroxylase modifies flower pigments and colour in cyclamen. AB - BACKGROUND: Cyclamen is a popular and economically significant pot plant crop in several countries. Molecular breeding technologies provide opportunities to metabolically engineer the well-characterized flavonoid biosynthetic pathway for altered anthocyanin profile and hence the colour of the flower. Previously we reported on a genetic transformation system for cyclamen. Our aim in this study was to change pigment profiles and flower colours in cyclamen through the suppression of flavonoid 3', 5'-hydroxylase, an enzyme in the flavonoid pathway that plays a determining role in the colour of anthocyanin pigments. RESULTS: A full-length cDNA putatively identified as a F3'5'H (CpF3'5'H) was isolated from cyclamen flower tissue. Amino acid and phylogeny analyses indicated the CpF3'5'H encodes a F3'5'H enzyme. Two cultivars of minicyclamen were transformed via Agrobacterium tumefaciens with an antisense CpF3'5'H construct. Flowers of the transgenic lines showed modified colour and this correlated positively with the loss of endogenous F3'5'H transcript. Changes in observed colour were confirmed by colorimeter measurements, with an overall loss in intensity of colour (C) in the transgenic lines and a shift in hue from purple to red/pink in one cultivar. HPLC analysis showed that delphinidin-derived pigment levels were reduced in transgenic lines relative to control lines while the percentage of cyanidin derived pigments increased. Total anthocyanin concentration was reduced up to 80% in some transgenic lines and a smaller increase in flavonol concentration was recorded. Differences were also seen in the ratio of flavonol types that accumulated. CONCLUSION: To our knowledge this is the first report of genetic modification of the anthocyanin pathway in the commercially important species cyclamen. The effects of suppressing a key enzyme, F3'5'H, were wide ranging, extending from anthocyanins to other branches of the flavonoid pathway. The results illustrate the complexity involved in modifying a biosynthetic pathway with multiple branch points to different end products and provides important information for future flower colour modification experiments in cyclamen. PMID- 20540806 TI - Acupuncture for chronic low back pain: protocol for a multicenter, randomized, sham-controlled trial. AB - BACKGROUND: Use of acupuncture has widely increased in patients with chronic low back pain. However, the evidence supporting its efficacy remains unclear. In this article, we report the design and the protocol of a multi-center randomized sham controlled trial to treat chronic low back pain. Our goal is to verify the effect of acupuncture on chronic low back pain. METHODS/DESIGN: This study is a multi center randomized sham-controlled trial with 2 parallel arms. Participants included in the study met the following criteria: 1) low back pain lasting for at least the last 3 months, 2) a documented >or= 5 points on a 10 cm visual analog scale for bothersomeness of low back pain at the time of screening and 3) between 18 and 65 years of age. Participants were blinded to the real and sham acupuncture treatments. The real acupuncture treatment group received real acupuncture 2 times a week, during a total of 12 sessions over 6 weeks. The control group received sham acupuncture during the same period. In order to assess the primary and secondary outcome measures, the participants were asked to fill out a questionnaire at the baseline and 6, 8, 12 and 24 weeks after starting the treatments. The primary outcome was measured using the visual analog scale for bothersomeness of low back pain at 8 weeks after the initiation of treatments. DISCUSSION: The result of this trial (which will be available in 2010) will demonstrate the efficacy of using acupuncture to treat chronic low back pain. TRIAL REGISTRATION: This study is registered with the U.S. National Institutes of Health Clinical Trials registry: NCT00815529. PMID- 20540807 TI - Effects of preoperative neuromuscular electrical stimulation on quadriceps strength and functional recovery in total knee arthroplasty. A pilot study. AB - BACKGROUND: Supervised preoperative muscle strengthening programmes (prehabilitation) can improve recovery after total joint arthroplasty but are considered resource intensive. Neuromuscular electrical stimulation (NMES) has been shown to improve quadriceps femoris muscle (QFM) strength and clinical function in subjects with knee osteoarthritis (OA) however it has not been previously investigated as a prehabilitation modality. METHODS: This pilot study assessed the compliance of a home-based, NMES prehabilitation programme in patients undergoing total knee arthroplasty (TKA). We evaluated its effect on preoperative and postoperative isometric quadriceps femoris muscle (QFM) strength, QFM cross-sectional area (CSA) and clinical function (subjective and objective). Seventeen subjects were recruited with 14 completing the study (NMES group n = 9; Control group n = 5). RESULTS: Overall compliance with the programme was excellent (99%). Preoperative QFM strength increased by 28% (p > 0.05) with associated gains in walk, stair-climb and chair-rise times (p < 0.05). Early postoperative strength loss (approximately 50%) was similar in both groups. Only the NMES group demonstrated significant strength (53.3%, p = 0.011) and functional recovery (p < 0.05) from 6 to 12 weeks post-TKA. QFM CSA decreased by 4% in the NMES group compared to a reduction of 12% in the control group (P > 0.05) at 12 weeks postoperatively compared to baseline. There were only limited associations found between objective and subjective functional outcome instruments. CONCLUSIONS: This pilot study has shown that preoperative NMES may improve recovery of quadriceps muscle strength and expedite a return to normal activities in patients undergoing TKA for OA. Recommendations for appropriate outcome instruments in future studies of prehabilitation in TKA have been provided. PMID- 20540808 TI - Household smoking and dental caries in schoolchildren: the Ryukyus Child Health Study. AB - BACKGROUND: Secondhand smoke exposure (SHSe) is perhaps one of the most important toxic exposures in childhood. However, epidemiological studies on the relation between SHSe and dental caries are limited and have yielded inconsistent results. The present cross-sectional study examined the potential association between SHSe at home and the prevalence of dental caries in children. METHODS: Subjects were 20,703 schoolchildren aged 6 to 15 years in Okinawa, Japan. Information on SHSe at home and potential confounding factors was obtained through questionnaires. Data on dental caries were obtained from school records. Children were classified as having decayed and/or filled teeth (DFT) if a dentist diagnosed these conditions. Additionally, we analyzed decayed teeth (DT) and filled teeth (FT) separately. Adjustment was made for sex, age, region of residence, toothbrushing frequency, use of fluoride, sugar intake, and paternal and maternal educational level. RESULTS: The prevalence of DFT was 82.0%. Compared with never smoking in the household, former and current household smoking were independently associated with an increased prevalence of DFT (adjusted prevalence ratios [95% confidence intervals] for former household smoking and current light and heavy household smoking were 1.03 [1.00-1.05], 1.04 [1.02-1.05], and 1.04 [1.03-1.06], respectively); when analyzed separately there was an increased prevalence of DT (adjusted prevalence ratios [95% confidence intervals] for former household smoking and current light and heavy household smoking were 1.06 [1.02-1.11], 1.10 [1.06-1.13], and 1.10 [1.07-1.14], respectively) but not FT. A statistically significant dose-response relationship between cumulative smoking in the household and the prevalence of DFT and DT (P for trend < 0.0001), but not FT, was observed. In an analysis of 2 subgroups, subjects who had at least 1 deciduous tooth and subjects who had at least 1 permanent tooth, household smoking exposure was associated with an increased prevalence of DFT and DT not only in those with deciduous but also those with permanent dentition. CONCLUSION: Our findings suggested that household smoking might be associated with an increased prevalence of dental caries in children. PMID- 20540809 TI - Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells. AB - BACKGROUND: Homeobox (HOX) genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited. METHODS: To determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR) expressions were examined in primary granulosa cells (hGCs), an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1 HOAX7 vector. Cell proliferation was measured by the MTT assay. RESULTS: Our results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect. CONCLUSIONS: Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation. PMID- 20540810 TI - A probit- log- skew-normal mixture model for repeated measures data with excess zeros, with application to a cohort study of paediatric respiratory symptoms. AB - BACKGROUND: A zero-inflated continuous outcome is characterized by occurrence of "excess" zeros that more than a single distribution can explain, with the positive observations forming a skewed distribution. Mixture models are employed for regression analysis of zero-inflated data. Moreover, for repeated measures zero-inflated data the clustering structure should also be modeled for an adequate analysis. METHODS: Diary of Asthma and Viral Infections Study (DAVIS) was a one year (2004) cohort study conducted at McMaster University to monitor viral infection and respiratory symptoms in children aged 5-11 years with and without asthma. Respiratory symptoms were recorded daily using either an Internet or paper-based diary. Changes in symptoms were assessed by study staff and led to collection of nasal fluid specimens for virological testing. The study objectives included investigating the response of respiratory symptoms to respiratory viral infection in children with and without asthma over a one year period. Due to sparse data daily respiratory symptom scores were aggregated into weekly average scores. More than 70% of the weekly average scores were zero, with the positive scores forming a skewed distribution. We propose a random effects probit/log-skew normal mixture model to analyze the DAVIS data. The model parameters were estimated using a maximum marginal likelihood approach. A simulation study was conducted to assess the performance of the proposed mixture model if the underlying distribution of the positive response is different from log-skew normal. RESULTS: Viral infection status was highly significant in both probit and log-skew normal model components respectively. The probability of being symptom free was much lower for the week a child was viral positive relative to the week she/he was viral negative. The severity of the symptoms was also greater for the week a child was viral positive. The probability of being symptom free was smaller for asthmatics relative to non-asthmatics throughout the year, whereas there was no difference in the severity of the symptoms between the two groups. CONCLUSIONS: A positive association was observed between viral infection status and both the probability of experiencing any respiratory symptoms, and their severity during the year. For DAVIS data the random effects probit -log skew normal model fits significantly better than the random effects probit -log normal model, endorsing our parametric choice for the model. The simulation study indicates that our proposed model seems to be robust to misspecification of the distribution of the positive skewed response. PMID- 20540811 TI - Influenza A H5N1 and HIV co-infection: case report. AB - BACKGROUND: The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this. CASE PRESENTATION: A 30-year-old male was admitted on day 4 of influenza-like-illness with tachycardia, tachypnea, hypoxemia and bilateral pulmonary infiltrates. Influenza A/H5N1 and HIV tests were positive and the patient was treated with Oseltamivir and broad-spectrum antibiotics. Initially his condition improved coinciding with virus clearance by day 6. He clinically deteriorated as of day 10 with fever recrudescence and increasing neutrophil counts and died on day 16. His admission CD4 count was 100/microl and decreased until virus was cleared. CD8 T cells shifted to a CD27+CD28- phenotype. Plasma chemokine and cytokine levels were similar to those found previously in fatal H5N1. CONCLUSIONS: The course of H5N1 infection was not notably different from other cases. Virus was cleared despite profound CD4 T cell depletion and aberrant CD8 T cell activation but this may have increased susceptibility to a fatal secondary infection. PMID- 20540812 TI - Association of the genetic polymorphisms of the ACE gene and the eNOS gene with lupus nephropathy in northern Chinese population. AB - BACKGROUND: It has been reported that some single nucleotide polymorphisms (SNPs) of the angiotensin converting enzyme (ACE) gene and the endothelial nitric oxide synthase (eNOS) gene are associated with the development of systemic lupus erythematosus (SLE) and the progression of nephropathy. The aim of this study was to evaluate the possible association between six SNPs (A-5466C, T-3892C, A-240T, C1237T, G2215A and A2350G) of the ACE gene and two SNPs (T-786C and G894T) of the eNOS gene with lupus nephropathy in a northern Chinese population. METHODS: In this study, 225 patients with lupus nephropathy were compared to 232 healthy controls, matched by gender, age and ethnicity. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, the genotypes of the eight selected SNPs were determined by the method of PCR-RFLP; the haplotypes were inferred using PHASE 2.1. The associations between the SNPs and the risk of lupus nephropathy were analyzed using Chi-square test and Logistic regression with SPSS13.0 software. RESULTS: Statistically significant differences of the allele frequency distribution of three SNPs (A-5466C, A2350G and G894T) were observed between cases and controls (P<0.05). Among the 53 haplotypes identified, the frequencies of five haplotypes (CTTCGA, ACTTAA, ACATGG, ACACGG and ATTCGA) were significantly different between cases and controls (P<0.05). CONCLUSIONS: Our study indicated an association between the risk of lupus nephropathy and the sequence variations of both the ACE gene and the eNOS gene, which may play an important role in the pathogenesis of lupus nephropathy in the northern Chinese population. Further studies are warranted to validate our findings. PMID- 20540813 TI - Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system. AB - BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl) concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis. RESULTS: Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS). Microarray data were verified by reverse transcriptase polymerase chain reactions (RT-PCR). Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system. CONCLUSIONS: B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei. PMID- 20540814 TI - New regulations regarding Postgraduate Medical Training in Spain: perception of the tutor's role in the Murcia Region. AB - BACKGROUND: Recently introduced regulatory changes have expanded the Tutor role to include their primary responsibility for Postgraduate Medical Training (PMT). However, accreditation and recognition of that role has been devolved to the autonomic regions. The opinions of the RT may be relevant to future decisions; METHODS: A comprehensive questionnaire, including demographic characteristics, academic and research achievement and personal views about their role, was sent to 201 RTs in the Murcia Region of Spain. The responses are described using median and interquartile ranges (IQR); RESULTS: There were 147 replies (response rate 73%), 69% male, mean age 45 +/- 7 yrs. RTs perception of the residents' initial knowledge and commitment throughout the program was 5 (IQR 4-6) and 7 (IQR 5-8), respectively. As regards their impact on the PMT program, RTs considered that their own contribution was similar to that of senior residents. RTs perception of how their role was recognised was 5 (IQR 3-6). Only 16% did not encounter difficulties in accessing specific RT training programs. Regarding the RTs view of their various duties, supervision of patient care was accorded the greatest importance (64%) while the satisfactory completion of the PMT program and supervision of day-to-day activities were also considered important (61% and 59% respectively). The main RT requirements were: a greater professional recognition (97%), protected time (95%), specific RT training programs (95%) and financial recognition (86%); CONCLUSIONS: This comprehensive study, reflecting the feelings of our RTs, provides a useful insight into the reality of their work and the findings ought to be taken into consideration in the imminent definitive regulatory document on PMT. PMID- 20540815 TI - Young men's intimate partner violence and relationship functioning: long-term outcomes associated with suicide attempt and aggression in adolescence. AB - BACKGROUND: Longitudinal research supports that suicidal thoughts and behaviors in adolescence predict maladjustment in young adulthood. Prior research supports links between suicide attempt and aggression, perhaps because of a propensity for impulsive behavior in states of high negative affect that underlies both problems. Such vulnerability may increase risk for intimate partner violence and generally poor young adulthood relational adjustment. METHOD: A total of 153 men participated in annual assessments from ages 10-32 years and with a romantic partner at three assessments from ages 18-25 years. Multi-method/multi-informant constructs were formed for parent/family risk factors, adolescent psychopathology (e.g. suicide-attempt history, mother-, father-, teacher- and self-reported physical aggression) and young adulthood relational distress (jealousy and low relationship satisfaction) and maladaptive relationship behavior (observed, self- and partner-reported physical and psychological aggression toward a partner, partner-reported injury, official domestic violence arrest records and relationship instability). RESULTS: Across informants, adolescent aggression was correlated with suicide-attempt history. With few exceptions, aggression and a suicide attempt in adolescence each predicted negative romantic relationship outcomes after controlling for measured confounds. Adolescent aggression predicted young adulthood aggression toward a partner, in part, via relationship dissatisfaction. CONCLUSIONS: Boys' aggression and suicide-attempt history in adolescence each predict poor relationship outcomes, including partner violence, in young adulthood. Findings are consistent with the theory of a trait-like vulnerability, such as impulsive aggression, that undermines adaptation across multiple domains in adolescence and young adulthood. Prevention and intervention approaches can target common causes of diverse public health problems. PMID- 20540816 TI - A single nucleotide polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene ( HMGCR) influences the serum triacylglycerol relationship with dietary fat and fibre in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study. AB - The objective of the present study was to investigate the influence of the single nucleotide polymorphism (rs17238540) at the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (HMGCR) on the relationship between serum lipids and dietary fat and fibre (NSP). FFQ and pyrosequencing were used to assess cross-sectional dietary intake and HMGCR genotype in a population study with data for serum lipids available. Genotype frequencies and allele distributions for 23 011 participants were: TT 95.65 %, TG 4.29 % and GG 0.06 %; T 97.8 % and G 2.2 %. In regression analyses, the TG+GG group showed a significant positive relationship between TAG and SFA intake (+0.11 (95 % CI 0.02, 0.20) mmol TAG/l; P = 0.017; per 3 % SFA energy increase) while the TT individuals showed no change in the TAG levels related to SFA intake ( - 0.0007 (95 % CI - 0.02, 0.02) mmol TAG/l; P = 0.99). TG+GG individuals showed an inverse relationship between TAG and fibre intake higher ( - 0.14 (95 % CI - 0.22, - 0.05) mmol TAG/l than the TT group ( - 0.04 (95 % CI - 0.06, - 0.02) mmol TAG/l). In both cases the respective coefficient regressions of TAG were different between the genotype groups (Z = 2.27, P = 0.023 for SFA intake; Z = 2.19, P = 0.029 for fibre intake). Individuals carrying the G allele may show a greater response in lower TAG levels with reduced SFA intake and increased fibre intake compared with those homozygous for the T allele. The effectiveness of different dietary interventions to control serum lipids may vary according to HMGCR genotype. PMID- 20540817 TI - Presence of alkylresorcinols, potential whole grain biomarkers, in human adipose tissue. AB - Alkylresorcinols (AR) in plasma samples have been suggested to be short- to medium-term biomarkers of whole grain wheat and rye intake. In the present study, we investigated whether AR are present in human adipose tissues, and if content correlated with long-term whole grain bread intake. Furthermore, we investigated if the relative AR homologue composition reflected what has been found previously in the habitual diet of Swedes. Biopsy samples (10-25 mg) from free-living Swedish women (n 20) were analysed by GC-MS. The mean total AR concentration in the samples was 0.54 (SD 0.35) microg/g, ranging from below limit of quantification ( < 0.08 microg/g) to 1.50 microg/g. Whole grain bread intake was significantly correlated with plasma total AR content (r 0.48, P < 0.05), and the C17 : 0/C21 : 0 ratio was 0.35 (sd 0.24), which is similar to what is found in plasma among free-living subjects consuming a mixed whole grain wheat and rye diet. These results suggest that AR in the adipose tissue should be evaluated as a long-term biomarker of whole grain wheat and rye intake. PMID- 20540818 TI - Apoptosis-inducing factor and caspase-dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2. AB - Consumption of grape seed extract (GSE) is widely marketed as a dietary supplement and is considered safe for human health. Nevertheless, the analytical composition of GSE from different grape cultivars, growing in special agronomic constraints, differs greatly in flavan-3-ols content. The major concern with GSE studies is a lack of availability of uniformly standardised preparations, which raises an important question whether different GSE samples have comparable activity and trigger the same mechanisms of action on a given biological system. Therefore, it is tempting to speculate that GSE, obtained from different cultivars, could exert differentiated anticancer effects. The focus of the present study is to determine the selective biological efficacy of GSE obtained from three different sources on the human colon cancer cell line Caco-2. Irrespective of its source, high doses of GSE induced a significant inhibition on Caco-2 cell growth. Moreover, apoptosis was enhanced through both caspase dependent and caspase-independent mechanisms, leading to an early apoptosis inducing factor release and, further, to a dramatic increase in caspase 7 and 3 activity. However, a significant difference in apoptotic rates induced by the three grape sources clearly emerged when treating cancer cells with low and intermediate GSE concentrations (25 and 50 microg/ml). PMID- 20540819 TI - Developmental origins of cardiovascular risk in Jamaican children: the Vulnerable Windows Cohort study. AB - Both intra-uterine and early childhood development contribute to the risk of developing CVD in adult life. We therefore evaluated the maternal, placental, fetal, birth, infant and childhood determinants of cardiovascular risk in a cohort of Afro-Jamaican children. The Vulnerable Windows Cohort is a longitudinal survey of 569 mothers and their offspring recruited from the first trimester. The offspring's anthropometry was measured at birth, at 6 weeks, every 3 months to 1 year and then every 6 months. At mean age 11.5 years, fasting blood was sampled for glucose, insulin and lipids. Analyses were confined to 296 women and their offspring who had complete data. Waist circumference (WC) was related to maternal weight and BMI, placental weight and to the size of the offspring in utero, at birth and the rate of growth in childhood (P < 0.05). Total cholesterol, TAG and glucose concentrations were unrelated to maternal, placental, fetal, neonatal and childhood measurements. Fasting insulin and homeostasis model assessment of insulin resistance were related to maternal weight and BMI (P < 0.05), but not after adjusting for WC. HDL-cholesterol was inversely related to placental and birth weight, and inversely related to weight and BMI throughout childhood (P < 0.001), but not after adjusting for WC. Systolic blood pressure was directly related to maternal weight, child's height, weight and BMI (P < 0.05), but not after adjustment for WC. Systolic blood pressure and fasting glucose concentration were inversely related to birth weight in boys but directly associated in girls. We concluded that maternal anthropometry during pregnancy, fetal size, and childhood growth rate contribute to cardiovascular risk factors in childhood. PMID- 20540820 TI - Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load. AB - The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with 13C6 fructose. Incorporation of 13C into breath CO2, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After 13C fructose ingestion, 44.0 (sd 3.2)% of labelled carbons were recovered in plasma glucose in males v. 41.9 (sd 2.3)% in females (NS), and 42.9 (sd 3.7)% of labelled carbons were recovered in breath CO2 in males v. 43.0 (sd 4.5)% in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for 13C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P < 0.05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16.4 (sd 5.2), P < 0.05), but it was not suppressed in females ( -1.3 (sd 4.7)%). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation. PMID- 20540821 TI - Effects of dietary lipid, vitamins and minerals on total amounts and redox status of glutathione and ubiquinone in tissues of Atlantic salmon (Salmo salar): a multivariate approach. AB - The hypothesis of the present study was that Atlantic salmon (Salmo salar) would respond to large variations in supplementation of dietary pro- and antioxidants, and marine lipid, with adjustment of the endogenously synthesised antioxidants, glutathione (GSH) and ubiquinone (UQ). An experiment with 2(7-3) reduced factorial design (the number of cases reduced systematically from 2(7) (full design) to 2(4) (reduced design)) was conducted, where vitamins, minerals and lipid were supplemented in the diet at high and low levels. For the vitamins and minerals the high levels were chosen to be just below anticipated toxic levels and the low levels were just above the requirement (vitamin C, 30 and 1000 mg/kg; vitamin E, 70 and 430 mg/kg; Fe, 70 and 1200 mg/kg; Cu, 8 and 110 mg/kg; Mn, 12 and 200 mg/kg). For astaxanthin, the dietary levels were 10 and 50 mg/kg and for lipid, 150 and 330 g/kg. The experiment was started with post-smolts (148 (sd 17 g)) and lasted for 5 months. The only effect on GSH was a minor increase ( < 10 %) in total concentration in the liver in response to high dietary lipid. GSH redox state was not affected. UQ responded to dietary lipid, astaxanthin and vitamin E, both with regard to total concentration and redox state. Except for an effect of Fe on plasma GSH, the trace elements and vitamin C had no effect on tissue levels and oxidation state of GSH and UQ. This shows that the endogenous redox state is quite robust with regard to variation of dietary pro- and antioxidants in Atlantic salmon. PMID- 20540822 TI - Probiotics: beneficial factors of the defence system. AB - Probiotics, defined as living micro-organisms that provide a health benefit to the host when ingested in adequate amounts, have been used traditionally as food components to help the body to recover from diarrhoea. They are commonly ingested as part of fermented foods, mostly in fresh fermented dairy products. They can interact with the host through different components of the gut defence systems. There is mounting clinical evidence that some probiotics, but not all, help the defence of the host as demonstrated by either a shorter duration of infections or a decrease in the host's susceptibility to pathogens. Different components of the gut barrier can be involved in the strengthening of the body's defences: the gut microbiota, the gut epithelial barrier and the immune system. Many studies have been conducted in normal free-living subjects or in subjects during common infections like the common cold and show that some probiotic-containing foods can improve the functioning of or strengthen the body's defence. Specific probiotic foods can be included in the usual balanced diet of consumers to help them to better cope with the daily challenges of their environment. PMID- 20540823 TI - Probiotics and the immune response to vaccines. AB - Probiotics are bacteria, but sometimes fungi, which when taken by the oral route may give some health benefits. The most compelling evidence for beneficial effects of probiotics is in the prevention and reduction in the duration of symptoms related to gut infectious disease. There is also evidence to show that some specific probiotics are beneficial in Clostridium difficile diarrhoea in the elderly. As further and better controlled clinical studies have appeared, some specific probiotics also appear to have beneficial effects in perhaps preventing and reducing the duration of symptoms due to acquired upper respiratory tract infections. In an attempt to explain these effects, attention has turned to the effects of some specific probiotics on the immune system. There is evidence that some specific probiotics can alter monocyte and natural killer cell function in the blood. Evidence is also accumulating that taking some specific probiotics can boost antibody responses to oral and systemically administered vaccines. The effect when shown is modest and is not always seen in different studies to all vaccines, but there is enough of a trend to make the area worthy of further investigation, particularly to tease out the mechanisms involved. PMID- 20540824 TI - Inflammatory biomarker profile in children with cystic fibrosis: preliminary study. AB - The aim of this preliminary study was to determine specific proteins, related to inflammation process and nutritional status as well as to total antioxidant capacity, in children suffering from cystic fibrosis (CF). The study was performed on 17 nonhospitalized children (12 boys and 5 girls) with CF aged 3 months to 10 years, who were assisted at the Nutrition Service from Pedro de Elizalde Hospital. Transferrin, transthyretin, ceruloplasmin (Cp), haptoglobin, C reactive protein (CRP) and fibrinogen were measured by single radial immunodiffusion techniques. Total antioxidant capacity (TAC) was determined by a decolorization assay. Statistical analyses were performed by the Student's t test. Transferrin and transthyretin values were lower in CF patients in comparison with data obtained from healthy children (reference group, RG). The decreased transferrin concentration and the tendency towards low plasma transthyretin values suggested an abnormal nutritional status. However, higher Cp and haptoglobin levels were shown in patients than in RG. The fact that 23 and 50% of patients exceeded the desirable values for fibrinogen (<285.0 mg/dl) and CRP (<0.2 mg/dl), respectively, should be highlighted. The TAC (mM; Trolox equivalents) was shown to be lower in the CF group than in RG. The diminished TAC concomitant with an increased plasma Cp concentration would exacerbate the inflammatory status and could explain the depression of the immune system. These preliminary results could explain the need to include biochemical and functional parameters in the early nutritional status evaluation in CF patients in order to use appropriate nutritional and pharmacological therapies and consequently to improve their survival and quality of life. PMID- 20540825 TI - Regulation of adipokine secretion by n-3 fatty acids. AB - Obesity leads to several chronic morbidities including type 2 diabetes, dyslipidaemia, atherosclerosis and hypertension, which are major components of the metabolic syndrome. White adipose tissue (WAT) metabolism and WAT-derived factors (fatty acids and adipokines) play an important role in the development of these metabolic disturbances. In fact, dysregulated adipokine secretion from the expanded WAT of obese individuals contributes to the development of systemic low grade inflammation, insulin resistance and metabolic syndrome. The n-3 PUFA EPA and DHA have been widely reported to have protective effects in a range of chronic inflammatory conditions including obesity. In fact, n-3 PUFA have been shown to ameliorate low-grade inflammation in adipose tissue associated with obesity and up-regulate mitochondrial biogenesis and induce beta-oxidation in WAT in mice. Moreover, the ability of n-3 PUFA to regulate adipokine gene expression and secretion has been observed both in vitro and in vivo in rodents and human subjects. The present article reviews: (1) the physiological role of adiponectin, leptin and pre-B cell colony-enhancer factor/visfatin, three adipokines with immune-modulatory properties involved in the regulation of metabolism and insulin sensitivity and (2) the actions of n-3 PUFA on these adipokines focusing on the underlying mechanisms and the potential relationship with the beneficial effects of these fatty acids on obesity-associated metabolic disorders. It can be concluded that the ability of n-3 PUFA to improve obesity and insulin resistance conditions partially results from the modulation of WAT metabolism and the secretion of bioactive adipokines including leptin, adiponectin and visfatin. PMID- 20540826 TI - Gut microbiota in obesity and metabolic disorders. AB - Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders. PMID- 20540827 TI - Neuropsychiatric disorders following stroke. PMID- 20540828 TI - Poststroke depression: a review. AB - OBJECTIVE: To review the world's (English-language) publications related to depression following stroke. METHOD: The databases from MEDLINE and PubMed were reviewed for articles related to poststroke depression (PSD), depression and cerebral vascular accident, depression and cerebral vascular disease, and depression and cerebral infarction. RESULTS: Most studies examined prevalence rates of depression and the clinical correlates of depression. Based on pooled data, the overall prevalence of major depression was 21.7% and minor depression was 19.5%. The strongest single correlate of depression was severity of impairment in activities of daily living. However, the existence of depression at baseline was found to be associated with greater impairment at follow-up, ranging from 6 weeks to 2 years in 83% of studies. Further, depression following acute stroke was also associated with greater cognitive impairment and increased mortality. PSD has been shown in 6 double-blind controlled studies to be effectively treated with antidepressants, and 1 study has recently shown that PSD can be effectively prevented. CONCLUSIONS: During the past 20 years, significant progress has been made in the identification and treatment of depression following stroke. In the future, antidepressant treatment will likely play an increasing role in the management of patients with acute stroke. Further research is needed to identify the mechanisms of depression and why antidepressants lead to improved physical and cognitive recovery and decreased mortality. PMID- 20540829 TI - Apathy following stroke. AB - OBJECTIVE: We will review the available evidence on the frequency, clinical correlates, mechanism, and treatment of apathy following stroke. METHODS: We have explored relevant databases (that is, PubMed, MEDLINE, and PsycINFO) using the following key words and their combinations: apathy, motivation, abulia, stroke, cerebrovascular disease, basal ganglia, prefrontal cortex, anterior cerebral infarction, and thalamus. RESULTS: The frequency of apathy following stroke has been consistently estimated between 20% and 25%. It appears to be associated with the presence of cognitive impairment, a chronic course characterized by progressive functional decline, and with disruption of neural networks connecting the anterior cingulate gyrus, the dorsomedial frontal cortex, and the frontal pole with the ventral aspects of the caudate nucleus, the anterior and ventral globus pallidus, and the dorsomedian and intralaminar thalamic nuclei. Published treatment studies have been mostly limited to anecdotal case reports, generally using dopamine agonists or stimulant medications. Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication. CONCLUSION: Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline. However, there is no conclusive evidence about which is the best treatment for this condition. PMID- 20540830 TI - The frequency, clinical correlates, and mechanism of anosognosia after stroke. AB - OBJECTIVE: To review the frequency, clinical correlates, and mechanism of anosognosia after stroke. METHODS: We searched the most recent relevant literature on anosognosia after stroke and carried out a critical analysis of the main findings. RESULTS: Anosognosia is present in about 10% of acute stroke patients and its diagnosis is relatively simple. Nevertheless, a valid and reliable standardization of diagnostic instruments and criteria for research purposes is more difficult to achieve. This limitation may partially account for various instruments available to assess anosognosia and the different strategies used to diagnose this phenomenon. Anosognosia is a fleeting phenomenon and chronic cases are infrequent. There is a robust association between anosognosia and right-hemisphere lesions involving cortical (insular, temporal, and parietal lobes) and subcortical structures (thalamus and basal ganglia). The main clinical correlates of anosognosia are the presence of neglect, cognitive deficits, previous strokes, and older age. Anosognosia has a negative impact on the rehabilitation of stroke patients. The mechanism of anosognosia remains unknown but was explained as owing to psychological denial, disconnection between left and right hemispheres, and dysfunction of a system that monitors the intention to move and actual movements. CONCLUSION: Anosognosia is a relatively frequent complication of acute stroke and may become an excellent model to understand the mechanism of human awareness. PMID- 20540831 TI - Adults with mood disorders have an increased risk profile for cardiovascular disease within the first 2 years of treatment. AB - OBJECTIVES: People with bipolar disorder (BD) and major depressive disorder (MDD) are at risk for premature death from various physical illnesses. A large component of this risk may be accounted for by an elevated risk of metabolic syndrome (MeS) and coronary heart disease (CHD). The objective of our study was to examine patients' physical health prior to first treatment and over 2 years of follow-up. METHODS: Ten-year risk for CHD and incidence of MeS were calculated for newly diagnosed patients with MDD (n = 30) and BD (n = 24) at baseline and over a 2-year follow-up. Age and sex-matched control subjects were obtained from the National Health and Nutrition Examination Survey III dataset. RESULTS: At baseline, 11.2% of patients met diagnostic criteria for MeS and this increased to 16.8% at follow-up. Women had higher rates of MeS but rates were similar across diagnosis. There was a significant increase within all MeS criteria. The 10-year CHD risk was low for patients at baseline and follow-up but increased across the follow-up period. Changes in CHD and MeS risk were not associated with a specific type of pharmacotherapy, as all medication classes appeared to increase risk. CONCLUSION: Prior to treatment, MeS and CHD risk rates for patients were similar to the general population, but their risk of CHD increased appreciably. PMID- 20540832 TI - Suicide mortality by occupation in Canada, 1991-2001. AB - OBJECTIVE: To describe the association between occupation and risk of suicide among working-age men and women in Canada. METHOD: This study of suicide mortality over an 11-year period is based on a broadly representative 15% sample of the noninstitutionalized population of Canada aged 30 to 69 years at cohort inception. Age-standardized mortality rates (ASMRs) and rate ratios were calculated for men and women in 5 categories of skill level and 80 specific occupational groups, as well as for people not occupationally active. RESULTS: The suicide mortality rate was 20.1/100 000 person years for occupationally active men (during 9 600 000 person years of follow-up) and 5.3/100 000 person years for occupationally active women (during 8 100 000 person years of follow up). Among occupationally active men, elevated rates of suicide mortality were observed for 9 occupational groups and protective effects were observed for 6 occupational groups. Among women, elevated rates of suicide were observed in 4 occupational groups and no protective effects were observed. For men and women, ASMRs for suicide were inversely related to skill level. CONCLUSIONS: The limited number of associations between occupational groups and suicide risk observed in this study suggests that, with few exceptions, the characteristics of specific occupations do not substantially influence the risk for suicide. There was a moderate gradient in suicide mortality risk relative to occupational skill level. Suicide prevention strategies in occupational settings should continue to emphasize efforts to restrict and limit access to lethal means, one of the few suicide prevention policies with proven effectiveness. PMID- 20540833 TI - The relation between maternal schizophrenia and low birth weight is modified by paternal age. AB - OBJECTIVE: Paternal characteristics have never been considered in the relation between maternal schizophrenia and adverse pregnancy outcomes. The aim of our study was to consider different paternal ages while investigating the relation between maternal schizophrenia and low birth weight (LBW), using a nationwide population-based dataset. METHOD: Our study used data from the 2001 to 2003 Taiwan National Health Insurance Research Dataset and birth certificate registry. A total of 543 394 singleton live births were included. We performed multivariate logistic regression analyses to explore the relation between maternal schizophrenia and the risk of LBW, taking different paternal age groups into account (aged 29 years or younger, 30 to 39 years, and 40 years and older), and after adjusting for other characteristics of infant, mother, and father as well as the difference between the parent's ages. RESULTS: Mothers with schizophrenia had a higher percentage of LBW infants than mothers who did not (11.8%, compared with 6.8%). For infants whose mothers had schizophrenia, the adjusted odds ratios of LBW were 1.47 (95% CI 1.02 to 2.27, P < 0.05) and 2.80 (95% CI 1.42 to 5.51, P < 0.01) times greater than for infants whose mothers did not have schizophrenia, for paternal age groups of 30 to 39 years and 40 years or older, respectively. However, maternal schizophrenia was not a significant predictor of LBW for infants whose fathers were aged 29 years and younger. CONCLUSIONS: The relation between LBW and maternal schizophrenia is modified by paternal age. More attention should be paid to the interaction of paternal characteristics and maternal psychiatric disorders in producing adverse pregnancy outcomes. PMID- 20540834 TI - [Using psychostimulants in end-of-life patients with hypoactive delirium and cognitive disorders: A literature review]. AB - OBJECTIVE: To review the research about psychostimulant effects on cognitive functions in end-of-life patients diagnosed with hypoactive delirium or cognitive disorders. METHOD: The MEDLINE (1966-March 2008), Embase (1974-March 2008), PsycINFO (1806-March 2008), IPA (1970-March 2008), CINAHL (1982-March 2008), ISI Web of Science (1945-March 2008), Current Contents (March 2007-March 2008), Access Medicine (2001-March 2008), and ProQuest Dissertations & Theses (1980 March 2008) databases were searched with keywords related to delirium, cognition, psychostimulants, and palliative care for French or English articles in a dementia-free and hyperactive delirium-free end-of-life population. Cognitive functions had to be assessed before and after initiation of the psychostimulant treatment. Moreover, treatment had to be initiated after the onset of cognitive impairments. RESULTS: A total of 173 studies were screened. Five studies on methylphenidate and 1 study on caffeine met inclusion criteria and were included in this review. Two studies were case reports, 2 were open-label trials, and 2 were double-blind, crossover randomized placebo-controlled trials. Three studies were conducted with hypoactive delirium patients and all studies were conducted in an advanced cancer patient population. CONCLUSIONS: The reviewed studies support the use of methylphenidate to improve end-of-life patient cognitive functions, particularly in the case of hypoactive delirium. Caffeine seems to have beneficial effects on psychomotor activity. Further well-designed studies are needed to consolidate these findings. PMID- 20540835 TI - Role of Thermo-responsiveness and Poly(ethylene glycol) Diacrylate Cross-link Density on Protein Release from Poly(N-isopropylacrylamide) Hydrogels. AB - Thermo-responsive hydrogels have shown promise as injectable materials for local drug delivery. However, the phase-induced changes in polymer properties of N isopropylacrylamide (NIPAAm) can pose additional challenges for achieving controlled protein release. In this work, thermo-responsive hydrogels derived from NIPAAm and cross-linked with poly(ethylene glycol) diacrylate (PEG-DA) were synthesized via free radical polymerization. The volume phase transition temperature (VPTT) of the hydrogels ranged from 32.9 degrees C to 35.9 degrees C. Below the VPTT, swelling ratios of the hydrogels decreased with cross-linker concentration, and showed a sharp drop (at least 4-fold) upon phase change. Protein encapsulation efficiency was high (84-90%) and decreased with cross linker concentration. Release of bovine serum albumin, a model protein, at body temperature was significantly higher than at room temperature (67% at 37 degrees C compared to 44% at 23 degrees C after 48 h). The release kinetics of proteins from the hydrogels were initially expected to be a function of cross-link density. However, at the hydrogel compositions explored in this work, protein release did not change significantly with cross-linker mol fraction. The thermo responsive hydrogels offer a promising platform for the localized delivery of proteins. PMID- 20540836 TI - A CB protective firefighter turnout suit. AB - This paper describes research that developed a prototype chemical and biological (CB) protective firefighter suit. It is presented as a case study demonstrating an integrated systems approach to designing, developing and evaluating a protective clothing ensemble based on end user requirements. It includes a discussion of the process that was used to gain an understanding of firefighter performance needs for a structural turnout suit that also incorporated chemical protection. It describes the design features of the turnout suit that were developed to meet these expectations as well as the program of testing and evaluation used to characterize garment performance. It discusses ensemble level performance evaluations in instrumented fire manikin tests and man-in-stimulant test procedures. It describes studies conducted to determine the impact of prototype garment design features on heat stress, wear comfort and ergonomic function in structural firefighting applications. PMID- 20540837 TI - Optimizing the protection against the physiological burden of CBRN clothing. AB - Soldiers can wear chemical, biological, radiological and nuclear (CBRN) protective clothing to be protected against warfare agents. The disadvantage of that clothing is that higher protection introduces higher physiological burden. Therefore an optimum between comfort and protection must be found. Models of all relevant processes were created to find this optimum. The airflow profile around a cylinder with clothing-representing a dressed human body part-was modelled. This flow profile was used for calculating the agent vapour breakthrough through the clothing and for calculating the deposition of agents onto the skin (as indicators for protection). The flow profile was also used for calculating the temperature profile around the body part and the relative humidity underneath and in the clothing (as representative for physiological burden). As a result a tool was created, which can be used to identify the optimum properties of CBRN protective clothing, depending on the intended mission of the soldiers. PMID- 20540838 TI - Effect of protective glove exposure to industrial contaminants on their resistance to mechanical risks. AB - In several industrial environments, mechanical risks are often combined with various contaminants such as oils and greases, which may reduce the performance of protective gloves against mechanical hazards. However, glove properties are characterized on new and clean specimens, and little is known about their residual resistance once contaminated and over time. In this study, a series of protective gloves used in metalworking companies and garages were exposed to relevant oils and greases. Used gloves were also obtained from a food processing center and a garage. Their residual resistance to mechanical risks (cutting, puncture and tearing) was evaluated using standard test methods. Results revealed in some instances a large decrease in resistance to mechanical risks. Since a corresponding change in the material aspect may not always be easily observable, this may lead to serious safety breaches. These findings demonstrate the need to further the research in this domain. PMID- 20540839 TI - The effect of cold protective clothing on comfort and perception of performance. AB - The physiological properties of clothing designed to provide protection against cold, windy and damp conditions affect comfort. The weight, thickness, stiffness of the fabrics and friction between the clothing layers affect physical performance. The comfort and perception of performance associated with 3 military winter combat clothing systems from different decades (the new M05 system, the previous M91 system and traditional clothing) were observed during a winter military manoeuvre. Subjective experiences concerning comfort and performance were recorded for 319 subjects using questionnaires. The most challenging conditions for comfort and performance were perspiration in the cold and external moisture. The new M05 system provided warmer thermal sensations (p < .010), dryer moisture sensations in the presence of external dampness (p < .001), dryer perspiration moisture sensations (p < .050) and better perception of physical (p < .001) and mental performance (p < .001) than the other systems. Careful development of the clothing system guarantees good comfort and performance during cold exposure. PMID- 20540840 TI - Testing sleeping bags according to EN 13537:2002: details that make the difference. AB - The European Standard on sleeping bag requirements (EN 13537:2002) describes a procedure to determine environmental temperature limits for safe usage of sleeping bags regarding their thermal insulation. However, there are several possible sources of error related to this procedure. The main aim of this work was to determine the influence of the various measuring parameters on the acuity of the respective parameters in order to judge the requirements. The results indicated that air velocity, mattress insulation and time between unpacking the bag and measurement had a significant impact on the result, with a difference of up to 5-15% in thermal insulation between minimum and maximum allowable parameter levels. On the other hand, manikin weight, thickness of the artificial ground and presence of a face mask were found to have a negligible influence. The article also discusses more general aspects of the standard including the calculation methods used. PMID- 20540841 TI - Analysis of steam formation and migration in firefighters' protective clothing using X-ray radiography. AB - X-ray radiography was used to quantify evaporation and moisture transfer in a multilayer firefighter protective clothing system with defined wetted layers exposed to low thermal radiation. Evaporation was faster and took place at higher temperatures if the moisture was located in the outer layers of the clothing system. Moisture that evaporated in the outer layers of the clothing system was found to move inwards and condense in the inner layers and on the cap of the measurement cell. Results found in this study correlated well with the findings of our former study based on simple temperature distribution measurements to determine moisture transfer in protective clothing layers at low level thermal radiation. PMID- 20540842 TI - Heat gain from thermal radiation through protective clothing with different insulation, reflectivity and vapour permeability. AB - The heat transferred through protective clothing under long wave radiation compared to a reference condition without radiant stress was determined in thermal manikin experiments. The influence of clothing insulation and reflectivity, and the interaction with wind and wet underclothing were considered. Garments with different outer materials and colours and additionally an aluminised reflective suit were combined with different number and types of dry and pre-wetted underwear layers. Under radiant stress, whole body heat loss decreased, i.e., heat gain occurred compared to the reference. This heat gain increased with radiation intensity, and decreased with air velocity and clothing insulation. Except for the reflective outer layer that showed only minimal heat gain over the whole range of radiation intensities, the influence of the outer garments' material and colour was small with dry clothing. Wetting the underclothing for simulating sweat accumulation, however, caused differing effects with higher heat gain in less permeable garments. PMID- 20540843 TI - Analytical study of the heat loss attenuation by clothing on thermal manikins under radiative heat loads. AB - For wearers of protective clothing in radiation environments there are no quantitative guidelines available for the effect of a radiative heat load on heat exchange. Under the European Union funded project ThermProtect an analytical effort was defined to address the issue of radiative heat load while wearing protective clothing. As within the ThermProtect project much information has become available from thermal manikin experiments in thermal radiation environments, these sets of experimental data are used to verify the analytical approach. The analytical approach provided a good prediction of the heat loss in the manikin experiments, 95% of the variance was explained by the model. The model has not yet been validated at high radiative heat loads and neglects some physical properties of the radiation emissivity. Still, the analytical approach provides a pragmatic approach and may be useful for practical implementation in protective clothing standards for moderate thermal radiation environments. PMID- 20540844 TI - Aspects of tests and assessment of filtering materials used for respiratory protection against bioaerosols. Part I: type of active substance, contact time, microorganism species. AB - This paper presents the results of a study on antimicrobial activity of polymer filter nonwovens produced by needle-punching or melt-blowing with an addition of disinfecting agents. The first part of the paper discusses how the biocidal activity of nonwovens is a function of the active agent added to the nonwovens, the duration of the contact of microorganisms with nonwovens and the type of microorganisms. The types of fibres and disinfecting agents had a considerable effect on the biocidal activity of nonwovens. The biocidal effect of nonwovens increased with the duration of their contact with microorganisms. Fibre activity differed considerably depending on the species of the microorganism. The microorganisms most sensitive to biocidal activity of the active filter nonwoven were S. aureus, M. flavus and E. coli. There were no biocidal effects on spore forming bacterium B. subtilis. PMID- 20540845 TI - Aspects of tests and assessment of filtering materials used for respiratory protection against bioaerosols. Part II: sweat in the environment, microorganisms in the form of a bioaerosol. AB - The second part of the article presents the results of a study of antimicrobial activity of filter nonwovens with an addition of biocides, as a function of the presence of sweat in the environment and the method of microbe deposition on a nonwoven in the form of a liquid and a bioaerosol. At the same time, the filtration efficiency of nonwovens against microorganisms in the form of a bioaerosol was tested with the dynamic method. The results showed that the addition of sweat on the surface of a nonwoven resulted in an insignificant decrease of biological activity that still remained high. Moreover, an active nonwoven showed biostatic and biocidal activity only when microbes were deposited on the surface in the form of a solution. The nonwoven did not show any biological activity after deposition of microorganisms with the dynamical method in the form of a bioaerosol. PMID- 20540846 TI - Predisposing factors, incidence and mortality of pneumothorax in a neonatal intensive care unit in Isfahan, Iran. AB - OBJECTIVE: To assess the predisposing factors, frequency and mortality of pneumothorax (PTX) among the newborns hospitalized in a neonatal intensive care unit (NICU) in Isfahan, Iran. METHODS: The data of 43 cases of PTX among the 738 neonates hospitalized in the NICU were analyzed retrospectively according to gestational age, birth weight, Apgar score, type of delivery, age of mother, parity, perinatal asphyxia, resuscitation at birth, side of PTX, mechanical ventilation, surfactant therapy, and underlying lung disorders. RESULTS: Mean gestational age was 31 weeks and birth weight was 1 596 g in the PTX cases. The gestational age of 12 (28%) neonates was less than 28 weeks. Twenty-eight (65%) neonates were below 1,500 g. In total, PTX occurred in 43 (5.8%) neonates. Sixty three episodes of PTX (97%) were unilateral and 2 (3%) were bilateral. Respiratory distress syndrome (RDS) (40/43, 93%) and mechanical ventilation (37/43, 86%) were common predisposing factors of PTX. Overall, 28 (65%) neonates with PTX died. Birth weight, gestational age and chest tube duration were significantly different between dead and surviving infants. The mortality rate was significantly higher in neonates who required surfactant therapy than that in those who did not require it. CONCLUSIONS: The incidence and mortality of PTX in this study were higher than some other reports and this might be attributed to lower birth weight and gestational age. RDS and mechanical ventilation were the most common predisposing factors for the development of neonatal PTX, and mortality increased with lower birth weight, lower gestational age and more severe underlying primary lung disease. PMID- 20540847 TI - [A control study of aripiprazole and tiapride treatment for tic disorders in children]. AB - OBJECTIVE: To evaluate the efficacy and safety of aripiprazole in the treatment of tic disorder when tiapride is used as a control. METHODS: Sixty-five children aged 6-14 years old with tic disorders were randomly assigned to two groups: aripiprazole (2.5-10 mg/d) and tiapride treatment (25- 400 mg/d). After 12 weeks treatment, the clinical efficacy was assessed by the Yale Global Tie Severity Scale (YGTSS) score and the adverse reactions were observed. RESULTS: The YGTSS score in both groups decreased from the second week of treatment. Compared with the tiapride treatment group, the aripirazole treatment group showed a more decreased YGTSS score (29+/-13)% vs (16+/-14)%; P<0.01 by the second week of treatment. The overall effective rate in the aripiprazole and tiapride treatment groups was 91% and 84%, respectively (P>0.05) 12 weeks after treatment. There were no significant differences in the incidence of adverse reactions between the aripiprazole and tiapride treatment groups and no severe adverse events were found in either group. CONCLUSIONS: Low dose aripiprazole is safe and effective for treatment of tic disorders in children, suggesting that it represents a new valid option for the treatment of tic disorder. PMID- 20540848 TI - [Clinical application of proton magnetic resonance spectroscopy in children with idiopathic epilepsy]. AB - OBJECTIVE: This study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children. METHODS: Thirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls. RESULTS: MRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups. CONCLUSIONS: 'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy. PMID- 20540849 TI - [Effect of UGTIA6 A541G genetic polymorphism on the metabolism of valproic acid in Han epileptic children from Henan]. AB - OBJECTIVE: To investigate the distribution and frequency of UGTIA6 A541G genetic polymorphism in Han epileptic children from Henan and to evaluate the effect of UGTIA6 A541G genetic polymorphism on serum concentrations of valproic acid. METHODS: The method of gas chromatography was used to assay serum concentrations of valproic acid. UGTIA6 A541G genetic polymorphism was screened by PCR-RFLP. Direct sequencing was used to confirm the expected sequences of each genotype. RESULTS: The genotypic frequencies of UGTIA6 A541G were as follows: AA in 76 cases, AG in 65 cases and GG in 6 cases. The mean values of serum concentrations of valproic acid in patients with A541G AA, AG and GG were 3.91+/-1.57, 3.59+/ 1.39 and 3.73+/-1.28 microg/mL, respectively (dose-adjusted trough concentration on a mg/kg basis). There were no significant differences in serum concentrations of valproic acid among the three groups. CONCLUSIONS: UGT1A6 A541G gene polymorphism does not influence serum concentrations of valproic acid in Han epileptic children. Individual differences in serum concentrations of valproic acid may be attributed to many factors. PMID- 20540850 TI - [Gynecomastia in 38 children: etiology and treatment]. AB - OBJECTIVE: To summarize the etiology and treatment of gynecomastia in male children. METHODS: The clinical data of 38 boys with gynecomastia at ages of 2-14 years were retrospectively studied. RESULTS: In the 38 cases, 17 cases were identified as adolescent breast hyperplasia, 2 cases were relevant to primary disease, 4 cases were caused by ingestion of drugs containing hormone, and 15 cases did not show identifiable causes and were diagnosed as idiopathic gynecomastia. For the 3 children with breast development in B3 stage, oral rupixiao was administered (1.34 g, tid) for one month. For 16 children at ages of over 12 years with breast development in B2 stage and with obvious clinical symptoms, oral rupixiao was administered (1.34 g, tid) for 3-5 days. The other patients did not receive drug treatment. In a one month to one year follow-up, most of the patients recovered well. CONCLUSIONS: The etiology of gynecomastia in male children includes adolescent breast hyperplasia, ingestion of drugs containing hormone and secondary causes. Most gynecomastia can be attributed to physiological reasons. Only a few children with obvious clinical symptoms need drug treatment. PMID- 20540851 TI - [Correlation between right ventricular function and the indexes of blood gas in neonates with hypoxic pulmonary hypertension]. AB - OBJECTIVE: To evaluate the relationship of right ventricular function with the indexes of blood gas in neonates with hypoxic pulmonary hypertension (HPH). METHODS: Sixty-seven neonates with HPH (29 mild, 23 moderate and 15 severe) and 22 gestational age- and weight-matched neonates without HPH (control group) were enrolled. On postnatal days 1, 3 and 7, pulmonary artery systolic pressure (PASP) was measured by pulsed Doppler echocardiography. Systolic wave of ventricular (Sa), early diastolic wave (Ea), late diastolic wave (Aa), and Ea/Aa ratio were determined by the tissue Doppler imaging (TDI) technology. Artery oxygen pressure (PaO(2)), fractional concentration of inspired oxygen (FiO(2)), and PaO(2)/ FiO(2) ratio were simultaneously observed. RESULTS: On postnatal day 1, PaO(2) and PaO(2)/FiO(2) ratio as well as Ea and Ea/Aa ratio were significantly lower, while PASP was significantly higher in the HPH groups than those in the control group. Sa decreased in the moderate and severe HPH groups, Aa increased in the moderate HPH group, and Aa decreased significantly in the severe HPH group compared with that in the control group. On postnatal day 3, PaO(2) and PaO(2)/FiO(2) ratio returned to normal level in the mild and moderate HPH groups, while other indexes remained abnormal. On postnatal day 7, all the indexes above returned to normal level in the mild HPH group; Ea and Ea/Aa ratio were still significantly lower in the moderate HPH group, and the other indexes returned to normal level; in the severe HPH group, only PaO(2) and PaO(2)/FiO(2) ratio returned to normal level. CONCLUSIONS: The changes and recovery of diastolic and systolic functions of right ventricular are not paralleled with hypoxia and PASP in neonates with HPH. It is helpful for the diagnosis and treatment of HPH by monitoring PASP and right ventricular function with TDI. PMID- 20540852 TI - [Erythrocyte oxidative stress in children with left to right shunt congenital heart disease]. AB - OBJECTIVE: To study erythrocyte oxidative stress status and its association with left to right shunt congenital heart disease (CHD) in children. METHODS: A total of 31 children with left to right shunt CHD were enrolled, including 7 cases of atrial septal defect (ASD), 12 ventricular septal defect (VSD), 4 patent ductus arteriosus (PDA), 6 patent foramen ovale (PFO), and 2 complete endocardial cushion defect. Twenty healthy age-matched (1 month to 3 years old) children severed as the control group. The contents of superoxide dismutase (SOD) and malonaldehyde (MDA) in erythrocytes were determined using ELISA. ESR was measured by Westergen. PaO(2) and PaCO(2) were measured by Blood Gas Analyzer (GEM Premier 3000). RESULTS: The MDA content in erythrocytes in the CHD group was significantly higher, in contrast, SOD content was significantly lower than that in the control group (P<0.05). The CHD children with heart failure had more decreased SOD and more increased MDA contents compared with the control group (P<0.01). The SOD level was the highest in the PFO group and was the lowest in the complete endocardial cushion defect group. The SOD level in the PFO group was significantly higher than that in the ASD, VSD and complete endocardial cushion defect groups (P<0.05). The MDA level was the highest in the VSD group and was the lowest in the complete endocardial cushion defect group. There were significant differences in the MDA level among CHD subgroups (P<0.05). The ESR was negatively correlated to the SOD level (r=-0.191, P<0.05), while positively correlated to PaO(2) level in CHD children (r=0.216, P<0.05). There was a negative correlation between SOD and MDA levels (r=-0.312, P<0.05). CONCLUSIONS: Oxidative stress exists in children with left to right shunt CHD. The SOD and MDA contents in erythrocytes can be used as markers for the assessment of severity of the disease. PMID- 20540853 TI - [Expression of IL-8, SP-A and TGF-beta1 in bronchoalveolar lavage fluid of neonates with bronchopulmonary dysplasia]. AB - OBJECTIVE: To investigate the expression of interleukin 8 (IL-8), surfactant protein-A (SP-A) and transforming growth factor beta1 (TGF-beta1) in bronchoalveolar lavage fluid (BALF) of neonates with bronchopulmonary dysplasia (BPD). METHODS: Thirty neonates with BPD and 30 gestational age-, gender-, and birth weight-matched neonates without BPD (control group) were enrolled from December 2007 to October 2009. Non-brochoscopic bronchoalveolar lavage was performed. The levels of IL-8, SP-A and TGF-beta1 in BALF were measured using ELISA. RESULTS: The levels of TGF beta1 (47+/-15 microg/mL vs 34+/-13 microg/mL) and IL-8 (54+/-16 microg/mL vs 28+/-13 microg/mL) in the BPD group were significantly higher than those in the control group (P<0.01). In contrast, the contents of SP-A in the BPD group were significantly lower than those in the control group (35+/-16 microg/mL vs 42+/-14 microg/mL;P<0.05). CONCLUSIONS: The increased expression of TGF-beta1 and IL-8 in BALF may be involved in abnormal lung development and maturation in neonates with BPD. The low expression of SP-A in the BPD group suggests that the exogenous SP-A administration may be an option for the treatment of BPD. PMID- 20540854 TI - [Findings of electric bronchoscopy in 67 children with recurrent wheezing]. AB - OBJECTIVE: To investigate the common causes of recurrent wheezing in young children. METHODS: Electronic bronchoscopy was performed on 67 children with recurrent wheezing or who did not respond to the conventional treatment. RESULTS: The electronic bronchoscopy showed intimitis in trachea and bronchi in 19 cases, intimitis and inflammatory stricture in 11 cases, foreign bodies in the bronchi in 11 cases, trachea and bronchus softening in 19 cases, and bronchopulmonary dysplasia in 3 cases. The other 4 cases presented endometrial tuberculosis, epiglottic cyst, laryngeal papilloma or compression outside trachea (thymus) under the electronic bronchoscope. CONCLUSIONS: In addition to inflammation, trachea and bronchus softening as well as foreign bodies in the bronchi are also the common causes in children with recurrent wheezing or who do not respond to the conventional treatment. Electronic bronchoscopy appears to be an effective way to determine the cause in these children. PMID- 20540855 TI - [Detection of Mycoplasma pneumoniae, Chlamydia trachomatis and common respiratory viruses in children with acute respiratory infection in Nanjing]. AB - OBJECTIVE: To investigate the nonbacterial pathogens in children with acute respiratory infection (ARI) in Nanjing. METHODS: The presence of Mycoplasma pneumoniae (MP) and Chlamydia trachomatis (CT) was determined by quantitative PCR in the nasopharyngeal samples from 1 592 hospitalized children with ARI. Common respiratory viruses, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus types A and B (IVA and IVB), parainfluenza virus types 1, 2, 3(PIV-1, 2, 3) and human metapneumovirus (hMPV), were detected using direct immunofluorescence assay. RESULTS: MP and CT were detected in 25.7% and 2.4% of the 1 592 samples respectively. The overall positive rate of respiratory viruses was 40.9%. Among the viruses, the top detected virus was RSV (61.3%), followed by PIV-3 (6.7%) and hMPV (4.9%). Mixed infection among MP, CT and viruses was observed in 107 cases (6.7%). The infants under 1 year old were susceptible to mix-infection (68/107, 63.6%). CONCLUSIONS: Respiratory virus is the main pathogen responsible for ARI in children from Nanjing. RSV is the most commonly identified virus. MP is also the frequently identified pathogen for ARI in children. Mixed infection is common in infants under 1 year old. PMID- 20540856 TI - [Determination and clinical significance of tissue inhibitors of metalloproteinase-1 and -2 in serum of children with nonalcoholic fatty liver disease]. AB - OBJECTIVE: To examine serum tissue inhibitors of metalloproteinases (TIMP) -1 and -2 levels in children with nonalcoholic fatty liver disease and to investigate possible roles of the two markers. METHODS: One hundred and five obese children were classified into 4 groups: simple obesity (n=44), simple nonalcoholic fatty liver (SNAFL, n=25), and nonalcoholic steatohepatitis (NASH, n=36). Serum TIMP-1 and -2 levels were measured using ELISA. Serum ALT and gamma-GT levels were measured with totally automatic enzymatic method. RESULTS: Serum levels of TIMP-1 and gamma-GT increased with the disease development from simple obesity to SNAFL and NASH (P<0.05). Both serum TIMP-1 and -2 levels were positively correlated with gamma-GT levels (r=0.534, P<0.01; r=0.351, P<0.05, respectively). Ninety seven percent of children in the NASH group had serum TIMP-1 levels over 2 standard deviations of healthy controls (83.35 microg/ L) compared with 76% in the SNAFL group (P<0.05). There were no significant differences in the case proportion with TIMP-2 levels over 2 standard deviations of healthy controls between the NASH and the SNAFL groups. CONCLUSIONS: Both TIMP-1 and -2 may reflect the state of liver fibrosis in children with nonalcoholic fatty liver disease, and serum TIMP-1 appears to be more reliable. PMID- 20540857 TI - [Insulin-like growth factor 1 levels and their association with growth and development in infants aged 1-24 months]. AB - OBJECTIVE: To study serum insulin-like growth factor 1 (IGF-1) levels and their association with growth and development in infants aged 1-24 mouths. METHODS: A total of 525 healthy infants (125 preterm, 400 term) were enrolled. Serum IGF-1 levels were measured using ELISA 1.5, 4, 6, 8, 12, 18 and 24 months after birth. The body weight and body length were simultaneously measured. RESULTS: Serum IGF 1 levels were the lowest in preterm infants 1.5 months after birth (86+/-60 ng/mL). Thereafter, serum IGF-1 levels increased, and were significantly higher than those in term infants between 4 and 12 months after birth. Serum IGF-1 levels in term infants were the highest (116+/-52 ng/mL) 1.5 months after birth during their life of 12 months old. Thereafter, serum IGF-1 levels decreased and reached to a nadir (69+/-58 ng/mL) 8 months after birth. IGF-I levels were positively correlated with the weight and the height (SDS) in both preterm and term infants. CONCLUSIONS: Serum IGF-1 levels are closely associated with growth and development in infants. PMID- 20540858 TI - [Effectiveness of educational interventions in children with chronic diseases and their parents]. AB - OBJECTIVE: To evaluate the effectiveness of educational interventions in children with chronic illness and their parents. METHODS: Fifty children with chronic illness and 75 parents participated in the study. Children who were hospitalized between August 2007 and January 2008 and their parents received educational sessions and those who were hospitalized between February and July 2007 and who did not receive the sessions served as the control group. The content of the educational sessions included knowledge of chronic disease, drugs and self-care, and coping skills. The knowledge level, stressors, coping strategies, and psychological conditions of children with chronic illness and their parents were evaluated before discharge and three months after discharge. RESULTS: After educational interventions, the knowledge levels of children and their parents increased and the stressors decreased significantly in the intervention group compared with those in the control group. The children's parents in the intervention group used more active coping strategies (understanding the medical situations through communication with medical staff) than those in the control group. The differences in the medication compliance of children between the two groups were not found. CONCLUSIONS: The educational interventions may result in an improved knowledge level and decrease stressors in children and their parents, and improve stress coping strategies in parents. There is no evidence that the educational intervention can improve the psychosocial conditions of children and their parents. PMID- 20540859 TI - [Effects of different severities of hypoxia-ischemia on brain injury in neonatal rats]. AB - OBJECTIVE: To compare the features of brain injury in neonatal rats with different severities of hypoxia-ischemia (HI), and explore the role of microglial activation and cytokines. METHODS: One hundred and twenty 7-day-old rats were randomized to three groups: sham control, mild HI, and severe HI. The rats in the HI groups were subjected to right carotid artery occlusion and 8% oxygen hypoxia exposure (40 minutes, 34.5 Celsius degree in the mild HI group; 65 minutes, 35.5 Celsius degree in the severe HI group). MRI, microtubule associated protein (MAP2) and TUNEL staining were used to confirm the severity of brain injury. Changes in expression of activated microglia (ED1) and signs of cytokine involvement or oxidative stress (TNF-alpha, nitrotyrosine) were assessed immunohistochemically. RESULTS: In the mild HI group, MRI scans demonstrated increased T2 values in the ipsilateral subcortical white matter and a slight loss of T2 values in the cortex, corresponding to a medium loss of MAP2 in the ipsilateral cortex. There was an increase in the number of TUNEL positive cells compared to the control group within the subcortical white matter. In the severe HI group, the T2 value increased in the majority of the hemisphere, corresponding to a severe loss of staining for MAP2 in the ispilateral hemisphere. The number of TUNEL positive cells significantly increased in the ipsilateral cortex and white matter. In the mild HI group, ED1, TNF-alpha and nitrotyrosine expression increased only in the acute stage and was only observed in subcortical white matter. In contrast, after severe HI, the increase in ED1, TNF-alpha and nitrotyrosine expression was observed in the whole ipsilateral hemisphere and prolonged for weeks. CONCLUSIONS: Following a mild HI a relatively selective white matter injury compares to the pannecrosis in the cortex and white matter following a severe HI. Microglial activation and over-expression of cytokines might contribute to the development of hypoxic-ischemic brain damage. PMID- 20540860 TI - [Immortalized mouse brain endothelial cell line Bend.3 displays the comparative barrier characteristics as the primary brain microvascular endothelial cells]. AB - OBJECTIVE: The purpose of this study was to assess weather the immortalized mouse brain endothelial cell line Bend.3 displays the comparative barrier characteristics as the primary brain microvascular endothelial cells (BEMC). METHODS: Immortalized mouse brain endothelial cell line, Bend.3 cells were cultured in transwell inserts and their restrictive characteristics were assessed by transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) permeability assays. Western blot and direct fluorescent staining methods were used to detect the tight junction protein expression and F-actin distribution. RESULTS: The TEER in Bend.3 cells increased with the prolonged culture time and increased to 82.3+/-6.0 Omega cm2 10 days after culture, which was significantly higher than that 3 days after culture (37.3+/-3.1 Omega cm2; P<0.05). There were significant differences in the permeability rates for HRP 3 and 10 days after culture (4.3+/-0.20)% vs (2.2+/-0.05)% (P<0.05). Western blot indicated high level expression of tight junction proteins occludin and ZO-1 in Bend.3 cells 10 days after culture. F-actin was visualized around the cell membrane and presented scrobiculate linear fluorescence 10 days after culture. CONCLUSIONS: Bend.3 cells have similar barrier characteristics to BEMC, and their barrier function may reach to the best effect 10 days after culture. PMID- 20540861 TI - [Effects of valproate acid on blood lipid, serum leptin and cerebral cortex in juvenile and adult rats]. AB - OBJECTIVE: To study the effects of valproate acid (VPA) on serum lipid and leptin levels and cerebral cortex in juvenile and adult rats. METHODS: Twenty healthy juvenile female Sprague-Dawley (SD) rats (21-day-old) and twenty healthy adult female SD rats (2-month-old) were randomly divided into four groups (n=10 each): juvenile control, juvenile VPA, adult control and adult VPA. Juvenile and adult VPA groups were fed with VPA 200 mg/kg daily, while the two control groups were fed with normal saline. The body weights were recorded weekly. Six weeks after feeding, serum and brain samples were obtained. Serum lipid levels including total cholesterol (TC), triglycerides (TG) and lower density lipoprotein cholesterol (LDL-C) were determined. Serum leptin (LEP) levels were measured by radioimmunoassay (RIA). Myelin staining and Nissl staining were used to evaluate the changes of brain tissues. RESULTS: The weight and serum LEP and lipid levels in both juvenile and adult VPA groups increased significantly compared with those in the control groups (P<0.05). The juvenile VPA group had more increased serum LEP and lipid levels than the adult VPA group (P<0.05). The Myelin staining showed that the average fiber density in the VPA groups was significantly lower than that in the control groups (P<0.05). The Nissl staining showed that the number of toluidine blue staining neurons in the VPA groups was not statistically different from the control groups. CONCLUSIONS: VPA may increase serum LEP and lipid levels in both juvenile and adult rats, and more increased levels may be found in juvenile rats. Long-term VPA treatment may have an adverse effect on brain myelination, but no effect on neurons. PMID- 20540862 TI - [Bone mesenchymal stem cell transplantation repairs glomerular podocytes in rats with puromycin aminonucleoside-induced nephrosis]. AB - OBJECTIVE: To investigate the effect of bone mesenchymal stem cell (BMSC) transplantation on repair of glomerular podocytes and on the Nephrin expression in rats with puromycin aminonucleoside (PAN) -induced nephrosis. METHODS: Forty five Sprague-Dawley rats were randomly divided into three groups (n=15 each): a nephrosis model group that received a single intraperitoneal injection of PAN (0.15 mg/g); a BMSC transplantation group that received a single intraperitoneal injection of PAN (0.15 mg/g) followed by BMSC transfusion; a control group that received a single intraperitoneal injection of normal saline. Ten days after injection, the rats were sacrificed. The 24 hrs urinary protein content and serum albumin and cholesterol levels were measured 24 hrs before sacrifice. Changes of glomerular podocytes were observed under an electron microscope. Brdu labeled positive cells in kidneys were measured by immunohistochemical technology. RT-PCR and Western blot were used to assess the expression of mRNA and protein of Nephrin. RESULTS: In the nephrosis model group, urinary protein and blood cholesterol contents increased, plasma albumin content decreased compared with those in the control group. Extensive fusion of podocyte foot processes was observed in the nephrosis model group. The BMSC transplantation group had decreased urinary protein and blood cholesterol contents and increased plasma albumin content compared with the nephrosis model group. Fusion of podocyte foot processes was also improved. Brdu labeled positive cells were seen in kidneys in the BMSC transplantation group, but not in the nephrosis model and the control groups. Nephrin mRNA and protein expression decreased significantly in the nephrosis model group compared with that in the control group. The BMSC transplantation group had increased Nephrin mRNA and protein expression compared with the nephrosis model group. CONCLUSIONS: BMSCs can repair glomerular podocytes in PAN-induced nephrosis rats, and the changes of Nephrin expression may be involved in the process. PMID- 20540863 TI - [Changes of body mass index and plasma galanin in children with epilepsy following valproate sodium treatment]. PMID- 20540864 TI - [Severe Bacillus Calmette-Guerin lymphadenitis and X-linked chronic granulomatous disease in children]. PMID- 20540865 TI - [Brucellosis in children: report of 6 cases and literature review]. PMID- 20540866 TI - [Congenital neuromuscular disease with uniform type 1 fiber complicated by brain atrophy: a case report]. PMID- 20540867 TI - [Cutaneous T-cell lymphomas complicated by renal injury: a case report]. PMID- 20540868 TI - [Strategies for the prevention and treatment of intravascular catheter related complications]. PMID- 20540869 TI - [Research advance in glucocorticoids therapy for meconium aspiration syndrome]. PMID- 20540870 TI - [Use of sildenafil in children with pulmonary arterial hypertension]. PMID- 20540871 TI - [Hypertrophic cardiomyophthy: a family report]. PMID- 20540872 TI - [World Health Organization manual for the processing of human semen-2010]. PMID- 20540873 TI - [Penile morphometric changes after radical prostatectomy: Evidence-based]. AB - INTRODUCTION: Radical prostatectomy in all its approaches is the treatment of choice for localized prostate cancer and especially in young, sexually active patients with a desire to keep their sex life. In addition to the well-known and defined postoperative erectile dysfunction, erectile silent period causes, in many patients (9-1%), structural changes, in the penile structure, sometimes irreversible. These tissue changes, resulting in a loss of length and girth, that concern patients. OBJECTIVE: To systematically review to date published data in the literature regarding penile changes after radical prostatectomy. MATERIAL AND METHODS: We performed a systematic search in: PubMed, EMBASE, Cochrane, SCOPUS, Science Citation Index period January 1990 to September 2009 for the terms prostatectomy, organ size, fibrosis, sexual activity, erectile dysfunction, penile size, radical prostatectomy, prostatic neoplasms, body weights and penis measures. Seven series of patients were selected for analysis. RESULTS: We described the different measurement methods and their potential biases and differences. Also, we reviewed main physiopathogenic theories to explain this phenomenon. Finally, we detail the results of different series of patients reported. CONCLUSIONS: It seems to be a proven fact that the penis undergoes major changes in its length and girth after radical prostatectomy. Several authors have communicated the data of their series and the different treatment options (5PDE inhibitors, vacuum devices, penile extenders, etc.). Strategies addressed to preserve and protect cavernous tissue and tunica albuginea after the procedure, as well as to increase oxygenation and allow erection to be recovered in the shortest possible time positive will impact on the quality of life of our patients. PMID- 20540874 TI - [Management of adrenal mass: What urologists should know]. AB - Adrenal incidentaloma's prevalence is rising because of the big volume of radiologic explorations that we daily do. No comprehensive guidelines have been published by professional societies to guide the evaluation of patients with adrenal incidentalomas. All adrenal masses should be inspected for malignancy or hypersecreting disorders. In our point of view, adrenal surgery should be performed by the urologist, because it's the medical speciality which knows the best this anatomical region. The objective of this review is to present the main points that the urologist may know in the management of adrenal masses. Together with the department of Endocrinology of our hospital, we describe the main studies to perform in front of adrenal mass diagnosis and the current therapeutical diagram utilized in our center. PMID- 20540875 TI - [Stem cells and regenerative medicine in urology, part 2: urothelium, urinary bladder, urethra and prostate]. AB - INTRODUCTION: Investigation in cell therapy and regenerative medicine, mainly developed around stem cell research, is reaching promising results in every medical specialities. There are also being great advances in Urology, despite the difficulties researchers are facing, as complete identification and isolation of human urothelial and prostatic stem cells has not been possible yet, although many groups are close to achieve it. MATERIAL AND METHODS: We performed an electronic research through the Pubmed database, of both original and review publications, with the following search criteria: "stem cells urology", "urothelial stem cells", "bladder stem cells", "prostate stem cells", "urethra stem cells", "cell therapy urology", "tissue engineering urology" y "regenerative medicine urology". RESULTS: We reviewed 30 articles published up to November 2009, trying to summarize thoroughly the most relevant findings and the last advances in this field, from the first steps to this day. CONCLUSION: Despite the great lack of knowledge existing, especially the need for achieving the identification of kidney, urothelium and prostate stem cells, this shouldn't prevent researchers from translating the laboratory results to the clinical work. PMID- 20540876 TI - [Extraperitoneal endoscopic radical prostatectomy: How steep is the learning curve? Overheads on the personal evolution technique in 5-years experience]. AB - OBJECTIVE: Prospectively investigate endoscopic extra peritoneal radical prostatectomy (EERP) learning curve impact on outcomes. MATERIALS AND METHODS: In a 5 year period (2004-2008) 270 patients underwent 5-6 ports laparoscopic radical prostatectomy at a referral center in Brazil. The initial 70 cases learning curve protocol included low body mass index patients with low volume, low grade prostate cancer. After that there were no criteria to exclude laparoscopic surgery. The patients were analyzed in two groups: Group 1, first 70 patients (30 transperitoneal and 40 extra peritoneal)-learning curve and Group 2, last 200 patients - EERP only. Surgical and outcome parameters were compared through Student's t test and Fisher's Exact Test. RESULTS: The mean age was 65 years (+/ 8.2) and comparing Groups 1 and 2, mean operative time was 300 (+/-190) versus 180 (+/-100) minutes, blood loss 330 (+/-210) versus 210 (+/-180) mL, hospital stay 3 (2 to 5) versus 2 (1 to 3) days, positive surgical margins 15% versus 10%, erection sufficient to penetration in previous potent patients 73.3% versus 75%, respectively with no difference between groups. Overall, 78% of patients referred no previous impotence with groups' equivalence. Severe urinary incontinence, transfusion and complications rates were higher in group 1 (p<0.05): 10% versus 2%, 12% versus 2.25% and 30% versus 12.5%, respectively. Peritoneum perforation occurred in 40% and conversion to open surgery was not required. Nerve sparing procedure was applied in 85%. In 3.5-years mean follow-up 90% of patients were free of PSA recurrence with no difference between groups. CONCLUSION: Severe urinary incontinence, transfusion and complications rates are related to learning curve which is continuous, although a significant improvement is pragmatic after 70 cases. An intensive mentored training program should be considered to minimize the learning outlays. PMID- 20540877 TI - [Practical treatment approach of radiation induced cystitis]. AB - OBJECTIVE: Establish a pattern of behavior and treatment algorithm at the onset of hematuria in patients with a previous history of pelvic radiation, checking for this different treatment options reflected in the literature. MATERIAL AND METHODS: Through performing a PubMed literature review of articles related to IC lies, searching items includes the different treatment options: intravesical hyaluronic acid, conjugated estrogens, pentosan polysulfate, oral aminocaproic acid, recombinant factor VIIa, hyperbaric chamber, embolization, aluminum intravesical, Helmstein ball and formalin. Limits the search to english or spanish publications and excluding those related to animal experimentation. RESULTS: Every option is exposed, referring to the physiopathology, dosage regimen and administration, side effects and treatment efficacy. CONCLUSIONS: Once patient hemodynamic stabilization is achieved, and after rule out bladder tumors injuries and /or haemathuria originating from the upper urinary tract, treatment should start rolling. To know different treatment options and patterns of administration will allow the urologist to obtain a higher rate of success in the difficult management of this condition. PMID- 20540878 TI - [Metastatic progression, cancer-specific mortality and need for secondary treatments in patients with clinically high-risk prostate cancer treated initially with radical prostatectomy]. AB - PURPOSE: To determine our results in high risk (HR) prostate cancer (PCa) patients treated with radical prostatectomy (RP) and to establish preoperative prognosis factors. MATERIAL AND METHODS: Retrospective study of 925 RP. Mean follow-up for the HR group was 89.8+/-53.6 months. Following NCCN criteria, we operated 210 (22.7%) HR and 715 (77.3%) low/intermediate risk patients. End point was metastatic progression. Kaplan-Meier method for survival comparison among groups and Cox regression model for multivariate analysis of preoperative prognostic factors were used. RESULTS: Revised period; 1986-2007. Fifty-four patients (25.7%) were free of disease and 8 patients (3.8%) died for other causes free of disease. Disease progressed in 148 patients (70.5%); death due to tumour progression occurred in 42 cases (20%) and due to other causes in 25 patients (11.9%). Seventy-nine patients in HR group (38%) vs 549 low/intermediate risk group (78.5%) did not deserve further treatments (p<0.001). The uni and multivariate analysis for metastatic progression showed both Gleason score at biopsy (RR=1.922; 95% CI 1.106-3.341, p=0.020) and clinical stage (RR=2.290; 95% CI 1.269-4.133, p=0.006) showed independent prognostic value for metastatic progression, but not PSA. CONCLUSIONS: A HR patient can be cured in a third of the cases and will need multimodal treatments in more than half of the times. We prompt surgery in a young healthy patient with a resectable tumour, mainly if just one bad prognostic factor is present and defiantly if this is just PSA elevation. PMID- 20540879 TI - [Analysis of overactive bladder and urinary incontinence in working women aged between 25 and 64 years. EPICC study]. AB - INTRODUCTION: Urinary symptoms Overactive Bladder (OAB) and Urinary Incontinence (UI) result in an important personal and economic impact. This work concentrates on the detailed analysis of OAB and UI (derived symptoms and tendencies in medical consultation and resource consumption), in a sample of working women aged 25-64. MATERIAL AND METHODS: Study within the framework of the EPICC study of the Spanish Association of Urology (epidemiologic, observational, multicentric, national study) and concentrates on the detailed analysis of the characteristics of the sample of working women aged 25-64 (N=3090) and of the subgroup of individuals with VH and/or IU (N=307). RESULTS: 4.01% of the subjects presented UI alone, 2.69% OAB alone, 3.24% presented both pathologies. There exists association between UI and/or VH presence and frequent urinary infections, hypertension and diabetes. Taking into account individuals with UI and/or OAB, 28.01% had problems to retain urine, and 16.94% suffered leakage daily; 27.36% suffered uncontrollable urge to urinate daily; 57.65% had never sought medical advice, 35.40% had visited an specialist, 23.13% would like to visit an specialist in incontinence; 28.01% had received treatment, from which 55.81% had received physiotherapy and 25.58% pharmacologic treatment. CONCLUSION: In this study, specific data about VH and IU in working women aged 25-64 are presented, including those referring to the magnitude of these conditions and use of sanitary resources in subjects with UI and/or OAB, aiming at contributing to a better diagnose and handling of patients and resources. PMID- 20540880 TI - [Relation between selenium plasma levels and different prostatic pathologies]. AB - Several studies have demonstrated an inverse relation between serum selenium levels (Se) and advanced prostate cancer (PCa). OBJECTIVE: To determine and compare selenium plasma levels in patients with different prostatic pathologies. MATERIAL AND METHODS: It is a transversal, descriptive and comparative study. A sample of 64 men between 50 and 80 years old were selected for the study between 2007 and 2009. All volunteers underwent a digital rectal examination, prostate specific antigen level, ultrasound and transrectal prostate biopsy (12-14 chips). Prostate cancer was subclassified according to Gleason Score. Selenium was determined indirectly by serum Glutathione peroxidase (Kit Ransel, Randox SRL, Crumlin, UK). Statistical analysis was performed using ANOVA I (p<0.05). RESULTS: Glutathione Peroxidase level was 33.75+/-2.36 mg/ml in control patients. A decrease of 31.6% was observed in patients with BPH (23.08+/-1.57 mg/ml) and of (63.6%) in subjects with prostate cancer (12.28+/-1.03 mg/ml) (p<0,0001). There was no correlation with the Gleason Score. CONCLUSION: Serum Seleniun is lower in patients with prostatic pathologies being even more important in cancer patients regardless the Gleason Score. PMID- 20540881 TI - [Is it possible to predict postoperative ileus following radical cystectomy?]. AB - OBJECTIVE: Radical cystectomy with urinary diversion is a procedure in which a reduction of morbidity, quick postoperative rehabilitation, limited length of stay and cost containment are difficult to achieve. Postoperative ileus has been identified as the most common cause of delayed recovery and prolonged length of stay. With our review, we try to establish the main causes. MATERIAL AND METHODS: A total of 154 patients underwent radical cystectomy from 1990 to 2008. We examined demographic and perioperative variables of the patients who did and did not develop ileus. RESULTS: No significant association was found between ileus and all the factors we studied. CONCLUSIONS: Postoperative ileus stands out as one of the most frequent complications that causes increased length of stay. More detailed studies are required to determine perioperative regimens to reduce this complication. PMID- 20540882 TI - [Is age a predictor for the development of hypertension in conservatively managed unilateral renal artery occlusion secondary to blunt abdominal trauma?]. AB - OBJECTIVE: To present 2 cases with unilateral renal artery occlusion after blunt trauma conservatively treated and review, in the literature, the role of age as a prognostic factor for the development of hypertension. MATERIAL AND METHODS: A 14 and 12 y/o male and female passengers, who were unrestrained in the back seat of a car, were involved in different motor vehicle accidents. Both remained in the seat and arrived at the Pediatric Emergency Department with normal vital signs. Computerized tomography scans showed unenhancing kidneys. Conservative management was advocated. RESULTS: After 38 and 36 months follow-up, respectively, normal renal function and arterial pressure. We found only 7 cases in the literature where age < or =16 was reported and treatment was conservative. Nine in total, hypertension developed in 2(22%). CONCLUSIONS: No conclusion could be made with such a small sample. There is enough evidence in the literature supporting conservative management at all ages. PMID- 20540883 TI - [Unusual presentation of Castleman's disease like an upper urinary tract carcinoma]. PMID- 20540884 TI - [Collecting duct carcinoma. Case report and a review of the literature]. PMID- 20540885 TI - [Delayed scrotal trauma consultation]. PMID- 20540886 TI - [Prenatal hydronephrosis due to congenital ureteral valves]. PMID- 20540887 TI - [Metrorrhagia as form of presentation of ovary metastases from a primary renal cell carcinoma]. PMID- 20540888 TI - [Phyllodes tumour of the seminal vesicle: case report and revision of literature]. PMID- 20540889 TI - [Renal artery pseudoaneurysm after partial nephrectomy. Diagnosis, treatment and literature review]. PMID- 20540890 TI - [Melanoma of male urethra: A clinical case]. PMID- 20540895 TI - [Introduction. Relevant problems in cardiology 2009]. PMID- 20540896 TI - [From complex multivessel disease to cardiovascular health]. AB - The development of drug-eluting stents has raised great hopes that percutaneous coronary intervention has a potential role in the revascularization of patients with three-vessel disease and left main coronary artery disease. However, recent results from the SYNTAX clinical trial have shown that, compared with drug eluting stents, bypass surgery is associated with a lower restenosis rate and a reduced incidence of major cardiovascular events. This study used an index that quantifies the severity of coronary artery disease on the basis of a number of anatomical criteria of lesion complexity (i.e. the SYNTAX score). The study results indicate that the higher the index (i.e. the more complex the lesion), the greater the benefits of surgery. Other recent studies (e.g. PROSPECT and FAME) have used imaging to investigate the natural history of acute coronary syndrome, or the role of functional parameters in identifying vulnerable plaque that can lead to complications during follow-up. The sum of the evidence available shows that therapeutic approaches to complex disease should take into account both the anatomical and structural characteristics of lesions, as well as functional parameters, and that high-resolution imaging techniques are essential for establishing both an individual's risk profile and the potential benefits of treatment. In diabetic patients with multivessel disease, the results of the FREEDOM study (currently ongoing) could be crucial for incorporating this new knowledge into practice and for defining the optimum management for this group of high-risk patients. PMID- 20540897 TI - [Progress in reperfusion after acute myocardial infarction. The situation in Latin America]. AB - Reperfusion therapy for acute myocardial infarction has dramatically reduced mortality. Coronary angioplasty and thrombolysis are the most effective reperfusion techniques. The controversy about which of the two methods is best has been superseded by a search for the most rapid and effective way of inducing reperfusion, given the overriding importance of time for saving myocardial tissue. Consequently, pharmaco-invasive strategies, prehospital thrombolysis and rapid patient transport systems have all been implemented. Typically, a certain percentage of patients do not undergo reperfusion for a range of reasons, one of the most important being treatment delay. Trends in Latin America are similar to those in other parts of the world: there is an increasing use of angioplasty instead of thrombolysis and a significant number of patients do not undergo reperfusion. Some patient registries indicate that hospital mortality tends to be higher than in Europe or the United States. There are numerous reasons for the difference, among which are a delay in presentation and a lack of access to properly equipped hospitals because of social inequality. Scientific societies have a key role to play in promoting awareness about the importance of early diagnosis and treatment throughout the health-care community, health authorities, and society in general. PMID- 20540898 TI - [Importance of HDL cholesterol in atherothrombosis: how did we get here? Where are we going?]. AB - The association between cardiovascular events and a high low-density lipoprotein (LDL) cholesterol level has been clearly established by numerous clinical trials. Moreover, reducing the LDL-cholesterol level using statins has been shown to be highly effective in both primary and secondary prevention. Nevertheless, despite statin treatment, the residual cardiovascular risk remains high and a large number of cardiovascular events still occur. On the other hand, a growing number of studies have demonstrated that there is an inverse association between the high-density lipoprotein (HDL) cholesterol level and cardiovascular risk. The most recent observations indicate that increasing the HDL-cholesterol level confers an additional benefit to reducing the LDL-cholesterol level with statins. Together, these findings justify turning our attention to HDL-cholesterol to provide a novel additional strategy for reducing cardiovascular risk. This review article describes: firstly, epidemiological studies that endorse HDL cholesterol as a therapeutic target; secondly, the different alternative treatments available for increasing the HDL-cholesterol level; and, finally, the benefits associated with such an increase. PMID- 20540899 TI - [Lineage tracing of epicardial cells during development and regeneration]. AB - Tracing the history of individual cells during embryonic morphogenesis in a structure as complex as the cardiovascular system is one of the major challenges of developmental biology. It involves determining the relationships between the various lineages of cells forming an organ at different stages, describing the topological rearrangements tissues undergo during morphogenesis, and characterizing the interactions between cells in different structures. However, despite the great expectations raised in the field of regenerative medicine, only limited progress has been made in using regenerative therapy to repair the cardiovascular system. Recent research has highlighted the role of the epicardium during cardiac regeneration, but it is still unclear whether it is important for molecular signaling or acts as a source of progenitor cells during this process. Consequently, increasing knowledge about the origin, diversification and potential of epicardial cells during development and homeostasis and under pathological conditions is of fundamental importance both for basic research and for the development of effective cellular therapies. The aims of this article were to provide a general overview of the classical techniques used for tracing cell lineages, including their potential and limitations, and to describe novel techniques for studying the origin and differentiation of the epicardium and its role in cardiac regeneration. PMID- 20540900 TI - [Cardiovascular prevention: current progress and the long road to travel]. AB - This article describes the limitations of the currently available screening modalities used for determining cardiovascular risk in the general population. In addition, it contains an analysis of the potential ways in which the predictive and classificatory abilities of the cardiovascular risk charts used in primary care can be improved to enable them to function more effectively. Also included are discussions of existing opportunities for improving current strategies for screening and cardiovascular prevention, of the value of measuring new biomarkers in individual patients, including genetic predisposition to coronary heart disease, and of some of the clinical measures used in practice, such as the ankle brachial index and the carotid intima-media thickness. In addition, the most important subgroups of individuals at a high cardiovascular risk, as judged by their size and the number of cardiovascular events experienced at 10 years, are described. Finally, there is a brief review of the potential role that image modalities currently being developed could play in particular subgroups of asymptomatic individuals with an elevated disease risk. PMID- 20540901 TI - Morphological and functional MRI of kidney. PMID- 20540902 TI - Compartmental modelling for magnetic resonance renography. AB - A basic formalism is presented for generating and interpreting compartmental models for dynamic contrast-enhanced MRI data in the kidney. A graphical convention is introduced to represent and design compartmental models in a transparent and physically intuitive manner. A systematic system of notations and a simple set of rules allows direct translation of the graphical representation into a mathematical solution. The rules are derived from the physical principle of mass conservation, and the interpretation provided by the general tracer kinetic theory of linear and stationary systems. The power of the formalism is illustrated using examples of models that have been proposed in the literature on perfusion MRI, and by generating a number of advanced models that may be of use in the kidney. PMID- 20540903 TI - Structural and functional MRI in children with renal disease: first experience. AB - PURPOSE: This MRI study demonstrates our first clinical experiences with structural and functional evaluation in children with renal dysfunction, and communicates our experience with quantitative measurements of renal function compared to reference values found employing radionucleotides. MATERIAL AND METHODS: We included renal impaired children who were recruited for clinical radioisotopic GFR measurements (n=8). MRI was performed 2 hours after Cr-EDTA measurements and was conducted using a protocol involving both anatomical/structural sequences and a dynamic contrast-enhanced sequence. Data obtained with the dynamic MRI sequence were processed using the graphical Patlak approach to obtain estimates of GFR. RESULTS: We were able to characterize the intrarenal configuration (cortex, medulla, pelvicalyceal arrangement) in all cases. Functional analyses of dynamic contrast-enhanced MRI revealed an overall underestimation of GFR measured by MRI compared to Cr-EDTPA measures (range: -2% to -43%). CONCLUSIONS: We advocate the use of MRI as a single-modality approach in the structural and functional evaluation of impaired kidneys in children, and concurrently, we presented a clinically available strategy for estimations of renal cortical volume and single kidney function. However, the use of MRI contrast agents have recently become controversial in renal patients due to the risk of NSF. PMID- 20540904 TI - Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging. AB - INTRODUCTION: Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. METHODS: Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2*, and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. DISCUSSION: This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2* was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. PMID- 20540905 TI - Susceptibility weighted imaging (SWI) of the kidney at 3T--initial results. AB - Susceptibility weighted imaging provides diagnostic information in strokes, hemorrhages, and cerebral tumors and has proven to be a valuable tool in imaging venous vessels in the cerebrum. The SWI principle is based on the weighting of T(2)* weighted magnitude images with a phase mask, therewith improving image contrast of veins or neighbouring structures of different susceptibility, in general. T(2)* weighted MRI is already used for assessment of kidney function. In this paper, the feasibility of SWI on kidneys was investigated. Translation of SWI from the brain to the kidneys comes along with two main challenges: (i) organ motion due to breathing and (ii) a higher oxygenation level of renal veins compared to the brain. To handle these problems, the acquisition time has been cut down to allow for breath-hold examinations, and different post-processing methods including a new phase mask were investigated to visualize renal veins. Results showed that by a new post-processing strategy SWI contrast was enhanced on average by a factor of 1.33 compared to the standard phase mask. In summary, initial experiences of SWI on the kidneys demonstrated the feasibility. However, further technical developments have to be performed to make this technology applicable in clinical abdominal MRI. PMID- 20540906 TI - Has the time come for bibliometrics and the h-index in academic radiology? PMID- 20540908 TI - A quantitative method for estimating individual lung cancer risk. AB - RATIONALE AND OBJECTIVES: Lung cancer is caused primarily by repeated exposure to carcinogenic particulate matter and noxious gasses with high particulate deposition localized to airway bifurcations and the lung periphery. The quantitative measurement and analysis of these sites has the potential to stratify lung cancer risk. The aim of this preliminary study was to assess the performance of a new method for estimating individual lung cancer risk based on the analysis of airway bifurcations on high-resolution (HR) computed tomographic (CT) scanning and spirometry. MATERIALS AND METHODS: One hundred eight subjects with spirometry and thin-slice CT data were selected from a CT screening study including 15 patients with early lung cancer and 93 age-matched and pack-year matched controls. A subset of seven patients with cancer and 72 controls were scanned with 1-mm CT slice thickness, representing an HR case subset. A quantitative lung cancer risk index method was developed on the basis of airway bifurcation x-ray attenuation combined with the ratio of forced expiratory volume in 1 second to forced vital capacity. Cochran-Mantel-Haenszel and conditional logistic regression tests were used to analyze performance. RESULTS: Cochran Mantel-Haenszel crude analysis revealed a cancer detection sensitivity and specificity of 67% and 72% for all cases and 100% and 73% for the HR case subset, respectively. Conditional logistic regression showed that a 0.0328 increase in lung cancer risk index was associated with odds ratios of 1.84 (95% confidence interval, 1.18-2.85) for the full data set (P = .0067) and 2.89 (95% confidence interval, 1.02-8.19) for the HR subset (P = .0467). CONCLUSIONS: A preliminary evaluation of a new lung cancer risk estimation method based on thin slice CT and spirometry showed a statistically significant association with lung cancer. PMID- 20540907 TI - Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers. AB - RATIONALE AND OBJECTIVES: To conduct a preclinical evaluation of the robustness of our computerized system for breast lesion characterization on two breast magnetic resonance imaging (MRI) databases that were acquired using scanners from two different manufacturers. MATERIALS AND METHODS: Two clinical breast MRI databases were acquired from a Siemens scanner and a GE scanner, which shared similar imaging protocols and retrospectively collected under an institutional review board-approved protocol. In our computerized analysis system, after a breast lesion is identified by the radiologist, the computer performs automatic lesion segmentation and feature extraction and outputs an estimated probability of malignancy. We used a Bayesian neural network with automatic relevance determination for joint feature selection and classification. To evaluate the robustness of our classification system, we first used Database 1 for feature selection and classifier training, and Database 2 to test the trained classifier. Then, we exchanged the two datasets and repeated the process. Area under the receiver operating characteristic curve (AUC) was used as a performance figure of merit in the task of distinguishing between malignant and benign lesions. RESULTS: We obtained an AUC of 0.85 (approximate 95% confidence interval [CI] 0.79-0.91) for (a) feature selection and classifier training using Database 1 and testing on Database 2; and an AUC of 0.90 (approximate 95% CI 0.84-0.96) for (b) feature selection and classifier training using Database 2 and testing on Database 1. We failed to observe statistical significance for the difference AUC of 0.05 between the two database conditions (P = .24; 95% confidence interval 0.03, 0.1). CONCLUSION: These results demonstrate the robustness of our computerized classification system in the task of distinguishing between malignant and benign breast lesions on dynamic contrast-enhanced (DCE) MRI images from two manufacturers. Our study showed the feasibility of developing a computerized classification system that is robust across different scanners. PMID- 20540909 TI - Ultrasound elastography: Its potential role in assessment of cervical lymphadenopathy. AB - RATIONALE AND OBJECTIVES: The aims of this study were to investigate the value of ultrasound elastography (UE) in the diagnosis of lymphadenopathy and to explore whether UE could improve the differentiation between benign and malignant cervical lymph nodes (LNs). MATERIALS AND METHODS: B-mode ultrasound, power Doppler imaging, and UE were performed in 107 consecutive patients with 128 cervical LNs. Only LNs that unequivocally matched between sonography and pathology were analyzed. The results of B-mode ultrasound, power Doppler imaging, and UE were interpreted separately to assess cervical LNs, using histopathologic analysis as the reference standard. RESULTS: A marked difference (P = .000) was found in the strain ratio between 70 malignant LNs (median, 2.71; range, 1.36 36.09) and 58 benign LNs (median, 1.44; range, 0.62-3.90). Receiver-operating characteristic curves showed that a strain ratio > 1.5 had high utility in enlarged cervical LN classification, with 92.5% sensitivity, 53.4% specificity, and a Youden's index of 0.463. These results were significantly better than those obtained using the best grayscale criterion, a ratio of long-axis to short-axis diameter > 2, which yielded 58.6% sensitivity, 70% specificity, and a Youden's index of 0.286. The kappa values for interobserver agreement were highest using UE, at 0.881 (observer 1 vs observer 2), 0.828 (observer 1 vs observer 3), and 0.946 (observer 2 vs observer 3). CONCLUSIONS: UE as an adjunct ultrasound modality holds some promise in screening and monitoring lymphadenopathy. PMID- 20540910 TI - Influence of using manual or automatic breast density information in a mass detection CAD system. AB - RATIONALE AND OBJECTIVES: The goal of this article is to analyze and compare the performance of a developed mass computer-aided detection (CAD) system that takes breast density information into account when using manual or automatic breast density annotations in the training step. The advantages of considering this breast density information will be highlighted. MATERIALS AND METHODS: The image database used in this article is 92 mediolateral oblique (MLO) and 92 craniocaudal (CC) mammograms obtained by a full-field digital mammographic unit. All mammograms contain at least one mass. The evaluation of the experiments is performed using free receiver operating characteristic analysis for evaluating the detection performance and pixel-based receiver operating characteristic analysis for evaluating the segmentation accuracy. In addition, the performance of the automatic breast density classifier is shown using confusion matrices. RESULTS: When the breast density information is not considered and at a specificity of two false positives per image, the sensitivity obtained by the CAD system is 0.747 for the CC views and 0.853 for the MLO views. Considering the breast density information, the sensitivity for CC and MLO mammograms increases to 0.800 and 0.893, respectively, using manual classification, and 0.827 and 0.907, respectively, using automatic estimation. The same trend is observed when evaluating the CAD segmentation accuracy for detected masses in terms of area under the curve values: without considering breast density, these are 0.920 +/- 0.057 and 0.917 +/- 0.072; using manual classification, 0.934 +/- 0.039 and 0.932 +/- 0.046; and using automatic estimation, 0.947 +/- 0.038 and 0.946 +/- 0.045 for CC and MLO views, respectively. CONCLUSIONS: The experiments showed improved results when breast density information was taken into account. Moreover, the results obtained when using automatic breast density estimation outperformed those based on the manual annotations provided by expert radiologists. In this sense, the experiments showed that breast density information can be beneficial for CAD systems, and this information can be estimated robustly by an automatic procedure, which reduces the inter- and intra-class variability of the radiologists. PMID- 20540911 TI - Microwave ablation: An experimental comparative study on internally cooled antenna versus non-internally cooled antenna in liver models. AB - RATIONAL AND OBJECTIVES: Microwave ablation is an alternative therapy with high cost-effectiveness for liver malignancy. The authors designed this experiment to compare the effect of microwave ablation using a non-internally cooled (NIC) antenna with that using an internally cooled (IC) antenna in both an ex vivo and an in vivo liver models. MATERIALS AND METHODS: Sixty-two microwave ablations were performed in ex vivo porcine and in vivo canine liver models (NIC antenna, 28 coagulations; IC antenna, 34 coagulations). Pair comparisons were executed in terms of the coagulation parameters, including short-axis diameter (SD), long axis diameter (LD), and spherical ratio (SR, SD/LD). The distributions of tissue temperatures were compared in ex vivo ablation. During in vivo ablation, the temperatures of antenna shaft were measured and unintended tissue coagulation were observed and compared. RESULTS: In both ex vivo and in vivo ablations, less charring areas were found around the IC antenna shaft. With a longer SD (P < .01) and a shorter LD (P < .01), the coagulations of IC antenna appeared to be more spherical than those of NIC antenna (P < .01). During ablations in vivo, the temperatures of NIC antennas shaft were up to 90 degrees C or even higher, which resulted in some unintended tissue coagulation, whereas the temperatures of IC antennas shaft were lower than 20 degrees C in all ablation processes without any unintended tissue coagulation (P < .01). CONCLUSION: The IC antenna performed better than NIC antenna in microwave ablation for liver models and might be more suitable for therapy for liver malignancy in clinical practice. PMID- 20540912 TI - Effect of work hours, caseload, shift type, and experience on resident call performance. AB - RATIONALE AND OBJECTIVES: To analyze the independent effects of multiple variables on resident call performance. MATERIALS AND METHODS: Independent radiology resident "on call" cross-sectional imaging interpretation quality assurance (QA) data obtained during a 171-day period at a single tertiary care Level 1 trauma teaching institution was reviewed. Clinically significant resident faculty discrepancies were compared among three different call types: traditional single-day overnight call (OC, 15 hours/night after 9 daytime hours on weekdays), 7-night nightfloat (NF, 9 hours/night), and weekend day call (WD, 10 hours/day). Logistic regression analyses were performed to evaluate associations. RESULTS: There were 119 (0.89%) clinically significant resident-faculty discordances from 13,424 cross-sectional interpretations: 56 (0.79%) from 7102 interpretations on 172 OC shifts, 39 (0.85%) from 4567 interpretations on 165 NF shifts, and 24 (1.4%) from 1755 interpretations on 49 WD shifts. Individual residents (n = 20) had a mean discrepancy rate of 0.9% (0.45%-1.9%). Overall, 102 (26.2%) of the shifts had at least one discordance. The following were associated with significantly (P < .001) increased discrepancy rates: junior vs. senior residents (odds ratio [OR] = 1.3 [1.2-1.4]), OC vs. NF (OR = 1.5 [1.3-1.6], WD vs. NF (OR = 1.4 [1.2-1.6]), weekend vs. weekday (OR = 1.3 [1.2-1.4]), and increasing cases/hour (OR = 1.6 [1.5-1.7]). Weekend OC shifts had a higher discrepancy rate (OR 1.3[1.2-1.5], P < .001) than weekday OC shifts despite a shorter workday (15 vs. 24 hours). CONCLUSION: Increasing caseload, junior residents, and weekends are associated with a significantly higher discrepancy rate. OC is associated with a significantly higher discrepancy rate than NF. Measured discrepancy rates are low, regardless of call type. PMID- 20540913 TI - Banking. PMID- 20540914 TI - Wings of the big iron bird. PMID- 20540915 TI - Introduction. PMID- 20540916 TI - Bowel displacement and protection techniques during percutaneous renal tumor thermal ablation. AB - Although bowel injury is a rare complication of renal radiofrequency ablation, the potential consequences can be devastating. Therefore, it is prudent to perform bowel displacement/protection procedures when feasible. The main bowel displacement techniques include hydrodissection, gas-insufflation, balloon interposition, and electrode torquing. In this article, these techniques are discussed and the steps involved in performing these procedures are enumerated. PMID- 20540917 TI - Transcatheter renal artery embolization for management of renal and adrenal tumors. AB - Transcatheter arterial embolization is a minimally invasive procedure that is increasingly used for the management of angiomyolipomas and to augment and/or palliate the management of malignant renal and adrenal neoplasms. The most common indications for renal artery embolization include (1) prenephrectomy and preradiofrequency ablation infarction of renal tumors, (2) management of renal angiomyolipomas, (3) palliations of unresectable renal malignancy, and (4) malignant renal hemorrhage (life-threatening or chronic debilitating hematuria). The increasing use of renal artery embolization for these conditions reflects the procedure's effectiveness and safety. Although there is less extensive literature available regarding the use of transcatheter embolization of adrenal tumors, this technique appears to be effective and safe for palliation and preadrenalectomy of adrenal metastatic disease, adrenocortical carcinomas, as well as treatment of symptomatic aldosteronomas. This article reviews the indications and techniques involved in performing transcatheter arterial embolization for renal and adrenal tumors. PMID- 20540918 TI - Percutaneous ablation of adrenal tumors. AB - Adrenal tumors comprise a broad spectrum of benign and malignant neoplasms and include functional adrenal adenomas, pheochromocytomas, primary adrenocortical carcinoma, and adrenal metastases. Percutaneous ablative approaches that have been described and used in the treatment of adrenal tumors include percutaneous radiofrequency ablation, cryoablation, microwave ablation, and chemical ablation. Local tumor ablation in the adrenal gland presents unique challenges, secondary to the adrenal gland's unique anatomic and physiological features. The results of clinical series employing percutaneous ablative techniques in the treatment of adrenal tumors are reviewed in this article. Clinical and technical considerations unique to ablation in the adrenal gland are presented, including approaches commonly used in our practices, and risks and potential complications are discussed. PMID- 20540920 TI - Adrenal vein sampling. AB - Adrenal vein sampling is the gold standard for localizing aldosterone-secreting adenomas and for distinguishing adenomas from bilateral adrenal hyperplasia in patients with primary hyperaldosteronism. The importance of this distinction cannot be overstated because the former is curable surgically, whereas the latter is managed medically. Primary hyperaldosteronism has historically been underdiagnosed as a cause of hypertension, but recent reports highlight its ubiquitous nature with a prevalence of 5%-10% in screened hypertensive patients. Of such patients, up to 62.5% have a potentially curable adenoma as the underlying etiology. Adrenal vein sampling is a safe, highly effective procedure that is shown to alter the clinical management in 35.7% of primary hyperaldosteronism patients who would have otherwise been treated improperly based on the results of CT or other modalities. Although adrenal vein sampling is hindered by the inherent difficulty of catheterizing the right adrenal vein, technical success is reported as high as 97% in experienced hands. In this article, we review aldosterone physiology and the clinical workup of primary aldosteronism as well as the anatomic, technical, and analytical factors to be considered with adrenal vein sampling. PMID- 20540919 TI - Image-guided adrenal and renal biopsy. AB - Image-guided biopsy is a safe and well-established technique that is familiar to most interventional radiologists. Improvements in image guidance, biopsy tools, and biopsy techniques now routinely allow for safe biopsy of renal and adrenal lesions that traditionally were considered difficult to reach or technically challenging. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal mass lesions that cannot be fully characterized with imaging or laboratory tests alone. It is also used to establish definitive diagnosis in some cases of renal parenchymal disease and has an expanding role in diagnosis and characterization of renal masses before treatment. Although basic principles and techniques for image-guided needle biopsy are similar regardless of organ, this paper highlights some technical considerations, indications, and complications that are unique to the adrenal gland and kidney because of their anatomic location and physiological features. PMID- 20540921 TI - Treatment of renal artery fibromuscular dysplasia. AB - Fibromuscular dysplasia is a nonatherosclerotic and noninflammatory disease that can result in stenoses of the renal arteries and hypertension, most commonly affecting middle-aged women. Percutaneous transluminal angioplasty has long been considered the mainstay of therapy and offers high rates of improved or cured hypertension. The disease involves the mid and distal renal arteries and branchpoints and poses endovascular treatment challenges that separate fibromuscular dysplasia from atherosclerotic disease. The development of smaller balloon dilation systems offers safe and highly effective endovascular treatment options for technically difficult lesions. Newer technologies such as cutting balloons also add to the armamentarium of treatment choices, which may be useful in the setting of resistant stenoses. This article focuses on the modern technical considerations in the diagnostic evaluation and endovascular treatment of renal artery fibromuscular dysplasia. PMID- 20540922 TI - Stenting for atherosclerotic renal artery stenosis. AB - Atherosclerotic renal artery stenosis (ARAS) is the most common cause of renal artery stenosis in the adult population. ARAS may result in progressive renal impairment, renovascular hypertension, and/or cardiac disturbance syndromes. Because medical therapy does not affect the progressive nature of this disease process, more aggressive treatments are needed to definitively treat ARAS. When performed correctly, renal artery stenting has been shown to stabilize or improve renal function and/or renovascular hypertension in 65-70% of carefully selected patients with ARAS. Therefore, percutaneous renal artery stenting should be considered the primary treatment for patients with symptomatic ARAS. PMID- 20540926 TI - A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM. AB - Many organisms display rhythms of physiology and behavior that are entrained to the 24-h cycle of light and darkness prevailing on Earth. Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day ("circadian"), but it is usually not exactly 24h. Recent discoveries have uncovered stunning similarities among the molecular circuitries of circadian clocks in mice, fruit flies, and bread molds. A consensus picture is coming into focus around two proteins (called PER and TIM in fruit flies), which dimerize and then inhibit transcription of their own genes. Although this picture seems to confirm a venerable model of circadian rhythms based on time-delayed negative feedback, we suggest that just as crucial to the circadian oscillator is a positive feedback loop based on stabilization of PER upon dimerization. These ideas can be expressed in simple mathematical form (phase plane portraits), and the model accounts naturally for several hallmarks of circadian rhythms, including temperature compensation and the per(L) mutant phenotype. In addition, the model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch. PMID- 20540927 TI - Solvent-induced free energy landscape and solute-solvent dynamic coupling in a multielement solute. AB - Molecular dynamics simulations using a simple multielement model solute with internal degrees of freedom and accounting for solvent-induced interactions to all orders in explicit water are reported. The potential energy landscape of the solute is flat in vacuo. However, the sole untruncated solvent-induced interactions between apolar (hydrophobic) and charged elements generate a rich landscape of potential of mean force exhibiting typical features of protein landscapes. Despite the simplicity of our solute, the depth of minima in this landscape is not far in size from free energies that stabilize protein conformations. Dynamical coupling between configurational switching of the system and hydration reconfiguration is also elicited. Switching is seen to occur on a time scale two orders of magnitude longer than that of the reconfiguration time of the solute taken alone, or that of the unperturbed solvent. Qualitatively, these results are unaffected by a different choice of the water-water interaction potential. They show that already at an elementary level, solvent-induced interactions alone, when fully accounted for, can be responsible for configurational and dynamical features essential to protein folding and function. PMID- 20540928 TI - Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin. AB - Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance. PMID- 20540930 TI - Beyond the 'back yard': Lay knowledge about Aedes aegypti in northern Australia and its implications for policy and practice. AB - Controlling dengue fever in Australia and internationally, relies heavily upon the actions of residents as well as community education and awareness of the risks. Although it has been well established in medical anthropology that the success of health interventions is highly dependent upon a clear grasp of lay knowledge of disease, limited attention has been given to lay understandings of dengue fever and its vectors in the extant literature. We begin addressing this hiatus through an examination of north Queensland residents' knowledge of the breeding habitats of Aedes aegypti mosquitoes. Building on the insights of earlier social research, we use factor analysis to examine the results of a series of randomly selected telephone surveys and compare responses over time and between cities. Our analysis confirms that many people assume that Ae. aegypti is ubiquitous in the landscape, that it lives and breeds not only around the home, but also in a variety of geographical spaces located beyond the suburban 'backyard', and beyond the control of local residents. Lay understandings appear to be placing people at risk from dengue, influencing the mosquito management practices of local residents and acting as a source of resistance to public health messages that focus on individual responsibility. A way forward through the provision of new information that challenges key assumptions is provided in the discussion. We argue that rather than dismissing lay understandings as ignorance, strategies, practices and policy based on a detailed understanding of this knowledge will mean that practitioners are better able to address these assumptions and will likely be more effective at educating the public of the risks posed by dengue. PMID- 20540931 TI - The effect of oral anthelmintics on the survivorship and re-feeding frequency of anthropophilic mosquito disease vectors. AB - In the Tropics, there is substantial temporal and spatial overlap of diseases propagated by anthropophilic mosquito vectors (such as malaria and dengue) and human helminth diseases (such as onchocerciasis and lymphatic filariasis) that are treated though mass drug administrations (MDA). This overlap will result in mosquito vectors imbibing significant quantities of these drugs when they blood feed on humans. Since many anthelmintic drugs have broad anti-invertebrate effects, the possibility of combined helminth control and mosquito-borne disease control through MDA is apparent. It has been previously shown that ivermectin can reduce mosquito survivorship when administered in a blood meal, but more detailed examinations are needed if MDA is to ever be developed into a tool for malaria or dengue control. We examined concentrations of drugs that follow human pharmacokinetics after MDA and that matched with mosquito feeding times, for effects against the anthropophilic mosquito vectors Anopheles gambiae s.s. and Aedes aegypti. Ivermectin was the only human-approved MDA drug we tested that affected mosquito survivorship, and only An. gambiae s.s. were affected at concentrations respecting human pharmacokinetics at indicated doses. Ivermectin also delayed An. gambiae s.s. re-feeding frequency and defecation rates, and two successive ivermectin-spiked blood meals following human pharmacokinetic concentrations compounded mortality effects compared to controls. These findings suggest that ivermectin MDA in Africa may be used to decrease malaria transmission if MDAs were administered more frequently. Such a strategy would broaden the current scope of polyparasitism control already afforded by MDAs, and which is needed in many African villages simultaneously burdened by many parasitic diseases. PMID- 20540932 TI - Fluorescence-based assays for the assessment of drug interaction with the human transporters OATP1B1 and OATP1B3. AB - Hepatic disposition plays a significant role in the pharmacokinetics and pharmacodynamics of a variety of drugs. Sinusoidal membrane transporters have been shown to participate in the hepatic disposition of many pharmaceuticals. Two sinusoidal membrane transporters with an established role in hepatic disposition are OATP1B1 and OATP1B3 (organic anion-transporting polypeptides 1B1 and 1B3, respectively). OATP1B1 and OATP1B3 have been implicated in the hepatic uptake of statin drugs, and polymorphisms linked to OATP1B1 have been associated with deleterious patient endpoints. As a result, OATP1B1 and OATP1B3 represent sites for potential drug-drug interactions. Numerous methods exist for identifying potential drug-drug interactions with transporters. However, relatively few offer the convenience and speed of fluorescence-based assays. Here a fluorescence-based assay was developed for measuring the OATP1B1- and OATP1B3-mediated transport of 8-fluorescein-cAMP (8-FcA). The OATP1B1- and OATP1B3-mediated transport of 8-FcA was time dependent and saturable (K(m)=2.9 and 1.8 microM, V(max)=0.20 and 0.33 pmol/min/cm(2), respectively). Molecules known to interact with OATPs, including cyclosporin A, rifampicin, and glibenclamide, each demonstrated concentration dependent inhibition of 8-FcA transport by OATP1B1 and OATP1B3. The in vitro fluorescence-based assays described here using 8-FcA as the substrate are convenient and rapid and have utility in screening drug candidates for potential drug-drug interactions with OATP1B1 and OATP1B3. PMID- 20540933 TI - Hispolon promotes MDM2 downregulation through chaperone-mediated autophagy. AB - Amplification and overexpression of murine double minute (MDM2) has been observed in several human cancers. Some chemotherapeutic agents cause MDM2 ubiquitination and degradation in a proteasome-dependent system. In addition to the proteasome system, chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective misfolded protein degradation. Molecular chaperone heat shock cognate 70 protein (Hsc70) recognizes the misfolded proteins, which are then delivered to lysosome associated membrane protein type 2A (LAMP2A) for lysosomal degradation. Our previous study reported that hispolon was able to induce cell apoptosis and downregulate MDM2 expression. In this study, our results showed that the proteasome inhibitor, MG132, could not inhibit hispolon-induced MDM2 downregulation. In contrast, both inhibition of lysosomes with NH(4)Cl and inhibition of LAMP2A using siRNA partially attenuated hispolon-induced MDM2 downregulation. To determine whether Hsc70 recognizes MDM2 on amino acids 135 141, SMP14 antibody was used to compete with Hsc70 for interaction with MDM2. After Hsc70 knockdown, SMP14 antibody immunoprecipitated increased MDM2. We also found that hispolon induced increased association of Hsp70, Hsc70, Hsp90 and LAMP2A with MDM2. This association was inhibited in cells pretreated with geldanamycin (GA), an Hsp90 inhibitor. GA also attenuated hispolon-induced MDM2 downregulation. Meanwhile, inhibition of Hsc70 using siRNA attenuated hispolon induced MDM2 downregulation. Our study provides the first example of the ability of hispolon to mediate MDM2 downregulation in lysosomes through the CMA pathway. PMID- 20540934 TI - Sonic hedgehog expression during Xenopus laevis forebrain development. AB - We have analyzed the developing expression pattern of x-Shh in the Xenopus forebrain, interpreting the results within the framework of the neuromeric model to assess evolutionary trends and clues. To achieve this goal, we have characterized phenotypically the developing x-Shh expressing forebrain subdivisions and neurons by means of the combination of in situ hybridization for x-Shh and immunohistochemistry for the detection of forebrain essential regulators and markers, such as the homeodomain transcription factors Islet 1, Orthopedia, NKX2.1 and NKX2.2 and tyrosine hydroxylase. Substantial evidence was found for x-Shh expression in the telencephalic commissural preoptic area and this is strongly correlated with the presence of a pallidum and/or a basal telencephalic cholinergic system. In the diencephalon, x-Shh was demonstrated in the zona limitans intrathalamica and the x-Shh expressing cells were extended into the prethalamus. Throughout development and in the adult hypothalamic x-Shh expression was strong in basal regions but, in addition, in the alar suprachiasmatic region. The findings obtained in the forebrain of Xenopus revealed a largely conserved pattern of Shh expression among tetrapods. However, interesting differences were also noted that could be related to evolutive changes in forebrain organization. PMID- 20540935 TI - Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone. AB - Peroxisome proliferator-activated receptor (PPAR)-gamma agonists such as troglitazone, pioglitazone and thiazolidine have been shown to induce apoptosis in human colon cancer cells. The molecular mechanism of PPARgamma agonist-induced apoptosis of colon cancer cells, however, is not clear. Glycogen synthase kinase 3beta (GSK-3beta) is an indispensable element for the activation of nuclear factor-kappa B (NF-kappaB) which plays a critical role in the mediation of survival signals in cancer cells. To investigate the mechanisms of PPARgamma agonist-induced apoptosis of colon cancer cells, we examined the effect of troglitazone (0-16muM) on the activation of GSK-3beta and NF-kappaB. Our study showed that the inhibitory effect of troglitazone on colon cancer cell growth was associated with inhibition of NF-kappaB activity and GSK-3beta expression in a dose-dependent manner. Cells were arrested in G(0)/G(1) phase followed by the induction of apoptosis after treatment of troglitazone with concomitant decrease in the expression of the G(0)/G(1) phase regulatory proteins; Cdk2, Cdk4, cyclin B1, D1, and E as well as in the anti-apoptosis protein Bcl-2 along with an increase in the expression of the pro-apoptosis-associated proteins; Caspase-3, Caspase-9 and Bax. Transient transfection of GSK-3beta recovered troglitazone induced cell growth inhibition and NF-kappaB inactivation. In contrast, co treatment of troglitazone with a GSK-3beta inhibitor (AR-a014418) or siRNA against GSK-3beta, significantly augmented the inhibitory effect of troglitazone on the NF-kappaB activity, the cancer cell growth and on the expression of G(0)/G(1) phase regulatory proteins and pro-apoptosis regulatory proteins. These results suggest that the PPARgamma agonist, troglitazone, inhibits colon cancer cell growth via inactivation of NF-kappaB by suppressing GSK-3beta activity. PMID- 20540936 TI - Performance evaluation of three liquid chromatography mass spectrometry methods for broad spectrum drug screening. AB - BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS) and tandem LC-MS (LC MS/MS) are increasingly used in toxicology laboratories as a complementary method to gas chromatography-mass spectrometry (GC-MS) and liquid chromatography ultraviolet detection (LC-UV) for comprehensive drug screening (CDS). This study was designed to characterize the sensitivity and specificity of three LC-MS(/MS) vendor-supplied methods for targeted CDS and identify the current limitations associated with the use of these technologies. METHODS: Five methods for broad spectrum CDS, including LC-UV (REMEDi), full scan GC-MS, LC-MS (ZQ-Mass Detector with MassLynx-software), LC-QTRAP-MS/MS (3200-QTRAP with Cliquid-software) and LC LIT-MS/MS (LXQ Linear Ion Trap with ToxID-software) were evaluated based on their ability to detect drugs in 48 patient urine samples. RESULTS: The tandem MS methods identified 15% more drugs than the single stage MS or LC-UV methods. Use of two broad spectrum screening methods identified more drugs than any single system alone. False negatives and false positives generated by the LC-MS(/MS) software programs were identified upon manual review of the raw data. CONCLUSIONS: The LC-MS/MS methods detected a broader menu of drugs; however, it is essential to establish manual data review criteria for all LC-MS(/MS) drug screening methods. Use of an EI-GC-MS and ESI-LC-MS/MS combination for targeted CDS may be optimal due to the complementary nature of the chromatographic and ionization techniques. PMID- 20540937 TI - Simultaneous determination of l-citrulline and l-arginine in plasma by high performance liquid chromatography. AB - OBJECTIVE: To develop a method for simultaneously determining l-citrulline and L arginine levels in plasma using RP-HPLC with ultraviolet detection. DESIGN AND METHODS: Plasma samples were deproteinized by trichloroacetic acid and heat. Phenyl-isothiocyanate (PITC) solution was used as derivatization reagent and a gradient elution was carried out. RESULTS: The linearity for L-citrulline and L arginine ranged from 0 to at least 1000 micromol/L. R(2) values were above 0.9999 for both. LODs for L-citrulline and L-arginine were 0.0201 micromol/L and 0.0476 micromol/L, respectively, while LOQs were 0.240 micromol/L and 0.448 micromol/L, respectively. Intra- and inter-day CVs were less than 3.40% and 7.2%, respectively. The average recovery was from 86.22% to 118.9%. L-citrulline and L arginine concentrations in healthy controls were 60.77+/-9.18 micromol/L and 58.19+/-16.43 micromol/L, respectively. CONCLUSION: This approach offers a reliable, efficient analytical platform for the simultaneous determination of citrulline and arginine levels in plasma. PMID- 20540938 TI - RBx-0597, a potent, selective and slow-binding inhibitor of dipeptidyl peptidase IV for the treatment of type 2 diabetes. AB - Dipeptidyl peptidase IV (DPP-IV) inhibiton is a well recognized approach to treat Type 2 diabetes. RBx-0597 is a novel DPP-IV inhibitor discovered in our laboratory. The aim of the present study was to characterize the pharmacological profiles of RBx-0597 in vitro and in vivo as an anti-diabetic agent. RBx-0597 inhibited human, mouse and rat plasma DPP-IV activity with IC(50) values of 32, 31 and 39nM respectively. RBx-0597 exhibited significant selectivity over dipeptidyl peptidase8 (DPP-8), dipeptidyl peptidase9 (DPP-9) (150-300 fold) and other proline-specific proteases (>200-2000 fold). Kinetic analysis revealed that RBx-0597 is a competitive and slow binding DPP-IV inhibitor. In ob/ob mice, RBx 0597 (10mg/kg) inhibited plasma DPP-IV activity upto 50% 8h post-dose and showed a dose-dependent glucose excursion. RBx-0597 (10mg/kg) showed a significant glucose lowering effect (~25% AUC of ? blood glucose) which was sustained till 12h, significantly increased the active glucagon-like peptide-1(GLP-1) and insulin levels. It showed a favourable pharmacokinetic profile (plasma clearance:174ml/min/kg; C(max) 292ng/ml; T(1/2) 0.28h; T(max) 0.75h and V(ss) 4.13L/kg) in Wistar rats with the oral bioavailability (F(oral)) of 65%. In summary, the present studies indicate that RBx-0597 is a novel DPP-IV inhibitor with anti-hyperglycemic effect and a promising candidate for further development as a drug for the treatment of type 2 diabetes. PMID- 20540939 TI - Impaired calcium influx despite hyper-reactivity in contralateral carotid following balloon injury: eNOS involvement. AB - Balloon catheter injury results in hyper-reactivity to phenylephrine in contralateral carotids. Decreased nitric oxide (NO) modulation and/or increased intracellular calcium concentration triggers vascular smooth muscle contraction. Therefore, this study explores the participation of NO signaling pathway and calcium mobilization on hyper-reactivity to phenylephrine in contralateral carotids. Concentration-response curves for calcium (CaCl(2)) and phenylephrine were obtained in control and contralateral carotids four days after balloon injury, in the presence and absence of the inhibitors (L-NAME, L-NNA, 1400W, 7 NI, Oxyhemoglobin, ODQ or Tiron). Confocal microscopy using Fluo-3AM or DHE was performed to detect the intracellular levels of calcium and reactive oxygen species, respectively. The modulation of NO on phenylephrine-induced contraction was absent in the contralateral carotid. Phenylephrine-induced intracellular calcium mobilization was not altered in contralateral carotids. However, extracellular calcium mobilization by phenylephrine was reduced in the contralateral carotid compared to control arteries, and this result was confirmed by confocal microscopy. L-NAME increased phenylephrine-induced extracellular calcium mobilization in the contralateral carotid to the control levels. Results obtained with L-NNA, 1400W, 7-NI, OxyHb, ODQ or Tiron showed that this response was mediated by products from endothelial NOS (eNOS) different from NO and without soluble guanylate cyclase activation, but it involved superoxide anions. Furthermore, Tiron or L-NNA reduced the levels of reactive oxygen species in contralateral carotids. Data suggest that balloon catheter injury promoted eNOS uncoupling in contralateral carotids, which generates superoxide rather than NO, and reduces phenylephrine-induced extracellular calcium mobilization, despite the hyper-reactivity to phenylephrine in contralateral carotids. PMID- 20540940 TI - Flow cytometric screening for anti-leishmanials in a human macrophage cell line. AB - High-throughput drug screening methods against the intracellular stage of Leishmania have been facilitated by the development of in vitro models of infection. The use of cell lines rather than primary cells facilitates these methods. Peripheral blood mononuclear cell (PBMC) derived macrophages and THP-1 cells were infected with stationary phase egfp transfected Leishmania amazonensis parasites and then treated with anti-leishmanial compounds. Drug activity was measured using a flow cytometric approach, and toxicity was assessed using either the MTT assay or trypan blue dye exclusion. Calculated EC(50)'s for amphotericin B, sodium stibogluconate, and miltefosine were 0.1445+/-0.0005MUg/ml, 0.1203+/ 0.018mg/ml, and 26.71MUM using THP-1 cells, and 0.179+/-0.035MUg/ml, 0.1948+/ 0.0364mg/ml, and 13.77+/-10.74MUM using PBMC derived macrophages, respectively. We conclude that a flow cytometric approach using egfp transfected Leishmania species can be used to evaluate anti-leishmanial compounds against the amastigote stage of the parasite in THP-1 cells with excellent concordance to human PBMC derived macrophages. PMID- 20540941 TI - Mcl-1; the molecular regulation of protein function. AB - Apoptosis, an essential and basic biological phenomenon, is regulated in a complex manner by a multitude of factors. Myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of the B-cell lymphoma 2 (Bcl-2) family of apoptosis regulating proteins, exemplifies a number of the mechanisms by which a protein's contribution to cell fate may be modified. The N-terminus of Mcl-1 is unique amongst the Bcl-2 family, in that it is rich in experimentally confirmed and putative regulatory residues and motifs. These include sites for ubiquitination, cleavage and phosphorylation, which influence the protein's stability, localisation, dimerization and function. Here we review what is known about the regulation of Mcl-1 expression and function, with particular focus on post translational modifications and how phosphorylation interconnects the complex molecular control of Mcl-1 with cellular state. PMID- 20540942 TI - Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. AB - BACKGROUND & AIMS: There is no consistency between the individual studies in the literature on whether organ failure (OF) or infected pancreatic necrosis (IPN) is the main determinant of severity in acute pancreatitis. We aimed to statistically aggregate the available data and determine the pooled influence of OF and IPN on mortality in patients with acute pancreatitis. METHODS: The search for relevant observational studies was undertaken in the MEDLINE, EMBASE, and Scopus electronic databases, as well as in the proceedings of major gastroenterology meetings. The summary estimates are presented as relative risk (RR) and 95% confidence interval (CI). RESULTS: Fourteen studies comprising 1478 patients with acute pancreatitis were meta-analyzed. A total of 600 patients developed OF and 179 of them died (mortality, 30%); 314 patients developed IPN and 102 of them died (mortality, 32%). In a stratified analysis, patients with OF and IPN had a significantly higher risk of death in comparison with patients with OF and no IPN (RR = 1.94; 95% CI: 1.32-2.85; P = .0007) and in comparison with patients with IPN and no OF (RR = 2.65; 95% CI: 1.30-5.40; P = .0007). CONCLUSIONS: In patients with acute pancreatitis, the absolute influence of OF and IPN on mortality is comparable and thus the presence of either indicates severe disease. The relative risk of mortality doubles when OF and IPN are both present and indicates extremely severe disease or critical acute pancreatitis. PMID- 20540943 TI - Psychosocial stressor effects on cortisol and ghrelin in emotional and non emotional eaters: influence of anger and shame. AB - Food consumption in stressful situations vary as a function of individual difference factors (e.g., emotional vs. non-emotional eating), and may be related to hormonal responses elicited by the stressful event. These hormonal responses may be tied to specific emotions elicited by the stressful event. The present investigation examined the emotional and hormonal (cortisol, ghrelin) responses of high and low emotional eaters following a laboratory stressor (Trier Social Stress Test; TSST). Women (n=48) either high or low in emotional eating status were tested in a TSST or served as controls during which blood samples were taken for analysis of cortisol and ghrelin, both of which have been implicated in eating and in response to stressors. The TSST promoted elevated cortisol levels, being somewhat more pronounced in emotional than in non-emotional eaters. Both shame and anger were provoked by the TSST, and although both these emotions were correlated with cortisol levels, only anger significantly mediated the relationship between the stressor and cortisol levels. As well, baseline ghrelin levels in low emotional eaters exceeded that of high emotional eaters, and increased moderately in response to the stressor situation, irrespective of emotional eating status. Interestingly, when provided with food, ghrelin levels declined in the non-emotional eaters, but not in emotional eaters. The possibility is offered that the lack of a decline of ghrelin in emotional eaters may sustain eating in these individuals. PMID- 20540944 TI - Fecal glucocorticoids as indicators of metabolic stress in female Sykes' monkeys (Cercopithecus mitis albogularis). AB - Because of their mediating role in the stress response and potential effects on fitness, glucocorticoid (GC) hormones are increasingly used to assess the physiological costs of environmental and behavioral variation among wild vertebrates. Identifying the proximate causes of GC variation, however, is complicated by simultaneous exposure to multiple potentially stressful stimuli. Here, we use data from a partially provisioned social group of Sykes' monkeys to evaluate the effects of potential psychological and metabolic stressors on temporal and individual variation in fecal GC (fGC) excretion among 11 adult females. Despite high rates of agonism over provisioned foods fGCs declined during periods of high provisioning frequency when fruit availability was dominated by neem (Azadirachta indica), an item requiring great feeding effort. Provisioned foods did not prevent fGC increases when availability of the most preferred main fruit item, tamarind (Tamarindus indica), declined drastically. Although rank-related differences in access to provisioned foods and rates of agonism did not lead to an overall effect of rank on fGCs, low-ranking females excreted more fGCs than high-ranking females during a period of high provisioning intensity and low fruit availability. The emergence of this rank effect was associated with elevated feeding effort in all females, a greater access to provisioned items by high-ranking females, and a higher proportion of time spent moving in low-ranking females. Our findings suggest that metabolic stressors were the primary determinants of both temporal and individual variation in fGCs, indicating potential fitness benefits for high-ranking females when food availability is limited. PMID- 20540946 TI - Feeding and hemolymph trehalose concentration influence sex pheromone production in virgin Heliothis virescens moths. AB - Previously, we demonstrated that sex pheromone production in mated female Heliothis virescens moths is dependent upon hemolymph trehalose concentration (HTC), which is influenced by activities such as the feeding of adults on sucrose. In this paper we demonstrate, for the first time, that this effect also occurs in starved (i.e., sugar-stressed) virgin females. Females allowed to feed on sugar for 6 days, following eclosion, had significantly greater titers than females that had fed only on water (i.e., were starved). No differences in pheromone titer were observed between sugar- and water-fed females at shorter (1 or 3 days) periods following eclosion. The relatively short-term effects of HTC on sex pheromone titer of virgins, were demonstrated by feeding experiments, in which starved (for 4 days) virgins fed on 10% sucrose solution had significantly greater HTC and pheromone titers than ones fed only on water; an increase in HTC was apparent within an hour, while the increase in pheromone titer was apparent within 2.5h, of sugar feeding. Starvation also showed similar effects on titers of pheromone gland fatty acids (pheromone intermediates) and HTC. Over 6 days of starvation, fatty acid titers and HTC declined gradually. After feeding on sucrose, titers of hexadecanoic, (Z)-9-hexadecanoic, (Z)-11-hexadecanoic and (Z) 9-octadecanoic, acids, as well as HTC, increased significantly 24h later, but titers of octadecanoic and (Z,Z)-9,12-octadecanoic (linoleic) acids did not. Lepidoptera cannot biosynthesize polyunsaturated acids, but the lack of change in octadecanoic acid titer suggests this acid may not participate in pheromone biosynthesis. In addition to these short-term changes in pheromone and fatty acid production, mediated by HTC, a longer-term effect of age, regardless of HTC, on pheromone titer was observed. Overall, these results are consistent with hemolymph trehalose and glandular fatty acids acting as twin metabolite reservoirs for pheromone biosynthesis. Hemolymph trehalose, able to be refilled through feeding on exogenous sugars, has a one-way flow of metabolites for synthesis of glandular free fatty acids (FFAs) and pheromone, while glandular glycerolipids provide a reversible reservoir for metabolites, accepting surplus FFAs when glandular concentrations are high, and providing FFAs for pheromone biosynthesis when concentrations are low. PMID- 20540945 TI - Stromal cell-free conditions favorable for human B lymphopoiesis in culture. AB - Progress has been slow in defining molecular requirements for human B lymphopoiesis in part because of differences from experimental animals and also because of the lack of culture conditions that efficiently support the process. We recently found that human CD10+ lymphocytes were produced when CD34+ hematopoietic stem and progenitor cells were cultured in contact with human mesenchymal stem cells (hMSC). Further investigation revealed that it occurred even when progenitors were separated from hMSC by membrane filters. Experiments with neutralizing antibodies suggested that important heat labile factors produced by hMSC are unlikely to be IL-7, TSLP, CXCL12 or hemokinin-1. Further manipulation of culture conditions revealed that optimal lymphopoiesis required careful selection of fetal calf serum lots, maintenance of high cell densities, as well as recombinant cytokines (SCF, FL and G-CSF). G-CSF was particularly important when adult bone marrow rather than umbilical cord blood derived CD34+ cells were used to initiate the cultures. These improved methods should facilitate identification of molecules that can be used to speed regeneration of the humoral immune system following chemotherapy and might suggest ways to inhibit growth of B lineage malignancies. PMID- 20540947 TI - Remodelling of Ca2+ handling organelles in adult rat ventricular myocytes during long term culture. AB - It is well known that for cardiomyocytes, isolation and culturing induce largely unknown remodelling processes. We analysed changes in the structure of cell compartments with optical techniques such as confocal microscopy and fluorescence redistribution after photobleaching employing adenoviral-mediated transduction of targeted fluorescent proteins and small molecule dyes. We identified characteristic remodelling processes: the T-tubular membrane system was gradually lost by a process referred to as "sequential pinching off", in an outward direction. Mitochondria fell in one of three classes, very small (0.9 microm length), medium long (1.8 microm) or extended shape (3.6 microm) organelles. Over the culturing time mitochondria gradually fused. Bleaching of individual mitochondria revealed association between apparently separated mitochondria by "tunnelling" via sub-resolution organelle-tubes. This tunnelling process was increasing over the culturing time. A gradual loss of the cross-striation arrangement in the endoplasmic/sarcoplasmic reticulum was visualised. Analysis of large populations of Ca(2+) sparks by video-rate confocal 2D-scanning revealed significant albeit small changes of these elementary SR-Ca(2+) release events in adult cardiomyocytes that could be related to changes in SR-Ca(2+) content rather than resting Ca(2+) concentration. In conclusion, primary isolated cardiomyocytes from adult hearts undergo a well-defined, but reproducible subcellular remodelling during optimised long term culture. PMID- 20540948 TI - Stability and CDR composition biases enrich binder functionality landscapes. AB - The rugged protein sequence-function landscape complicates efforts, both in nature and in the laboratory, to evolve protein function. Protein library diversification must strike a balance between sufficient variegation to thoroughly sample alternative functionality versus the probability of mutant destabilization below an expressible threshold. In this work, we explore the sequence-function landscape in the context of screening for molecular recognition from an Ig scaffold library. The fibronectin type III domain is used to explore the impact of two sequence diversification strategies: (a) partial wild-type conservation at structurally important positions within the paratope region and (b) tailored amino acid composition mimicking antibody binding-site composition at putative paratope positions. Structurally important positions within the paratope region were identified through stability, structural, and phylogenetic analyses and partially or fully conserved in sequence. To achieve tailored antibody-like diversity, we designed a set of skewed nucleotide mixtures yielding codons approximately matching the distribution observed in antibody complementarity-determining regions without incurring the expense of triphosphoramidite-based construction. These design elements were explored via comparison of three library designs: a random library, a library with wild-type bias in the DE loop only and tyrosine-serine diversity elsewhere, and a library with wild-type bias at 11 positions and the antibody-inspired amino acid distribution. Using pooled libraries for direct competition in a single tube, selection and maturation of binders to seven targets yielded 19 of 21 clones that originated from the structurally biased, tailored-diversity library design. Sequence analysis of the selected clones supports the importance of both tailored compositional diversity and structural bias. In addition, selection of both well and poorly expressed clones from two libraries further elucidated the impact of structural bias. PMID- 20540949 TI - Structural and kinetic effects of PAK3 phosphorylation mimic of cTnI(S151E) on the cTnC-cTnI interaction in the cardiac thin filament. AB - Residue Ser151 of cardiac troponin I (cTnI) is known to be phosphorylated by p21 activated kinase 3 (PAK3). It has been found that PAK3-mediated phosphorylation of cTnI induces an increase in the sensitivity of myofilament to Ca(2+), but the detailed mechanism is unknown. We investigated how the structural and kinetic effects mediated by pseudo-phosphorylation of cTnI (S151E) modulates Ca(2+) induced activation of cardiac thin filaments. Using steady-state, time-resolved Forster resonance energy transfer (FRET) and stopped-flow kinetic measurements, we monitored Ca(2+)-induced changes in cTnI-cTnC interactions. Measurements were done using reconstituted thin filaments, which contained the pseudo phosphorylated cTnI(S151E). We hypothesized that the thin filament regulation is modulated by altered cTnC-cTnI interactions due to charge modification caused by the phosphorylation of Ser151 in cTnI. Our results showed that the pseudo phosphorylation of cTnI (S151E) sensitizes structural changes to Ca(2+) by shortening the intersite distances between cTnC and cTnI. Furthermore, kinetic rates of Ca(2+) dissociation-induced structural change in the regulatory region of cTnI were reduced significantly by cTnI (S151E). The aforementioned effects of pseudo-phosphorylation of cTnI were similar to those of strong crossbridges on structural changes in cTnI. Our results provide novel information on how cardiac thin filament regulation is modulated by PAK3 phosphorylation of cTnI. PMID- 20540950 TI - SDS-induced fibrillation of alpha-synuclein: an alternative fibrillation pathway. AB - A structural investigation of the sodium dodecyl sulfate (SDS)-induced fibrillation of alpha-synuclein (alphaSN), a 140-amino-acid protein implicated in Parkinson's disease, has been performed. Spectroscopic analysis has been combined with isothermal titration calorimetry, small-angle X-ray scattering, and transmission electron microscopy to elucidate a fibrillation pathway that is remarkably different from the fibrillation pathway in the absence of SDS. Fibrillation occurs most extensively and most rapidly (starting within 45 min) under conditions where 12 SDS molecules are bound per alphaSN molecule, which is also the range where SDS binding is associated with the highest enthalpy. Fibrillation is only reduced in proportion to the fraction of SDS below 25 mol% SDS in mixed surfactant mixtures with nonionic surfactants and is inhibited by formation of bulk micelles and induction of alpha-helical structure. In this fibrillogenic complex, 4 alphaSN molecules initially associate with 40-50 SDS molecules to form a shared micelle that gradually grows in size. The complex initially exhibits a mixture of random coil and alpha-helix, but incubation results in a structural conversion into beta-sheet structure and concomitant formation of thioflavin-T-binding fibrils over a period of several hours. Based on small-angle X-ray scattering, the aggregates elongate as a beads-on-a-string structure in which individual units of ellipsoidal SDS-alphaSN are bridged by strings of the protein, so that aggregates nucleate around the surface of protein stabilized micelles. Thus, fibrillation in this case occurs by a process of continuous accretion rather than by the rate-limiting accumulation of a distinct nucleus. The morphology of the SDS-induced fibrils does not exhibit the classical rod-like structures formed by alphaSN when aggregated by agitation in the absence of SDS. The SDS-induced fibrils have a flexible worm-like appearance, which can be converted into classical straight fibrils by continuous agitation. SDS-induced fibrillation represents an alternative and highly reproducible mechanism for fibrillation where protein association is driven by the formation of shared micelles, which subsequently allows the formation of beta-sheet structures that presumably link individual micelles. This illustrates that protein fibrillation may occur by remarkably different mechanisms, testifying to the versatility of this process. PMID- 20540951 TI - Molecular modeling of BAD complex resided in a mitochondrion integrating glycolysis and apoptosis. AB - BAD (Bcl-2 antagonist of cell death) and GK (glucokinase) reside in a mitochondrial complex together with PKA and PP1 catalytic units (PKAc and PP1c) and WAVE-1 that integrates glycolysis and apoptosis. Our research results reveal that BAD is phosphorylated and inactivated on Ser 75 in a BAD-Bcl-xL complex by PKA (targeted to mitochondria through association with WAVE1), resulting in the dissociation of BAD and its binding to GK. Moreover, GK can interact with PP1c and also distinguish WAVE1. On the other hand, BAD is dephosphorylated and activated on Ser75 by PP1c, leading to the separation of PKAc and its binding to the regulatory (R) subunit of PKA which by the dimerization domain of its R subunit connects with WAVE1 linked with GK of the complex. This may be the reason of the complex existing in liver mitochondria, regardless of phosphorylated and dephosphorylated BAD. Additionally, GK like PKA may also prevent Bcl-xL from rebinding to BAD by phosphorylating BAD at Ser 118. The BAD complex model reveals that BAD and GK play key roles because of BAD as a substrate for the PKA-PP1 pair and by BH3 domain directly interacting with GK. This is helpful for our development and research of the molecular mechanism of BAD integrating glycolysis and apoptosis. PMID- 20540953 TI - The dynamics of plant disease models with continuous and impulsive cultural control strategies. AB - Plant disease mathematical models including continuous cultural control strategy and impulsive cultural control strategy are proposed and investigated. This novel theoretical framework could result in an objective criterion on how to control plant disease transmission by replanting of healthy plants and removal of infected plants. Firstly, continuous replanting of healthy plants and removing of infected plants is taken. The existence and stability of disease-free equilibrium and positive equilibrium are studied and continuous cultural control strategy is given. Secondly, plant disease model with impulsive replanting of healthy plants and removing of infected plants is also considered. Using Floquet's theorem and small amplitude perturbation, the sufficient conditions under which the infected plant free periodic solution is locally stable are obtained. Moreover, permanence of the system is investigated. Under certain parameter spaces, it is shown that a nontrivial periodic solution emerges via a supercritical bifurcation. Finally, our findings are confirmed by means of numerical simulations. The modeling methods and analytical analysis presented can serve as an integrating measure to identify and design appropriate plant disease control strategies. PMID- 20540952 TI - Anti-social punishment can prevent the co-evolution of punishment and cooperation. AB - The evolution of cooperation is one of the great puzzles in evolutionary biology. Punishment has been suggested as one solution to this problem. Here punishment is generally defined as incurring a cost to inflict harm on a wrong-doer. In the presence of punishers, cooperators can gain higher payoffs than non-cooperators. Therefore cooperation may evolve as long as punishment is prevalent in the population. Theoretical models have revealed that spatial structure can favor the co-evolution of punishment and cooperation, by allowing individuals to only play and compete with those in their immediate neighborhood. However, those models have usually assumed that punishment is always targeted at non-cooperators. In light of recent empirical evidence of punishment targeted at cooperators, we relax this assumption and study the effect of so-called 'anti-social punishment'. We find that evolution can favor anti-social punishment, and that when anti social punishment is possible costly punishment no longer promotes cooperation. As there is no reason to assume that cooperators cannot be the target of punishment during evolution, our results demonstrate serious restrictions on the ability of costly punishment to allow the evolution of cooperation in spatially structured populations. Our results also help to make sense of the empirical observation that defectors will sometimes pay to punish cooperators. PMID- 20540954 TI - cis-4-decenoic acid provokes mitochondrial bioenergetic dysfunction in rat brain. AB - AIMS: In the present work we investigated the in vitro effect of cis-4-decenoic acid, the pathognomonic metabolite of medium-chain acyl-CoA dehydrogenase deficiency, on various parameters of bioenergetic homeostasis in rat brain mitochondria. MAIN METHODS: Respiratory parameters determined by oxygen consumption were evaluated, as well as membrane potential, NAD(P)H content, swelling and cytochrome c release in mitochondrial preparations from rat brain, using glutamate plus malate or succinate as substrates. The activities of citric acid cycle enzymes were also assessed. KEY FINDINGS: cis-4-decenoic acid markedly increased state 4 respiration, whereas state 3 respiration and the respiratory control ratio were decreased. The ADP/O ratio, the mitochondrial membrane potential, the matrix NAD(P)H levels and aconitase activity were also diminished by cis-4-decenoic acid. These data indicate that this fatty acid acts as an uncoupler of oxidative phosphorylation and as a metabolic inhibitor. cis-4 decenoic acid also provoked a marked mitochondrial swelling when either KCl or sucrose was used in the incubation medium and also induced cytochrome c release from mitochondria, suggesting a non-selective permeabilization of the inner mitochondrial membrane. SIGNIFICANCE: It is therefore presumed that impairment of mitochondrial homeostasis provoked by cis-4-decenoic acid may be involved in the brain dysfunction observed in medium-chain acyl-CoA dehydrogenase deficient patients. PMID- 20540955 TI - Nuclear proteome analysis of cisplatin-treated HeLa cells. AB - Cisplatin has been widely accepted as one of the most efficient anticancer drugs for decades. However, the mechanisms for the cytotoxic effects of cisplatin are still not fully understood. Cisplatin primarily targets DNA, resulting in the formation of DNA double strand breaks and eventually causing cell death. In this study, we applied two-dimensional electrophoresis coupled with LC-MS/MS to analyze the nuclear proteome of HeLa cells treated with cisplatin, in an effort to uncover new mechanistic clues regarding the cellular response to cisplatin. A total of 19 proteins were successfully identified, and these proteins are involved in a variety of basal metabolic and biological processes in cells, including biosynthesis, cell cycle, glycolysis and apoptosis. Six were related to the regulation of mRNA splicing, and we therefore asked whether the Fas gene might undergo alternative splicing following cisplatin treatment. This proved to be the case, as the splicing forms of Fas were modified in cisplatin-treated HeLa cells. This work provides novel information, from the perspective of the nuclear response, for understanding the cytotoxicity caused by cisplatin-induced DNA damage. PMID- 20540956 TI - Real world referencing and schizophrenia: are we experiencing the same reality? AB - Psychotic symptoms in schizophrenia patients encompass the difficulty to distinguish between the respective points of view of self and others. The capacity to adopt and switch between different perspectives is, however, fundamental for ego- and allocentric spatial referencing. We tested whether schizophrenia patients are able to adopt and maintain a non-egocentric point of view in a complex visual environment. Twenty-four chronic schizophrenic outpatients (11 females) and 25 controls matched for age, gender, years of education and handedness were recruited from a population-based sample. In a virtual environment, participants had to make a decision as to which of two trash cans was closest to themselves (viewer-centered, egocentric), to a ball (object centered, unstable allocentric), or to a palace (landmark-centered, stable allocentric). Main outcome measures were reaction time, error rate, learning rate and local task switch cost. While egocentric reaction time was preserved, patients showed an increased reaction time in both allocentric referencing conditions (stable and unstable) and an overall increased error rate. Switch cost was diminished in patients when changing from the egocentric to the landmark centered condition and elevated when changing from the landmark-centered to the egocentric condition. The results imply that schizophrenia patients' adoption of an egocentric perspective is preserved. However, adopting an allocentric point of view and switching between egocentric and landmark-centered perspectives are impaired. Perturbations in non-egocentric referencing and transferring efficiently between different referential systems might contribute to altered personal and social world comprehension in schizophrenia. PMID- 20540957 TI - The marine polyether gambierol enhances muscle contraction and blocks a transient K(+) current in skeletal muscle cells. AB - Gambierol is a complex marine toxin first isolated with ciguatoxins from cell cultures of the toxic dinoflagellate Gambierdiscus toxicus. Despite the chemical complexity of the polycyclic ether toxin, the total successful synthesis of gambierol has been achieved by different chemical strategies. In the present work the effects of synthetic gambierol on mouse and frog skeletal neuromuscular preparations and Xenopus skeletal myocytes have been studied. Gambierol (0.1-5 muM) significantly increased isometric twitch tension in neuromuscular preparations stimulated through the motor nerve. Less twitch augmentation was observed in directly stimulated muscles when comparing twitch tension-time integrals obtained by nerve stimulation. Also, gambierol induced small spontaneous muscle contraction originating from presynaptic activity that was completely inhibited by d-tubocurarine. Gambierol slowed the rate of muscle action potential repolarization, triggered spontaneous and/or repetitive action potentials, and neither affected action potential amplitude nor overshoot in skeletal muscle fibers. These results suggest that gambierol through an action on voltage-gated K(+) channels prolongs the duration of action potentials, enhances the extent and time course of Ca(2+) release from the sarcoplasmic reticulum, and increases twitch tension generation. Further evidence is provided that gambierol at sub-micromolar concentrations blocks a fast inactivating outward K(+) current that is responsible for action potential prolongation in Xenopus skeletal myocytes. PMID- 20540958 TI - Material and lighting dimensions of object colour. AB - The dimensionality of the object colour manifold was studied using a multidimensional scaling technique, which allows for the representation of a set of coloured papers as a configuration in a Euclidean space where the distance between papers corresponds to the perceptual dissimilarities between them. When the papers are evenly illuminated they can be arranged as a three-dimensional configuration. This is in line with the generally accepted view that the object colour space is three-dimensional. Yet, we show that under variegated illumination another three dimensions emerge. We call them lighting dimensions of object colour in order to distinguish from the traditional three referred to as material dimensions of object colour. PMID- 20540960 TI - A Kazal-type serine proteinase inhibitor SPIPm2 from the black tiger shrimp Penaeus monodon is involved in antiviral responses. AB - A five-domain Kazal-type serine proteinase inhibitor, SPIPm2, from Penaeus monodon has recently been implicated in antiviral responses for it is up regulated upon viral infection and needs further studies. The SPIPm2 genomic gene was composed of seven exons and six introns. The genomic DNA segments coding for each Kazal domain were separated by introns of variable lengths supporting the hypothesis of gene duplication in the Kazal-type gene family. RT-PCR and Western blot analysis revealed that the SPIPm2 transcript and its five-domain protein product were expressed mainly in the hemocytes and less in gill, heart and antennal gland. Upon white spot syndrome virus (WSSV) infection, the SPIPm2 was only detected in the hemocytes and plasma. Immunocytochemical study of P. monodon hemocytes showed that the percentage of SPIPm2-producing hemocytes was reduced by about half after WSSV infection. Quantitative RT-PCR revealed further that the SPIPm2 was up-regulated early in the hemocytes of WSSV-infected shrimp and gradually reduced as the infection progressed. Injection of the recombinant SPIPm2 (rSPIPm2) prior to WSSV injection resulted in a significant inhibition of WSSV replication. The rSPIPm2 injection also prolonged the mortality rate of WSSV infected shrimp. Therefore, the SPIPm2 was involved in the innate immunity against WSSV infection in shrimp. PMID- 20540961 TI - What's on the mind of a jellyfish? A review of behavioural observations on Aurelia sp. jellyfish. AB - Aurelia sp. (scyphozoa; Moon Jellies) are one of the most common and widely distributed species of jellyfish. Their behaviours include swimming up in response to somatosensory stimulation, swimming down in response to low salinity, diving in response to turbulence, avoiding rock walls, forming aggregations, and horizontal directional swimming. These are not simple reflexes. They are species typical behaviours involving sequences of movements that are adjusted in response to the requirements of the situation and that require sensory feedback during their execution. They require the existence of specialized sensory receptors. The central nervous system of Aurelia sp. coordinates motor responses with sensory feedback, maintains a response long after the eliciting stimulus has disappeared, changes behaviour in response to sensory input from specialized receptors or from patterns of sensory input, organizes somatosensory input in a way that allows stimulus input from many parts of the body to elicit a similar response, and coordinates responding when stimuli are tending to elicit more than one response. While entirely different from that of most animals, the nervous system of Aurelia sp. includes a brain that creates numerous adaptive behaviours that are critical to the survival of these phylogenetically ancient species. PMID- 20540962 TI - Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty. AB - OBJECTIVES: In the treatment of prosthetic joint infections (PJI), the benefit of antibiotic therapy for more than 6 weeks after surgery is uncertain. We compared PJI cure rates according to the duration of antibiotics, 6 versus 12 weeks. METHODS: A prospective observational non-randomized study in Geneva University Hospitals 1996-2007. RESULTS: A total of 144 PJI (62 hip arthroplasties, 62 knee arthroplasties, and 20 hip hemiarthroplasties) were included with a prolonged follow-up ranging from 26 to 65 months. Surgical treatment included 60 debridements with implant retention, 10 one-stage exchanges of the prosthesis, 57 two-stage exchanges, and 17 Girdlestone procedures or knee arthrodeses. Seventy episodes (49%) received 6 weeks antibiotic therapy and 74 episodes, 12 weeks. Cure was achieved in 115 episodes (80%). Cure rate did not change according to the duration of intravenous antibiotics (>8 days, 8-21 days, >21 days) (Kruskal Wallis-test; p = 0.37). In multivariate analysis, none of the following parameters was statistically significantly associated with cure: two-stage exchange (odds ratio 1.1,95%CI 0.2-4.8); number of debridements (0.9, 0.4-1.9); six weeks antibiotherapy (2.7, 0.96-8.3); duration of intravenous course (1.0, 0.96-1.03); sinus tract (0.6, 0.2-1.7); or MRSA infection (0.5, 0.2-1.5), although implant retention showed a tendency for less cure (0.3, 0.1-1.1). CONCLUSIONS: Following surgery for treatment of PJI, antibiotic therapy appears able to be limited to a 6-week course, with one week of intravenous administration. This approach needs confirmation in randomized trials. PMID- 20540963 TI - Clindamycin-resistant Staphylococcus aureus in foot ulcers of patients with diabetes. PMID- 20540964 TI - Optimization of a cAMP response element signal pathway reporter system. AB - A sensitive cAMP response element (CRE) reporter system is essential for studying the cAMP/protein kinase A/cAMP response element binding protein signal pathway. Here we have tested a few CRE promoters and found one with high sensitivity to external stimuli. Using this optimal CRE promoter and the enhanced green fluorescent protein as the reporter, we have established a CRE reporter cell line. This cell line can be used to study the signal pathway by fluorescent microscope, fluorescence-activated cell analysis and luciferase assay. This cell line's sensitivity to forskolin, using the technique of fluorescence-activated cell sorting, was increased to approximately seven times that of its parental HEK 293 cell line, which is currently the most commonly used cell line in the field for the signal pathway study. Therefore, this newly created cell line is potentially useful for studying the signal pathway's modulators, which generally have weaker effect than its mediators. Our research has also established a general procedure for optimizing transcription-based reporter cell lines, which might be useful in performing the same task when studying many other transcription-based signal pathways. PMID- 20540965 TI - Effects of co-administration of amitriptyline and fluoxetine on inhibitory avoidance in mice. AB - We have previously observed that, while the impairing effects of amitriptyline on inhibitory avoidance in mice are consistently observed, those of acute fluoxetine are negligible. Two experiments were designed to investigate whether a regular dose of fluoxetine potentiates the effect of a low dose of amitriptyline that is ineffective when administered alone. Male and female CD1 mice were administered i.p. 30 min before training, as follows. In the first experiment, they were injected with saline, one of three doses of amitriptyline (2.5, 5, 10mg/kg), one dose of fluoxetine (15 mg/kg), or a combination of amitriptyline (2.5mg/kg) and fluoxetine (15 mg/kg). In the second experiment, the mice were injected with saline, amitriptyline (2.5mg/kg), one of three doses of fluoxetine (10, 15, 20mg/kg), or a combination of 2.5mg/kg of amitriptyline and one of the three mentioned doses of fluoxetine. Drug doses were selected based on previous experiments in our laboratory reported in other publications. The behavioural procedure used to test the effects of these treatments was step-through inhibitory avoidance. The joint administration of amitriptyline 2.5mg/kg and fluoxetine 15 mg/kg had a clear impairing effect on inhibitory avoidance as observed in the two experiments. The dose of 2.5mg/kg of amitriptyline, given alone, was ineffective. Doses of 5mg/kg, or higher, of amitriptyline impaired inhibitory avoidance. The only effect detected when fluoxetine was administered separately was in the males of the experiment 1, which exhibited less avoidance than controls. Our preclinical research throws light on the benefits of the combined administration of antidepressants. PMID- 20540966 TI - Translating rodent behavioral repertoire to zebrafish (Danio rerio): relevance for stress research. AB - The current study provides a detailed description of the pattern of exploratory behaviors encountered in adult zebrafish when exposed to a novel/unfamiliar environment using the light/dark box and open field tests. We also document the impact of an acute stressor (restraint stress) given just prior the onset of behavioral testing. We report the following main findings: (1) zebrafish display anxiety-like behaviors including dark-avoidance (in light/dark box test) and thigmotaxis (in open field test), (2) upon exposure to a novel environment (first 2 min), zebrafish display place preference for the outer zone of the testing apparatus where they seek escape via the transparent wall, and exhibit high locomotor activity accompanied by high swimming speed, (3) thigmotaxis, behavioral hyperactivity, and swimming speed habituate (decrease) over time, (4) prior history of stress attenuates the natural tendency to engage in dark avoidance behavior and thigmotaxis, reduces attempts to escape via the transparent wall, and greatly increased behavioral hyperactivity and swimming speed. Stress-induced patterns of behavior normalize to levels comparable to that of non-stressed controls by the end of the 5-min test session. Taken together, these findings suggest that novel environment can elicit anxiety-like behaviors in zebrafish such as dark-avoidance and thigmotaxis and the prior history of stress greatly affects patterns of exploration, defensive behaviors, and coping strategies in the light/dark box and open field tests. These findings are consistent with previous findings in rodents and support the usefulness of such behavioral paradigms in zebrafish. PMID- 20540967 TI - Female urine-induced male mice ultrasonic vocalizations, but not scent-marking, is modulated by social experience. AB - Despite the evidence for a communicative function of rodent scent marks and ultrasonic vocalizations, relatively little is known about the impact of social factors on these two forms of communication. Here, we tested the effects of two important social factors, prior exposure to a female and freshness of female urine, on male scent marks and ultrasonic vocalizations elicited by female urine. We also asked whether a recently reported strain difference between the highly social strain C57BL/6J (B6) and the mouse model of autism BTBR T+tf/J (BTBR) herein is specifically seen in response to female urine or also detectable in response to male urine traces. Results show that the emission of female urine elicited ultrasonic vocalizations was dependent on previous female experience, while scent-marking behavior was not affected. A positive correlation was detected between scent-marking behavior and ultrasonic calling in the most biologically relevant context, male mice exposed to fresh female urine after female experience. Correlations were less prominent or missing in less biologically relevant contexts, e.g. in male mice exposed to fresh female urine without previous female experience, indicating that previous female experience is affecting both the emission of female urine-elicited ultrasonic vocalizations and the correlation between olfactory and acoustic communication. The strain difference in scent-marking behavior and ultrasonic calling between B6 and BTBR appears to be specific to female urine-elicited behavior as it was not seen in response to male urine traces, highlighting the relevance of the social context in which mouse communication is evaluated. PMID- 20540968 TI - p-Hydroxyamphetamine causes prepulse inhibition disruptions in mice: contribution of dopamine neurotransmission. AB - It is well known that amphetamine induces disrupted prepulse inhibition (PPI) in humans and rodents. We have previously reported that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA) induces multiple behavioral responses, such as increased locomotor activity and head-twitch response in rodents. To reveal the characteristics of p-OHA on sensorimotor function in rodents, herein we tested the effects of p-OHA on PPI in mice. i.c.v. administration of p-OHA dose-dependently induced PPI disruptions for all prepulse intervals tested. This effect of p-OHA on PPI was attenuated by pretreatment with haloperidol or clozapine. p-OHA-induced PPI disruptions were also attenuated by pretreatment with L-741,626 (a selective D(2) receptor antagonist), L-745,870 (a selective D(4) receptor antagonist) or 6-hydroxydopamine (a neurotoxin which targets DA-containing neurons), but not by SCH 23390 (a selective D(1) receptor antagonist), eticlopride (a D(2)/D(3) receptor antagonist) or GBR 12909 (a DA reuptake inhibitor). These results indicate that selective blockade of either the D(2) or D(4) receptor subtype may prevent disruption of PPI induced by p-OHA via presynaptic DA release. PMID- 20540969 TI - Localization of apical sushi protein in Plasmodium falciparum merozoites. AB - Plasmodium falciparum belongs to the Apicomplexan group of parasites and is characterised by presence of specialized secretory organelles at the apical end. These apical organelles, referred to as microneme and rhoptries, contain proteins that play important roles during host cell invasion by mediating specific functions such as initial attachment, apical reorientation and junction formation. Recently, a protein referred to as P. falciparum apical sushi protein (PfASP), which is expressed at late schizont stage, was localized to micronemes of P. falciparum merozoites. In the present study, we have used indirect immunofluorescence assays and immunoelectron microscopy to demonstrate that PfASP is localized in the neck of rhoptries and not in micronemes as previously described. PMID- 20540970 TI - A schizont-derived protein, TpSCOP, is involved in the activation of NF-kappaB in Theileria parva-infected lymphocytes. AB - Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the nuclear factor-kappa B (NF-kappaB) is activated in schizont-infected cells, making T. parva-transformed cells resistant to apoptosis. However, the mechanism by which the parasite triggers the activation of NF-kappaB remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP (T. parvaschizont-derived cytoskeleton-binding protein), which is expressed in the schizont stage of T. parva. TpSCOP was shown to interact with F-actin in vitro. Expression of TpSCOP in a murine lymphocytic cell line resulted in the activation of NF-kappaB signaling pathways, leading to apoptosis resistance. The activation of mitogen-activated protein kinase (MAPK), including extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), was also detected. Furthermore, the introduction of TpSCOP into T. parva-infected cells also enhanced the activation of NF-kappaB. This is the first report to demonstrate that a parasite-derived molecule has the ability to activate the host NF-kappaB pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection. PMID- 20540971 TI - Global assessment of protein turnover in recombinant antibody producing myeloma cells. AB - The global turnover rates of cellular proteins and the secretion rate of a recombinant immunoglobulin G (IgG) in a myeloma cell line, NS0, were determined using SILAC proteomic analysis. After complete labeling of cellular proteins with (13)C(6), (15)N(4)-arginine, cells were transferred to unlabeled medium and the decay of the labeled arginine in proteins was monitored during exponential cell growth. After PAGE separation and mass-spectrometric identification of proteins, those detected with high confidence over at least three time points were used for the determination of turnover rates. Among the 224 proteins quantified with a protein half-life, about 15% have a degradation rate constant lower than one tenth of specific growth rate. For most proteins, the turnover rate is insignificant in its overall dynamics. Only 6.3% of proteins have a half-life shorter than the cell doubling time. For IgG secretion, both heavy and light chain molecules follow the same kinetic behavior with a half-life estimated to be 2h. The label decay curve appears to show a second region with very slow kinetics, raising the possibility of two populations of IgG molecules with different secretion characteristics. PMID- 20540972 TI - Immobilization of laccase in kappa-carrageenan based semi-interpenetrating polymer networks. AB - Laccase enzyme (L) was immobilized by entrapment into semi-interpenetrating polymer networks (semi-IPNs) prepared from kappa-carrageenan with either poly(acrylamide-acrylic acid) [P(AAm-AA)/kappa-car] or poly(acrylamide-itaconic acid) [P(AAm-IA)/kappa-car]. For both systems, immobilized enzymes achieved the same optimum values observed for free enzyme (pH=5.0 and T=40 degrees C), except for P(AAm-IA)/kappa-car system there was a shift to 5.5 in optimum pH value. At the end of 42 days of storage immobilized enzymes retained more than 80% of their original activities while the retained activities of both systems after 10 uses in batch type application were found to be higher than 50%. K(m) values were calculated as 2.52x10(-2) mM and 1.08x10(-2) mM and V(max) values were found as 6.8x10(-3) mM min(-1) and 4.4x10(-3) mM min(-1), for P(AAm-AA)/kappa-car-L and P(AAm-IA)/kappa-car-L, respectively. When methyl orange containing solutions (10 mg/L) were treated with the immobilized laccases (68.2U), enzymatic decolorization of methyl orange in 6 h was achieved to the level of 35% for both systems. Supplementing the reaction medium with ABTS as the redox mediator increased this value to about 70%. These initial results show that, laccase containing semi-IPNs can find some applications in decolorization of the industrial wastes. PMID- 20540973 TI - Enzymatic hydrolysis and ethanol production using xyloglucanase and Debaromyces hansenii from tamarind kernel powder: galactoxyloglucan predominant hemicellulose. AB - The hydrolysis and ethanol production from tamarind kernel powder (TKP), a rich source of galactoxyloglucan (GXG) was investigated for the first time using xyloglucanase and thermotolerant Debaromyces hansenii. The acid hydrolysis of TKP with 2N H(2)SO(4) at 120 degrees C for 30 min yielded an overall saccharification of 94% based on the total available carbohydrate content and further fermentation at 40 degrees C with thermotolerant D hansenii produced an ethanol yield of 0.35 g/g. A maximum hydrolysis of 55 and 78% for GXG was obtained in 48 h at 50 degrees C using Thermomonospora xyloglucanase (TXy) and accellerase1000, respectively. The synergistic effect of beta-galactosidase and xyloglucanase was demonstrated by the exogenous addition of beta-galactosidase to TXy which improved the overall hydrolysis of GXG by 30%. The rate of hydrolysis of GXG with TXy and accellerase was increased by 15-20% in the presence of chemical surfactants (tween 80 and toluene) or protein additive (BSA). The fermentation of enzymatic hydrolysates of GXG by TXy and accellerase with free cells at 40 degrees C produced an ethanol yield of 0.39 and 0.41 g/g whereas with immobilized cells produced 0.45 and 0.43 g/g, respectively, with a theoretical conversion efficiencies of 78-88%. The immobilized yeast cells were reused six times at 40 degrees C with 100% fermentation efficiency. PMID- 20540974 TI - Three-dimensional perfusion cultures of mouse and pig fetal liver cells in a packed-bed reactor: effect of medium flow rate on cell numbers and hepatic functions. AB - To develop a tissue-engineered bioartificial liver (BAL), perfusion cultures of mouse and pig fetal liver cells (FLCs) immobilized within a three-dimensional (3D) porous scaffold were performed utilizing a packed-bed reactor system. These FLCs were cultured under different medium flow rate conditions, and the effects of the flow rates on cell growth and the hepatic functions of the FLCs were investigated. In the cultures of mouse FLCs, the medium flow suppressed cell growth and the albumin secretion activity of the FLCs, and considerably lower albumin secretion than that in the 3D stationary control cultures was obtained in the perfusion cultures. In the case of pig FLCs, cell growth was also inhibited by the medium flow, however, the cells exhibited higher tolerance to the medium flow compared with mouse FLCs. The albumin secretion activity of pig FLCs was well maintained under an extremely low flow rate condition (4.8 mm/min in the reactor), and activity higher than the 3D stationary cultures was detected at a later stage (after 20 days in the perfusion cultures). These results revealed that FLCs are quite sensitive to medium flow and an extremely low shear stress is required for the perfusion cultures of FLCs. PMID- 20540975 TI - Porcine reproductive and respiratory syndrome virus replication is suppressed by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. AB - Viruses are known to develop the ability to manipulate a variety of host cell signal transduction pathways in order to facilitate successful virus survival. However, to date, little is known about the intracellular signaling mechanisms involved in porcine reproductive and respiratory syndrome virus (PRRSV) replication. The extracellular signal-regulated kinase (ERK) pathway that transduces signals to modulate a wide range of cellular functions has been shown to regulate a number of viral infections. The present study therefore aimed to determine the role of this pathway during PRRSV infection in porcine alveolar macrophages. We found that the PRRSV infection induces early robust but transient activation of ERK1/2 by 6h postinfection and thereafter the progressive decrease of its phosphorylation. However, the maximal induction of phosphorylated ERK1/2 seen at 6h postinfection was inconsistent with synthesis of a viral nucleocapsid protein that was first evident by 12h postinfection. These results indicate that ERK1/2 activation is mediated independently of viral gene expression during PRRSV replication. Notably, infection with UV-irradiated, inactivated virus, which is capable of receptor binding and internalization but prevents viral gene synthesis, was sufficient to trigger ERK1/2 phosphorylation, suggesting that the viral entry process may be responsible for early ERK activation. Treatment of cells with U0126, a selective ERK1/2 inhibitor, markedly diminished PRRSV infection and its inhibitory effect on PRRSV replication was exerted at the early stage in virus infection. Furthermore, inhibition of ERK activation resulted in significant suppression of subgenomic RNA transcription, viral protein translation, and progeny virus production. Taken together, the findings in this study suggest that the ERK signaling pathway plays an important role in postentry steps of the PRRSV replication cycle and beneficially contributes to viral infection. PMID- 20540976 TI - Respiratory echovirus 30 and coxsackievirus B5 can induce production of RANTES, MCP-1 and IL-8 by human bronchial epithelial cells. AB - Human Enteroviruses (HEV) (picornaviridae) are considered as one the major viral causes of childhood acute respiratory wheezing illnesses including bronchiolitis and asthma exacerbation. To identify the mechanisms that can regulate the development of airway mucosa inflammation during HEV respiratory lower tract infection, we investigated the profile and the levels of mRNA and protein secretion for CC and CXC human chemokines by HEV-infected primary human bronchial epithelial cells (SAE cells) using RT-PCR array and Bio-Plex assay. Cultures of SAE cells were infected by reference and wild-type HEV respiratory strains, demonstrating a replicative and productive viral infection. We observed that the replicative infection of the SAE cells by reference and wild-type HEV strains induced specific dose and time-dependent increases in mRNA and protein secretion only for RANTES, MCP-1 and IL-8 and not for all other CC and CXC human chemokines tested. The protein secretion of these chemokines appeared to be significantly increased at 48 or 72h post-infection in cultures treated by low-doses of IFN gamma comparatively to mock-infected cells (P<0.001), and was correlated to the viral replication activity. In conclusion, our findings demonstrated a selective production of RANTES, IL-8 and MCP-1 released by HEV-infected epithelial cells of the small bronchioles along with mechanisms of amplification mediated by IFN gamma. PMID- 20540977 TI - Genetic structure and molecular variability of Grapevine fanleaf virus populations. AB - To gain insights into the evolutionary mechanisms of Grapevine fanleaf virus (GFLV) from the genus Nepovirus, family Secoviridae, the sequences of the complete coding region of RNA2, including genes 2A(HP), 2B(MP) and 2C(CP), and partial sequence from the RNA1-encoded gene 1E(Pol) of 14 GFLV isolates from three naturally infected California vineyards were characterized. Phylogenetic analyses suggested two to three evolutionarily divergent lineages that did not reflect the vineyard origin of the isolates or an association with rootstock genotype or scion cultivar. Examination of the genetic variability of the California isolates alongside isolates worldwide, for which three RNA1 and 44 RNA2 coding sequences are available, revealed similar patterns of molecular evolution for the different regions within the GFLV genome but distinct selection constraints with the strongest pressure exerted on genes 2C(CP) and 2B(MP), an intermediate level of pressure exerted on gene 1E(Pol), and the weakest pressure exerted on gene 2A(HP). Some of the California isolates resulted from interspecies recombination events between GFLV and Arabis mosaic virus with crossover sites suspected in gene 1E(Pol) and identified in genes 2A(HP) and 2B(MP); and intraspecies recombination events inferred in the four target genes but most frequently observed within gene 2C(CP). This study suggested that purifying selection and recombination are important evolutionary mechanisms in the genetic diversification of GFLV. PMID- 20540978 TI - Molecular characterization of a new species of Begomovirus and betasatellite causing leaf curl disease of tomato in India. AB - A new tomato-infecting begomovirus and cognate betasatellite were characterized from the gangetic plain of northern India. Genome organization of this virus was found to be similar to those of other old world begomoviruses. The DNA-A molecule (2752nt) shared maximum (85.8%) identity with Tomato leaf curl Laos virus-[Laos] (ToLCLV-[LA]; AF195782) from Laos and betasatellite molecule (1349nt) shared maximum (75.8%) identity with Tomato leaf curl Joydebpur betasatellite (ToLCJoB [BD:Gaz:05]; AJ966244) from Bangladesh. Interestingly, both these molecules showed less identity with known tomato-infecting begomoviruses and their satellites from India. The recombination detection program (RDP) revealed that these molecules are not an outcome of direct exchange of sequences between existing begomovirus species. According to International Committee on Taxonomy of viruses (ICTV) species/strains demarcations norms for viruses belonging to the family Geminiviridae, this is a new Begomovirus species and we named this virus as Tomato leaf curl Patna virus (ToLCPaV) and new beta species as Tomato leaf curl Patna betasatellite (ToLCPaB). Partial tandem repeats of ToLCPaV and ToLCPaB could induce typical leaf curl symptom on tomato (Solanum lycopersicum) and Nicotiana benthamiana. Although, DNA-A could alone infect tomato typical to a monopartite Begomovirus, co-inoculation of DNA-A and DNA-beta resulted more stunting and severe symptoms. Interestingly, association of ToLCPaB did not assist in increased ToLCPaV accumulation in systemic leaves. ToLCPaV neither transreplicate DNA-B of Tomato leaf curl New Delhi virus (ToLCNDV) nor of Tomato leaf curl Gujarat virus (ToLCGV), presumably due to difference in rep-binding sequences. However, ToLCPaB formed viable pseudorecombinant with mono-bipartite ToLCGV DNA-A infecting both N. benthamiana and tomato but could not cause systemic infection on natural host tomato when co-inoculated with ToLCNDV DNA-A, which is a bipartite Begomovirus. PMID- 20540979 TI - Fat bodies and thin bodies. Cultural, biomedical and market discourses on obesity. AB - This article addresses the question of why dieting, health, and the care of the body have come to play such a central role in our daily lives, and explores the relationship of these practices to the emergence of obesity as a social and health problem. Messages urging people to regulate their food intake and get more exercise in order to avoid obesity conflict with warnings that anorexia and bulimia are among the possible consequences of overly strict diets and excessive physical activity. The relationship between diet, beauty and health has been appropriated and re-elaborated as a marketing strategy with wide-ranging cultural consequences. "Being on a diet" is no longer only a matter of biology, nutrition, medicine or science; it is also about culture, politics and society. PMID- 20540980 TI - Restrained eating and memory specificity. AB - Autobiographical memories are personal experiences that we store across our life span. A reduced ability to retrieve specific autobiographical experiences has been reported for a number of clinical populations. Previous research has found that the size of the memory specificity effect can predict disorder occurrence, severity, and treatment success. The current research examined whether a similar relationship could be found between memory specificity and restrained eating in a female college student population. Participants retrieved autobiographical memories that related to cue-words associated with dieting and body image. Individual differences in restrained eating were measured with the Restraint Scale (RS). Participants who scored higher on the concern-with-dieting sub-scale of the RS retrieved fewer specific autobiographical memories regardless of their current dieting activity. The memory specificity effect has the potential to serve as a predictor of eating disorder occurrence and treatment success, and may also assist with the development of interventions targeting such disorders. PMID- 20540981 TI - Beta-alanine as a small molecule neurotransmitter. AB - This review discusses the role of beta-alanine as a neurotransmitter. Beta alanine is structurally intermediate between alpha-amino acid (glycine, glutamate) and gamma-amino acid (GABA) neurotransmitters. In general, beta alanine satisfies a number of the prerequisite classical criteria for being a neurotransmitter: beta-alanine occurs naturally in the CNS, is released by electrical stimulation through a Ca(2+) dependent process, has binding sites, and inhibits neuronal excitability. beta-Alanine has 5 recognized receptor sites: glycine co-agonist site on the NMDA complex (strychnine-insensitive); glycine receptor site (strychnine sensitive); GABA-A receptor; GABA-C receptor; and blockade of GAT protein-mediated glial GABA uptake. Although beta-alanine binding has been identified throughout the hippocampus, limbic structures, and neocortex, unique beta-alaninergic neurons with no GABAergic properties remain unidentified, and it is impossible to discriminate between beta-alaninergic and GABAergic properties in the CNS. Nevertheless, a variety of data suggest that beta-alanine should be considered as a small molecule neurotransmitter and should join the ranks of the other amino acid neurotransmitters. These realizations open the door for a more comprehensive evaluation of beta-alanine's neurochemistry and for its exploitation as a platform for drug design. PMID- 20540982 TI - Tryptophan metabolism in allergic rhinitis: the effect of pollen allergen exposure. AB - This study evaluates serum tryptophan, kynurenine, kynurenine-to-tryptophan ratio, and neopterin levels in patients with pollen-induced allergic rhinitis (AR) during and outside of the pollen season, along with these values in healthy subjects. A total of 102 patients (56 female and 46 male, median age 28.7 years) were included in this study: 56 with seasonal AR evaluated outside of the pollen season and thus without allergic inflammation and symptoms, and 46 with seasonal AR evaluated during the pollen season with symptoms. A skin prick test and blood sampling for assessing serum concentrations of tryptophan and kynurenine and of immune activation marker neopterin were performed in all subjects. Tryptophan and kynurenine serum concentrations were higher in AR patients than in controls and were also higher out of pollen season than during this season. In conclusion, this preliminary study demonstrates that serum tryptophan metabolism could serve as a biomarker in patients with AR. PMID- 20540983 TI - Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice. AB - Magnetite iron nanoparticles have been widely used as contrast agents and in thermal therapy for cancer. However, their adverse effects on human health have not been fully investigated. In this study, iron oxide nanoparticles were prepared using inorganic iron chloride (size: 5.3+/-3.6 nm in phosphate buffered saline, surface charge: 23.14 mV), and their inflammatory responses were investigated. When mice were treated with iron oxide nanoparticles (250 microg/kg, 500 microg/kg, and 1mg/kg) by a single intratracheal instillation, the level of intracellular reduced glutathione (GSH) was decreased in the cells of bronchoalveolar lavage (BAL) fluid. The arrest of cell cycles in G1 phase was observed, but S-phase was significantly decreased. The concentrations of pro inflammatory cytokines (IL-1, TNF-alpha, and IL-6) were dose-dependently increased at day 1 after instillation in the BAL fluid and in the blood. During the experimental period of 28 days, pro-inflammatory cytokines (IL-1, TNF-alpha, and IL-6), Th0 cytokine (IL-2), Th1 type cytokine (IL-12), Th2 type cytokines (IL 4 and IL-5), TGF-beta, and IgE were also elevated. Expressions of many genes related with inflammation or tissue damage such as heat shock protein, matrix metalloproteinase, tissue inhibitors of metalloproteinases, and serum amyloid A were significantly induced. Formation of microgranuloma, which is one of the indicators for chronic inflammatory response, was observed in the alveolar space. In addition, distribution of B cell and CD8+ T cell in blood lymphocytes was increased at day 28. Based on the result, iron oxide nanoparticles may subchronic induce inflammatory responses via oxidative stress in mice by a single intratracheal instillation. PMID- 20540984 TI - Glycogen synthase kinase--3beta inhibitors suppress leukemia cell growth. AB - OBJECTIVE: The objective of this study was to investigate the effect of small molecule inhibitors of glycogen synthase kinase-3beta (GSK-3beta) on leukemia cell growth and survival. MATERIALS AND METHODS: Analysis of cytotoxicity and cell proliferation was conducted using the MTS assay, cell-cycle analysis, and division tracking. Apoptosis was investigated by Annexin-V/7-aminoactinomycin D and caspase-3 expression. The effect of GSK-3beta inhibitors was also tested in vivo in an animal model of leukemia. Gene expression analysis was performed to identify the genes modulated by GSK-3beta inhibition in leukemia cells. RESULTS: GSK-3beta inhibitors suppress cell growth and induce apoptosis in seven leukemia cell lines of diverse origin, four acute myeloid leukemia, one myelodysplastic syndrome, and one acute lymphoblastic leukemia samples. GSK-3beta inhibitors are cytotoxic for rapidly dividing clonogenic leukemia blasts, and higher doses of the inhibitors are needed to eliminate primitive leukemia progenitor/stem cells. Slow cell-division rate, low drug uptake, and interaction with bone marrow stroma make leukemia cells more resistant to apoptosis induced by GSK-3beta inhibitors. Global gene expression analysis combined with functional approaches identified multiple genes and specific signaling pathways modulated by GSK-3beta inhibition. An important role for Bcl2 in the regulation of apoptosis induced by GSK-3beta inhibitors was defined by expression analysis and confirmed by using pharmacological inhibitors of the protein. In vivo administration of GSK-3beta inhibitors delayed tumor formation in a mouse leukemia model. GSK-3beta inhibitors did not affect hematopoietic recovery following irradiation. CONCLUSIONS: Our data support further evaluation of GSK-3beta inhibitors as promising novel agents for therapeutic intervention in leukemia and warrant clinical investigation in leukemia patients. PMID- 20540985 TI - Induction of the renal stanniocalcin-1 gene in rodents by water deprivation. AB - Stanniocalcin-1 (STC-1) is made by kidney collecting duct cells for targeting of nephron mitochondria to promote respiratory uncoupling and calcium uniport activity. However, the purpose of these actions and how the renal gene is regulated are poorly understood. This study has addressed the latter issue by monitoring renal STC-1 gene expression in different models of kidney function. Unilateral nephrectomy and over-hydration had no bearing on renal gene activity in adult Wistar rats. Dehydration, on the other hand, had time-dependent stimulatory effects in male and female kidney cortex, where STC-1 mRNA levels increased 8-fold by 72h. Medullary gene activity was significantly increased as well, but muted in comparison ( approximately 2-fold). Gene induction was accompanied by an increase in mitochondrial sequestration of STC-1 protein. Aldosterone and angiotensin II had no bearing on STC-1 gene induction, although there was evidence of a role for arginine vasopressin. Gene induction was unaltered in integrin alpha1 knockout mice, which have an impaired tonicity enhancer binding protein (TonEBP) response to dehydration. The STC-1 gene response could be cytoprotective in intent, as dehydration entails a fall in renal blood flow and a rise in medullary interstitial osmolality. Alternatively, STC-1 could have a role in salt and water balance as dehydration necessitates water conservation as well as controlled natriuresis and kaliuresis. PMID- 20540986 TI - High-temperature requirement factor A3 (Htra3): a novel serine protease and its potential role in ovarian function and ovarian cancers. AB - The high-temperature requirement factor A (Htra) family of serine proteases is conserved from bacteria to humans. In the mouse and human, Htra3, a member of the Htra family, is transcribed into two transcripts through alternative splicing. In the rat, Htra3 is located on chromosome 14q21 and the overall intron/exon structure of Htra3 is conserved between the rat, mouse and human. Rat Htra3, similar to the mouse and human, is alternatively spliced into two transcripts (long and short). The expression and regulation of Htra3 gene and protein in the rat ovary was recently determined. The long form Htra3 has the dominant expression throughout rat ovarian postnatal development, folliculogenesis and luteinization compared to short form Htra3. The expression of the HTRA3 gene and the cellular localization of the protein in the rhesus monkey ovary were investigated. Protein expression increased during folliculogenesis and was significantly higher in the granulosa-lutein cells compared to the theca-lutein cells, suggesting a role for HTRA3 in folliculogenesis and luteinization in the primate ovary. A preliminary study has also revealed a significant decrease in HTRA3 mRNA expression in ovarian cancer and granulosa cell tumor cell lines, suggesting that HTRA3 may act as a tumor suppressor. The role of the PDZ domain, specific to the long form Htra3, and the specific substrates of Htra3 in vivo, need to be defined to better understand the roles of HtrA3 in the normal and malignant ovary. PMID- 20540987 TI - Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease. AB - DJ-1 and alpha-synuclein are leading biomarkers for Parkinson's disease diagnosis and/or monitoring disease progression. A few recent investigations have determined DJ-1 and alpha-synuclein levels in plasma or serum, a more convenient sample source than cerebrospinal fluid; but the results were variable or even contradictory. Besides limitations in detection technology and limited number of cases in some studies, inadequate control of several important confounders likely has contributed to these inconsistent results. In this study, the relative contribution of each blood component to blood DJ-1 and alpha-synuclein was evaluated, followed by quantification of plasma levels of both markers in a larger cohort of patients/subjects ( approximately 300 cases) whose cerebrospinal fluid DJ-1 and alpha-synuclein levels have been determined recently. The results demonstrated that the DJ-1 and alpha-synuclein in blood resided predominantly in red blood cells (>95%), followed by platelets (1-4%), white blood cells and plasma (< or =1%), indicating that variations in hemolysis and/or platelet contamination could have a significant effect on plasma/serum DJ-1 and alpha synuclein levels. Nonetheless, after adjusting for the age, although there was a trend of decrease in DJ-1 and alpha-synuclein in patients with Parkinson's or Alzheimer's disease compared with healthy controls, no statistical difference was observed in this cohort between any groups, even when the extent of hemolysis and platelet contamination were controlled for. Additionally, no correlation between DJ-1 or alpha-synuclein and Parkinson's disease severity was identified. In conclusion, unlike in cerebrospinal fluid, total DJ-1 or alpha-synuclein in plasma alone is not useful as biomarkers for Parkinson's disease diagnosis or progression/severity. PMID- 20540988 TI - Signalling of sphingosine-1-phosphate in Muller glial cells via the S1P/EDG family of G-protein-coupled receptors. AB - Signalling of sphingosine-1-phosphate (S1P) via G-protein-coupled receptors of the Endothelial Differentiation Gene family differentially regulates cellular processes such as migration, proliferation and morphogenesis in a variety of cell types. Proliferation and migration of retinal Muller glial cells are involved in pathological events such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Investigation of possible functional roles of S1P receptors might thus open new insights into Muller cell pathophysiology. Here we show that cultured Muller cells from the guinea pig retina respond to application of S1P with an increase in the intracellular calcium content in a concentration dependent manner (EC(50) 11nM). This calcium increase consists of two components; an initial fast peak and a slow plateau component. The initial transient is caused by a release of calcium from intracellular stores and is suppressed by U 73122, a selective phospholipase C inhibitor. The slow plateau component is caused by a calcium influx. These results suggest that the S1P-induced calcium response in Muller cells partially involves signalling via G-protein-coupled receptors. Moreover, S1P slightly induced Muller cell migration but no proliferation. Thus, the data indicate that Muller cells might be involved in S1P signalling in the retina. PMID- 20540989 TI - Decreased Fos protein expression in rat caudal vestibular nucleus is associated with motion sickness habituation. AB - We investigated the temporal change of Fos protein expression in the caudal vestibular nucleus of rats exposed to daily 2-h Ferris-wheel like (FWL) rotation. Repeated rotation (2h daily for 14 consecutive days) caused an initial increase in defecation, followed by a gradual decline back to the baseline level after 8 rotation sessions. Unlike defecation, the Kaolin consumption of rats showed a bitonic function during the daily rotation sessions (2h daily for 33 consecutive days) and finally recovered to the baseline after about 31 sessions. Immunohistochemistry study revealed increased Fos immunolabeled (Fos-LI) neurons in the medial vestibular nucleus and spinal vestibular nucleus during the initial 7 rotation sessions, and it decreased to the baseline level after 10 rotation sessions. There was a strong linear relationship between the amount of Fos-LI neurons and rat defecation level throughout the whole rotation sessions. These results suggest that the change of neuronal plasticity in the caudal vestibular nucleus might contribute to attenuation of gastrointestinal symptoms during motion sickness habituation process. PMID- 20540990 TI - Amyloid-beta production in aged guinea pigs: atropine-induced enhancement is reversed by naloxone. AB - Advanced age, cholinergic deficit, and elevated brain levels of enkephalin are associated with sporadic Alzheimer's disease. The influence of these factors on production of amyloidogenic peptides (Abeta) is uncertain. In the present experiments, the levels of 40/42 amino acid-residue Abeta were measured in the brain cortex of guinea pigs aged 15-16 weeks (young) and 25-26 months (aged). As was found, injections of atropine (21 days, 5mg/kg/day) increase Abeta levels in aged but not young animals. This atropine-induced effect was antagonized by simultaneous injections of naloxone (3mg/kg/day) whereas naloxone alone failed to affect Abeta accumulation. These results are discussed in the light of a possible "acetylcholine - Abeta" feedback loop and an influence of enkephalin on the loop function. PMID- 20540991 TI - Role of neurokinin receptors and ionic mechanisms within the respiratory network of the lamprey. AB - We have suggested that in the lamprey, a medullary region called the paratrigeminal respiratory group (pTRG), is essential for respiratory rhythm generation and could correspond to the pre-Botzinger complex (pre-BotC), the hypothesized kernel of the inspiratory rhythm-generating network in mammals. The present study was performed on in vitro brainstem preparations of adult lampreys to investigate whether some functional characteristics of the respiratory network are retained throughout evolution and to get further insights into the recent debated hypotheses on respiratory rhythmogenesis in mammals, such as for instance the "group-pacemaker" hypothesis. Thus, we tried to ascertain the presence and role of neurokinins (NKs) and burst-generating ion currents, such as the persistent Na(+) current (I(NaP)) and the Ca(2+)-activated non-specific cation current (I(CAN)), described in the pre-Botzinger complex. Respiratory activity was monitored as vagal motor output. Substance P (SP) as well as NK1, NK2 and NK3 receptor agonists (400-800 nM) applied to the bath induced marked increases in respiratory frequency. Microinjections (0.5-1 nl) of SP as well as the other NK receptor agonists (1 microM) into the pTRG increased the frequency and amplitude of vagal bursts. Riluzole (RIL) and flufenamic acid (FFA) were used to block I(NaP) and I(CAN), respectively. Bath application of either RIL or FFA (20-50 microM) depressed, but did not suppress respiratory activity. Coapplication of RIL and FFA at 50 microM abolished the respiratory rhythm that, however, was restarted by SP microinjected into the pTRG. The results show that NKs may have a modulatory role in the lamprey respiratory network through an action on the pTRG and that I(NaP) and I(CAN) may contribute to vagal burst generation. We suggest that the "group-pacemaker" hypothesis is tenable for the lamprey respiratory rhythm generation since respiratory activity is abolished by blocking both I(NaP) and I(CAN), but is restored by enhancing network excitability. PMID- 20540992 TI - Immunohistochemical evidence for synaptic release of glutamate from orexin terminals in the locus coeruleus. AB - Orexin (Orx or hypocretin) is critically important for maintaining wakefulness, since in its absence, narcolepsy with cataplexy occurs. In this role, Orx containing neurons can exert their influence upon multiple targets through the brain by release of Orx but possibly also by release of other neurotransmitters. Indeed, evidence was previously presented to suggest that Orx terminals could utilize glutamate (Glu) in addition to Orx as a neurotransmitter. Using fluorescence and confocal laser scanning microscopy, we investigated whether Orx varicosities contain the presynaptic markers for synaptic release of Glu or GABA and come into contact with postsynaptic markers for excitatory synapses within the locus coeruleus of the rat brain. We found that a proportion of the Orx+ varicosities were immunostained for the vesicular transporter for Glu, VGluT2. None were immunostained for vesicular glutamate transporter 1 (VGluT1) or VGluT3 or for the vesicular transporter for GABA, vesicular GABA transporter (VGAT). Among the Orx+ varicosities, 4% of all and 28% of large varicosities contained VGluT2. A similar proportion of the large Orx+ varicosities contained synaptophysin (Syp), a presynaptic marker for synaptic vesicles. Orx+ varicosities also contacted elements immunostained for postsynaptic density protein-95 (PSD)-95, a postsynaptic marker for glutamatergic synapses. We thus conclude that synaptic release of Glu occurs from Orx terminals within the locus coeruleus and can thus be important for the engagement of noradrenergic neurons in stimulating and maintaining arousal. PMID- 20540994 TI - Categorical counting. AB - Pigeons pecked on three keys, responses to one of which could be reinforced after a few pecks, to a second key after a somewhat larger number of pecks, and to a third key after the maximum pecking requirement. The values of the pecking requirements and the proportion of trials ending with reinforcement were varied. Transits among the keys were an orderly function of peck number, and showed approximately proportional changes with changes in the pecking requirements, consistent with Weber's law. Standard deviations of the switch points between successive keys increased more slowly within a condition than across conditions. Changes in reinforcement probability produced changes in the location of the psychometric functions that were consistent with models of timing. Analyses of the number of pecks emitted and the duration of the pecking sequences demonstrated that peck number was the primary determinant of choice, but that passage of time also played some role. We capture the basic results with a standard model of counting, which we qualify to account for the secondary experiments. PMID- 20540993 TI - Modeling a sensitization stage and a precipitation stage for Parkinson's disease using prenatal and postnatal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. AB - Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder of mature and older individuals. Since all aged individuals do not develop PD, predisposing conditions may exist that pair with the stress placed on the basal ganglia during aging to produce the symptoms of PD. In this project we used 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) to test the hypothesis that a sensitization stage and a precipitating stage underlie idiopathic PD. To induce the sensitization stage, pregnant C57BL/6J mice were treated with MPTP (10 mg/kg/day) during gestation days 8-12 to target the emerging fetal nigrostriatal dopamine neurons. For the precipitating stage, the 3-months old offspring were administered MPTP for 7 days, to simulate the changes that occur during aging. The weights and motor activity of the offspring, high performance liquid chromatography (HPLC) striatal dopamine and its metabolites and Western blot for tyrosine hydroxylase (TH) were determined. Offspring exposed to prenatal MPTP showed lower birth weights that eventually recovered. Prenatal MPTP also reduced motor activity by 10-30%, striatal TH by 38%, dopamine by 14%, homovanillic acid by 16.5% and 3-methoxytyramine by 66%. The postnatal MPTP was more potent in the prenatal MPTP-exposed offspring. MPTP at 10, 20 and 30 mg/kg, dose-relatedly, reduced striatal TH by 9.4%, 48.6% and 82.4% in the prenatal-phosphate buffered saline (PBS) mice and by 48%, 78.7% and 92.7% in the prenatal-MPTP groups. More importantly, postnatal MPTP at 10 mg/kg that showed slight effects on DA, DOPAC, HVA and 3-MT in the prenatal-PBS offspring, showed 69.9%, 80.0%, 48.4% and 65.4% reductions in the prenatal-MPTP mice. The study may identify a new model for PD, and the outcome suggests that some cases of idiopathic PD may have a fetal basis in which early subtle nigrostriatal impairments occurred and PD symptoms are precipitated later by deteriorating changes in the nigrostriatum, that would not caused symptoms in individuals with normal nigrostriatal system. PMID- 20540995 TI - Structural and functional characterization of the mouse tescalcin promoter. AB - Tescalcin, an EF-hand calcium binding protein that regulates the Na(+)/H(+) exchanger 1 (NHE1), is highly expressed in various mouse tissues such as heart and brain. Despite its potentially important role in cell physiology, the mechanisms that regulate tescalcin gene (Tesc) expression are unknown. In this study, we report two new Tesc mRNA variants (V2 and V3) and characterize the mouse Tesc promoter. The V2 and V3 transcripts result from alternative splicing of intron 5. Our results show that Tesc mRNA variants are expressed in various mouse tissues. Primer extension analysis located the transcription start site at 94 nucleotides upstream of the translation start codon. The DNA nucleotide sequence of the 5'-flanking region contained a CpG island spanning the promoter region from nucleotides -372 to +814, a canonical TATA box (-38/-32), and putative transcription factor binding sites for Sp1, EGR1, ZBP-89, KLF3, MZF1, AP2, ZF5, and CDF-1. Transient transfection of the Y1 and msc-1 cell lines with a series of 5'-deleted promoter constructs indicated that the minimal promoter region was between nucleotides -130 and -40. Electrophoresis mobility shift assays, supershift assays, and mutation studies demonstrated that Sp1 and Sp3 bind to the GC-rich motifs, a CACCC box and three GC boxes, located within the Tesc proximal promoter. Nonetheless, mutations that abolished interaction of Sp1 and Sp3 with the GC-rich motifs located within the minimal promoter region did not abrogate promoter activity in Y1 cells. Mithramycin A, an inhibitor of Sp1 DNA interaction, reduced Tesc promoter activity in msc-1 cells in a dose dependent manner. Sp3 was a weaker transactivator compared to Sp1 in Drosophila D.mel-2 cells. However, when Sp1 and Sp3 were coexpressed, they transactivated the Tesc promoter in a synergistic manner. In Y1 cells, mutation analysis of a putative ZF5 motif located within the Tesc minimal promoter indicated that this motif was critical for activity of Tesc promoter. Taken together, the data demonstrated that Sp1 and Sp3 transcription factors cooperate positively in the regulation of Tesc promoter, and that the putative ZF5 motif is critical for its activation. PMID- 20540996 TI - Drug release from hydroethanolic gels. Effect of drug's lipophilicity (logP), polymer-drug interactions and solvent lipophilicity. AB - We demonstrate drug release properties from hydroethanolic formulations as a function of the drug's lipophilicity (logP), solvent lipophilicity and drug polymer interactions, for the first time. A hydrophilic polymer, hydroxypropyl cellulose (HPC), provides the non-Fickian slower release of the lipophilic drug, lidocaine (logP=2.6) and the burst (Fickian) release of hydrophilic drug, lidocaine hydrochloride (logPGSSG+ASC) as a chemical pathway of ascorbate regeneration. Here, we report the formation of a novel conjugation product between GSH and the decomposition of DHA denoted as GS-DHA*. On the basis of MS and NMR analyses, the structure of GS-DHA* consists of an intact GSH moiety attached via the thiol group to a five-carbon fragment of DHA. The conjugation product appears as a mixture of four diastereomers with very similar proton and carbon chemical shifts. The formation of GS-DHA* adducts is demonstrated in Jurkat cells upon incubation with DHA in culture followed by analysis of the whole-cell extracts by HPLC coupled to tandem mass spectrometry. This novel conjugation product may be a useful biomarker of DHA stress and model system of protein modification. PMID- 20541007 TI - Hypoxia and reoxygenation-induced oxidant production increase in microvascular endothelial cells depends on connexin40. AB - Connexins (Cx) are recognized as structural constituents of gap-junctional intercellular communication (GJIC). However, their function may extend beyond facilitating the exchange of metabolites and electrical signals between cells. In this study we asked if increased production of reactive oxygen species (ROS) in microvascular endothelial cells challenged by hypoxia/reoxygenation (H/R) requires Cx40, independent of GJIC. Because we showed that this ROS increase depends on NADPH oxidase, we also asked if Cx40 function (i.e., Cx40-dependent reduction in interendothelial electrical coupling after H/R) requires NADPH oxidase. ROS increase was assessed in confluent monolayers of cultured endothelial cells derived from skeletal muscle blood vessels of wild-type (WT) and Cx40(-/-) mice and in monolayers of GJIC-deficient SKHep1 cells overexpressing GFP-tagged Cx40. Electrical coupling was assessed in WT cells and in cells lacking the NADPH oxidase subunit gp91phox or p47phox. H/R elicited a 70 80% ROS increase in WT but not in Cx40(-/-) cells. The increase was not affected by the gap junction blocker 18alpha-glycyrrhetinic acid or by preventing the cells from establishing cell-to-cell contact. H/R increased ROS in SKHep1 cells expressing Cx40-GFP, but not in cells expressing the control vector. Finally, H/R reduced electrical coupling in WT and gp91phox(-/-) but not in p47phox(-/-) cells. Our data indicate that (i) the H/R-induced ROS increase in microvascular endothelial cells requires Cx40, independent of its role in GJIC, and (ii) p47phox rather than NADPH oxidase-derived ROS affects modulation of intercellular coupling. Together, the results raise an intriguing possibility that H/R-induced signaling in endothelial cells involves a cross-talk between Cx40 and NADPH oxidase. PMID- 20541008 TI - Role of autophagy in protection afforded by hypoxic preconditioning against MPP+ induced neurotoxicity in SH-SY5Y cells. AB - A sublethal preconditioning has been proposed as a neuroprotective strategy against several CNS neurodegenerative diseases. In this study, the involvement of autophagy in the protection provided by hypoxic preconditioning against 1-methyl 4-phenylpyridinium (MPP(+))-induced neurotoxicity was studied in SH-SY5Y neuroblastoma cells. In contrast to the cytotoxicity of 0.1% oxygen, 1% oxygen hypoxia for 24h did not cause significant cell death. A transient increase in LC3 II level, a biomarker of autophagy, was demonstrated during hypoxic treatment. At the same time, 8-h hypoxia increased fluorescence due to monodansylcadaverine, a specific dye for autophagosomes, in the treated cells. Co-incubation with bafilomycin A1 (10 nM) further increased hypoxia-induced LC3-II levels but 3 methyladenine (3-MA; 10 mM) reduced the elevation in LC3-II levels induced by 8-h hypoxia. Moreover, 8-h hypoxia increased free radical formation and nuclear HIF 1alpha level. Glutathione was found to diminish hypoxia-induced LC3-II elevation. In contrast to the elevated LC3-II level, 8-h hypoxia significantly decreased mitochondrial mass. Furthermore, a rebound elevation in mitochondrial mass was observed under 8-h hypoxia and subsequent 12-h normoxia. Prior hypoxia attenuated the MPP(+)-induced elevation in LC3-II levels and cell death. Moreover, hypoxic pretreatment inhibited MPP(+)-induced activation of caspase-3 and DNA fragmentation. Co-incubation with 3-MA during hypoxia prevented the protection afforded by hypoxic preconditioning against MPP(+)-induced increases in LC3-II levels and neurotoxicity. Taken together, our results suggest that sublethal hypoxia induces autophagy that is mediated by oxidative stress. Furthermore, autophagy may be involved in the protection provided by hypoxic preconditioning against MPP(+)-induced neurotoxicity, indicating a neuroprotective role of autophagy in hypoxic preconditioning. PMID- 20541009 TI - Investigation on a pertussis outbreak in a military school: risk factors and approach to vaccine efficacy. AB - INTRODUCTION: Pertussis (whooping cough) is a toxic bacterial infection caused mainly by Bordetella pertussis. In mid-January 2006, several cases of pertussis were diagnosed in a military boarding-school. An investigation was carried out at the end of January to identify the risk factors for infection and to evaluate the efficacy of vaccination. SUBJECTS AND METHODS: Three definitions were used to distinguish the cases; confirmed biologically, confirmed epidemiologically and suspected cases. The risk factor study was carried out after the exclusion of suspect cases. Vaccine efficacy (VE) was evaluated from a case-control study where only biologically confirmed cases were included. For each case, five controls were matched according to age, sex and class. A logistic regression and a conditional logistic regression were performed for the risk factor study and vaccine efficacy, respectively. Statistical analysis was carried out using Stata 9.2 software. RESULTS: A total of 206 cases were included, 17 of them biologically confirmed, 66 epidemiologically and 123 suspected cases. The attack rate was 17.8 per 100. Girls were 1.8 times more likely to catch pertussis (p=0.04), pupils in the first year of college, as well as those in high school were at 5 times greater risk of catching pertussis (p=0.008) than those in the second year of college. For pupils who benefited from at least 5 doses, the VE was at 80% when the last dose dated from less than 6 years earlier. DISCUSSION/CONCLUSION: The attack rate observed in our study was similar to those normally seen during epidemics occurring within a community. Vaccine efficacy declined depending on the time lapse since the last vaccination. Since April 2008, the Public Health Authorities have planned to provide pertussis booster vaccinations for children aged 16-18 who missed those for 11-13-year-old, and for adults aged 26-27 and those who have not been vaccinated for more than 10 years. PMID- 20541010 TI - Digital imaging as a process analytical technology tool for fluid-bed pellet coating process. AB - Pellet coating processes are usually driven by fairly well optimized procedures, while coating suspension sprayed on pellets and adverse effects, such as agglomeration, can not be seen during coating process and are only detected at the very end of the process, when it is too late for any adjustments of the coating process. The aim of this study is to evaluate digital visual imaging as process analytical technology (PAT) tool for fluid-bed pellet coating processes. The method accurately estimates spherical diameter, coating thickness and adverse agglomeration of pellets by contactless measurements, classification and analysis of pellets based on digital imaging. Calibration and thorough assessment of the accuracy, precision, stability and speed of the proposed method was performed with high precision bearing balls. The obtained results on real pellets indicated that the method is feasible for real-time controlling, understanding, designing and optimizing of fluid-bed pellet coating processes according to PAT guidance. PMID- 20541011 TI - Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition. AB - Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2(-/-)-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2(-/-)-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2(-/-)-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2(-/-)-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2(-/-)-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2(-/-)-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2(-/-)-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2(-/-)-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2(-/-)-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2(-/-)-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling. PMID- 20541012 TI - Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy. AB - Only limited data is available concerning the role of unconjugated Delta(5) C19 steroids and almost no data exists regarding the neuroactive C21 and C19 3alpha hydroxy-5alpha/beta-metabolites in men with epilepsy. To evaluate the alterations in serum neuroactive steroids and related substances in adult men with epilepsy on valproate and carbamazepine monotherapy, we have measured 26 unconjugated steroids, 18 steroid polar conjugates, gonadotropins and sex hormone binding globulin (SHBG) in 6 and 11 patients on valproate and carbamazepine monotherapy, respectively, and in 19 healthy adult men, using the GC-MS and immunoassays. Decreased testosterone, free androgen index, free testosterone, androstenediol, 5alpha-androstane-3alpha,17beta-diol (androstanediol), androsterone, epiandrosterone, DHEA, 7beta-hydroxy-DHEA, and DHEAS levels were associated with epilepsy per se. Valproate (VPA) therapy increased 5alpha-dihydrotestosterone, androsterone, epiandrosterone, DHEA, DHEAS, and 7beta-hydroxy-DHEA levels. Decrease in pregnenolone and 17-hydroxypregnenolone were associated with epilepsy with no effect of antiepileptic drugs (AEDs). Alternatively, the increase in progesterone levels was linked to epilepsy and VPA further increased progesterone levels. Reduced steroid 20alpha-hydroxy-metabolites and cortisol were connected with epilepsy without an effect of AEDs. Carbamazepine induced only slight decrease in isopregnanolone, 5alpha,20alpha-tetrahydroprogesterone, and androstanediol levels. PMID- 20541013 TI - Genomic rearrangements in inherited disease and cancer. AB - Genomic rearrangements in inherited disease and cancer involve gross alterations of chromosomes or large chromosomal regions and can take the form of deletions, duplications, insertions, inversions or translocations. The characterization of a considerable number of rearrangement breakpoints has now been accomplished at the nucleotide sequence level, thereby providing an invaluable resource for the detailed study of the mutational mechanisms which underlie genomic recombination events. A better understanding of these mutational mechanisms is vital for improving the design of mutation detection strategies. At least five categories of mutational mechanism are known to give rise to genomic rearrangements: (i) homologous recombination including non-allelic homologous recombination (NAHR), gene conversion, single strand annealing (SSA) and break-induced replication (BIR), (ii) non-homologous end joining (NHEJ), (iii) microhomology-mediated replication-dependent recombination (MMRDR), (iv) long interspersed element-1 (LINE-1 or L1)-mediated retrotransposition and (v) telomere healing. Focussing on the first three of these general mechanisms, we compare and contrast their hallmark characteristics, and discuss the role of various local DNA sequence features (e.g. recombination-promoting motifs, repetitive sequences and sequences capable of non-B DNA formation) in mediating the recombination events that underlie gross genomic rearrangements. Finally, we explore how studies both at the level of the gene (using the neurofibromatosis type-1 gene as an example) and the whole genome (using data derived from cancer genome sequencing studies) are shaping our understanding of the impact of genomic rearrangements as a cause of human genetic disease. PMID- 20541014 TI - Solving novel RNA structures using only secondary structural fragments. AB - The crystallographic phase problem is the primary bottleneck encountered when attempting to solve macromolecular structures for which no close crystallographic structural homologues are known. Typically, isomorphous "heavy-atom" replacement and/or anomalous dispersion methods must be used in such cases to obtain experimentally-determined phases. Even three-dimensional NMR structures of the same macromolecule are often not sufficient to solve the crystallographic phase problem. RNA crystal structures present additional challenges due to greater difficulty in obtaining suitable heavy-atom derivatives. We present a unique approach to solve the phase problem for novel RNA crystal structures that has enjoyed a reasonable degree of success. This approach involves modeling only those portions of the RNA sequence whose structure can be predicted readily, i.e., the individual A-form helical regions and well-known stem-loop sub structures. We have found that no prior knowledge of how the helices and other structural elements are arranged with respect to one another in three-dimensional space, or in some cases, even the sequence, is required to obtain a useable solution to the phase problem, using simultaneous molecular replacement of a set of generic helical RNA fragments. PMID- 20541015 TI - Genomic SELEX: a discovery tool for genomic aptamers. AB - Genomic SELEX is a discovery tool for genomic aptamers, which are genomically encoded functional domains in nucleic acid molecules that recognize and bind specific ligands. When combined with genomic libraries and using RNA-binding proteins as baits, Genomic SELEX used with high-throughput sequencing enables the discovery of genomic RNA aptamers and the identification of RNA-protein interaction networks. Here we describe how to construct and analyze genomic libraries, how to choose baits for selections, how to perform the selection procedure and finally how to analyze the enriched sequences derived from deep sequencing. As a control procedure, we recommend performing a "Neutral" SELEX experiment in parallel to the selection, omitting the selection step. This control experiment provides a background signal for comparison with the positively selected pool. We also recommend deep sequencing the initial library in order to facilitate the final in silico analysis of enrichment with respect to the initial levels. Counter selection procedures, using modified or inactive baits, allow strengthening the binding specificity of the winning selected sequences. PMID- 20541016 TI - Identification and molecular analysis of a stress-inducible Hsp70 from Sciaenops ocellatus. AB - Hsp70 proteins are a family of molecular chaperones that are involved in many aspects of protein homeostasis. In this study, an Hsp70 homologue (SoHsp70) was identified from red drum Sciaenops ocellatus and analyzed at molecular level. The open reading frame of SoHsp70 is 1920 bp and intronless, with a 5'-untranslated region (UTR) of 399 bp and a 3'-UTR of 241 bp. The deduced amino acid sequence of SoHsp70 shares 84-92% overall identities with the Hsp70s of a number of fish species. In silico analysis identified in SoHsp70 three conserved Hsp70 domains involved in nucleotide and substrate binding. The coding sequence of SoHsp70 was subcloned into Escherichia coli, from which recombinant SoHsp70 was purified and, upon ATPase assay, found to exhibit apparent ATPase activity. Expressional analysis showed that constitutive expression of SoHsp70 was detectable in heart, liver, spleen, kidney, brain, blood, and gill. Experimental challenges with poly(I:C) and bacterial pathogens of Gram-positive and Gram-negative nature induced SoHsp70 expression in kidney to different levels. Stress-responsive analysis of SoHsp70 expression in primary cultures of red drum hepatocytes showed that acute heat shock treatment elicited a rapid induction of SoHsp70 expression which appeared after 10 min and 30 min of treatment. Exposure of hepatocytes separately to iron, copper, mercury, and hydrogen peroxide significantly upregulated SoHsp70 expression in time-dependent manners. Vaccination of red drum with a Streptococcus iniae bacterin was also found to induce SoHsp70 expression. Furthermore, recombinant SoHsp70 enhanced the immunoprotective effect of a subunit vaccine. Taken together, these results suggest that SoHsp70 is a stress inducible protein that is likely to play a role in immunity and in coping with environmental and biological stresses. PMID- 20541017 TI - Learning related activation of somatosensory cortex by an auditory stimulus recorded with magnetoencephalography. AB - Advances in non-invasive neuroimaging technology now provide a means of directly observing learning within the brain. Classical conditioning serves as an ideal starting point for examining the dynamic expression of learning within the human brain, since this paradigm is well characterized using multiple levels of analysis in a broad range of species. We used MEG to expand the characterization of conditioned responses (CR) recorded from the human brain with a simultaneous examination of their spatial, temporal and spectral properties. We paired an auditory conditioned stimulus (CS+) with a somatosensory unconditioned stimulus (US). We found that when the US was randomly omitted, presentations of CS+ alone, elicited greater desynchronization of beta-band activity in contralateral somatosensory cortex compared to presentations of an auditory stimulus that was never paired with the US (CS-), and compared the CS+ following a non-reinforced extinction session. This differentiation was largest between 150 and 350ms following US omission. We show that cross-modal CRs in the primary sensorimotor system are predominantly characterized by modulation of ongoing cortical oscillations. PMID- 20541018 TI - Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia. AB - Aphasia after middle cerebral artery (MCA) stroke shows highly variable degrees of recovery. One possible explanation may be offered by the variability of the occlusion location. Branches from the proximal portion of the MCA often supply the mesial temporal lobe including parts of the hippocampus, a structure known to be involved in language learning. Therefore, we assessed whether language recovery in chronic aphasia is dependent on the proximity of the MCA infarct and correlated with the integrity of the hippocampus and its surrounding white matter. Language reacquisition capability was determined after 2weeks of intensive language therapy and 8months after treatment in ten chronic aphasia patients. Proximity of MCA occlusion relative to the internal carotid artery was determined by magnetic resonance imaging (MRI) based on the most proximal anatomical region infarcted. Structural damage to the hippocampus was assessed by MRI-based volumetry, regional microstructural integrity of hippocampus adjacent white matter by fractional anisotropy. Language learning success for trained materials was correlated with the proximity of MCA occlusion, microstructural integrity of the left hippocampus and its surrounding white matter, but not with lesion size, overall microstructural brain integrity and a control region outside of the MCA territory. No correlations were found for untrained language materials, underlining the specificity of our results for training-induced recovery. Our results suggest that intensive language therapy success in chronic aphasia after MCA stroke is critically dependent on damage to the hippocampus and its surrounding structures. PMID- 20541019 TI - Decoding brain states from fMRI connectivity graphs. AB - Functional connectivity analysis of fMRI data can reveal synchronised activity between anatomically distinct brain regions. Here, we extract the characteristic connectivity signatures of different brain states to perform classification, allowing us to decode the different states based on the functional connectivity patterns. Our approach is based on polythetic decision trees, which combine powerful discriminative ability with interpretability of results. We also propose to use ensemble of classifiers within specific frequency subbands, and show that they bring systematic improvement in classification accuracy. Exploiting multi band classification of connectivity graphs is also proposed, and we explain theoretical reasons why the technique could bring further improvement in classification performance. The choice of decision trees as classifier is shown to provide a practical way to identify a subset of connections that distinguishes best between the conditions, permitting the extraction of very compact representations for differences between brain states, which we call discriminative graphs. Our experimental results based on strict train/test separation at all stages of processing show that the method is applicable to inter-subject brain decoding with relatively low error rates for the task considered. PMID- 20541020 TI - Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: a combined MRI and 1H-MRS study. AB - BACKGROUND: Volume deficits assessed with magnetic resonance imaging (MRI) and neurochemical dysfunctions (N-acetylaspartate, NAA) diagnosed using proton MR spectroscopy ((1)H-MRS) are reliable observations in the hippocampus of schizophrenic patients. NAA is an important cerebral amino acid in the synthesis pathways of glutamate, which has been implicated as a pathobiological core of schizophrenic symptomatology, of histological alterations and brain volume deficits in schizophrenia. However, the possible interaction between regional NAA reduction and volume deficits has been targeted only marginally in previous investigations. METHODS: In 29 schizophrenic patients and 44 control subjects, a multimodal imaging study with (1)H-MRS and MRI volumetry of the left hippocampus was performed on a 3-Tesla scanner. RESULTS: Compared to the control group, the hippocampus of the patients exhibited a significant volume reduction and a significant NAA concentration decrease. In schizophrenic patients, but not in healthy controls, a significant negative correlation between hippocampal NAA concentration and volume (r=-0.455, p=0.017) was observed. None of the imaging parameters was associated with clinical parameters. CONCLUSIONS: The results argue for a coexistent neurochemical and structural deficit in the hippocampus of schizophrenic patients. The inverse relationship between the two parameters observed in patients only may reflect an interaction of neurochemistry and brain morphology as a pathobiological mechanism in schizophrenia. This observation is compatible with the important role of NAA in the synthesis of excitatory neurotransmitters and the hypothesized role of glutamate for brain morphology. The independence of the measured imaging parameters from clinical parameters is in line with the neurodevelopmental hypothesis of schizophrenia. PMID- 20541021 TI - Polyphyly of the genus Axinella and of the family Axinellidae (Porifera: Demospongiaep). AB - The genus Axinella is difficult to define on the basis of morphological characters and includes a heterogeneous assemblage of species. Several previous authors have suspected the polyphyly of both this genus and the family Axinellidae. To clarify the phylogeny of Axinellidae and Axinella, we propose a new hypothesis based on two molecular markers. In our analyses, Axinellidae and Axinella are polyphyletic assemblages. The 15 species of Axinellidae in our dataset belong to five clades and the nine species of Axinella to three clades. One Axinella clade, named Axinella(p), contains the type-species of the genus: A. polypoides (plus A. aruensis, A. dissimilis, A. infundibuliformis and A. vaceleti). A new clade, Cymbaxinella(p), is proposed, following the PhyloCode, it includes C. damicornis, C. verrucosa, C. corrugata and C. cantharella. The species Axinella cannabina is reallocated to a clade named Acanthella(p). The clades Agelas(p) and Cymbaxinella(p) constitute a new clade: Agelasida(p). Few morphological, biochemical and secondary structures characters support these groupings, highlighting the need for new characters for such problematic sponge groups. This work is an attempt to build a framework for the phylogeny of taxa allocated to Axinella and Axinellidae in the traditional classification. PMID- 20541022 TI - Investigation of the intestinal microbiota in preterm infants using different methods. AB - Modifications in microbial colonization of the human gut are believed to affect intestinal homeostasis and increase the risk of gastrointestinal diseases. The present study examined different methods for investigating the dynamic characterization of the intestinal microbiota in preterm infants. Fecal samples were collected weekly from ten preterm infants during their stay in a neonatal intensive care unit. The infants had a mean gestational age of 29 weeks (range: 28-32 weeks) and a mean birth weight of 1233g (range: 935-1450g). Bacterial colonization was assessed using conventional culture techniques and molecular biological methods. More specifically, the recently developed denaturing high performance liquid chromatography (dHPLC) technique was compared to established methods such as temporal temperature gradient gel electrophoresis (TTGE) and rRNA gene library sequencing. Our results indicate that the gastrointestinal tract of preterm infants, born at a gestational age of less than 33 weeks, has a low biodiversity of mainly, culturable bacteria. Finally, dHPLC was evaluated in terms of speed, labor and sensitivity for its use as a tool to analyze microbial colonization in preterm infants. We found that this technique provided major improvements over gel-based fingerprinting methods, such as TTGE, that are commonly used for studying microbial ecology. As such, it may become a common analytical tool for this purpose. PMID- 20541023 TI - The occurrence and high diversity of Clostridium difficile genotypes in rivers. AB - Clostridium difficile is mainly associated with nosocomial infections but can be present also in other environments. In this study we compared three methods (culturing with and without ethanol shock and real-time PCR) for detection of C. difficile in water and have used them on a series of river water samples. C. difficile was present in 17 of 25 rivers tested (68.0%) and in 42 of 69 water samples tested (60.9%). Positive sampling sites correlated with increased population densities. Isolates were distributed into 34 PCR ribotypes, of which more than half are present also in humans and animals. PCR ribotype 014 was the predominate type (16.2% of all isolates). PMID- 20541025 TI - The potential utility of bone marrow or umbilical cord blood transplantation for the treatment of type I diabetes mellitus. AB - The pathology of type 1 diabetes mellitus (T1D) involves the autoimmune destruction or malfunction of pancreatic beta cells, leading to a lack of insulin. The absence of insulin is life-threatening, necessitating daily hormone injections from an exogenous source. Insulin injections do not adequately mimic the precise regulation of beta cells on glucose homeostasis, however, eventually leading to complications in diabetic patients. There currently is no definitive cure for T1D. Pancreas transplantation, although quite successful, is an invasive intervention that is restricted to patients with advanced complications, requires constant immunosuppression, and is severely limited by donor availability. Recent progress in human islet cell isolation and immunosuppressive protocols has restored euglycemia in patients who received islet cells from 2 or 3 pancreas donors. However, because of the scarcity of cadaver pancreata and the low yield of islet cells obtained by the procedure, not all patients have access to this surgical intervention. Thus, other therapeutic approaches are needed to arrest immune aggression, preserve beta cell mass, and provide efficient replacement. In this sense, bone marrow and umbilical cord blood transplantation are promising possibilities that merit exploration. In this review, we summarize multiple strategies that have been proposed and tested for potential therapeutic benefit in patients with T1D. PMID- 20541024 TI - Graft-versus-host disease treatment: predictors of survival. AB - Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplant (HCT) is the major reason for nonrelapse mortality (NRM), and thus is a major determinant of long-term survival. Clinical trials of new aGVHD treatments are needed to identify approaches that will ultimately improve upon HCT survival. At present, it is not clear how quickly response to GVHD treatment needs to be established to reliably categorize patients at high risk for death or to promptly identify those who might benefit from alternate treatment. Therefore, we analyzed time to response from onset of aGVHD treatment in 180 patients who were enrolled on a national, randomized, phase II aGVHD treatment clinical trial whose initial treatment of GVHD consisted of high-dose steroids plus a second immunosuppressive agent. The aim of this analysis was to determine whether time to aGVHD treatment response predicts patient outcomes, especially survival. We used response at 14, 28, and 56 days from initiation of aGVHD treatment to categorize patients for NRM and survival. Multivariate analyses and specificity/sensitivity analyses identified that day 28 response (complete or partial response) best categorized patients by NRM and survival at 9 months from start of aGVHD treatment. If verified as a reliable predictor of late outcomes following other aGVHD treatment approaches, day 28 response should serve as a standard early endpoint for future trials of aGVHD therapy. PMID- 20541026 TI - Genetic variations of interleukin-23R (1143A>G) and BPI (A645G), but not of NOD2, are associated with acute graft-versus-host disease after allogeneic transplantation. AB - Single nucleotide polymorphisms (SNPs) in genes of the immune system predict for aGVHD and mortality after allo-SCT. We investigated the effect of SNPs in the NOD2, BPI, and IL-23R genes on posttransplantation outcome in a cohort of 304 patients. NOD2 patient and donor genotype and BPI recipient genotype were not associated with the occurrence of aGVHD. However, IL-23R-SNP in the donor was correlated with less aGVHD. This association could be confirmed in multivariate analysis (odds ratio [OR], 0.39; P = .039), which identified in vivo T cell depletion (OR, 0.32; P < .001) and multiagent GVHD prophylaxis (OR, 0.51; P = .031) as other independent factors predicting for less-severe aGVHD. This multivariate model also revealed a trend toward less aGVHD in patients receiving a BPI G allele transplant (OR, 0.60; P = .067) and in those receiving a transplant from an HLA-matched donor (OR, 0.57; P = .058). In contrast, relapse was more frequent in patients with NOD2-SNPs (46.2% for SNP vs 33.2% for wild type; P = .020). This association was found to be of borderline significance in multivariate analysis. Neither BPI nor IL-23R genotype predicted for relapse, and none of the investigated SNPs was correlated with 5-year overall survival. In our analysis, NOD2 SNPs did not predict aGVHD, but IL-23R(1142A>G) and BPI(A645G) SNPs appeared to be promising markers in this regard. The importance of these markers in prediction models for GVHD and relapse remain to be defined in large prospective clinical trials. PMID- 20541027 TI - Tumor necrosis factor polymorphism affects transplantation outcome in patients with myelodysplastic syndrome but not in those with chronic myelogenous leukemia, independent of the presence of HLA-DR15. AB - Both the presence of HLA-DR15 and tumor necrosis factor (TNF)-alpha levels have been reported to affect outcome after hematopoietic cell transplantation (HCT). Patients with a myelodysplastic syndrome (MDS) show a high prevalence of HLA-DR15 and express high levels of TNF-alpha in the bone marrow. The present analysis involving 7950 patients showed an HLA-DR15 frequency of 31% in patients with MDS, compared with only 23% in patients with chronic myelogenous leukemia (CML). HLA DR15 was more prevalent in Caucasian patients than in non-Caucasian patients (P = .01). The numbers of patients in the non-Caucasian subgroups were too small to allow further analysis. Among Caucasian patients with MDS and CML, the presence of HLA-DR15 did not significantly affect the occurrence of graft-versus-host disease, relapse, nonrelapse mortality (NRM), or survival. However, there was a significant correlation between DR15 and TNF polymorphisms at position -308 among patients with MDS, and the TNF-308 AG genotype conferred an increased risk of NRM compared with the GG genotype (hazard ratio [HR], 1.49; P = .02), even after adjusting for DR15. Conversely, the TNF-863 AA genotype was correlated with decreased overall mortality and NRM compared with the CC genotype (HR, 0.36, P = .04 vs HR, 0.13, P = .04), even after adjusting for DR15. There was no significant association between TNF-308 or -863 polymorphisms and transplantation outcome in CML patients. These results suggest that TNF polymorphisms, but not DR15, affect transplantation outcome in a disease-dependent manner. PMID- 20541028 TI - Validation of the human activity profile questionnaire in patients after allogeneic hematopoietic stem cell transplantation. AB - Chronic graft-versus-host disease (cGVHD) associated morbidity and mortality remain major barriers for successful allogeneic hematopoietic stem cell transplantation (alloHSCT). Currently, no reliable measures are established to monitor cGVHD activity changes for use in clinical trials. The Human Activity Profile (HAP) patient self-report was proposed by the National Institutes of Health (NIH) cGVHD consensus project as an independent measure of patients' functional status that could also indirectly reflect improvement of cGVHD, but that has not been validated in an alloHSCT patient population. One hundred seventy-six patients (median age 44 years [range: 18-72 years] after alloHSCT were evaluated with a German translation of the HAP, the NIH criteria-based cGVHD activity assessment, the Lee cGVHD Symptom-Scale, FACT-BMT, SF36, Berlin Social Support Scale, 24-Item Adjective Measure (24-AM), Hospital Anxiety and Depression Scale, and the NCCN-Distress-Thermometer. Enrollment occurred a median of 286 (range: 85-4003) days after alloHSCT. Follow-up surveys were conducted at 1, 2, 3, 5, 8, and 12 months after the baseline survey. Although 117 patient had cGVHD at time of enrollment (mild n = 33, moderate n = 50, or severe n = 34), 59 patients were included into the study in the absence of cGVHD between days 85 and 395 after transplantation. The maximum activity score (MAS) and adjusted activity score (AAS) of the HAP correlated inversely with grading of cGVHD severity (mild, moderate, or severe) (r = -0.25 for MAS and -0.24 for AAS). Lung manifestations of cGVHD correlated with AAS (r = 0.17), but not with MAS. HAP scores correlated with subscales from other instruments measuring physical domains, especially the physical functioning scale of the SF36. Performance was improved by use of an HSCT-modified HAP scoring system that excluded activities prohibited within the first year after alloHSCT. No significant correlation of the HAP was found with personality, age, sex, symptom burden, or social functioning or social well being. Moreover, the HAP displayed a higher sensitivity to change of cGVHD activity compared to the SF36 and the FACT-BMT. In addition, steroid myopathy correlated with both HAP scores, but not the SF36. The HAP is a simple and valid questionnaire for the evaluation of the physical activity in patients after alloHSCT, with the advantage of detecting changes in cGVHD status independently of other quality-of-life measures and with a superior sensitivity compared to the SF36. PMID- 20541029 TI - The endocannabinoid system: its roles in energy balance and potential as a target for obesity treatment. AB - Obesity and cardiometabolic risk continue to be major public health concerns. A better understanding of the physiopathological mechanisms leading to obesity may help to identify novel therapeutic targets. The endocannabinoid system discovered in the early 1990s is believed to influence body weight regulation and cardiometabolic risk factors. This article aims to review the literature on the endocannabinoid system including the biological roles of its major components, namely, the cannabinoid receptors, their endogenous ligands the endocannabinoids and the ligand-metabolising enzymes. The review also discusses evidence that the endocannabinoid system constitutes a new physiological pathway occurring in the central nervous system and peripheral tissues that has a key role in the control of food intake and energy expenditure, insulin sensitivity, as well as glucose and lipid metabolism. Based on the important finding that there is a close association between obesity and the hyperactivity of the endocannabinoid system, interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development has become an important area of research. Among the pharmacological strategies proposed, the antagonism of the cannabinoid receptors has been particularly investigated and several clinical trials have been conducted. One challenging pharmacological task will be to target the endocannabinoid system in a more selective, and hence, safe way. As the management of obesity also requires lifestyle modifications in terms of healthy eating and physical activity, the targeting of the endocannabinoid system may represent a novel approach for a multifactorial therapeutic strategy. PMID- 20541030 TI - Human exercise-mediated skeletal muscle hypertrophy is an intrinsic process. AB - Muscle cells (fibres) are post-mitotic and thus undergo changes in phenotype by modifying their existing structure. Hypertrophy is a hallmark change that occurs in response to increased loading and can be achieved in humans through repeated bouts of resistance exercise (i.e., training). In resistance exercise, contractions are initiated by neural drive leading to immediate perturbations such as calcium influx, cross-bridge cycling and tension/stress on the cytoskeleton, sarcolemma and extracellular matrix, as well as more delayed cellular events such as the production/release of potential local growth factors (e.g., IGF-1). Resistance exercise can also elevate the systemic concentration of certain hormones (growth hormone, testosterone, IGF-1) that are hypothesized to drive hypertrophy. However, while these hormones are clearly anabolic during childhood and puberty, or when given at supraphysiological exogenous doses, the transient post-exercise elevations in hormone concentration are of little consequence to the either the acute protein synthetic response or to a hypertrophic phenotype after resistance training. Thus, the acute post-exercise increases in systemic hormones are in no way a proxy marker for anabolism since they do not underpin the capacity of the muscle to hypertrophy in any measurable way. In contrast, the acute activation of intrinsically located signalling proteins such as p70(S6K) and the acute elevation of muscle protein synthesis are more reflective of the potential to increase in muscle mass with resistance training. Ultimately, local mechanisms are activated by the stress imposed by muscle loading and prime the muscle for protein accretion. Membrane-derived molecules and tension-sensing pathways are two intrinsic mechanisms implicated in upregulating the synthesis and incorporation of muscle proteins into the myofibre in response to mechanical stress derived from loaded contractions. PMID- 20541032 TI - The glomerulus--a view from the inside--the endothelial cell. AB - The glomerular endothelial cells are unique both in location and anatomy compared to most other endothelial cells throughout the body. The absence of a diaphragm with retention of a basement membrane and fenestrations enable these uniquely situated cells to have a key role in filtration performed by the kidney. Interaction with other glomerular cells such as the podocytes and mesangial cells, as well as with circulating and infiltrating inflammatory cells, contribute to the final impact of the glomerular endothelial cells on maintenance of body fluid homeostasis and modulation of disease. Thus, endothelial cells contribute to hemodynamic function, reactive oxygen stress, regulate the balance between pro-thrombotic and anti-thrombotic forces, and importantly, contribute to fibrosis, the key injury of progressive chronic kidney disease. Repair of endothelial cell damage and restoration of segmentally sclerosed glomeruli are key areas considered for intervention in chronic kidney disease. This review will focus on the structure, function, and interplay of endothelial cells with other glomerular cells and systemic factors, their impact on renal disease and give rationale for possible intervention that may forestall progressive injuries. PMID- 20541031 TI - A novel strategy for therapeutic intervention for the genetic disease: preventing proteolytic cleavage using small chemical compound. AB - Haploinsufficiency is a state of genetic disease, which is caused by hemizygous mutations of functional alleles. Lissencephaly is a typical example of haploinsufficiency disorders characterized by a smooth cerebral surface, thick cortex and dilated lateral ventricules associated with mental retardation and seizures due to defective neuronal migration. LIS1 was the first gene cloned in an organism, which was deleted or mutated in patients with lissencephaly in a heterozygous fashion. Series of studies uncovered that LIS1 is an essential regulator of cytoplasmic dynein. In particular, we reported that LIS1 is essential for dynein transport to the plus-end of microtubules by kinesin, which is essential for maintaining proper distribution of cytoplasmic dynein within the cell. Fortuitously, we found that a substantial fraction of LIS1 is degraded by the cystein protease, calpain after reaching the plus-end of microtubules. We further demonstrated that inhibition of calpain-mediated LIS1 degradation increased LIS1 level at the cortex of the cell, resulting in therapeutic benefit using genetic mouse models with reduced levels of LIS1. Our work might provide a potential therapeutic approach for the treatment of a fraction of haploinsufficiency disorders through augmenting reduced proteins by the targeting inhibition of degradation machinery. PMID- 20541033 TI - Skeletal muscle: increasing the size of the locomotor cell. AB - Skeletal muscle is the most abundant tissue in the body comprising 40-50% of body mass in humans and playing a central role in maintaining metabolic health. Skeletal muscle protein undergoes rapid turnover, a process that is intricately regulated by the balance between the rates of protein synthesis and degradation. The process of skeletal muscle hypertrophy and regeneration is an important adaptive response to both contractile activity (i.e., exercise) and nutrient availability (i.e., protein ingestion). Ageing and physical inactivity are two conditions associated with a loss of skeletal muscle protein (sarcopenia). Sarcopenia is characterised by a deterioration of muscle quantity and quality, although the precise mechanism(s) underlying this condition remain to be elucidated. This review will (1) summarise our current understanding of the origin and plasticity of skeletal muscle, (2) discuss the major effectors of muscle growth, and (3) highlight the importance of skeletal muscle health in the prevention of several common pathologies. PMID- 20541034 TI - Colorectal carcinoma cells--regulation of survival and growth by SGK1. AB - Colorectal carcinoma is among the most common malignancies. The tumour cells may arise from mutations in genes encoding proteins involved in the regulation of cell survival and proliferation. Recent evidence disclosed the sensitivity of colon carcinoma to the expression of ubiquitous serum and glucocorticoid inducible kinase-1 (SGK1). The kinase is activated by insulin and growth factors via the phosphatidylinositide-3-kinase (PI3K) and the 3-phosphoinositide dependent kinase (PDK1). SGK1 regulates channels, carriers and Na(+)/K(+)-ATPase, enzymes such as glycogen-synthase-kinase-3 (GSK3) and ubiquitin-ligase Nedd4-2, as well as several transcription factors. SGK1 regulates transport, hormone release, neuroexcitability, inflammation, cell proliferation and apoptosis. SGK1 contributes to metabolic syndrome and the pathophysiology of neurodegeneration, allergy, peptic ulcer, fibrosing disease and response to ischemia. SGK1 is upregulated in some tumours but downregulated in others. SGK1-sensitive mechanisms fostering tumour growth include activation of K(+) channels and Ca(2+) channels, Na(+)/H(+) exchanger, amino acid transporters and glucose transporters, upregulation of the nuclear factor NFkappaB and beta-catenin as well as downregulation of the transcription factors Foxo3a/FKHRL1 and p53. SGK1 enhances survival, invasiveness, motility, epithelial to mesenchymal transition and adhesiveness of tumour cells. Following deficiency of APC (adenoma polyposis coli) or chemical cancerogenesis, SGK1 knockout mice develop less intestinal tumours than their wild-type littermates and pharmacological SGK1 inhibition counteracts growth of prostate cancer cells. PMID- 20541035 TI - Tenascin-W: an extracellular matrix protein associated with osteogenesis and cancer. AB - Tenascin-W was the last member of a family of four large extracellular matrix glycoproteins to be discovered. The original member of the tenascin family, tenascin-C, has been widely studied due to its association with asthma, fibrosis, infection, inflammation and cancer. Recent studies report multiple common features between tenascin-W and tenascin-C in terms of structure, expression and function, especially in the context of tumorigenesis. Furthermore, specific functions for tenascin-W in osteogenesis have been revealed. This review presents an update on our current knowledge concerning tenascin-W and discusses potential medical applications of this cancer-enriched extracellular matrix protein. PMID- 20541036 TI - What made sesquiterpene lactones reach cancer clinical trials? AB - Sesquiterpene lactones (SLs) are plant-derived compounds often used in traditional medicine against inflammation and cancer. This review focuses on the chemical and biological properties of SLs that lead to enhanced anticancer and anti-inflammatory effects. The chemical properties comprise alkylating center reactivity, lipophilicity, and molecular geometry and electronic features. SLs in clinical trials are artemisinin, thapsigargin and parthenolide and many of their synthetic derivatives. These drugs are selective toward tumor and cancer stem cells by targeting specific signaling pathways, which make them lead compounds in cancer clinical trials. PMID- 20541037 TI - Artesunate, a potential drug for treatment of Babesia infection. AB - The effects of artesunate, a water-soluble artemisinin derivative, against Babesia species, including Babesia bovis, Babesia gibsoni and Babesia microti were studied. Cultures of B. bovis and B. gibsoni were treated with 0.26, 2.6, 26 and 260microM artesunate, showing inhibition of parasite growth at concentrations equal to and greater than 2.6microM artesunate by days 3 post-treatment for B. gibsoni and B. bovis in a dose-dependent manner. Consistent with in vitro experiments, artesunate was effective in the treatment of mice infected with B. microti at doses equal to and greater than 10mg/kg of body weight on days 8-10 post-infection. Taken together, these results suggest that artesunate could be a potential drug against Babesia infection. PMID- 20541038 TI - Left cardiac sympathetic denervation for the prevention of life-threatening arrhythmias: the surgical supraclavicular approach to cervicothoracic sympathectomy. PMID- 20541039 TI - Ivabradine: appropriate treatment for inappropriate sinus tachycardia. PMID- 20541040 TI - Local unipolar and bipolar electrogram criteria for evaluating the transmurality of atrial ablation lesions at different catheter orientations relative to the endocardial surface. AB - BACKGROUND: Recognition of the creation of transmural lesions (TLs) during atrial ablation procedures is important. OBJECTIVE: The purpose of this study was to characterize local unipolar electrograms (UEs) and bipolar electrograms (BEs) recorded from a TL at different catheter orientations. METHODS: In 13 porcines, 125 point-by-point ablations were performed in the smooth myocardial areas of the atria during recording of UE and BE. Catheter orientation was adjusted to be perpendicular or oblique (nonparallel; 80 sites) or parallel (75 sites) to the endocardial surface based on left atriograms. RESULTS: Microscopic examination revealed TLs in 54 sites and non-TLs in 71 sites. Irrespective of catheter orientation, the distal UE recorded from TLs consistently exhibited elimination of a negative deflection, whereas that from non-TLs did not. BE recorded from TLs with nonparallel catheter orientation consistently exhibited elimination of a positive deflection, whereas that with parallel catheter orientation exhibited one of two different patterns: (1) predominant attenuation (> or =75%) of the R wave at sites exhibiting QRS pattern preablation or (2) complete elimination of the R' wave at sites exhibiting RSR' pattern preablation. The heterogeneity of the patterns of morphologic change in BE at the different catheter orientations was due to the different degree of contribution of the proximal UE to BE. CONCLUSION: UE and BE criteria successfully differentiated TLs from non-TLs. Different BE criteria should be applied for recognizing TL formation in different catheter orientations. PMID- 20541041 TI - Long QT syndrome with compound mutations is associated with a more severe phenotype: a Japanese multicenter study. AB - BACKGROUND: Long QT syndrome (LQTS) can be caused by mutations in the cardiac ion channels. Compound mutations occur at a frequency of 4% to 11% among genotyped LQTS cases. OBJECTIVE: The purpose of this study was to determine the clinical characteristics and manner of onset of cardiac events in Japanese patients with LQTS and compound mutations. METHODS: Six hundred three genotyped LQTS patients (310 probands and 293 family members) were divided into two groups: those with a single mutation (n = 568) and those with two mutations (n = 35). Clinical phenotypes were compared between the two groups. RESULTS: Of 310 genotyped probands, 26 (8.4%) had two mutations in the same or different LQTS-related genes (compound mutations). Among the 603 LQTS patients, compound mutation carriers had significantly longer QTc interval (510 +/- 56 ms vs 478+/- 53 ms, P = .001) and younger age at onset of cardiac events (10 +/- 8 years vs 18 +/- 16 years, P = .043) than did single mutation carriers. The incidence rate of cardiac events before age 40 years and use of beta-blocker therapy among compound mutation carriers also were different than in single mutation carriers. Subgroup analysis showed more cardiac events in LQTS type 1 (LQT1) and type 2 (LQT2) compound mutations compared to single LQT1 and LQT2 mutations. CONCLUSION: Compound mutation carriers are associated with a more severe phenotype than single mutation carriers. PMID- 20541042 TI - Parasympathetic regulation of the heart. PMID- 20541043 TI - Coronary sinus complex fractionated atrial electrograms: when elusive is beautiful. PMID- 20541044 TI - A de novo 7.9 Mb deletion in 22q13.2->qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. AB - We report a 5-year-old boy with mental retardation, autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2->qter. This region contains the SHANK3, NCAPH2 and CYP2D6 genes which are associated with T-cell immune response. The present case provides evidence that 22q13 deletion syndrome may be associated with immune system dysfunction in addition to neuropsychiatric disorders. PMID- 20541045 TI - Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity, aberrant morphology, and resistance to serum deprivation. AB - Neurofibromatosis 1 syndrome (NF1) presents with skeletal involvement suggesting that altered bone dynamics is associated with NF1. Histological analysis of three cases of NF1-related pseudarthrosis revealed numerous osteoclasts in contact with adjacent bone, and within the pseudarthrosis tissue itself. These findings prompted us to evaluate the differentiation and resorption capacity of NF1 osteoclast like cells (OLCs) in vitro. Osteoclast progenitors were isolated from peripheral blood of 17 patients with NF1 and allowed to differentiate into OLCs on bone slices. The following differences were found between NF1 and control samples: samples from NF1 patients resulted in a higher number of resorbing OLCs; NF1 OLCs were larger in size; their nuclei were more numerous; actin rings were more frequent; and the resorption pits in NF1 samples were more numerous and larger. Bone resorption markers revealed that the resorption activity in NF1 OLC cultures was approximately two times higher than in controls. Following deprivation from serum, the number of NF1 OLCs remained essentially the same during 24h, whereas the number of control OLCs was dramatically reduced during the same time. Three patients had NF1-related lytic bone lesions, and their in vitro results differed from those of other patients. Our results demonstrate that OLCs derived from blood of patients with NF1 display elevated resorption activity under conditions isolated from microenvironment operative in vivo. Thus, increased osteoclast activity may be a phenotypic property of the NF1 syndrome, and at least in part explain selected skeletal findings in NF1, such as osteoporosis/osteopenia. PMID- 20541047 TI - Effects of the bone marrow microenvironment on hematopoietic malignancy. AB - The bone marrow (BM) is contained within the bone cavity and is the main site of hematopoiesis, the continuous development of blood cells from immature hematopoietic stem and progenitor cells. The bone marrow consists of developing hematopoietic cells and non-hematopoietic cells, the latter collectively termed the bone marrow microenvironment. These non-hematopoietic cells include cells of the osteoblast lineage, adipocytes and endothelial cells. For many years these bone marrow microenvironment cells were predicted to play active roles in regulating hematopoiesis, and recent studies have confirmed such roles. Importantly, more recent data has indicated that cells of the BM microenvironment may also contribute to hematopoietic diseases. In this review we provide an overview of the roles of the data suggesting that the cells of the bone marrow microenvironment may play an active role in the initiation and progression of hematopoietic malignancy. PMID- 20541046 TI - Col3.6-HSD2 transgenic mice: a glucocorticoid loss-of-function model spanning early and late osteoblast differentiation. AB - The goal of this study was to characterize the bone phenotype and molecular alterations in Col3.6-HSD2 mice in which a 3.6-kb Col1a1 promoter fragment drives 11beta-HSD2 expression broadly in the osteoblast lineage to reduce glucocorticoid signaling. Serum corticosterone was unchanged in transgenic females excluding a systemic effect of the transgene. Adult transgenic mice showed reduced vertebral trabecular bone volume and reduced femoral and tibial sub-periosteal and sub endosteal areas as assessed by microCT. In adult female transgenic mice, histomorphometry showed that vertebral bone mass and trabecular number were reduced but that osteoblast and osteoclast numbers and the mineral apposition and bone formation rates were not changed, suggesting a possible developmental defect in the formation of trabeculae. In a small sample of male mice, osteoblast number and percent osteoid surface were increased but the mineral apposition bone formation rates were not changed, indicating subtle sex-specific phenotypic differences in Col3.6-HSD2 bone. Serum from transgenic mice had decreased levels of the C-terminal telopeptide of alpha1(I) collagen but increased levels of osteocalcin. Transgenic calvarial osteoblast and bone marrow stromal cultures showed decreased alkaline phosphatase and mineral staining, reduced levels of Col1a1, bone sialoprotein and osteocalcin mRNA expression, and decreased cell growth and proliferation. Transgenic bone marrow cultures treated with RANKL and M-CSF showed greater osteoclast formation; however, osteoclast activity as assessed by resorption of a calcium phosphate substrate was decreased in transgenic cultures. Gene profiling of cultured calvarial osteoblasts enriched in the Col3.6-HSD2 transgene showed modest but significant changes in gene expression, particularly in cell cycle and integrin genes. In summary, Col3.6 HSD2 mice showed a low bone mass phenotype, with decreased ex vivo osteogenesis. These data further strengthen the concept that endogenous glucocorticoid signaling is required for optimal bone mass acquisition and highlight the complexities of glucocorticoid signaling in bone cell lineages. PMID- 20541048 TI - Sex-averaged recombination and mutation rates on the X chromosome: a comment on Labuda et al. PMID- 20541052 TI - Effects of distal embolization on the timing of platelet and inflammatory cell activation in interventional coronary no-reflow. AB - INTRODUCTION: Myocardial hypoperfusion following percutaneous coronary intervention, termed "no-reflow", may be initiated by distal coronary embolization. This study examined the effects of distal embolization on the extent and timing of inflammation and platelet activation in an experimental model of coronary no-reflow. MATERIAL AND METHODS: A no-reflow model was established in 9 Yorkshire pigs by injecting incremental doses of biologically inert polystyrene microspheres into the left anterior descending artery every 20 minutes via a transit catheter. A control group included 3 pigs that received corresponding intra-coronary boluses of normal saline. At predefined time points, coronary sinus blood samples were drawn and immediately analyzed by flow cytometry analysis for a panel of white blood cell and platelet activation markers, and the inflammatory cytokine TNFalpha. RESULTS: No-reflow was achieved after delivery of 1,169,000+/-303,000 (range: 680,000 to 2,600,000) microspheres. In the distal embolization group, there were significant increases above baseline values in polymorphonuclear-platelet aggregates (146%-218%), in monocyte-platelet aggregates (51%-94%) and in TNFalpha levels (54%-84%) at multiple time points prior to no- reflow (15% cumulative dose and higher). For Annexin A5, there was a significant increase at 52% of cumulative dose (177% above baseline). Controls only showed one significant increase above baseline value for polymorphonuclear platelet aggregates at the time of the last injection. CONCLUSIONS: Widespread activation of interacting inflammatory and coagulation pathways following microsphere embolization occurred prior to the onset of angiographic no-reflow. This activation pattern cannot be attributed to prolonged coronary sinus instrumentation. Interactions between white blood cells (polymorphonuclears and monocytes) and platelets likely play an important role in the pathogenesis of no reflow following distal embolization and may represent important therapeutic targets. PMID- 20541053 TI - Sodas, high fructose corn syrup, and obesity: Let's focus on the right target. PMID- 20541054 TI - ACR Appropriateness Criteria. PMID- 20541055 TI - ACR Appropriateness Criteria: single brain metastasis. AB - Single brain metastasis represents a common neurologic complication of cancer. Given the number of treatment options that are available for patients with brain metastasis and the strong opinions that are associated with each option, appropriate treatment for these patients has become controversial. Prognostic factors such as recursive partitioning analysis and graded prognostic assessment can help guide treatment decisions. Surgery, whole brain radiation therapy (WBRT), stereotactic radiosurgery or combination of these treatments can be considered based on a number of factors. Despite Class I evidence suggestive of best therapy, the treatment recommendation is quite varied among physicians as demonstrated by the American College of Radiology's Appropriateness Panel on single brain metastasis. Given the potential concerns of the neurocognitive effects of WBRT, the use of SRS alone or SRS to a resection cavity has gained support. Since aggressive local therapy is beneficial for survival, local control and quality of life, the use of these various treatment modalities needs to be carefully investigated given the growing number of long-term survivors. Enrollment of patients onto clinical trials is important to advance our understanding of brain metastasis. PMID- 20541056 TI - ACR Appropriateness Criteria: local-regional therapy for resectable oropharyngeal squamous cell carcinomas. AB - The optimal management of resectable oropharyngeal squamous cell carcinomas is controversial with many treatment options, both surgical and nonsurgical approaches, supported by published experiences with no randomized trials comparing commonly accepted treatments. The treatment decisions are further complicated by the need for local-regional disease control and competing goals to preserve salivary and swallow function. Treatment decisions may also be affected by tumor and patient related factors and a history of environmental exposure to tobacco and evidence of human papilloma virus. We summarize the published literature and provide treatment consensus derived from the modified Delphi methodology. PMID- 20541057 TI - ACR Appropriateness Criteria: local excision in early-stage rectal cancer. AB - Low anterior resection or abdominoperineal resection is considered standard treatment for early rectal cancer. These procedures, however, carry a risk of morbidity and mortality that may not be warranted for early distal lesions, which may be treated with local excision. Emerging data has investigated the efficacy of local excision in patients with early stage rectal cancers. An expert panel designated by the American College of Radiology has reviewed supporting data, from a few prospective multi-institutional trials and a number of single institution, retrospective reviews. The consensus recognizes the importance of accurate staging to identify patients who may be candidates for a local excision approach. Optimal candidates for local excision alone include small, low-lying T1 tumors, without adverse pathologic features. A number of procedures may be safely used including transanal, posterior trans-sphincteric, posterior proctotomy, transanal excision, or transanal microsurgery. It is important to note that none of these include lymph node evaluation, and depending on the risk of lymph node metastases, adjuvant radiation with or without chemotherapy may be warranted. Patients with positive margins or T3 lesions are at high risk of local recurrence and should be offered immediate APR or LAR. However, patients with high-risk T1 tumors, T2 tumors, or those who are not amenable to more radical surgery may benefit from adjuvant treatment. Data have also reported excellent local control rates for neoadjuvant radiation +/- chemotherapy followed by local excision in higher risk patients, but it is not yet clear if this approach reduces recurrence rates over surgery alone. PMID- 20541058 TI - ACR Appropriateness Criteria: rectal cancer-metastatic disease at presentation. AB - In 2009, an estimated 40,870 new cases of rectal cancer will be diagnosed in the USA. After decades of treating metastatic colorectal cancer (CRC) with 5 fluorouracil alone, newer agents have resulted in significant improvements in disease-free and overall survival rates. These improvements stem from combinations of newer cytotoxic agents and targeted therapies. Based on performance status and burden of disease, metastatic CRC patients are generally treated with either a curative or palliative intent. Curative paradigm patients often have low burden liver or lung metastases which are technically resectable. Patients with resectable colorectal liver metastases and no evidence of any extrahepatic metastases have impressive 5-year survival rates of 30%-70% following resection. Unfortunately, only 20%-30% of patients with colorectal liver metastases are candidates for resection at initial presentation. Patients with unresectable liver or lung metastasis are candidates for local therapies including radioablation, chemoembolization, radioembolization, and stereotactic radiation therapy. In select patients with metastatic CRC, neoadjuvant or adjuvant pelvic chemoradiation (CRT) is indicated to prevent local recurrence. Patients who have resectable metastatic disease with symptomatic, obstructive, Stage T3-4 and N1, or low-lying (=10% viable). RESULTS: Median survivor follow-up was 112 months. Relative risks of disease progression and death were 0.656 (95% confidence interval, 0.472-0.912) and 0.638 (95% confidence interval, 0.449-0.908), favoring RTCH. Good response patients (345; 74%) had similar 10 year overall survival (OS) and progression-free survival (PFS) after RTH or RTCH (P > .47). Poor response patients after RTCH had superior OS (P = .046) and PFS (P = .084). Extrapelvic recurrences occurred more often in poor response patients. CONCLUSION: Posttherapy viable residual disease less than 10% was associated with reduced risk of progression and cancer-related death. PMID- 20541171 TI - The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. AB - OBJECTIVE: To introduce and promote the use of long-acting reversible methods of contraception (LARC; intrauterine contraceptives and subdermal implant) by removing financial and knowledge barriers. STUDY DESIGN: The Contraceptive CHOICE Project is a prospective cohort study of 10,000 women 14-45 years who want to avoid pregnancy for at least 1 year and are initiating a new form of reversible contraception. Women screened for this study are read a script regarding long acting reversible methods of contraception to increase awareness of these options. Participants choose their contraceptive method that is provided at no cost. We report the contraceptive choice and baseline characteristics of the first 2500 women enrolled August 2007 through December 2008. RESULTS: Sixty-seven percent of women enrolled (95% confidence interval, 65.3-69.0) chose long-acting methods. Fifty-six percent selected intrauterine contraception and 11% selected the subdermal implant. CONCLUSION: Once financial barriers were removed and long acting reversible methods of contraception were introduced to all potential participants as a first-line contraceptive option, two-thirds chose long-acting reversible methods of contraception. PMID- 20541172 TI - In utero beta 2 adrenergic agonist exposure and adverse neurophysiologic and behavioral outcomes. PMID- 20541173 TI - A patient with lichen sclerosus, Langerhans cell histiocytosis, and invasive squamous cell carcinoma of the vulva. AB - We report a patient with vulvar lichen sclerosus, Langerhans cell histiocytosis (LCH), and later vulvar cancer. In LCH, high amounts of non functional Langerhans cells are present in the affected tissue, making it possible that LCH may have contributed to vulvar cancer development in this patient. PMID- 20541175 TI - Relaxant effect of Levosimendan on human uterine contractility in vitro. AB - OBJECTIVE: Levosimendan, a compound that exerts effects on calcium sensitivity and intracellular free calcium, in addition to opening ATP-sensitive K-channels, is widely used in the treatment of heart failure. Because of its dual mechanism of action, we hypothesized that it would modulate human uterine contractility. STUDY DESIGN: Biopsies of human myometrium were obtained at elective cesarean section (n = 16). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of levosimendan in the concentration range of 1 nmol/L to 100 mmol/L. In separate experiments, the effects of prior exposure to the K-ATP antagonist glibenclmide (100 mmol) on the effects of levosimendan on myometrial contractility were evaluated. Simultaneous controls were performed for all experiments. RESULTS: Levosimendan exerted an inhibitory effect on spontaneous and agonist induced contractions, when compared with control strips. The mean maximal inhibition (MMI) values were as follows: 45.34% +/- 5.92% for spontaneous contractions (n = 6; P < .05), and 41.88% +/- 5.40% for oxytocin induced contractions (n = 6; P < .05). The inhibitory effect of levosimendan was significantly antagonized by glibenclamide, resulting in the mean maximal inhibition for levosimendan reduced to 19.04% +/- 3.61% for spontaneous contractions (n = 6; P < .05), and 16.53% +/- 4.08% for oxytocin induced contractions (n = 6; P < .05). CONCLUSION: Levosimendan exerted a potent relaxant effect on spontaneous and agonist-induced human uterine contractility in vitro. This effect was reduced in the presence of K-ATP blockade. Because of the putative role of levosimendan in inflammatory conditions, the findings here may have implications for its future use as therapy for preterm labor. PMID- 20541176 TI - Self-reported use of ICT (Information and communication technology) uptake in 2002 and discomfort amongst Finns aged 45-66. AB - In recent years the use of new technical equipment and the Internet by middle aged people has increased. This paper presents middle-aged people's (45 years old or older) usage of new technical equipment and analyses how their (2704 persons) symptoms are associated with the equipment. Over 70% of Finland's middle-aged population use mobile phones daily and less than 30% use desktop computers at leisure. For example, over 80% of middle-aged people had sometimes or often experienced pain, numbness or aches in the neck and about 70% had aches in the hip and lower back. The use of new technical equipment among the group of people who are outside working life was smaller than the people's usage in general. In the future, when new technical equipment is developed, it is important to take into account, that people (outside working life) do not use, e.g., the Internet as much as people in general. The working environment will be much more ergonomic also at home and the Internet services will be easy to use for almost everyone, even those who have little experience or knowledge of computers and the Internet. PMID- 20541177 TI - Antimicrobial activity of n-6, n-7 and n-9 fatty acids and their esters for oral microorganisms. AB - OBJECTIVE: This study is to assess the antibacterial activity of omega-6, -7, -9 (n-6, n-7, n-9) fatty acids against various oral microorganisms. METHODS: The n 6, n-7, n-9 fatty acids, such as gamma-linoleic acid (GLA), linoleic acid (LA), arachidonic acid (ARA), palmitoleic acid (PA), and oleic acid (OA), their fatty acid ethyl esters, GLA-EE, LA-EE, ARA-EE, PA-EE, OA-EE, and their fatty acid methyl esters, GLA-ME, LA-ME, ARA-ME, PA-ME, OA-ME, were investigated for antimicrobial activity against oral pathogens Streptococcus mutans, Candida albicans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Various concentrations of the fatty acids, their methyl and ethyl esters were tested against various oral pathogens in 96-well plates and blood-agar plate. The plates were incubated anaerobically or aerobically at 37 degrees C for 48h, and the colony forming units (CFU) were determined. RESULTS: The data demonstrated that select n-6, n-7, n-9 fatty acids and their esters exhibited strong antimicrobial activity against these oral microorganisms, demonstrating some specificity for individual microbial species. CONCLUSION: The potential use or the combinations of the n-6, n-7, n-9 fatty acids and/or their esters, provided in a local delivery vehicle to infected sites in the oral cavity, could be considered as an additional therapeutic approach to improving oral health. PMID- 20541178 TI - Personality prototypes in individuals with compulsive buying based on the Big Five Model. AB - Personality prototypes based on the Big Five factor model were investigated in a treatment-seeking sample of 68 individuals with compulsive buying (CB). Cluster analysis of the NEO Five-Factor Inventory (NEO-FFI) scales yielded two distinct personality clusters. Participants in cluster II scored significantly higher than those in cluster I on neuroticism and lower on the other four personality traits. Subjects in cluster II showed higher severity of CB, lower degree of control over CB symptoms, and were more anxious, interpersonally sensitive and impulsive. Furthermore, cluster II was characterized by higher rates of comorbid anxiety disorders, and cluster B personality disorders. The two personality prototypes did not differ with respect to obsessive-compulsive features. Finally and of considerable clinical significance, participants in cluster II reported lower remission rates after undergoing cognitive-behavioral therapy. Implications of the results for treatment are discussed. PMID- 20541179 TI - An examination of the construct validity of posttraumatic stress disorder with veterans using a revised criterion set. AB - Ongoing concerns exist in the literature regarding the construct of posttraumatic stress disorder (PTSD) and how to best conceptualize and measure this disorder. We compared the traditional DSM-IV PTSD symptom criteria (i.e., symptoms from clusters B, C, and D) to a revised criterion set that omits overlapping mood and other anxiety symptoms on PTSD prevalence, PTSD diagnostic caseness, associated psychiatric comorbidity, functional status, and structural validity using a cross sectional, multi-site primary care sample of 747 veterans. After removing items theorized to overlap with mood and other anxiety disorders, PTSD prevalence was identical using both criterion sets (i.e., 12%). Overall, there were few statistically significant differences in PTSD caseness, associated psychiatric comorbidity, functional status, and structural validity across the two diagnostic criterion sets. These data provide further support that removing items that overlap with other psychiatric disorders does not significantly impact the prevalence of PTSD, its associated comorbidity and functional impairment, or its structural validity. Although the revised criterion set represents a more parsimonious model, the current study findings generally support the strong construct validity of PTSD. The implications of these study findings for research and clinical practice are discussed. PMID- 20541180 TI - Treating chronic worry: Psychological and physiological effects of a training programme based on mindfulness. AB - The present study examines psychological and physiological indices of emotional regulation in non-clinical high worriers after a mindfulness-based training programme aimed at reducing worry. Thirty-six female university students with high Penn State Worry Questionnaire scores were split into two equal intervention groups: (a) mindfulness, and (b) progressive muscle relaxation plus self instruction to postpone worrying to a specific time of the day. Assessment included clinical questionnaires, daily self-report of number/duration of worry episodes and indices of emotional meta-cognition. A set of somatic and autonomic measures was recorded (a) during resting, mindfulness/relaxation and worrying periods, and (b) during cued and non-cued affective modulation of defence reactions (cardiac defence and eye-blink startle). Both groups showed equal post treatment improvement in the clinical and daily self-report measures. However, mindfulness participants reported better emotional meta-cognition (emotional comprehension) and showed improved indices of somatic and autonomic regulation (reduced breathing pattern and increased vagal reactivity during evocation of cardiac defense). These findings suggest that mindfulness reduces chronic worry by promoting emotional and physiological regulatory mechanisms contrary to those maintaining chronic worry. PMID- 20541181 TI - Downregulation of immune response by the human cytokines Interleukin-32alpha and beta in cell-mediated rejection. AB - Xenotransplantation of porcine organs has the potential to help overcome the severe shortage of human tissues and organs available for human transplantation. However, numerous hurdles such as immune-mediated xenograft rejection remain before clinical xenotransplantation. In this study, we elucidated the role of human TNF-alpha-inducing factor, Interleukin-32 (IL-32), in porcine kidney cells (PK-15) during cell-mediated rejection by examining host cell responses. CD8+ and CD4+ T cells numbers were reduced in the lymph nodes of PK-15/IL-32beta injected mice. CD3+ Tcells were in mice injected with control cells but PK-15/IL-32alpha- and PK-15/IL-32beta-injected cell numbers were lower in lymph nodes than un transfected controls. In Mixed lymphocyte reaction cultures, the rates of cell proliferation were increased in both PK-15/IL-32alpha- and PK-15/IL-32beta injected groups compared to the untransfected control groups. The Stable porcine PK-15 cells expression IL-32alpha and IL-32beta inhibited cytotoxic T lymphocyte (CTLs) after cellular xenograft. Our results suggest that human IL-32alpha and IL 32beta regulates on xenograft rejection in cellular xenotransplantation. PMID- 20541182 TI - Wavelet energy-guided level set-based active contour: a segmentation method to segment highly similar regions. AB - This paper introduces an approach to perform segmentation of regions in computed tomography (CT) images that exhibit intra-region intensity variations and at the same time have similar intensity distributions with surrounding/adjacent regions. In this work, we adapt a feature computed from wavelet transform called wavelet energy to represent the region information. The wavelet energy is embedded into a level set model to formulate the segmentation model called wavelet energy-guided level set-based active contour (WELSAC). The WELSAC model is evaluated using several synthetic and CT images focusing on tumour cases, which contain regions demonstrating the characteristics of intra-region intensity variations and having high similarity in intensity distributions with the adjacent regions. The obtained results show that the proposed WELSAC model is able to segment regions of interest in close correspondence with the manual delineation provided by the medical experts and to provide a solution for tumour detection. PMID- 20541183 TI - Genetic fuzzy classifier for sleep stage identification. AB - Soft-computing techniques are commonly used to detect medical phenomena and help with clinical diagnoses and treatment. In this work, we propose a design for a computerized sleep scoring method, which is based on a fuzzy classifier and a genetic algorithm (GA). We design the fuzzy classifier based on the GA using a single electroencephalogram (EEG) signal that detects differences in spectral features. Polysomnography was performed on four healthy young adults (males with a mean age of 27.5 years). The sleep classifier was designed using a sleep record and tested on the sleep records of the subjects. Our results show that the genetic fuzzy classifier (GFC) agreed with visual sleep staging approximately 84.6% of the time in detection of wakefulness (WA), shallow sleep (SS), deep sleep (DS), and rapid eye movement (REM) stages. PMID- 20541184 TI - Examining the effects of inversion on lateralisation for processing facial emotion. AB - There is an increasing amount of evidence which suggests that each hemisphere is differently specialised for processing facial stimuli, with the right hemisphere specialised for the processing of configural information and the left hemisphere specialised for the processing of featural information. While there is evidence for this distinction from studies of face recognition, it has not been shown in studies of lateralisation for processing facial emotion. In this study the chimeric faces test was used with faces expressing anger, disgust, fear, happiness, sadness or surprise, presented in either an upright or an inverted orientation. When presented upright, a significant right hemisphere bias was found for all six emotions. However, when inverted, a significant left hemisphere bias was found for the processing of happiness and surprise, but not for the processing of negative emotions (although the analysis was approaching significance for anger). These findings support the hypothesis that each hemisphere is differently specialised for processing facial emotion, but contradicts previous work that examined the effects of inversion on chimeric face stimuli. PMID- 20541185 TI - Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund. AB - BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. PMID- 20541186 TI - Evaluation of side-effects of glyphosate mediated control of giant reed (Arundo donax) on the structure and function of a nearby Mediterranean river ecosystem. AB - The aim of this study was to evaluate the effect of the application of the herbicide Herbolex (Aragonesas Agro, S.A., Madrid, Spain) to control giant reed (Arundo donax), which has glyphosate as active ingredient, on the structure and function of a nearby river ecosystem. Specifically, we assessed glyphosate environmental fate in the surrounding water and its effects on transplanted Daphnia magna, field collected caddisfly (Hydropsyche exocellata) and on benthic macroinvertebrate structure assemblages. Investigations were conducted in the industrialized and urbanized Mediterranean river Llobregat (NE Spain) before and after a terrestrial spray of glyphosate. Four locations were selected to include an upstream site and three affected ones. Measured glyphosate levels in river water following herbicide application were quite high (20-60 microg/l) with peak values of 137 microg/l after three days. After 12 days of its application, leaching of glyphosate from sprayed riverbanks was quite high in pore water (20 85 microg/l) but not in the river. Closely linked with the measured poor habitat and water physico-chemical conditions, macroinvertebrate communities were dominated by taxa tolerant to pollution and herbicide application did not affect the abundance or number of taxa in any location. Nevertheless, significant specific toxic effects on transplanted D. magna and field collected H. exocellata were observed. Effects included D. magna feeding inhibition and oxidative stress related responses such as increased antioxidant enzyme activities related with the metabolism of glutathione and increased levels of lipid peroxidation. These results emphasize the importance of combined chemical, ecological and specific biological responses to identify ecological effects of pesticides in the field. PMID- 20541187 TI - EUS-guided Nd:YAG laser ablation of normal pancreatic tissue: a pilot study in a pig model. AB - BACKGROUND: Laser ablation with a neodymium:yttrium aluminum garnet (Nd:YAG) laser can achieve a high rate of complete tissue necrosis and has been applied as a minimally invasive, palliative option in hepatocellular carcinoma, liver metastasis in colorectal cancer, and malignant thyroid nodules. OBJECTIVE: To assess the in vivo feasibility of EUS-guided laser ablation with an Nd:YAG laser of normal pancreatic tissue of a porcine model. DESIGN: Prospective investigation. SETTING: Hospital animal laboratory. SUBJECTS: Eight pigs. INTERVENTIONS: EUS-guided puncture of the pancreatic tail with a laser-beam fiber. An Nd:YAG laser (1.064 nm) was used, with an output power of 2 and 3 W and a total delivered energy of 500 and 1000 J in continuous mode. MAIN OUTCOME MEASUREMENTS: The 24-hour follow-up of the pigs was focused on clinical and laboratory aspects. Results of histological studies of the pancreas were obtained 24 hours after the procedure on necroscopy tissue. RESULTS: There were no technical limitations to the performance of the procedure. Tissue necrosis, localized in the pancreatic parenchyma, was observed in all animals on histological examination. The volume of ablation tissue ranged from a mean of 314 mm(3) to 483 mm(3). The ablation area ranged from a mean of 49 mm(2) to 80 mm(2). No major postprocedure complications were recorded, and all the pigs survived at 24 hours. LIMITATION: Animal study. CONCLUSIONS: EUS-guided laser ablation of the pancreas with an Nd:YAG laser is feasible in a porcine model. PMID- 20541188 TI - Endoscopic pyloric suturing to facilitate weight loss: a canine model. AB - BACKGROUND: More than 66% of adults in United States are overweight or obese. OBJECTIVE: To decrease gastric emptying and cause early and prolonged satiety by endoscopically narrowing the gastric pylorus. DESIGN: Thirteen dogs were randomized into 3 groups (suture, sham, and control). SETTING: Animal facility. INTERVENTIONS: Sutures were placed across the pylorus in the 7 dogs in the suture group by using an endoscopic suturing device. Three sham dogs had endoscopy without suturing, and 3 control dogs did not have any intervention. MAIN OUTCOME MEASUREMENTS: Gastric emptying studies were conducted on all of the dogs by using 13C-octanoic acid breath tests. All dogs were monitored for daily food intake and weight gain/loss. RESULTS: The suture dogs decreased their food consumption by 48% (P < .02), whereas the sham and control dogs showed 9.5% increase (P = .16). The suture dogs lost 12.7% (P = .001) of their initial body weight, whereas the sham and control dogs gained 13.4% (P = .03). There was a delay in gastric emptying between the presuturing baseline and last postsuturing measurement by 30.75% (P = .005) in the suture dogs. In the sham plus control dogs, there was a delay in gastric emptying during the same period by only 6.75% (P = .55). LIMITATIONS: Long-term efficacy of the sutures was not evaluated. CONCLUSIONS: There was a significant weight loss and decreased food consumption along with a significant prolongation of gastric emptying in the suture dogs compared with the sham and control dogs. PMID- 20541189 TI - Single-balloon enteroscopy: results from an initial experience at a U.S. tertiary care center. AB - BACKGROUND: Single-balloon enteroscopy (SBE) is a novel, deep-enteroscopy modality for diagnosis and treatment of disorders of the small bowel. OBJECTIVE: The aim of the study was to examine the performance, yield, and safety of SBE in the initial experience at a tertiary-care center. DESIGN: Retrospective analysis of all SBEs during a 10-month period in 2008. Data were extracted from electronic clinical and endoscopy records. SETTING: U.S. tertiary-care center. PATIENTS: All patients referred to our center for SBE during the study period were included in the current analysis. INTERVENTION: SBE. MAIN OUTCOME MEASUREMENTS: Anterograde SBE procedure time, diagnostic yield, and complications. RESULTS: Thirty-eight anterograde SBEs were performed. The mean patient age was 62 years (42% female). Patients were referred for GI bleeding (97%), Crohn's disease, suspected polyps or neoplasia, and abnormal capsule endoscopy results. The mean (+/- SD) procedure time was 49 +/- 19 minutes. The estimated depth of insertion was proximal jejunum (34%), mid-jejunum (45%), and distal jejunum (21%). The SBE diagnostic yield was 47%, with significant findings in 18 patients. Findings included angiectasias, bleeding, abnormal mucosa, ulceration, polyps, and a foreign body. The therapeutic yield was 42%, with lesion ablation performed in 24% of cases. Diagnostic biopsies were performed in 24% of cases and tattooing in 52%. There were no significant complications. LIMITATIONS: Single-center, retrospective study. CONCLUSION: Single-balloon enteroscopy appears to be a safe and efficient method for examination of the mid-small bowel. The significant therapeutic yield (42%) suggests that comparative studies with double-balloon and spiral enteroscopy are warranted. PMID- 20541190 TI - Case series of intra-abdominal adhesions induced by artificial ulceration after endoscopic submucosal dissection before additional laparoscopic gastrectomy. AB - BACKGROUND: As endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) increases, increasing numbers of patients require additional gastrectomy with lymph node dissection after noncurative ESD. ESD may cause intra-abdominal adhesions, making additional laparoscopic gastrectomy technically difficult. OBJECTIVE: To assess the relation of the presence of intra-abdominal adhesions and ESD treatment to allow safe laparoscopic gastrectomy. DESIGN: Case series from a retrospective review of additional gastrectomy after noncurative ESD. SETTING: Tertiary care center. PATIENTS AND INTERVENTIONS: Eight of 333 patients receiving ESD at Oita University Faculty of Medicine from 1999 to 2008 underwent additional laparoscopic gastrectomy because of noncurative ESD. MAIN OUTCOME MEASUREMENTS: Intra-abdominal adhesions were evaluated by using an adhesion scoring system (0-3 points) and clinicopathologic findings, including artificial ulcerations after ESD. RESULTS: All patients successfully underwent laparoscopic gastrectomy within 1 to 2 months after ESD. Three patients with large artificial ulceration (>25 mm) after ESD treatment had severe intra-abdominal adhesions (adhesion score > or =2). These patients tended to have a large blood loss and long operation times during laparoscopic gastrectomy. Despite the 2-month interval from ESD to laparoscopic gastrectomy, ulcerations in these patients were at healing stage with inflammatory cells infiltrating the muscular deep layer. LIMITATION: A retrospective study. CONCLUSIONS: After ESD with large artificial ulceration (>25 mm), the presence of intra-abdominal adhesions complicating additional laparoscopic gastrectomy was often observed. PMID- 20541191 TI - Removal of transanastomotic pancreatic stent tubes after pancreaticoduodenectomy: a new role for double-balloon enteroscopy. AB - BACKGROUND: Endoscopic interventions are usually very challenging in patients with anatomic changes caused by earlier GI surgery. The recent development of the double-balloon enteroscopy (DBE) system creates an opportunity to reach the biliary tract and the pancreatic duct in postsurgical conditions. OBJECTIVE: To report a further application of DBE in surgical patients; namely, extraction of pancreatic stents placed in pancreaticojejunal anastomosis during pancreaticoduodenectomy. DESIGN: Two case reports. SETTING: A single-center experience in a tertiary-care unit. PATIENTS AND INTERVENTIONS: Two patients who underwent Whipple resection with Roux-en-Y reconstruction presented with migration of pancreatic stent tubes inserted in pancreaticojejunal anastomoses. Stents had migrated to the end of the afferent limb and were causing abdominal pain. Because extraction failed by using conventional endoscopy, we used the DBE system. MAIN OUTCOME MEASURES: Successful extraction of the stents. RESULTS: Stents were successfully removed in both patients with no complications. After 1 year of follow-up, the patients remained free of painful symptoms. LIMITATIONS: Small volume case series. CONCLUSIONS: Double-balloon enteroscopy is a reliable way to investigate and treat patients with postsurgical altered anatomy. Here, we report the successful removal of pancreatic stents migrating into the jejunal loop through pancreaticojejunal anastomosis. PMID- 20541192 TI - Endosonographic features predictive of malignancy in mediastinal lymph nodes in patients with lung cancer. AB - BACKGROUND: EUS is useful in determining mediastinal lymph node (LN) metastases in patients undergoing staging for lung cancer. However, FNA of LNs is often performed only if suspicious features are present. The utility of individual LN features in predicting malignant cytology remains unclear. OBJECTIVE: To evaluate the utility of EUS-determined LN features for predicting malignant cytology. DESIGN: Prospective observational study. SETTING: Two U.S. tertiary-care centers. PATIENTS: This study involved 425 patients with primary lung cancer who underwent EUS. INTERVENTION: All mediastinal LNs were described according to size, shape, echogenicity, and margin characteristics. FNA was performed on LNs with any features suggestive of malignancy. EUS-guided FNA cytology was classified as benign or abnormal (suspicious/malignant). The utility of LN features in predicting malignant cytology was determined and further analyzed by logistic regression, and a predictive model was established. MAIN OUTCOME MEASUREMENTS: Accuracy of individual LN features for predicting malignancy. RESULTS: EUS detected 836 LNs in 425 patients, and FNA was obtained in 698 patients. On multivariable analysis, only round shape, a short axis of >8.3 mm, and sharp margins were predictive of malignant cytology. According to the predictive model, the calculated probability of having malignancy is less than 4% (95% confidence interval [CI], 0.022-0.064) when none of the LN features are present and 63% (95% CI, 51%-72.2%) when all features were seen. LIMITATIONS: No surgical histology as the criterion standard. CONCLUSION: Among patients with lung cancer, EUS features of round shape, sharp margins, and short axis of >8.3 mm are significant predictors of malignancy. The probability of malignancy is low when none of the features are present. PMID- 20541193 TI - Endoscopic lower esophageal sphincter bulking for the treatment of GERD: safety evaluation of injectable polymethylmethacrylate microspheres in miniature swine. AB - BACKGROUND: Endoscopic therapy for GERD is an appealing, minimally invasive alternative to medical treatment and surgery. Various materials have been tested to augment the lower esophageal sphincter (LES), with limited success. To our knowledge, safety and migration of polymethylmethacrylate (PMMA) microspheres has never been evaluated. OBJECTIVE: To assess the safety, migration, inflammatory reaction, and durability of PMMA injected into the LES of miniature swine to create a reflux barrier. DESIGN: Animal study. SETTING: Approved animal research facilities. INTERVENTION: Injection of the LES of miniature swine with PMMA. Histopathology of the injected site at certain intervals and postnecropsy microsphere counts of various organs. MAIN OUTCOME MEASUREMENTS: Minimal inflammatory reaction at the injection site, persistent bulking effect of the material, and no migration of microspheres. RESULTS: Injection of LES with PMMA caused a mild inflammatory reaction. The bulking effect of the injected material was persistent. Migration of microspheres was eliminated with the use of larger sized microspheres. LIMITATIONS: Animal model. CONCLUSION: Our phase I study documented that 40-microm polymethylmethacrylate microspheres are biocompatible and that PMMA microspheres are resistant to degradation when injected submucosally into the wall of the esophagus. The detection of 40-microm PMMA microspheres in local lymph nodes, liver, and lungs of some animals in the phase I study clearly documented transport of PMMA away from the injection site. This finding was eliminated by increasing the size of microspheres to 125 microm. The potential therapeutic effects of these larger microspheres for humans with GERD remains to be evaluated. PMID- 20541194 TI - Infectious spondylodiscitis caused by esophageal injury after blunt chest trauma. PMID- 20541195 TI - Endoscopic closure of a distal common bile duct perforation caused by papillary dilation with a large-diameter balloon (with video). PMID- 20541196 TI - GI vasculitis associated with systemic lupus erythematosus. PMID- 20541197 TI - Progression of solitary rectal ulcer syndrome over a 2-year period. PMID- 20541198 TI - Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). AB - BACKGROUND: Endoscopic submucosal dissection (ESD) was originally developed in Japan for en bloc resection of gastric neoplasms. OBJECTIVE: To clarify whether the novel ESD procedure is feasible and gives results that justify the pursuit of integrated minimally invasive procedures aimed at curing early squamous cell carcinoma of the esophagus (SCCE). DESIGN: Retrospective cohort study. SETTING: A single-institution trial by experienced endoscopists. PATIENTS: This study involved 300 consecutively enrolled patients with SCCE (Tumor, Nodes, Metastasis classification T1, N0) who underwent either EMR (n = 184) or ESD (n = 116) from March 1994 to July 2007. INTERVENTION: The patients underwent endoscopic resection and then were followed by periodic endoscopy for 8 to 174 months (mean 65 months). MAIN OUTCOME MEASUREMENTS: Resectability, cure rates, complications, disease-free survival of the two groups, and risk factors for local recurrence were explored. RESULTS: En bloc resection and the local recurrence rate were significantly better in the ESD group (P = .0009 and .065, respectively). The frequency of perforation was not significantly different between the two groups (P = .68). Four independent risk factors for local recurrence were identified by the Cox regression model: EMR, deep cancer invasion, upper esophagus location, and family history of esophageal cancer. Radical cure is mostly obtained by successful endoscopic retreatment of local recurrence after previous endoscopic resection. Disease-free survival was significantly better with ESD. LIMITATIONS: The study's retrospective nature prevents definitive conclusions. CONCLUSIONS: We provide evidence that ESD gives a higher cure rate and is safer than conventional endoscopic resection when applied to early SCCE. ESD warrants prospective comparative studies with conventional endoscopic resection. PMID- 20541199 TI - Endoscopic Doppler US for the prevention of ulcer bleeding after endoscopic submucosal dissection for early gastric cancer: a preliminary study (with video). AB - BACKGROUND: After endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), delayed bleeding occurs in 1.7% to 38% of cases. Routine coagulation of all nonbleeding visible vessels (NBVVs) in post-ESD ulcers is currently performed as standard practice, but it cannot eliminate bleeding. An endoscopic Doppler US (DOP-US) probe system has possible benefits for the prediction of recurrent bleeding in peptic ulcer hemorrhage. OBJECTIVE: To establish optimum use and evaluate feasibility of DOP-US for post-ESD ulcers. DESIGN: Case series study. SETTING: Cancer referral center. PATIENTS: Eight patients with mucosal EGC larger than 2 cm without ulceration or scarring and 2 patients with EGC less than 3 cm with scarring. INTERVENTIONS: We searched for a positive DOP-US signal (DOP-US+), which was defined as pulsatile sound at a depth of 1.5 mm, and NBVVs or areas with DOP-US+ were coagulated with hemostatic forceps. A multibending, double channel videoendoscope that was fitted with a transparent hood was used. MAIN OUTCOME MEASUREMENTS: Detectability of DOP-US signals in post-ESD ulcers. RESULTS: One of 13 oozing bleeding sites, 24 (18%) of 136 NBVVs, and 7 areas without any bleeding stigmata had DOP-US+ and were coagulated until the signal became silent. One hundred twelve NBVVs (82%) and 8 adherent clots without DOP-US signals were left untreated. No delayed bleeding was experienced at 30 days. Median time required for Doppler examination was 34 minutes, but it improved to 18 and 19 minutes in patients 9 and 10, respectively. CONCLUSIONS: DOP-US might be helpful in the endoscopic management of post-ESD ulcers in EGC. Our setting and maneuver warrant further investigation to clarify whether DOP-US can reduce delayed bleeding and avoid unnecessary coagulation for NBVVs in post-ESD ulcers. PMID- 20541200 TI - Gone but not forgotten. "Bubble gum enema" containing hydrogen peroxide and causing life-threatening colitis. PMID- 20541201 TI - Routine bile collection for microbiological analysis during cholangiography and its impact on the management of cholangitis. AB - BACKGROUND: Antibiotic treatment of cholangitis is often insufficient because of inappropriate antibiotic use or bacterial resistance. OBJECTIVE: To evaluate the role of routine bile collection during endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography for microbiological analysis in the antibiotic management of cholangitis and to identify risk factors of bacteriobilia. DESIGN: Prospective, observational, diagnostic study. SETTING: Hannover Medical School, Hannover, Germany. PATIENTS AND INTERVENTION: This study involved 243 consecutive patients undergoing endoscopic retrograde cholangiography/percutaneous transhepatic cholangiography for biliary complications after orthotopic liver transplantation (27%), malignancy (27%), primary sclerosing cholangitis (15%), benign strictures (11%), and choledocholithiasis (8%). MAIN OUTCOME MEASUREMENTS: Microbiological examination of bile samples. RESULTS: Patients with biliary stents or who were receiving repeated interventions after orthotopic liver transplantation were at increased risk of bacteriobilia (P < .05). The rate of gram-positive monomicrobial infection was higher in patients with primary sclerosing cholangitis (P < .01). In 40 examinations, patients presented with preprocedural cholangitis although they were receiving antibiotics. According to bile culture results, the antibiotic treatment was modified to a more specific therapy in 72.5% of patients. In patients who developed cholangitis after endoscopic retrograde cholangiography (27 examinations), specific antibiotic treatment was started or refined in 67% of cases, based on bile culture results. LIMITATIONS: Contamination of samples during intervention cannot be totally excluded. CONCLUSION: Orthotopic liver transplantation, biliary stenting, and repeated interventions are risk factors of bacteriobilia. In our patients with primary sclerosing cholangitis, gram-positive monomicrobial infections were more common. A bile sample collected during cholangiography for microbiological analysis is a simple, potentially valuable, diagnostic tool in patients with cholangitis. Each center should recognize its own patterns of infection to ensure ideal targeted therapy. PMID- 20541202 TI - Gastric perforations after ligation of GI stromal tumors in the gastric fundus. PMID- 20541203 TI - Obscure GI bleeding in the tropics: impact of introduction of double-balloon and capsule endoscopies on outcome. AB - BACKGROUND: Innovative but costly small-bowel enteroscopies, capsule endoscopy (CE), and double-balloon endoscopy (DBE) have revolutionized the management of obscure GI bleeding (OGIB). OBJECTIVE: To measure the impact of these procedures on outcomes of OGIB in a resource-poor setting. DESIGN: Prospective cohort study and comparison with a historical cohort. SETTING: Tertiary-care center in India. PATIENTS: Fifty-three patients with OGIB, diagnosed by American Gastroenterological Association criteria. INTERVENTIONS: DBE and/or CE were performed. Patients were then offered specific treatment and/or hematinics. MAIN OUTCOME MEASUREMENTS: The etiology of OGIB in a tropical country and yield of DBE and/or CE. The number of investigations required, follow-up hemoglobin, rebleeds, and interventions/transfusions needed were compared between the present and historical cohort. RESULTS: Mean age was 46.4 years with hemoglobin (mean +/- standard deviation) of 8.3 +/- 2.3 g/dL at evaluation. OGIB was overt in 33 and occult in 20. They underwent 173 investigations before referral. DBE and/or CE localized the source of bleeding in 43 (yield 81%). Angiodysplasias, tumors, Crohn's disease, intestinal tuberculosis, and hookworm infestation were predominant etiologies. Compared with the historical cohort, DBE and/or CE have reduced the number of investigations per patient, increased the yield of mid intestinal source of OGIB, and reduced the number of surgeries, especially emergency laparotomies. There was no significant alteration in the overall yield, mortality, and rebleeding rates. LIMITATION: Small cohort without economic analysis. CONCLUSIONS: The demographic profile and etiological spectrum of OGIB in the tropics is different. DBE and/or CE have made a favorable impact on management. PMID- 20541204 TI - Surgical complications during laparotomy in patients with abdominopelvic tuberculosis. PMID- 20541206 TI - Effect of boot shaft stiffness on stability joint energy and muscular co contraction during walking on uneven surface. AB - Increased boot shaft stiffness may have a noticeable impact on the range of motion of the ankle joint. Therefore, the ability of the ankle joint to generate power for propulsion might be impaired. This might result in compensatory changes at the knee and hip joint. Besides, adaptability of the subtalar joint to uneven surface might be reduced, which could in turn affect stability. The aim of the study was therefore to investigate the influence of boot shaft stiffness on biomechanical gait parameters. Fifteen healthy young adults walked over coarse gravel wearing two different hiking boots that differed by 50% in passive shaft stiffness. Leg kinematics, kinetics and electromyography were measured. Gait velocity and indicators for stability were not different when walking with the hard and soft boot shaft over the gravel surface. However, the hard boot shaft decreased the ankle range of motion as well as the eccentric energy absorbed at the ankle joint. As a consequence, compensatory changes at the knee joint were observed. Co-contraction was increased, and greater eccentric energy was absorbed. Therefore, the efficiency of gait with hard boots might be decreased and joint loading at the knee might be increased, which might cause early fatigue of knee muscles during walking or hiking. The results of this study suggest that stiffness and blocking of joint motion at the ankle should not be equated with safety. A trade-off between lateral stiffness and free natural motion of the ankle joint complex might be preferable. PMID- 20541207 TI - The effects of aponeurosis geometry on strain injury susceptibility explored with a 3D muscle model. AB - In the musculoskeletal system, some muscles are injured more frequently than others. For example, the biceps femoris longhead (BFLH) is the most commonly injured hamstring muscle. It is thought that acute injuries result from large strains within the muscle tissue, but the mechanism behind this type of strain injury is still poorly understood. The purpose of this study was to build computational models to analyze the stretch distributions within the BFLH muscle and to explore the effects of aponeurosis geometry on the magnitude and location of peak stretches within the model. We created a three-dimensional finite element (FE) model of the BFLH based on magnetic resonance (MR) images. We also created a series of simplified models with a similar geometry to the MR-based model. We analyzed the stretches predicted by the MR-based model during lengthening contractions to determine the region of peak local fiber stretch. The peak along fiber stretch was 1.64 and was located adjacent to the proximal myotendinous junction (MTJ). In contrast, the average along-fiber stretch across all the muscle tissue was 0.95. By analyzing the simple models, we found that varying the dimensions of the aponeuroses (width, length, and thickness) had a substantial impact on the location and magnitude of peak stretches within the muscle. Specifically, the difference in widths between the proximal and distal aponeurosis in the BFLH contributed most to the location and magnitude of peak stretch, as decreasing the proximal aponeurosis width by 80% increased peak average stretches along the proximal MTJ by greater than 60% while slightly decreasing stretches along the distal MTJ. These results suggest that the aponeurosis morphology of the BFLH plays a significant role in determining stretch distributions throughout the muscle. Furthermore, this study introduces the new hypothesis that aponeurosis widths may be important in determining muscle injury susceptibility. PMID- 20541208 TI - A non-optimized follower load path may cause considerable intervertebral rotations. AB - Osseoligamentous spinal specimens buckle under even a small vertical compressive force. To allow higher axial forces, a compressive follower load (FL) was suggested previously that approximates the curvature of the spine without inducing intervertebral rotation in both the frontal and the sagittal planes. In in vitro experiments and finite element analyses, the location of the FL path is subjected to estimation by the investigator. Such non-optimized FLs may induce bending and so far it is still unknown how this affects the results of the study and their comparability. A symmetrical finite element model of the lumbar spine was employed to simulate upright standing while applying a follower load. In analogy to in vitro experiments, the path of this FL was estimated seven times by different members of our institute's spine group. Additionally, an optimized FL path was determined and additional moments of +/-7.5Nm were applied to simulate flexion and extension. Application of the optimized 500N compressive FL causes only a marginal alteration of the curvature (cardan angle L1-S1 in sagittal plane <0.25 degrees). An individual estimation of the FL path, however, results in flexions of up to 10.0 degrees or extensions of up to 12.3 degrees. The resulting angles for the different non-optimized FL paths depend on the magnitude of the bending moment applied and whether a differential or an absolute measurement is taken. A preceding optimization of the location of the FL path would increase the comparability of different studies. PMID- 20541209 TI - High energy X-ray scattering quantification of in situ-loading-related strain gradients spanning the dentinoenamel junction (DEJ) in bovine tooth specimens. AB - High energy X-ray scattering (80.7keV photons) at station 1-ID of the Advanced Photon Source quantified internal strains as a function of applied stress in mature bovine tooth. These strains were mapped from dentin through the dentinoenamel junction (DEJ) into enamel as a function of applied compressive stress in two small parallelepiped specimens. One specimen was loaded perpendicular to the DEJ and the second parallel to the DEJ. Internal strains in enamel and dentin increased and, as expected from the relative values of the Young's modulus, the observed strains were much higher in dentin than in enamel. Large strain gradients were observed across the DEJ, and the data suggest that the mantle dentin-DEJ-aprismatic enamel structure may shield the near-surface volume of the enamel from large strains. In the enamel, drops in internal strain for applied stresses above 40MPa also suggest that this structure had cracked. PMID- 20541210 TI - Simultaneous direct analysis of benzimidazole fungicides and relevant metabolites in agricultural products based on multifunction dispersive solid-phase extraction and liquid chromatography-mass spectrometry. AB - A fast and flexible multi-residue procedure for effective extraction of benzimidazole fungicides and the related transformation products in various raw agricultural commodities is developed for direct and simultaneous analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The new sample preparation method, introduced to allow direct extraction of the labile fungicides as the intact forms in complex matrices, is achieved using a conservative homogenizing extraction and multifunction adsorption cleanup (CHEMAC), which basically involves salting-out partitioning/extraction with acetate-buffered acetonitrile at low-temperature and sequential rapid solid-phase dispersive cleanup with a ternary sorbent mixture. The CHEMAC procedure was optimized and further modified by incorporating several pretreatment variables influencing sample stability and process efficiency, such as pH, temperature, salt and sorbent utilized. By using CHEMAC, a noteworthy improvement in extraction recoveries was obtained for the problematic fungicides, while no significant differential matrix effects were detected on the LC-MS/MS analysis in all 9 matrices. The in-source fragmentation of benomyl occurred but caused no cross-talk interference in multi-component analysis. Thus the CHEMAC-based LC MS/MS strategy can serve as an attractive approach to satisfactory overall process efficiencies (70-92%) with acceptable repeatability (relative standard deviations below 16%) for all the analyte-matrix combinations. Mean accuracies were obtained within the range of 70-110% at fortified levels of 1-500 ng/g, with intra-day and inter-day variations less than 15 and 20%, respectively. The successful practical application of the proposed method to real samples has also been demonstrated. PMID- 20541211 TI - A systematic investigation to optimize simultaneous extraction and liquid chromatography tandem mass spectrometry analysis of estrogens and their conjugated metabolites in milk. AB - In this study, the simultaneous extraction of estrone (E1), 17beta-estradiol (E2), estriol (E3), ethinylestradiol (EE2), and their glucuronated and sulfated metabolites in milk was optimized using solid-phase extraction (SPE). The aim of this research was to analyze estrogens and their conjugated metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in a single run, without the need to perform enzymatic cleavage and derivatization. Two SPE cartridges in tandem were used, consisting of sorbents based on the hydrophilic-lipophilic balance and amine-functionalized packing materials. To monitor analyte loss at every step of the SPE procedure (14)C-labeled E2 was spiked into the milk sample and the radioactivity was monitored at all stages of the SPE. In addition, non radiolabeled standards of estrogens and metabolites were used to optimize solvent systems for the SPE and LC-MS/MS. The optimized method described in this paper can achieve recoveries ranging from 72% to 117% for the free estrogens (E1, E2, E3, and EE2), and 62% to 112% for seven conjugated metabolites. The three doubly conjugated, highly polar metabolites included in this study gave lower recoveries (< or = 43%) due to poor retention in SPE. Finally, commercial milk samples were analyzed for the presence of estrogens and their conjugated metabolites. Estrone (concentration range: 23-67 ng/L) was found to be the major free estrogen present in all milk samples. Estradiol was consistently observed in milk, but the concentrations were below the limit of detection (LOD of 10 ng/L), and no estriol and ethinylestradiol were detected. Several conjugated estrogen metabolites were identified, 17beta-estradiol-3-glucuronide (71-289 ng/L), estrone-3-sulfate (60 240 ng/L), 17beta-estradiol-3,17beta-sulfate (< LOD to 30 ng/L), and estrone-3 glucuronide (< LOQ of 25 ng/L). This method proved efficient in the simultaneous analysis of estrogens and their metabolites in milk. PMID- 20541212 TI - Towards obtaining more information from gas chromatography-mass spectrometric data of essential oils: an overview of mean field independent component analysis. AB - Mean field independent component analysis (MF-ICA) along with other chemometric techniques was proposed for obtaining more information from multi-component gas chromatographic-mass spectrometric (GC-MS) signals of essential oils (mandarin and lemon as examples). Using these techniques, some fundamental problems during the GC-MS analysis of essential oils such as varying baseline, presence of different types of noise and co-elution have been solved. The parameters affecting MF-ICA algorithm were screened using a 2(5) factorial design. The optimum conditions for MF-ICA algorithm were followed by deconvolution of complex GC-MS peak clusters. The number of independent components (ICs) (chemical constituents) in each peak cluster was estimated using morphological score method. Eigenvalue profiles of evolving factor analysis (EFA) and pure variables from orthogonal projection approach (OPA) were used as initial mixing matrix (chromatograms) in iterative process. The resolved mass spectra were satisfactorily identified using NIST mass spectral search system. Finally, the results of optimized MF-ICA were compared with those obtained using multivariate curve resolution-alternating least square (MCR-ALS), multivariate curve resolution-objective function minimization (MCR-FMIN) and heuristic evolving latent projection (HELP) methods. It is demonstrated that MF-ICA can be used as an alternative method for a quick and accurate analysis of real multi-component problematic systems such as essential oils. PMID- 20541213 TI - Simulation-assisted evidence for the existence of two stable kaolinite/potassium acetate intercalate complexes. AB - Recent molecular simulation findings with several kaolinite intercalate complexes raised the question of the existence of more than one stable state, which has not been confirmed by experimental observations yet. Kaolinite/potassium acetate intercalate complexes were synthesized and examined by X-ray diffraction, and a molecular simulation study was performed for the system. Consistent with the suggestion from the simulations, an additional stable basal spacing was found experimentally at d(001)=1.168nm besides the well-known one at d(001)=1.403nm. PMID- 20541214 TI - Electrodeposition of latex particles in the presence of surfactant: Investigation of deposit morphology. AB - The deposition of micrometric latex particles on a polarized nickel surface was investigated using a laminar flow cell equipped with a video assembly used to observe and record particle behavior near the electrode. The effects of the nature of the counterions and the concentrations of surfactants on the deposit structure were studied. Negative polystyrene latex particles were turned positive by adsorption of cetyltrimethylammonium in the form of different salts: bromide (CTAB), chloride (CTAC), and hydrogenosulfate (CTAHS). Image analysis was used to gain information on the mechanisms of particle deposition on the electrode. At CTAB concentration 5x10(-5)M, mostly single particles were deposited on the electrode and their adhesion was irreversible. The adsorption mechanism was shown to be dependent on the succession of electrophoretic migration and attractive particle-surface interactions. At a higher CTAB concentration (5x10(-4)M) a transient 3D aggregation was observed which was attributed to electroosmotic and electrohydrodynamic phenomena in the vicinity of the electrode. In the presence of CTAC, aggregates were formed on the electrode for both concentrations. In the case of CTAHS the deposition rate was very low in comparison with CTAB and CTAC. This result was explained by the lower zeta potential of the particles with respect to the other cases. The formation of the aggregates was reversible; furthermore, their morphologies were strongly dependent on the kind of counterion. The aggregates formed in CTAB solution were dense while more open structures were observed with CTAC. PMID- 20541215 TI - Coordination chemistry approach for the end-to-end assembly of gold nanorods. AB - Gold nanorods synthesized by radiolysis were selectively end-functionalized by a fully conjugated thiol bearing a pendant terpyridine group; addition of ferrous ions led to the end-to-end 1D self-assembly of the nanorods. Similar results have been obtained when the preformed [(HStpy)Fe(tpySH)](2+) dithiol complex was directly added to the gold nanorods. PMID- 20541216 TI - Synthesis and characterization of bioactive hydroxyapatite-calcite nanocomposite for biomedical applications. AB - In a number of recent reports on the synthesis of hydroxyapatite (HA) by sol-gel method using citric acid as an organic modifier, washing was an essential step to remove the byproducts and citric acid. In the present study we made an attempt to synthesize HA by sol-gel method in the presence of citric acid, wherein we have employed calcination technique instead of the conventional washing process. The products thus obtained were analyzed by X-ray diffraction (XRD), Fourier Transform-Infrared (FT-IR) spectroscopy, thermogravimetry and scanning electron microscopy which confirmed the formation of a nanocomposite of HA and CaCO(3) (calcite) when citric acid was added during synthesis. HA is known to be bioactive and bioresorbable but the rates are too low. On the other hand, CaCO(3) is highly biodegradable. The combination of HA and CaCO(3) compromised the demerits of each others. The dissolved Ca ions from CaCO(3) enhanced the supersaturation of the surrounding fluid which resulted in higher bioactivity of HA. PMID- 20541217 TI - A systematic study of equilibrium structure, thermodynamics, and rheology of aqueous CTAB/NaNO(3) wormlike micelles. AB - We present a systematic study of the self-assembly of wormlike micelles (WLMs) comprised of cetyltrimethylammonium bromide (CTAB) and sodium nitrate (NaNO(3)) in aqueous solution as a function of CTAB concentration, NaNO(3) concentration, and temperature throughout the dilute and semi-dilute regions of the phase diagram where linear micelles are observed. Combining measurements using isothermal titration calorimetry, rheometry, flow-birefringence, cryo transmission electron microscopy (cryo-TEM), and small angle neutron scattering (SANS) enables complete characterization of the structure, thermodynamics, and rheology of CTAB/NaNO(3) micelles. The addition of NaNO(3) is found to increase the micellization enthalpy as well as the micellar scission energy, resulting in the elongation and growth of WLMs. We find quantitative agreement between the scission energy determined from rheology and the enthalpy of micellization determined from ITC, as well as for contour lengths extracted from rheology and SANS. At fixed molar ratio of NaNO(3) and CTAB, the solution rheology exhibits scaling consistent with dilute, semi-dilute overlapping, and semi-dilute entangled regimes typically found in polymer solutions, as confirmed by cryo-TEM and SANS. The transition between these scaling regimes coincides with the structural transitions identified by SANS. The results validate the relationship between structural parameters and rheological behavior underlying theories for ionic WLMs. PMID- 20541218 TI - Microemulsion phase as a medium for electrodeposition of nickel and electron transfer study of ferrocyanide-ferricyanide redox system. AB - We report our electrochemical studies in a W/O microemulsion phase consisting of a ternary mixture of water, Triton X-100, and toluene. The microemulsion phase plays the dual role of a template in the electrodeposition of nickel and as an electrolytic medium in the study of electron-transfer kinetics. The nickel electrodeposits obtained using this microemulsion phase as a template were characterized by surface analysis techniques such as scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies while cyclic voltammetry (CV) was used to determine the electro-active true surface area of the template-deposited nickel. For electron-transfer studies, CV and electrochemical impedance spectroscopy were employed using potassium ferro/ferricyanide as a redox probe. In contrast to the diffusion-controlled process of the redox probe in aqueous medium, a charge-transfer control was observed in the W/O microemulsion phase. We found that the rate constant value for this particular redox reaction in the microemulsion phase is decreased by about four orders of magnitude when compared to the corresponding value in aqueous medium. The observed phenomenon has been correlated to the structure of the W/O microemulsion phase at the interface, exhibiting a microelectrode array behavior. PMID- 20541219 TI - Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage. AB - Methylglyoxal (MGO) is a cytotoxic metabolite produced by in-vivo glycolysis that may result in diabetic complications. The aim of this study was to determine whether MGO and oxidative stress caused apoptosis of renal podocytes in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes mellitus. Male ZDF rats aged 21 weeks developed marked hyperglycaemia with proteinuria and albuminuria. Immunohistochemical evaluation of sections of kidney demonstrated expression of MGO and 8-hydroxydeoxyguanosine (8-OHdG) in the podocytes of both normoglycaemic and diabetic rats. Podocyte apoptosis was shown through application of the TUNEL method. These findings suggest that expression of MGO and 8-OHdG is caused by hyperglycaemia, and that this expression is associated with the observed apoptosis of podocytes and is related to diabetic nephropathy. PMID- 20541220 TI - Early symptom change and prediction of subsequent remission with olanzapine augmentation in divalproex-resistant bipolar mixed episodes. AB - Potential predictors of remission in mixed bipolar I disorder were identified using early Clinical Global Impression-Severity (CGI-S) improvement criteria in divalproex-resistant patients randomized to olanzapine augmentation (olanzapine + divalproex; N = 101) in a 6-week, double-blind, placebo-controlled trial. In a post-hoc analysis, receiver operating characteristics of 1-point decreases in the CGI-S total score after 2, 4, 7, and 14 days were examined as predictors of endpoint (Week 6 or last observation) remission of depression and/or mania as defined by 21-item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS) total score <=8. Based on a 1-point improvement in CGI-S as a predictor of remission, all odds ratios (ORs) and 95% confidence intervals (CIs) were statistically significant for depression or mania remission criteria. ORs for mixed symptom remission with a decrease >=1 in CGI-S scores at Day 2 for olanzapine augmentation were (6.727; CI: 2.382, 18.997; p < .001) with negative predictive value = 89.5% and positive predictive value = 44.2%. Changes in HDRS 21 and YMRS individual item scores after 2 days of augmentation as predictors of endpoint remission identified that decreases in HDRS-21 symptom item scores (early, middle, and/or late insomnia; paranoid; agitation; and somatic/gastrointestinal) predicted depressive symptom remission at endpoint, and decreases in YMRS item scores (language-thought disorder and irritability) were associated with manic symptom remission at endpoint. Because remission with augmentation therapy may occur in as few as one in ten individuals who lack very early symptom reduction, lack of early improvement may indicate a need to expediently reassess treatment strategy. PMID- 20541221 TI - Psychiatric diagnoses, comorbidity, and functioning in National Guard troops deployed to Iraq. AB - OBJECTIVE: Over 1.8 million troops have been deployed to Iraq (OIF) and Afghanistan. Estimates of mental health problems postdeployment have been based on screening instruments; no studies have examined the postdeployment mental health of troops returning from OIF using structured diagnostic interviews. The goal of the current study is to (a) report on rates of mental health diagnoses and comorbidity in soldiers after deployment to OIF using clinical interviews, and (b) examine the relationship between mental health diagnoses and overall functioning and quality of life. METHOD: Participants were 348 National Guard soldiers drawn from the Readiness and Resilience in National Guard Soldiers (RINGS) study, a longitudinal study of mental health after deployment to OIF from March 2006 to July 2007. Participants completed clinical interviews, including the Clinician Administered PTSD Scale and the Structured Clinical Interview for the DSM-IV, and self-report measures of social adjustment and quality of life 6 12 months following deployment. RESULTS: Most participants did not meet criteria for a mental health diagnosis. Non-PTSD anxiety disorders and depressive disorders were the most common. Mental health diagnoses were associated with poorer functioning and quality of life. PTSD had the strongest relationship with social functioning and quality of life. For those with PTSD, comorbid diagnoses were not associated with an incremental decrease in functioning or quality of life. CONCLUSIONS: The findings highlight the significant rate and burden of mental health disorders among this population and suggest that while PTSD is relatively uncommon, it is a particularly deleterious disorder. PMID- 20541222 TI - The epidemiology of stroke in the Middle East and North Africa. AB - Stroke is the second leading cause of death in the world. In the Middle East and North Africa stroke is increasingly becoming a major health problem, with projections that deaths from it will nearly double by 2030. This systematic review aims to bring together age-adjusted epidemiological data of stroke in this region. A literature review of five databases was conducted. Twenty-three papers met the criteria. The incidence of stroke varied extensively among studies. Studies reported rates from 29.8 per 100000 people in Saudi Arabia to 57 per 100000 people in Bahrain. Furthermore, the 28-day case mortality rate also differed among studies, ranging from 10% in Kuwait to 31.5% in Iran. The rates are comparable with those in the Western world; however, the population of the region is younger. The Middle East and North Africa are lacking in data on the epidemiology of stroke. There is an urgent need to develop strategies to prevent and better care for stroke patients in the Middle East and North Africa. PMID- 20541223 TI - Less invasive left ventricular assist device placement for difficult resternotomy. PMID- 20541225 TI - Successful resection of localized pulmonary mucormycosis after bone marrow transplantation using a virtual 3-dimensional pulmonary model on a personal computer. PMID- 20541224 TI - Changes in left ventricular twist after mitral valve repair. AB - OBJECTIVE: We performed echocardiographic tissue tracking to investigate whether mitral valve repair preserves left ventricular function. METHODS: We studied 16 subjects without heart disease (11 male; mean age, 54.6 +/- 15.1 years) and 18 patients in normal sinus rhythm undergoing solitary mitral valve repair (12 male; mean age, 53.6 +/- 16.6 years). Transthoracic echocardiography was performed before and after surgery, and left ventricular apical and basal short-axis images were recorded. Left ventricular rotation angle was measured with off-line Vector Velocity Imaging (Siemens Medical Solutions USA Inc, Mountain View, Calif) at each slice level. RESULTS: Left ventricular ejection fraction was significantly higher in the control (68.4% +/- 3.6%) and preoperative groups (70.9% +/- 6.5%) than the postoperative group (59.4% +/- 11.4%, P < .05). Left ventricular end diastolic and end-systolic volumes were significantly greater in the preoperative group than the control group (130.0 +/- 41.5 mL and 41.6 +/- 16.6 mL vs 80.0 +/- 16.7 mL and 26.6 +/- 9.2 mL, respectively, P < .05). Left ventricular end diastolic volume normalized postoperatively. Left ventricular twist was significantly greater in the preoperative group than the other groups (11.7 degrees +/- 4.1 degrees versus 7.1 degrees +/- 3.8 degrees and 8.2 degrees +/- 5.7 degrees , P < .05). Left ventricular twist did not differ significantly between control and postoperative groups. New York Heart Association functional class improved from 1.6 +/- 0.5 to 1.0 +/- 0.0 after surgery (P < .05). CONCLUSIONS: Although preoperative left ventricular ejection fraction seemed normal, left ventricular twist was greater. Left ventricular twist normalized after surgery, suggesting that it preserves left ventricular function. PMID- 20541226 TI - On the potential for climate change impacts on marine anthropogenic radioactivity in the Arctic regions. AB - Current predictions as to the impacts of climate change in general and Arctic climate change in particular are such that a wide range of processes relevant to Arctic contaminants are potentially vulnerable. Of these, radioactive contaminants and the processes that govern their transport and fate may be particularly susceptible to the effects of a changing Arctic climate. This paper explores the potential changes in the physical system of the Arctic climate system as they are deducible from present day knowledge and model projections. As a contribution to a better preparedness regarding Arctic marine contamination with radioactivity we present and discuss how a changing marine physical environment may play a role in altering the current understanding pertaining to behavior of contaminant radionuclides in the marine environment of the Arctic region. PMID- 20541227 TI - Mercury bioaccumulation in the spotted dogfish (Scyliorhinus canicula) from the Atlantic Ocean. AB - The annual and life-cycle mercury bioaccumulation pattern in selected tissues of the economically relevant Elasmobranchii species Scyliorhinus canicula was studied, and the risks associated with its consumption evaluated. Preferential mercury bioaccumulation occurred in muscle tissue, and followed the order muscle>heart>liver>gills>pancreas. Total mercury in muscle tissue ranged from 0.13mgkg(-1) (wwt) in 1+year old males to 0.8mgkg(-1) (wwt) in 8+ year old mature females, with no significant differences found between genders, and no clear lifespan bioaccumulation pattern observed, except for mature females. Organic mercury in the muscle ranged from 0.05mgkg(-1) (wwt) to 0.52mgkg(-1) (wwt), corresponding to an average of 70% of total mercury content. In mature females, a significant correlation (R=0.99, P=0.01) was found between size and organic mercury fraction, suggesting reproduction as an important factor controlling organic mercury bioaccumulation in the spotted dogfish. PMID- 20541228 TI - Modeling patterns of coral bleaching at a remote Central Pacific atoll. AB - A mild bleaching event (9.2% prevalence) at Palmyra Atoll occurred in response to the 2009 ENSO, when mean water temperature reached 29.8-30.1 degrees C. Prevalence among both abundant and sparse taxa varied with no clear pattern in susceptibility relating to coral morphology. Seven taxon-specific models showed that turbidity exacerbated while prior exposure to higher background temperatures alleviated bleaching, with these predictors explaining an average 16.3% and 11.5% variation in prevalence patterns, respectively. Positive associations occurred between bleaching prevalence and both immediate temperature during the bleaching event (average 8.4% variation explained) and increased sand cover (average 3.7%). Despite these associations, mean unexplained variation in prevalence equalled 59%. Lower bleaching prevalence in areas experiencing higher background temperatures suggests acclimation to temperature stress among several coral genera, while WWII modifications may still be impacting the reefs via shoreline sediment re-distribution and increased turbidity, exacerbating coral bleaching susceptibility during periods of high temperature stress. PMID- 20541229 TI - Recurrence of the world's largest green-tide in 2009 in Yellow Sea, China: Porphyra yezoensis aquaculture rafts confirmed as nursery for macroalgal blooms. AB - In the summer of 2008, the world's largest green-tide occurred in the Yellow Sea, China. The hypothesized cause was the expansion of Porphyra yezoensis aquaculture along the Jiangsu coastline and the re-occurrence of a green-tide in 2009 was predicted. In this study, satellite and field images showed the formation of the June 2009 green-tide which again originated from the Jiangsu coast. The responsible species, its source and biomass accumulation were studied to support the previous hypothesis. Morphological and phylogenetic analysis demonstrated the homology of Ulva prolifera in the 2008 green-tide with the U. prolifera from P. yezoensis aquaculture rafts. About 91-505kg/ha of U. prolifera was attached to the P. yezoensis aquaculture rafts and a total biomass of 4956 tonnes was estimated during the harvesting of P. yezoensis. This is sufficient to seed a bloom when they are dislodged from the rafts as a result of harvesting practices. PMID- 20541230 TI - [Carbapenem and multidrug-resistant Acinetobacter baumannii colonisation/infection: epidemiology and factors associated with infection]. AB - BACKGROUND AND OBJECTIVE: To study an outbreak of nosocomial colonisation/infection due to multidrug and carbapenem resistant A. baumannii (ABMDR-C). PATIENTS AND METHODS: Prospective study of patients with ABMDR-C colonisation/infection (January 2007-June 2008). Epidemiological and clinical variables and predictors of infection versus colonization were analysed. RESULTS: 24 out of 101 cases were considered colonisations and 77 infections (27 bacteraemia); global mortality (colonisations and infections) was 42% (4 colonisations and 38 infections -18 bacteraemia). All together, the incidence was 3.2/1000 admissions/day; 29% had been previously admitted and 79% had received previous antibiotic treatment (29% carbapenem; 34% piperacillin-tazobactam; 12.5% both); 78% had an underlying condition; 81% were UCI patients; 90% had gone through invasive procedures; 65% had another microorganism isolated. In multivariate analysis, infection predictor factors were isolation of ABMDR-C in respiratory samples (OR 5.406; 95% CI 1.419-20.599); male patients (OR 8.842; 95% CI 1.988-39.325); previous hospitalization (OR 9.720; 95% CI 1.383-68.291) and initial clinical severity (OR 30.897; 95% CI 5.533-172.543). CONCLUSIONS: Our cohort of patients with ABMDR-C colonisation/infection is characterised by their underlying comorbidity, the high rate of previous invasive procedures, previous hospitalisation and previous broad-spectrum betalactam treatments (especially carbapenem). Initial severity and respiratory samples with ABMDR-C isolates were predictors of infection versus colonisation. PMID- 20541231 TI - Diketopiperazines produced by endophytic fungi found in association with two Asteraceae species. AB - Diketopiperazine (DKP) derivatives, named colletopiperazine, fusaperazine C and E as well as four known DKPs were isolated from cultures of Colletotrichum gloeosporioides, Penicillium crustosum, both endophytic fungi isolated from Viguiera robusta, and a Fusarium spp., an endophyte of Viguiera arenaria, respectively. Their structures were established on the basis of their spectroscopic data. Conformational analysis of two known DKPs showed that folded conformations were as energetically stable as the extended one. PMID- 20541232 TI - Tobacco outlet density and demographics: analysing the relationships with a spatial regression approach. AB - OBJECTIVE: Studies of relationships between tobacco sales and socio economic/sociodemographic characteristics are well documented. However, when analysing the data that are collected on geographic areas, the spatial effects are seldom considered, which could lead to potential misleading analytical results. This study addresses this concern by applying the spatial analysis method in studying how socio-economic factors and tobacco outlet density are related in New Jersey, USA. STUDY DESIGN: A spatial regression method applied to tobacco outlet and socio-economic data obtained in 2004 in New Jersey, USA. METHOD: This study assessed the association between tobacco outlet density and three demographic correlates - income, race and ethnicity - at the tract level of analysis for one state in the north-eastern USA. Data for 1938 residential census tracts in the state of New Jersey were derived from 2004 licences for 13,984 tobacco-selling retail outlets. Demographic variables were based on 2000 census data. When applying a regression model, the residuals of an ordinary least squared (OLS) estimation were found to exhibit strong spatial autocorrelation, which indicates that the estimates from the OLS model are biased and inferences based on the estimates might be misleading. A spatial lag model was employed to incorporate the potential spatial effects explicitly. RESULTS: Agreeing with the OLS residual autocorrelation test, the spatial lag model yields a significant coefficient of the added spatial effect, and fits the data better than the OLS model. In addition, the residuals of the spatial regression model are no longer autocorrelated, which indicates that the analysis produces more reliable results. More importantly, the spatial regression results indicate that tobacco companies attempt to promote physical availability of tobacco products to geographic areas with disadvantageous socio-economic status. In New Jersey, the percentage of Hispanics seems to be the dominant demographic factor associated with tobacco outlet distribution, followed by median household income and percentage of African Americans. CONCLUSION: This research applied a spatial analytical approach to assess the association between tobacco outlet density and sociodemographic characteristics in New Jersey at the census tract level. The findings support the common wisdom in the public health research domain that tobacco outlets are more densely distributed in socio-economically disadvantaged areas. However, incorporating the spatial effects explicitly in the analysis provides less biased and more reliable results than traditional methods. PMID- 20541233 TI - Prevalence of stunting, underweight, overweight and obesity in adolescents in Velsk district, north-west Russia: a cross-sectional study using both international and Russian growth references. AB - OBJECTIVES: To study the prevalence of stunting, underweight, overweight and obesity among adolescents in a predominantly rural district in north-west Russia, and to assess the agreement between the findings obtained using international and Russian criteria. STUDY DESIGN: Cross-sectional study. METHODS: Body weight and height were measured in 1066 schoolchildren aged 14-17 years, and body mass index values were calculated. The prevalences of stunting, underweight, overweight/obesity and obesity were estimated according to the World Health Organization 2007 (WHO-2007), Centers for Disease Control and Prevention 2000 (CDC-2000), Russian and International Obesity Task Force (IOTF) criteria. Pearson's Chi-squared test and McNemar's test were used to compare categorical data. The agreement between estimates obtained using Russian and international criteria was assessed by Cohen's kappa. RESULTS: The prevalence of stunting was 3.3%, 5.2% and 4.5% using the WHO-2007, CDC-2000 and Russian criteria, respectively. The prevalence of overweight/obesity was 10.3%, 8.6%, 8.6% and 9.0% as estimated using the WHO-2007, CDC-2000, Russian and IOTF criteria. The corresponding proportions for obesity were 4.7%, 2.6%, 2.3% and 2.0%, and for underweight were 3.6%, 3.1%, 2.3% and 1.8%. The Russian criteria led to lower estimates for the prevalence of overweight/obesity in boys but not in girls. The agreement between the estimates obtained using international and Russian criteria varied between 0.3 and 0.9 in boys and between 0.2 and 1.0 in girls. CONCLUSIONS: The prevalence of stunting was higher in the study population than in most European countries, whereas the prevalences of underweight, overweight/obesity and obesity were lower. The choice of reference population considerably influences the prevalence estimates. Moreover, the agreement between the estimates varies by gender. PMID- 20541234 TI - Difference in the level of interferon gamma mRNA transcripts on stimulation of cattle and buffalo mononuclear cells with foot and mouth disease virus-antigen: a possible role of sequence variation in promoter region. AB - In an attempt to resolve the claim that buffaloes differ from cattle in disease progression, this study was undertaken to compare the mitogen (conA) or antigen (foot and mouth disease virus) induced expression levels of interferon gamma (IFN gamma mRNA in peripheral blood mononuclear cells (PBMCs) by real-time quantitative PCR. In general, the levels of IFN-gamma mRNA were lower in buffaloes than in crossbred cattle. Significantly higher levels of IFN-gamma mRNA were also observed in crossbred cattle when induced with FMD virus (1 MUg). Analysis of the partial promoter sequences of the IFN-gamma gene from the respective species revealed a conserved 4 base (GTCT) deletion in all the buffalo promoter sequences. In-silico analysis indicated the binding of glucocorticoid receptor (GR) and erythroid nuclear factor (NF-E) to this region in cattle. GR has been shown to be a transcription factor by itself and also regulates other major transcription factors like NF-kappaB and AP-1. The differential expression levels of IFN-gamma mRNA between these species could be due to this deletion in the promoter region of buffalo. Further studies involving mobility shift and promoter assays would throw more light on the differential expression levels. PMID- 20541235 TI - Polycyclic aromatic hydrocarbons are enriched but bioaccessibility reduced in brownfield soils adhered to human hands. AB - The health risk associated with exposure to urban brownfields is often driven by the incidental ingestion of soil by humans. Recent evidence found that humans likely ingest the fraction of soil that passes a 45-microm sieve, which is the particle size adhered to the hands. We evaluated if PAH concentrations were enriched in this soil fraction compared to the bulk soil and if this enrichment lead to an increase in bioaccessibility and thus an increase in incremental lifetime cancer risk for exposed persons. Soils (n=18) with PAH concentrations below the current Canadian soil quality guidelines for human health were collected from an Arctic urban site and were sieved to pass a 45-microm sieve. Soil PAH profiles were measured and bioaccessibility was assessed using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). PAHs were significantly enriched in the <45 microm size fraction (3.7-fold) and this enrichment could be predicted according to the fugacity capacity of soil (Enrichment=2.18-0.055Zsoil, r2=0.65, p<0.001). PAH release in the stomach and small intestine compartments of the SHIME was low (8%) and could not be predicted by PAH concentrations in 45-microm sieved soil. In fact, PAH release in the SHIME was lower from the <45 microm size fraction despite the fact that this fraction had higher levels of PAHs than the bulk soil. We postulate that this occurs because PAHs adsorbed to soil did not reach equilibrium with the small intestinal fluid. In contrast, PAH release in the colonic compartment of the SHIME reached equilibrium and was linked to soil concentration. Bioaccessibility in the SHIME colon could be predicted by the ratio of fugacity capacity of soil to water for a PAH (Bioaccessibility=0.15e(-6.4x10E-7Zsoil/Zwater), r2=0.53, p<0.01). The estimated incremental lifetime cancer risk was significantly greater for the <45 microm soil fraction compared to the bulk fraction; however, when bioaccessible PAH concentrations in a simulated small intestine were used in the risk assessment calculations, cancer risk was slightly lower in the <45 microm soil fraction for these soils. Our results highlight the importance of using a small soil size fraction, e.g. 45 microm, for contaminated site human health risk assessment. However, further work is needed to estimate the bioavailability of this size fraction in an in vivo model and to assess the correlation between in vitro and in vivo gastrointestinal models. PMID- 20541236 TI - UVA irradiation induces direct phototransformation of 2,4-dinitrophenol in surface water samples. AB - Lake water samples spiked with 2,4-dinitrophenol (24DNP) were irradiated under artificial UVA irradiance. It was found that the direct photolysis is the main photodegradation pathway of 24DNP in lake water. On the lake water samples it was also determined the formation and consumption rates of *OH, by means of the transformation reaction of benzene into phenol. It was found that the rate of direct photolysis prevails over the *OH phototransformation rate by one-two orders of magnitude. Moreover, the excited triplet states of chromophoric dissolved organic matter and singlet oxygen are expected to play a negligible role in the photodegradation of 24DNP. By modelling the direct photolysis of 24DNP in surface water bodies, one gets a half-life time of 2-10 summer sunny days for water-column depths up to 10 m. This would make the direct photolysis a major pathway for the transformation of 24DNP in freshwaters. PMID- 20541237 TI - Microfaunal remains at Middle Pleistocene Qesem Cave, Israel: Preliminary results on small vertebrates, environment and biostratigraphy. AB - Preliminary results of the investigation of the microfauna at the Acheulo Yabrudian Middle Pleistocene site of Qesem Cave, Israel, are presented. Thus far the assemblage includes ca. 10,000 bone and tooth fragments, of which 50% could be identified to the generic and some hundreds to the species level. Based on the current material, the fauna includes the following squamate reptiles: Laudakia sp., Chamaeleo sp., Gekkonidae indet., Lacertidae indet., Scincidae indet., Pseudopus sp., Varanus sp., Colubroidea indet. (at least three species) and micromammals: Suncus etruscus, Crocidura cf. leucodon, Crocidurinae indet. (large form), Chiroptera indet., Sciurus cf. anomalus, Cricetulus cf. migratorius, Microtus guentheri, Nannospalax ehrenbergi, Dipodillus cf. dasyurus, Meriones cf. tristrami, Gerbillidae indet., Mus cf. musculus, Apodemus cf. flavicollis. These results suggest that the fauna includes only taxa that occur recently in the territory of Israel. The ecological preferences of the nearest living relatives of the recorded taxa allow us to infer a paleoenvironment with a mosaic of open and woodland habitats. However, comparing the lower with the upper levels of the microfauna-bearing profile, a slight shift towards more wooded conditions might be detectable. Biostratigraphical inferences from the recorded micromammal taxa cover a rather wide age range, whereas the radiometric (U-series and preliminary TL) dating enable a provisionally estimated date for the microfauna-bearing levels at 360-300 ka. Detailed morphometric comparisons with material from other sites in the region are necessary and may yet provide further insights. PMID- 20541238 TI - Predicting assemblages and species richness of endemic fish in the upper Yangtze River. AB - The present work describes the ability of two modeling methods, Classification and Regression Tree (CART) and Random Forest (RF), to predict endemic fish assemblages and species richness in the upper Yangtze River, and then to identify the determinant environmental factors contributing to the models. The models included 24 predictor variables and 2 response variables (fish assemblage and species richness) for a total of 46 site units. The predictive quality of the modeling approaches was judged with a leave-one-out validation procedure. There was an average success of 60.9% and 71.7% to assign each site unit to the correct assemblage of fish, and 73% and 84% to explain the variance in species richness, by using CART and RF models, respectively. RF proved to be better than CART in terms of accuracy and efficiency in ecological applications. In any case, the mixed models including both land cover and river characteristic variables were more powerful than either individual one in explaining the endemic fish distribution pattern in the upper Yangtze River. For instance, altitude, slope, length, discharge, runoff, farmland and alpine and sub-alpine meadow played important roles in driving the observed endemic fish assemblage structure, while farmland, slope grassland, discharge, runoff, altitude and drainage area in explaining the observed patterns of endemic species richness. Therefore, the various effects of human activity on natural aquatic ecosystems, in particular, the flow modification of the river and the land use changes may have a considerable effect on the endemic fish distribution patterns on a regional scale. PMID- 20541239 TI - More than meets the eye. AB - A 27-year-old woman was hospitalized with fever and visual changes. She had been well until nine months earlier when she developed unilateral blurry vision in the left eye. Ophthalmologic examination revealed bilateral acute anterior uveitis. She was treated with topical steroids and her vision returned to baseline. However, over the next few months, she developed debilitating fatigue and experienced an unintentional fifteen pound weight loss. One month prior to presentation, she noted the onset of daily low grade fevers and chills. On the day of admission, she developed a temperature of 103 degrees F and a severe frontal headache. Here we describe a case where the overlap of clinical features led to an initially broad differential diagnosis of seemingly unrelated diseases. Ultimately, the discovery of a key radiographic finding allowed us to more clearly define the diagnosis. PMID- 20541240 TI - Acquired and congenital risk factors associated with cerebral venous sinus thrombosis. AB - The mechanistic paradigm underlying venous thrombosis at atypical locations stems from the observation that most events occur as a result of pathology of the organ system drained by the involved venous segment. Cerebral venous sinus thrombosis stands apart as an exception to this general rule. Although brain and sinus pathology are well established causes, these combined variables account for approximately one third of cases. The marked female preponderance and strong association with gender specific risk factors including hormonal manipulation, pregnancy and the puerperium are particularly notable. Factor V Leiden and prothrombin G20210A mutations and hyperhomocysteinemia represent important risk factors particularly when combined with acquired variables. The association with oral contraception use and the prothrombin G20210A gene mutation may offer insights into the anatomic predilection for cerebral venous sinus involvement as compared to venous thrombosis of the lower extremities. The intent of this review is to summarize the corporate literature of both acquired and congenital risk factors associated with cerebral venous sinus thrombosis in order to assist clinicians in their search for underlying mechanisms and to risk stratify patients for anticoagulation treatment duration and risk of recurrent thrombosis. PMID- 20541241 TI - Prevalence of urinary incontinence in men, women, and children--current evidence: findings of the Fourth International Consultation on Incontinence. AB - OBJECTIVES: To summarize existing evidence relating to the prevalence and risk factors of urinary incontinence in order to provide a concise reference source for clinicians, health researchers, and service planners. METHODS: For the Fourth International Consultation on Incontinence (4th ICI) world experts identified, collated, and reviewed the best available evidence. Estimates of prevalence from different studies are presented as ranges. RESULTS: Most studies report some degree of urinary incontinence (UI) in 25-45% of women; 7-37% of women aged 20-39 report some UI; "daily UI" is reported by 9% to 39% of women over 60. Pregnancy, childbirth, diabetes and increased body mass index are associated with an increased risk of UI. Prevalence of UI in men approximately half that in women: UI is seen in 11-34% of older men, with 2-11% reporting daily UI. Surgery for prostate disease is associated with an increased risk. Some 10% of children aged seven, 3% of 11-12 years olds and 1% of 16-17 year olds are not dry at night. CONCLUSIONS: UI is clearly common, but accurate prevalence data have proven difficult to establish because of heterogeneity between studies in terms of methodologies, definitions of UI and populations considered. Future research should use standardized, validated and more readily comparable methods. PMID- 20541242 TI - Late morbidity following nerve-sparing radical hysterectomy. PMID- 20541243 TI - Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (alphaE/beta7 Integrin) in high-grade serous ovarian cancer. AB - INTRODUCTION: Tumor-infiltrating CD8(+) T cells are strongly associated with survival in high-grade serous ovarian cancer, but their functional phenotype remains poorly defined. The mucosal integrin CD103 (alpha(E)/beta(7)) facilitates the infiltration of T cells into epithelial tissues, including gut and lung mucosa, solid organ allografts, and various epithelial cancers. We reasoned that CD103 might also be expressed by tumor-reactive T cells in ovarian cancer. METHODS: Flow cytometry was used to assess the frequency and phenotype of CD103 expressing T cells in primary ascites fluid from 13 patients with high-grade serous ovarian cancer and 2 patients with recurrent disease. RESULTS: We report that a subset of patients with advanced serous ovarian cancer have profoundly elevated frequencies of CD103-expressing CD8(+) cells in ascites (between 20% and 70% of CD8(+) cells in ascites were CD103(+)) and that CD103 expression correlated with levels of TGF-beta in ascitic fluid. Conversely, CD103 was not expressed on CD4(+) cells, even in those patients with very high frequencies of CD8(+)CD103(+) cells. CD8(+)CD103(+) cells were antigen-experienced (CD45RA( )CD45RO(+)CD62L(lo)CCR7(-)) and of an intermediate (EM2) effector memory phenotype (CD27(+)CD28(-)). TCR repertoire analysis indicated significant skewing between CD8(+)CD103(-) and CD8(+)CD103(+) T cell subsets, suggesting the two populations contain distinct antigenic specificities. Lastly, HLA pentamer analysis revealed that one patient in the cohort harbored a high frequency of CD8(+) T cells in ascites that were specific for the tumor antigen NY-ESO-1, and that approximately 75% of these NY-ESO-1 specific CD8(+) T cells were CD103(+). CONCLUSIONS: CD103(+) may be a marker of activated and tumor-reactive CD8(+) T cells in high-grade serous ovarian cancer. PMID- 20541244 TI - Sarcoma of the cervix: natural history and outcomes. AB - INTRODUCTION: Cervical sarcomas are rare neoplasms thought to follow an aggressive course. We examined the natural history of cervical sarcomas and compared their outcomes to that of squamous cell and adenocarcinomas of the cervix. In addition, we examined the prognostic significance of various demographic, clinical, and treatment related factors. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all women with primary cervical sarcomas diagnosed between 1988 and 2005. The clinical characteristics and outcomes of women with cervical sarcomas were compared to patients with squamous cell and adenocarcinomas of the cervix. Survival was examined using multivariable Cox proportional hazards models and the Kaplan-Meier method. RESULTS: A total of 33,074 women with invasive cervical neoplasms were identified including 323 (1%) patients with cervical sarcomas. Among women with cervical sarcomas, carcinosarcoma was the most common and accounted for 40% (128) of the cases while adenosarcomas and leiomyosarcomas each accounted for 21% (67). Compared to women with squamous cell and adenocarcinomas, patients with cervical sarcomas tended to be younger, diagnosed in the later years of the study, have larger tumors, and have more advanced stage disease (p<0.05 for all). After adjusting for other known prognostic factors, patients with cervical sarcomas were 60% more likely to die from their tumors (cancer-specific survival HR=1.60; 95% CI, 1.30-1.96), (overall survival HR=1.60; 95% CI, 1.36-1.89) than patients with squamous cell carcinomas. A separate multivariable analysis limited to women with cervical sarcomas revealed no difference in survival for any of the sarcoma subtypes. CONCLUSION: Primary cervical sarcomas are aggressive neoplasms. The prognosis for women with cervical sarcomas is inferior to that of squamous cell and adenocarcinomas matched by stage. PMID- 20541245 TI - Evaluation of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer: a multi-center study. AB - OBJECTIVE: To evaluate the role of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer (EEC). METHODS: We reviewed 413 patients with EEC from 6 tertiary medical centers between July 1996 and June 2008. All patients were divided into (1) 4 categories of preoperative serum CA 125 levels: <18 U/mL (n=203); 18-35 U/mL (n=114); 36-70 U/mL (n=53); >70 U/mL (n=43) or (2) 3 categories: low-risk (n=240); intermediate-risk (n=99); high-risk diseases (n=74). RESULTS: Receiver operative curves showed the best cut-off values of 16.2-40.8 U/mL for predicting prognostic factors with 53.4-84.2% of sensitivity, 43.9-81.7% of specificity, 48.8-82.1% of positive predictive value (PPV), 48.5-83.8% of negative predictive value (NPV) and 48.6-83.0% of accuracy. Especially, adnexal involvement was predicted with the highest accuracy (83.0%) at >or=40.8 U/mL. The best cut-off values for preoperative selection of intermediate- to high-risk, and high-risk diseases were 17.3 U/mL and 21.9 U/mL (62.4% and 68.9% of sensitivity; 54.6% and 64.3% of specificity; 57.9% and 64.2% of PPV; 59.2% and 67.4% of NPV, 58.5% and 65.8% of accuracy). Furthermore, >70 U/mL of preoperative serum CA-125 levels was a prognostic factor for poor progression-free and overall survivals. CONCLUSIONS: Serum CA-125 levels may not be useful for predicting most of prognostic factors, and may not contribute to preoperative selection of patients with intermediate- or high-risk disease who need adjuvant radiotherapy in EEC. However, serum CA-125 levels may be helpful in preoperative counseling for young patients who want ovarian preservation, and >70 U/mL could be considered as a risk factor for poor survival. PMID- 20541246 TI - Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia. AB - BACKGROUND: The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. OBJECTIVE: We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. METHODS: Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. RESULTS: During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. CONCLUSIONS: Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged. PMID- 20541247 TI - Algorithm for the diagnosis of anaphylaxis and its validation using population based data on emergency department visits for anaphylaxis in Florida. AB - BACKGROUND: Epidemiologic studies of anaphylaxis have been limited by significant underdiagnosis. OBJECTIVE: The purpose of this study was to develop and validate a method for capturing previously unidentified anaphylaxis cases by using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) based datasets. METHODS: Florida emergency department data for the years 2005 and 2006 from the Florida Agency for Health Care Administration were used. Patients with anaphylaxis were identified by using ICD-9-CM codes specifically indicating anaphylaxis or an ICD-9-CM algorithm based on the definition of anaphylaxis proposed at the 2005 National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network symposium. Cases ascertained with the algorithm were compared with the traditional case ascertainment method. Comparisons included demographic and clinical risk factors, proportion of monthly visits, and age/sex-specific rates. Cases ascertained with anaphylaxis ICD-9-CM codes were excluded from those ascertained with the algorithm. RESULTS: One thousand one hundred forty-nine patients were identified by using anaphylaxis ICD-9-CM codes, and 1,602 patients were identified with the algorithm. The clinical risk factors and demographics of cases were consistent between the 2 methods. However, the algorithm was more likely to identify older subjects (P < .0001), those with hypertension or heart disease (P < .0001), and subjects with venom-induced anaphylaxis (P < .0001). CONCLUSION: This study introduces and validates an ICD-9-CM-based diagnostic algorithm for the diagnosis of anaphylaxis to capture subjects missed by using the ICD-9-CM anaphylaxis codes. Fifty-eight percent of anaphylaxis cases would be missed without the use of the algorithm, including 88% of venom-induced cases. PMID- 20541248 TI - A single nucleotide polymorphism in the CCR3 gene ablates receptor export to the plasma membrane. AB - BACKGROUND: The chemokine receptor CCR3 orchestrates the migration of eosinophils, basophils, T(H)2 lymphocytes, and mast cells during the allergic response, with CCR3 blockade a potential means of therapeutic intervention. Non synonymous single nucleotide polymorphisms (SNPs) within the ccr3 gene have previously been described, with little information regarding their effects on CCR3 function. OBJECTIVE: To characterize the effects of nonsynonymous SNPs within the ccr3 gene. METHODS: Site-directed mutagenesis was used to generate N terminally tagged mutant CCR3 constructs corresponding to reported SNPs. Cell transfectants expressing either wild-type or mutant CCR3 were studied by flow cytometry, Western blotting, and confocal microscopy and examined for their ability to migrate to the CC chemokine ligand CCL11/eotaxin. RESULTS: An L324P mutant CCR3 protein corresponding to the previously identified T971C SNP was not expressed at the cell surface, and cells remained unresponsive to CCL11 in chemotaxis assays. Confocal microscopy confirmed that L324P-CCR3 had a predominantly intracellular distribution compared with wild-type CCR3. A L324A variant of CCR3 had an identical phenotype to the L324P mutant, suggesting that L324 per se is critical for successful trafficking of nascent CCR3 to the cell membrane. The processes involved appear to be specific for CCR3, because an identical mutation in the homologous receptor CCR1 had minor effects. CONCLUSION: Trafficking to the cell surface of nascent CCR3 is critically dependent on a C terminal leucine residue, suggestive of specific mechanisms for CCR3 export. Manipulation of these mechanisms may suggest novel means of antagonizing CCR3 function in the treatment of allergy. PMID- 20541249 TI - Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. AB - BACKGROUND: The diversity in the perceived prevalence, recovery, and risk factors for cow's milk allergy (CMA) necessitated a large-scale, population-based prospective study. OBJECTIVE: We sought to determine the prevalence, cross reactivity with soy allergy, and risk factors for the development of CMA. METHODS: In a prospective study the feeding history of 13,019 infants was obtained by means of telephone interview (95.8%) or questionnaire (4.2%). Infants with probable adverse reactions to milk were examined, skin prick tested, and challenged orally. RESULTS: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for IgE-mediated CMA was 0.5% (66/13,019 patients). The mean age of cow's milk protein (CMP) introduction was significantly different (P < .001) between the healthy infants (61.6 +/- 92.5 days) and those with IgE-mediated CMA (116.1 +/- 64.9 days). Only 0.05% of the infants who were started on regular CMP formula within the first 14 days versus 1.75% who were started on formula between the ages of 105 and 194 days had IgE mediated CMA (P < .001). The odds ratio was 19.3 (95% CI, 6.0-62.1) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more (P < .001). Sixty-four patients with IgE-mediated CMA tolerated soy, and none had a proved allergy to soy. CONCLUSIONS: IgE-mediated CMA is much less common than generally reported. Early exposure to CMP as a supplement to breast-feeding might promote tolerance. Finally, soy is a reasonable feeding alternative in patients with IgE-mediated CMA. PMID- 20541250 TI - Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. AB - Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets. PMID- 20541251 TI - Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. AB - The MLL1 gene is a frequent target for recurrent chromosomal translocations, resulting in transformation of hematopoietic precursors into leukemia stem cells. Here, we report on structure-function studies that elucidate molecular events in MLL1 binding of histone H3K4me3/2 marks and recruitment of the cyclophilin CyP33. CyP33 contains a PPIase and a RRM domain and regulates MLL1 function through HDAC recruitment. We find that the PPIase domain of CyP33 regulates the conformation of MLL1 through proline isomerization within the PHD3-Bromo linker, thereby disrupting the PHD3-Bromo interface and facilitating binding of the MLL1-PHD3 domain to the CyP33-RRM domain. H3K4me3/2 and CyP33-RRM target different surfaces of MLL1-PHD3 and can bind simultaneously to form a ternary complex. Furthermore, the MLL1-CyP33 interaction is required for repression of HOXA9 and HOXC8 genes in vivo. Our results highlight the role of PHD3-Bromo cassette as a regulatory platform, orchestrating MLL1 binding of H3K4me3/2 marks and cyclophilin-mediated repression through HDAC recruitment. PMID- 20541253 TI - Genetic and environmental determinants of vitamin D status. PMID- 20541254 TI - Imaging and cell targeting characteristics of magnetic nanoparticles modified by a functionalizable zwitterionic polymer with adhesive 3,4-dihydroxyphenyl-l alanine linkages. AB - Multifunctional magnetic nanoparticles (MNPs) modified by a zwitterionic polymer (pCBMA-DOPA(2)) containing one poly(carboxybetaine methacrylate) (pCBMA) chain and two 3,4-dihydroxyphenyl-L-alanine (DOPA) residue groups were developed. Results showed that MNPs modified by pCBMA were not only stable in complex media, but also provided abundant functional groups for ligand immobilization. The pCBMA DOPA(2) MNPs had a hydrodynamic particle size of about 130 nm, a strong saturation magnetization of 110.2 emu/g Fe and a high transverse relaxivity of 428 mM(-1)s(-1). Long-term stability in phosphate-buffered saline (PBS) and 10% NaCl solution was achieved for over six months. Compared to MNPs coated with dextran, pCBMA-DOPA(2) MNPs presented better stability in 100% human blood serum at 37 degrees C. Macrophage cell uptake studies revealed that the uptake ratio of pCBMA-DOPA(2) MNPs was much lower than that of dextran MNPs. Furthermore, quantitative analysis results showed that after pCBMA-DOPA(2) MNPs were conjugated with a targeting RGD peptide, uptake by human umbilical vein endothelial cell (HUVEC) was notably increased, which was further visualized by magnetic resonance imaging (MRI). PMID- 20541255 TI - Functionalization of matrices by cyclically stretched osteoblasts through matrix targeting of VEGF. AB - Vascular endothelial growth factor A (VEGF) plays a central role in load-induced bone gain. We previously showed that increasing cyclic stretch frequency from 0.05 to 5 Hz induce parallel increased in entrapment of VEGF (mVEGF) into osteoblast secreted extracellular matrix. We ask in this study if mVEGF could be protective against apoptotic signals and biologically active in vitro on endothelial cell migration as well as in vivo on angiogenesis. We established that mechanically-induced VEGF entrapment using stretched silicone membrane was saturable after 3 exposures at high frequency stretches (5Hz). We found that mVEGF stimulates microvascular cells migration and enhanced angiogenesis more importantly than VEGF 165 controls suggesting the absence of potent anti angiogenic factors in our functionalized matrices. Indeed we found that the anti angiogenic factors, tissue inhibitor of metalloproteinase (TIMP2) and pigment epithelium-derived factor (PEDF) were specifically downregulated for 5 Hz stretch and that the release of these potent factors was increased for low frequency of stretch (0.05 Hz). This study qualifies high frequency cyclic stretch as an interesting approach for surfaces activation of deformable biomaterials. PMID- 20541256 TI - On the mechanical properties of hierarchically structured biological materials. AB - Many biological materials are hierarchically structured which means that they are designed from the nano- to the macro-scale in a sometimes self-similar way. There are lots of papers published including very detailed descriptions of these structures at all length scales--however, investigations of mechanical properties are most often focused on either nano-indentation or bulk mechanical testing characterizing properties at the smallest or largest size scale. Interestingly, there are hardly any investigations that systematically interconnect mechanical properties of different length scales. Nevertheless there are often conclusions drawn like the one that "biological materials exhibit their excellent mechanical properties due to their hierarchical structuring". Thus, we think there is a gap and discrepancy between the detection and description of biological structures and the correlated determination and interpretation of their mechanical properties. Hence, in this paper we order hierarchically structured biological materials with high mineral content according to their hierarchical levels and attribute measured mechanical properties to them. This offers the possibility to gain insight into the mechanical properties on different hierarchical levels even though the entire biological materials were tested. On the other hand we use data of one material, namely enamel, where mechanical properties were measured on every length scale. This kind of data analysis allows to show how a theoretical model developed by Huajian Gao and co-workers can be used to get closer insights into experimental data of hierarchically structured materials. PMID- 20541252 TI - Common genetic determinants of vitamin D insufficiency: a genome-wide association study. AB - BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25 hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25 hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments). PMID- 20541257 TI - The control of stem cell morphology and differentiation by hydrogel surface wrinkles. AB - In this study, we investigated human mesenchymal stem cell (hMSC) interactions with uniform hydrogels and hydrogels with lamellar or hexagonal surface wrinkles to elucidate our ability to control hMSC morphology and differentiation. Wrinkled hydrogels were prepared from photocurable poly(2-hydroxyethyl methacrylate) (PHEMA) precursor solutions containing ethylene glycol dimethacrylate as a crosslinker, using depth-wise gradients in crosslinking and subsequent buckling with swelling to generate wrinkles. A replica molding process was used to fabricate a series of gels with uniform mechanics, but altered surface wrinkle size and shape. We found that hMSCs attached to lamellar wrinkles spread by taking the shape of the pattern, exhibit high aspect ratios, and differentiate into an osteogenic lineage. In contrast, cells that attached inside the hexagonal patterns remain rounded with low spreading and differentiate into an adipogenic lineage. This work aids in the development of material-based cell culture and scaffold systems to direct stem cell differentiation. PMID- 20541259 TI - Childhood experiences of sexual abuse and later parenting practices among non offending mothers of sexually abused and comparison girls. AB - OBJECTIVE: The primary goal of this study was to explore the relationship between childhood sexual abuse and parenting practices among non-offending mothers of sexually abused girls. Guided by a developmental-ecological perspective of parenting, several models with different potential pathways starting from the mothers' childhood experiences of sexual abuse and culminating in their parenting practices (e.g., direct, spurious, indirect effect) were hypothesized and explored in the context of the mothers' past and current psychosocial risks and resources. Two dimensions of parenting were considered: providing positive structure (i.e., ratings of how consistent, fair, easygoing), and using punitive discipline. METHODS: This study utilized a sample from a longitudinal, multigenerational study in which sexually abused girls, demographically similar comparison girls, and the mothers of both groups of girls participated. For the current study, the data regarding the mothers of the two groups of girls was of primary importance. RESULTS: The results from a series of model comparison tests supported the spurious effect of mothers' childhood sexual abuse on the positive structure dimension. A direct, inverse relationship was found as the most accurate model with the punitive discipline dimension. Overall, childhood experience of punitive discipline, current dissociative symptoms, and satisfaction with social support were indicated as possible correlates of parenting practices among the mothers. CONCLUSIONS: The significance of these findings is discussed in the context of theories concerning childhood trauma and parenting, as well as the intergenerational process of child maltreatment. Practice implications of the findings are also presented and discussed in terms of intervention programs for families where intrafamilial child sexual abuse occurs. PMID- 20541258 TI - Microarray profiling reveals that placental transcriptomes of early-onset HELLP syndrome and preeclampsia are similar. AB - BACKGROUND: The involvement of the placenta in the pathogenesis of preeclampsia and HELLP syndrome is well established, and placental lesions are also similar in these two syndromes. Here we aimed to examine the placental transcriptome and to identify candidate biomarkers in early-onset preeclampsia and HELLP syndrome. METHODS: Placental specimens were obtained at C-sections from women with early onset preeclampsia and HELLP syndrome, and from controls who delivered preterm or at term. After histopathological examination, fresh-frozen placental specimens were used for microarray profiling and validation by qRT-PCR. Differential expression was analysed using log-linear models while adjusting for gestational age. Gene ontology and pathway analyses were used to interpret gene expression changes. Tissue microarrays were constructed from paraffin-embedded placental specimens and immunostained. RESULTS: Placental gene expression was gestational age-dependent among preterm and term controls. Out of the 350 differentially expressed genes in preeclampsia and 554 genes in HELLP syndrome, 224 genes (including LEP, CGB, LHB, INHA, SIGLEC6, PAPPA2, TREM1, and FLT1) changed in the same direction (elevated or reduced) in both syndromes. Many of these encode proteins that have been implicated as biomarkers for preeclampsia. Enrichment analyses revealed similar biological processes, cellular compartments and biological pathways enriched in early-onset preeclampsia and HELLP syndrome; however, some processes and pathways (e.g., cytokine-cytokine receptor interaction) were over-represented only in HELLP syndrome. CONCLUSION: High throughput transcriptional and tissue microarray expression profiling revealed that placental transcriptomes of early-onset preeclampsia and HELLP syndrome largely overlap, underlying a potential common cause and pathophysiologic processes in these syndromes. However, gene expression changes may also suggest a more severe placental pathology and pronounced inflammatory response in HELLP syndrome than in preeclampsia. PMID- 20541260 TI - The use of paraphrasing in investigative interviews. AB - OBJECTIVE: Young children's descriptions of maltreatment are often sparse thus creating the need for techniques that elicit lengthier accounts. One technique that can be used by interviewers in an attempt to increase children's reports is "paraphrasing," or repeating information children have disclosed. Although we currently have a general understanding of how paraphrasing may influence children's reports, we do not have a clear description of how paraphrasing is actually used in the field. METHOD: The present study assessed the use of paraphrasing in 125 investigative interviews of allegations of maltreatment of children aged 4-16 years. Interviews were conducted by police officers and social workers. All interviewer prompts were coded into four different categories of paraphrasing. All children's reports were coded for the number of details in response to each paraphrasing statement. RESULTS: "Expansion paraphrasing" was used significantly more often and elicited significantly more details, while "yes/no paraphrasing" resulted in shorter descriptions from children, compared to other paraphrasing styles. Further, interviewers more often distorted children's words when using yes/no paraphrasing, and children rarely corrected interviewers when they paraphrased inaccurately. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Investigative interviewers in this sample frequently used paraphrasing with children of all ages and, though children's responses differed following the various styles of paraphrasing, the effects did not differ by the age of the child. The results suggest that paraphrasing affects the quality of statements by children. Implications for investigative interviewers will be discussed and recommendations offered for easy ways to use paraphrasing to increase the descriptiveness of children's reports of their experiences. PMID- 20541261 TI - A novel cyanide ion sensing approach based on Raman scattering for the detection of environmental cyanides. AB - This paper describes a direct optical approach based on Raman scattering for selective and sensitive detection of cyanide ions in aqueous environment without requiring time-consuming sample pretreatment and the formation of hydrogen cyanide. Due to the strong affinity between copper (I) and cyanide ion, evaporated copper (I) iodide (CuI) thin films are shown to be excellent substrates for selective recognition of free cyanide ions in aqueous matrices. The amount of cyanide ion retained by the copper (I) in the CuI thin films reflects its actual concentration in tested samples, and the subsequent Raman measurements of the substrate are shown to be capable of detecting toxic cyanide content at levels under international drinking water standard and environmental regulatory concentrations. Measurements obtained from the same batch of evaporated CuI thin films (approximately 100-nm thickness) show excellent linearity over a variety of cyanide concentrations ranging from 1.5 microM to 0.15 mM. This detection method offers the advantage of selectively detecting cyanides causing a health hazard while avoiding detection of other common interfering anions such as Cl-, Br-, PO4(3-), SO4(2-), NO2-, S2- and SCN-. Coupled with portable Raman systems that are commercially available, our detection approach will provide on-site monitoring capability with little sample preparation or instrument supervision, which will greatly expedite the assessment of potential environmental cyanide risks. PMID- 20541262 TI - Program theory evaluation: Logic analysis. AB - Program theory evaluation, which has grown in use over the past 10 years, assesses whether a program is designed in such a way that it can achieve its intended outcomes. This article describes a particular type of program theory evaluation-logic analysis-that allows us to test the plausibility of a program's theory using scientific knowledge. Logic analysis is useful for improving the intervention or finding alternatives for achieving intended outcomes; it influences the choice of type of evaluation to conduct and strengthens the validity of subsequent evaluations. The objective of this article is to present the methodological principles and the roots of this type of program theory evaluation. We illustrate two types of logic analysis with two actual evaluation cases. There are very few published examples of program theory evaluation. This article will provide evaluators with both theoretical and practical information to help them in conceptualizing their evaluations. PMID- 20541263 TI - Inverted internal limiting membrane flap technique for large macular holes. AB - PURPOSE: Large macular holes usually have an increased risk of surgical failure. Up to 44% of large macular holes remain open after 1 surgery. Another 19% to 39% of macular holes are flat-open after surgery. Flat-open macular holes are associated with limited visual acuity. This article presents a modification of the standard macular hole surgery to improve functional and anatomic outcomes in patients with large macular holes. DESIGN: A prospective, randomized clinical trial. PARTICIPANTS: Patients with macular holes larger than 400 MUm were included. In group 1, 51 eyes of 40 patients underwent standard 3-port pars plana vitrectomy with air. In group 2, 50 eyes of 46 patients underwent a modification of the standard technique, called the inverted internal limiting membrane (ILM) flap technique. METHODS: In the inverted ILM flap technique, instead of completely removing the ILM after trypan blue staining, a remnant attached to the margins of the macular hole was left in place. This ILM remnant was then inverted upside-down to cover the macular hole. Fluid-air exchange was then performed. Spectral optical coherence tomography and clinical examination were performed before surgery and postoperatively at 1 week and 1, 3, 6, and 12 months. MAIN OUTCOME MEASURES: Visual acuity and postoperative macular hole closure. RESULTS: Preoperative mean visual acuity was 0.12 in group 1 and 0.078 in group 2. Macular hole closure was observed in 88% of patients in group 1 and in 98% of patients in group 2. A flat-hole roof with bare retinal pigment epithelium (flat-open) was observed in 19% of patients in group 1 and 2% of patients in group 2. Mean (or median) postoperative visual acuity 12 months after surgery was 0.17 (range, 0.1 0.6) in group 1 and 0.28 (range, 0.02-0.8) in group 2 (P = 0.001). CONCLUSIONS: The inverted ILM flap technique prevents the postoperative flat-open appearance of a macular hole and improves both the functional and anatomic outcomes of vitrectomy for macular holes with a diameter greater than 400 MUm. Spectral optical coherence tomography after vitrectomy with the inverted ILM flap technique suggests improved foveal anatomy compared with the standard surgery. PMID- 20541264 TI - Magnetic resonance imaging of the medial rectus muscle of patients with consecutive exotropia after medial rectus muscle recession. AB - PURPOSE: To investigate the morphologic characteristics of the medial rectus muscle in patients with consecutive exotropia. DESIGN: Retrospective, nonrandomized, interventional study. PARTICIPANTS AND CONTROLS: Eleven eyes of 10 patients with consecutive exotropia were studied. Thirteen eyes of 13 age-matched normal subjects were studied as controls. METHODS: All of the patients underwent an advancement of a previously operated medial rectus muscle. Patients were divided into 3 groups based on the insertion of the medial rectus muscle: Normally recessed stretched scar, and slipped muscle. MAIN OUTCOME MEASURES: A comparison was made of the clinical findings, intraoperative findings, and distance from the limbus to the medial rectus muscle measured on magnetic resonance images among the groups. RESULTS: The medial rectus of 4 eyes of 3 patients had normally recessed insertions and 7 eyes had abnormal insertions (3 stretched scars, 4 slipped muscles). The clinical findings were not different among the 3 groups. The magnetic resonance images showed that the medial rectus muscle was located closest to the limbus in the control subjects and most distant in the patients with a slipped muscle (P<0.005). The clinical findings in the patients with a stretched scar and with normally recessed were indistinguishable. CONCLUSIONS: Magnetic resonance images of the medial rectus muscles of the control subjects and operated groups are significantly different morphologically. A slipped medial rectus muscle has characteristic magnetic resonance findings that are distinguishable from the muscle with normally recessed and stretched scar. PMID- 20541265 TI - The relationship between intraocular pressure reduction and rates of progressive visual field loss in eyes with optic disc hemorrhage. AB - PURPOSE: To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. DESIGN: Observational cohort study. PARTICIPANTS: The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. METHODS: Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). MAIN OUTCOME MEASURES: The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). RESULTS: During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages ( 0.88%/year vs. -0.38%/year, respectively, P<0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P<0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. CONCLUSIONS: There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 20541266 TI - Structure of duplex DNA containing the cisplatin 1,2-{Pt(NH3)2}2+-d(GpG) cross link at 1.77 A resolution. AB - We report the 1.77-A resolution X-ray crystal structure of a dodecamer DNA duplex with the sequence 5'-CCTCTGGTCTCC-3' that has been modified to contain a single engineered 1,2-cis-{Pt(NH(3))(2)}(2+)-d(GpG) cross-link, the major DNA adduct of cisplatin. These data represent a significant improvement in resolution over the previously published 2.6-A structure. The ammine ligands in this structure are clearly resolved, leading to improved visualization of the cross-link geometry with respect to both the platinum center and to the nucleobases, which adopt a higher energy conformation. Also better resolved are the deoxyribose sugar puckers, which allow us to re-examine the global structure of platinum-modified DNA. Another new feature of this model is the location of four octahedral [Mg(H(2)O)(6)](2+) ions associated with bases in the DNA major groove and the identification of 124 ordered water molecules that participate in hydrogen bonding interactions with either the nucleic acid or the diammineplatinum(II) moiety. PMID- 20541268 TI - Chemokines and chemokine receptors in the nervous system. Rome, 24/25 October, 2009, 2nd workshop. PMID- 20541267 TI - Ligand substitution reactions and cytotoxic properties of [Au(L)Cl2](+) and [AuCl2(DMSO)2]+ complexes (L=ethylenediamine and S-methyl-l-cysteine). AB - We have studied the kinetics of the complex formation of gold(III) complexes, [AuCl(2)(en)](+) (dichlorido(ethylenediamine)aurate(III)-ion) and [AuCl(2)(SMC)] (dichlorido (S-methyl-l-cysteine)aurate(III)) with four biologically N-donor nucleophiles. It was shown that studied ligands have a high affinity for gold(III) complex, which may have important biological implications, since the interactions of Au(III) with DNA is thought to be responsible for the anti-tumour activity. The [AuCl(2)(SMC)] complex is more reactive than [AuCl(2)(en)](+). L His reacts faster than the other N-donor nucleophiles in the reaction with [AuCl(2)(en)](+), but in the reaction with [AuCl(2)(SMC)] 5'-GMP is the best nucleophile. Gold(III) complexes are much more reactive than Pt(II) complexes with the same nucleophiles. The activation parameters for all studied reactions suggest an associative substitution mechanism. The cytotoxicity of gold(III) complexes, [AuCl(2)(en)](+), [AuCl(2)(SMC)] and [AuCl(2)(DMSO)(2)](+) was evaluated in vitro against chronic lymphocytic leukemia cells, obtained from blood of patients with chronic lymphocytic leukemia (CLL). The [AuCl(2)(en)](+) complex show comparable cytotoxicity profiles compared to cisplatin. PMID- 20541269 TI - Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair. AB - Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix proteins, which are important determinants of arterial stiffness. This study aimed to test the hypothesis that MMP-3 and MMP-9 polymorphisms may modulate aortic stiffness and magnitude of aortic root dilation in patients after surgical repair of tetralogy of Fallot (TOF). We analyzed the MMP-3 promoter and MMP-9 1562 C>T polymorphism in 79 TOF patients aged 19.9 +/- 9.5 years and determined their associations with aortic stiffness and sinotubular dimension. Genotypic and allelic frequencies of MMP-3 for the 6A6A genotype and MMP-9 for the T allele did not differ between patients and published control data (all p>0.05). For the MMP 3 locus, patients with a 6A6A genotype and those with a 6A6A/5A6A genotype had similar aortic stiffness (p=0.60), heart-femoral pulse wave velocity (p=0.63), and z score of sinotubular junction (p=0.81). For the MMP-9 locus, the -1562T allele carriers had significantly lower aortic stiffness (p=0.005), slower heart femoral pulse wave velocity (p=0.03), and smaller z score of sinotubular junction (p=0.047). Multivariate linear regression identified MMP-9 polymorphism (beta= 0.31, p=0.005) as a significant correlate of aortic stiffness after adjustments for age at study, age at operation, sex, body mass index, systolic and diastolic blood pressures, and MMP-3 polymorphism. In conclusion, MMP-9 but not MMP-3 polymorphism exerts a modulating influence on aortic stiffness and aortic root dilation in patients after TOF repair. PMID- 20541270 TI - Enhanced CO(2) fixation and biofuel production via microalgae: recent developments and future directions. AB - Unbalanced production of atmospheric CO(2) constitutes a major challenge to global sustainability. Technologies have thus been developed for enhanced biological carbon fixation (also referred to as CO(2) mitigation), and one of the most promising capitalizes on microalgae. However, the "best bioreactor", which would be able to achieve maximum productivity and maximum energy efficiency under a given set of operational costs, does not exist. This review briefly examines the current technologies available for enhanced microalgal CO(2) fixation, and specifically explores the possibility of coupling wastewater treatment with microalgal growth for eventual production of biofuels and/or added-value products, with an emphasis on productivity. In addition, an overview of reactor configurations for CO(2) fixation and bottlenecks associated with the underlying technology are provided. Finally, a review of life cycle analysis studies is presented, and routes for improvement of existing processes are suggested. PMID- 20541271 TI - Past, present and future applications of flow cytometry in aquatic microbiology. AB - Flow cytometry (FCM) is rapidly becoming an essential tool in the field of aquatic microbiology. It provides opportunities for microbial analysis at both the community and single-cell levels. Compared with other techniques, FCM facilitates rapid data acquisition and multi-parameter analysis, leading to increased popularity and widespread applications. Here, we briefly review the current status of FCM in the field of microbiology, focusing on its recent applications in aquatic microbiology. These developments range from straightforward total cell counts to community structure analysis, and further extend to physiological analysis at a single-cell level. Exciting future prospects for the applications of FCM in aquatic microbiology are also discussed based on current scientific and practical needs. PMID- 20541272 TI - The Groningen Radiotherapy-Induced Xerostomia questionnaire: development and validation of a new questionnaire. AB - PURPOSE: The purpose of this study was to develop and validate a questionnaire (Groningen Radiotherapy-Induced Xerostomia (GRIX) questionnaire) that has the ability to distinguish between patient-rated xerostomia during day and night and can be used to evaluate the impact of emerging radiation delivery techniques aiming at prevention of xerostomia in more detail. MATERIALS AND METHODS: All questions in the GRIX were generated from an exhaustive list of relevant questions according to xerostomia as reported in the literature and reported by patients and health care providers. Finally the GRIX was reduced from 56 questions to a 14-item questionnaire, with four subscales; xerostomia during day and night and sticky saliva during day and night. 315 patients filled out 2936 questionnaires and the GRIX was evaluated by calculating Crohnbach's alpha for all subscales. Criterion validity was evaluated to compare the GRIX with patient rated xerostomia scored with the EORTC QLQ-HN35 and physician-rated xerostomia, test-retest analysis and responsiveness were also tested. RESULTS: Crohnbach's alpha varied for all subscales between 0.88 and 0.94. The GRIX scored well for criterion-related validity on all subscales with high correlations with the EORTC QLQ-HN35 xerostomia and sticky saliva scale as well with physician-rated toxicity scoring. No significant differences were found between test and retest score and the GRIX showed good responsiveness with different time points for all subscales. CONCLUSION: The GRIX is a validated questionnaire which can be used in future research focusing on patient-rated xerostomia and sticky saliva during day and night in relation with the impact of emerging radiation delivery techniques aiming at reduction of xerostomia. PMID- 20541273 TI - A systematic review on the role of FDG-PET/CT in tumour delineation and radiotherapy planning in patients with esophageal cancer. AB - PURPOSE: FDG-PET/CT has proven to be useful in the staging process of esophageal tumours. This review analysed the role of FDG-PET/CT in tumour delineation and radiotherapy planning in comparison with CT alone among patients with esophageal cancer. Thereby we focused on the detection of the primary tumour and lymph nodes by FDG-PET/CT, changes in target volume (TV) delineation based on FDG-PET/CT and its validity, changes in inter- and intra-observer variability in TV delineation, consequences for radiotherapy treatment planning with regard to either target volumes or organs at risk and finally on the validation of FDG-PET/CT-based TVs in terms of treatment outcome. METHODS: A literature search was performed in MEDLINE and Cochrane library databases for studies concerning the current value of FDG-PET/CT in tumour detection and delineation and radiotherapy-planning procedures among patients with esophageal cancer. Both prospective and retrospective studies were included. RESULTS: Fifty publications met the eligibility criteria, of which 19 were review papers and one was a case report. The remaining 30 publications reported on the results of original studies. FDG PET was able to identify most primary tumours, with a sensitivity and specificity for the detection of metastatic lymph nodes of 30-93% and 79-100%. The use of FDG PET/CT resulted in changes of target volumes, and consequently in changes in treatment planning. However, evidence supporting the validity of the use of FDG PET/CT in the tumour delineation process is very limited. Only three studies reported a significant positive correlation between FDG-PET-based tumour lengths and pathological findings. There were two studies that tested the influence of FDG-PET/CT to the inter- and intra-observer variability. One of them found a significant decrease in inter- and intra-observer variability, while the others did not. Furthermore, there are no studies demonstrating the use of PET/CT in terms of improved locoregional control or survival. CONCLUSION: Since the literature is very limited standard implementation of FDG-PET/CT into the tumour delineation process for radiation treatment seems unjustified and needs further clinical validation first. PMID- 20541274 TI - Influence of smoking status on treatment outcomes after post-operative radiation therapy for non-small-cell lung cancer. AB - BACKGROUND AND PURPOSE: The role of post-operative radiotherapy in patients with resected non-small-cell lung cancer (NSCLC) is unclear. Modifiable factors, like smoking, may help guide therapy. We retrospectively evaluated the impact of smoking on control in patients undergoing post-operative radiation therapy (PORT) for NSCLC. MATERIALS AND METHODS: Between 1995 and 2007, 152 patients who underwent surgery for NSCLC were analyzed (median follow-up 26 months). Non smokers were defined as patients who never smoked or who had stopped smoking at the time of initial consultation. Sixty seven percent were non-smokers; 5% never smoked, 40% of the non-smokers had ceased smoking for a year or less, while 55% had stopped for more than a year. RESULTS: On univariate analysis, smokers had worse 5-year local control than non-smokers (70% versus 90%, p=0.001) and locoregional control (52% versus 77%, p=0.002). The 5-year survival rate was 21% for smokers and 31% for non-smokers (p=0.2). On multivariate analysis, smokers maintained a detrimental effect on locoregional control (HR 3.6, p=0.0006). CONCLUSIONS: Smokers at initial consultation have poorer local and locoregional control after PORT than non-smokers. In patients being considered for PORT for NSCLC, quitting smoking before treatment confers additional treatment advantage. PMID- 20541275 TI - How changing the focus of attention affects performance, kinematics, and electromyography in dart throwing. AB - Research has found an advantage for an external focus of attention in motor control and learning; instructing subjects to focus on the effects of their actions, rather than on body movements, can improve performance during training and retention testing. Previous research has mostly concentrated on movement outcomes, not on the quality of the movement itself. Thus, this study combined surface electromyography (EMG) with motion analysis and outcome measures in a dart throwing task, making this the first study that includes a comprehensive analysis of changes in motor performance as a function of attentional focus. An external focus of attention led to better performance (less absolute error), decreased preparation time between throws, and reduced EMG activity in the triceps brachii. There was also some evidence of increased variability for kinematic measures of the shoulder joint under an external focus relative to an internal focus. These results suggest improved movement economy with an external focus of attention. PMID- 20541276 TI - Proteinase-producing halophilic lactic acid bacteria isolated from fish sauce fermentation and their ability to produce volatile compounds. AB - Halophilic lactic acid bacteria were isolated from fish sauce mashes fermented at 1 to 12 months. Seven out of sixty-four isolates were selected according to their proteolytic activity and growth at 25% NaCl for characterization and investigation of volatile compound production. All selected isolates were Gram positive cocci with pairs/tetrads and grew at 0-25% NaCl, pH 4.5-9.0. Results of 16S rRNA gene sequence analysis showed 99% homology to Tetragenococcus halophilus ATCC 33315. The restriction fragment length polymorphism (RFLP) patterns of all isolates were also similar to those of T. halophilus ATCC 33315. These isolates were, thus, identified as T. halophilus. All isolates hydrolyzed fish protein in the medium containing 25% NaCl. Intracellular aminopeptidase of 7 isolates exhibited the highest activity of 2.85-3.67 U/ml toward Ala-p-nitroanilide (Ala pNA). T.halophilus strains MS33 and M11 showed the highest alanyl aminopeptidase activity (P<0.05), and produced histamine in mGYP broth containing 5 and 25% NaCl in the level of 6.62-22.55 and 13.14-20.39 mg/100ml, respectively. Predominant volatile compounds of fish broth containing 25% NaCl inoculated with T. halophilus MS33 and MRC5-5-2 were 1-propanol, 2-methylpropanal, and benzaldehyde, corresponding to major volatile compounds in fish sauce. T.halophilus appeared to play an important role in volatile compound formation during fish sauce fermentation. PMID- 20541277 TI - Factors related to insulin resistance in type 1 diabetic patients treated with intensive insulin therapy from the onset of the disease. PMID- 20541278 TI - A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy. AB - We describe the case of a 66-year-old man with chronic hepatitis C who developed type 1 diabetes mellitus (T1DM) and thyroid autoimmunity during Interferon alpha (INFalpha) therapy and then stiff-person syndrome (SPS). This is the first reported case in which SPS has appeared as complication of IFNalpha therapy. PMID- 20541279 TI - A policy to promote influenza vaccination: a behavioral economic approach. AB - The aims of this study were to identify the predictors of people's willingness to be vaccinated against influenza and to determine how to improve the inoculation rate. The study was based upon the results of our original large-scale survey conducted in the USA in 2005. A model of bounded rationality can explain vaccination behavior fairly well: (a) people evaluate the costs and benefits of vaccination by applying risk aversion and time preference; (b) the 'status quo bias' of those who were vaccinated in the past affects their decision to be vaccinated in the future; and (c) overconfidence indirectly affects the decision through the moderation of perceived variables. Policy implications include: (a) dissemination of information about the vaccine is especially important among people who are inexperienced with the vaccine since they undervalue the effectiveness of vaccination; (b) lowering the total cost of vaccination, including time costs (for example, by offering the vaccine at workplaces) may raise the inoculation rate, especially among those inexperienced with the vaccine, since those who have experience with the vaccine tend to take it on a regular basis. PMID- 20541280 TI - Monte Carlo randomization tests for large-scale abundance datasets on the GPU. AB - Statistical tests are often performed to discover which experimental variables are reacting to specific treatments. Time-series statistical models usually require the researcher to make assumptions with respect to the distribution of measured responses which may not hold. Randomization tests can be applied to data in order to generate null distributions non-parametrically. However, large numbers of randomizations are required for the precise p-values needed to control false discovery rates. When testing tens of thousands of variables (genes, chemical compounds, or otherwise), significant q-value cutoffs can be extremely small (on the order of 10(-5) to 10(-8)). This requires high-precision p-values, which in turn require large numbers of randomizations. The NVIDIA((r)) Compute Unified Device Architecture((r)) (CUDA((r))) platform for General Programming on the Graphics Processing Unit (GPGPU) was used to implement an application which performs high-precision randomization tests via Monte Carlo sampling for quickly screening custom test statistics for experiments with large numbers of variables, such as microarrays, Next-Generation sequencing read counts, chromatographical signals, or other abundance measurements. The software has been shown to achieve up to more than 12 fold speedup on a Graphics Processing Unit (GPU) when compared to a powerful Central Processing Unit (CPU). The main limitation is concurrent random access of shared memory on the GPU. The software is available from the authors. PMID- 20541281 TI - The platinum-based treatments for advanced non-small cell lung cancer, is low/negative ERCC1 expression better than high/positive ERCC1 expression? A meta analysis. AB - BACKGROUND: The predictive value of ERCC1 for prognosis and sensitivity to platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis was performed to provide an assessment of whether expression variations of ERCC1 are associated with objective response and median survival in patients with advanced NSCLC treated with platinum-based chemotherapy. METHODS: We searched MEDLINE, EMBASE and CNKI for all eligible studies and conducted a meta-analysis of 12 studies (n=836 patients) that evaluated the correlation between ERCC1 levels (detected by immunohistochemistry or real-time reverse transcriptase PCR) and objective response or median survival in patients receiving platinum-based chemotherapy for advanced NSCLC. Pooled odds ratios (OR) for the objective response were calculated using the Mantel-Haenszel method. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios from each individual study. RESULTS: Among 836 tumors, ERCC1 expression was high/positive in 416 (49.8%) and low/negative in 420 (50.2%). Response to platinum-based chemotherapy was significantly higher in patients with ERCC1 low/negative expression (OR=0.48; 95% CI, 0.35-0.64; P<0.00001). Median survival time was significantly prolonged when ERCC1 low/negative expression was compared with ERCC1 high/positive expression (MR: 0.77; 95% CI, 0.47-1.07; P<0.00001). CONCLUSIONS: Low/negative expression of ERCC1 was associated with higher objective response and median survival in advanced NSCLC patients treated with platinum-based chemotherapy. ERCC1 may be a suitable marker of prognosis and sensitivity to platinum-based chemotherapy in patients with advanced NSCLC. PMID- 20541282 TI - Relationship between cannabinoids and the immune system. Special Issue 8, 2010 Introduction. PMID- 20541283 TI - Cutaneous CD4+ CD56+ hematologic malignancies. AB - BACKGROUND: Hematologic malignancies expressing CD4 and CD56 are most commonly associated with the recently described CD4(+) CD56(+) hematodermic neoplasm. METHODS: Thirteen cases of CD4(+) CD56(+) hematologic malignancies were prospectively encountered in the routine and referral practices of the authors. RESULTS: Patients 1 and 2 were elderly men exhibiting an acute onset of skin, bone-marrow, and peripheral blood involvement, both dying of their disease within less than 12 months. CD3(+) phenotype and a clonal T-cell receptor beta rearrangement indicated categorization as a CD4(+) natural killer T-cell lymphoma. Patient 3 developed a CD56(+) anaplastic large cell lymphoma and is without disease after excision and radiation. Indolent CD4(+) CD56(+) poikilodermatous mycosis fungoides defined case 4. There were 7 patients with CD123(+) CD4(+) CD56(+) hematodermic neoplasm, 4 dying within 18 months of presentation with peripheral blood/marrow involvement in 6 of the 7 cases. Two patients with granulocytic sarcoma dying within 100 days of presentation defined the last two cases. LIMITATIONS: There were relatively small numbers in each of the categories and the follow-up was limited in those cases where death was not reported. CONCLUSION: Cutaneous malignancies composed of CD4(+) CD56(+) hematopoietic cells define a varied group and oftentimes have an aggressive clinical course although not in every case. PMID- 20541284 TI - The effect of triage diagnostic standing orders on emergency department treatment time. AB - STUDY OBJECTIVE: Triage standing orders are used in emergency departments (EDs) to initiate evaluation when there is no bed available. This study evaluates the effect of diagnostic triage standing orders on ED treatment time of adult patients who presented with a chief complaint for which triage standing orders had been developed. METHODS: We conducted a retrospective nested cohort study of patients treated in one academic ED between January 2007 and August 2009. In this ED, triage nurses can initiate full or partial triage standing orders for patients with chest pain, shortness of breath, abdominal pain, or genitourinary complaints. We matched patients who received triage standing orders to those who received room orders with respect to clinical and temporal factors, using a propensity score. We compared the median treatment time of patients with triage standing orders (partial or full) to those with room orders, using multivariate linear regression. RESULTS: Of the 15,188 eligible patients, 25% received full triage standing orders, 56% partial triage standing orders, and 19% room orders. The unadjusted median ED treatment time for patients who did not receive triage standing orders was 282 minutes versus 230 minutes for those who received a partial triage standing order or full triage standing orders (18% decrease). Controlling for other factors, triage standing orders were associated with a 16% reduction (95% confidence interval -18% to -13%) in the median treatment time, regardless of chief complaint. CONCLUSION: Diagnostic testing at triage was associated with a substantial reduction in ED treatment time for 4 common chief complaints. This intervention warrants further evaluation in other EDs and with different clinical conditions and tests. PMID- 20541285 TI - What's next? PMID- 20541286 TI - Boosting power for clinical trials using classifiers based on multiple biomarkers. AB - Machine learning methods pool diverse information to perform computer-assisted diagnosis and predict future clinical decline. We introduce a machine learning method to boost power in clinical trials. We created a Support Vector Machine algorithm that combines brain imaging and other biomarkers to classify 737 Alzheimer's disease Neuroimaging initiative (ADNI) subjects as having Alzheimer's disease (AD), mild cognitive impairment (MCI), or normal controls. We trained our classifiers based on example data including: MRI measures of hippocampal, ventricular, and temporal lobe volumes, a PET-FDG numerical summary, CSF biomarkers (t-tau, p-tau, and Abeta(42)), ApoE genotype, age, sex, and body mass index. MRI measures contributed most to Alzheimer's disease (AD) classification; PET-FDG and CSF biomarkers, particularly Abeta(42), contributed more to MCI classification. Using all biomarkers jointly, we used our classifier to select the one-third of the subjects most likely to decline. In this subsample, fewer than 40 AD and MCI subjects would be needed to detect a 25% slowing in temporal lobe atrophy rates with 80% power--a substantial boosting of power relative to standard imaging measures. PMID- 20541287 TI - Enrichment through biomarkers in clinical trials of Alzheimer's drugs in patients with mild cognitive impairment. AB - Clinical trials of disease modifying drugs for Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) might benefit from enrichment with true AD cases. Four hundred five MCI patients (143 converters and 262 nonconverters to AD within 2 years) of the Alzheimer's disease Neuroimaging Initiative (ADNI) were used. Markers for enrichment were hippocampal atrophy on magnetic resonance (MRI), temporoparietal hypometabolism on FDG PET, cerebrospinal fluid (CSF) biomarkers (Abeta42, tau, and phospho-tau), and cortical amyloid deposition (11C-PIB positron emission tomography (PET)). Two separate enrichment strategies were tested to A) maximize the proportion of MCI converters screened in, and B) minimize the proportion of MCI converters screened out. Based on strategy A, when compared with no enrichment and ADAS-Cog as an outcome measure (sample size of 834), enrichment with 18F-FDG PET and hippocampal volume lowered samples size to 260 and 277 cases per arm, but at the cost of screening out 1,597 and 434 cases per arm. When compared with no enrichment and clinical dementia rating (CDR-SOB) as an outcome measure (sample size of 674), enrichment with hippocampal volume and Abeta42 lowered sample sizes to 191 and 291 cases per arm, with 639 and 157 screened out cases. Strategy B reduced the number of screened out cases (740 for [11C]-PIB PET, 101 hippocampal volume, 82 ADAS-COG and 330 for [18F]-FDG PET) but at the expense of decreased power and a relative increase size (740 for [11C]-PIB PET, 676 for hippocampal volume, 744 for ADAS-Cog, and 517 for [18F]-FDG PET). Enrichment comes at the price of an often relevant proportion of screened out cases, and in clinical trial settings, the balance between enrichment of screened in and loss of screened out patients should be critically discussed. PMID- 20541288 TI - [Reducing psychological discomfort and overload in Alzheimer's family caregivers through a mindfulness meditation program]. AB - INTRODUCTION: This study analyzes the effects that a mindfulness development meditation program has on psychological discomfort and overload in main family caregivers of Alzheimer dementia patients. MATERIAL AND METHODS: A quasi experimental (group comparison) design with pretest/post-test/follow-up measurements was employed in an experimental and a control group. The evaluation instruments used were the SCL-90-R Questionnaire and the Caregiver Overload Scale. RESULTS: The statistical analyses done show a significant reduction in the three general indices and in the various dimensions of psychological discomfort, as well as in the caregiver overload variable in the experimental group compared to the control group at the end of the intervention. However, the improvements found in the experimental group were lower in the follow-up evaluation done four months after intervention, with significantly higher scores than in post-test in all the dimensions. CONCLUSIONS: These results are in agreement with other studies in which it was found that intervention for Alzheimer caregivers is effective in the short term, but the effect becomes diluted over time, so measurements and policies for these caregivers have to enable the beneficial effects of intervention reducing psychological discomfort and overload to be maintained. PMID- 20541289 TI - [Clopidogrel. Are our patients taking it adequately?]. PMID- 20541290 TI - [Onset of neurological symptoms during tuberculosis treatment: description of two cases]. PMID- 20541291 TI - [Skin lesions in a 33 year-old male]. PMID- 20541292 TI - Synthesis and characterization of polyester conjugates of ciprofloxacin. AB - Two-, three-, four and six-arm, star-shaped poly(epsilon-caprolactone) and polylactide homopolymers were synthesized via ring-opening polymerization of cyclic esters in the presence of glycerol, penthaerythritol, dipentaerythritol and poly(ethylene glycol) as initiators and stannous octoate as a catalyst. Thus obtained oligomers were successfully used in the synthesis of novel polyester conjugates of ciprofloxacin. The structures of the polymers and conjugates were determined by means of GPC, MALDI-TOF MS, NMR and IR studies. The in vitro release of ciprofloxacin from obtained conjugates was investigated. PMID- 20541293 TI - Cytotoxicity against cholangiocarcinoma cell lines of zerumbone derivatives. AB - Cholangiocarcinoma (CCA) is an aggressive malignancy with a very high morbidity and mortality for which an effective treatment is lacking. In this study, seventeen zerumbone derivatives were synthesized and evaluated for in vitro cytotoxicity against cholangiocarcinoma cell lines. 5 showed the most potent antiproliferative activity against KKU-100 cell line with an IC(50) value of 16.44 microM. To investigate the potential molecular target of the most active compound, the docking was performed using different enzymes and receptor proteins including CDK-2, CDK-5, EGFR, and GSK-3. The docking results revealed that 5 exhibited better binding interaction to EGFR than CDK-2, CDK-5 and GSK-3. All results indicate that 5 should be a promising candidate for treatment of cancer. PMID- 20541294 TI - Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles. AB - In this work we reported the synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities in vitro of three new compound series obtained from ethyl(5-methyl-1-H-imidazole-4-carboxylate): acylthiosemicarbazide analogues 3a d, 4-thiazolidinone analogues 4a-d and 1,3,4-thiadiazole analogues 5a-d. All synthesized compounds were characterized by IR, (1)H, (13)C NMR and HRMS. The majority of the tested compounds show excellent anti-T. gondii activity when compared to hydroxyurea and sulfadiazine. In addition it was also shown that most of the compounds in this study have a better performance against intracellular tachyzoites. The results for antimicrobial activity evaluation showed weak antibacterial and antifungal activities for all the tested molecules, when compared with the standard drugs (chloramphenicol and rifampicin for antibacterial activity; nistatin and ketoconazole for antifungal activity). PMID- 20541295 TI - [Recurrent aseptic meningitis secondary to nonsteroidal anti-inflammatory drugs in a patient with lupus]. AB - We report a 39-year-old woman with systemic lupus who presented with recurrent aseptic meningitis secondary to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). She presented two episodes following ibuprofen administration that were characterized by aseptic meningitis with high protein level in cerebrospinal fluid, and increased serum acute phase reactants. No evidence of an infection or vasculitis was documented. Clinical manifestation resolved rapidly with ibuprofen discontinuation, and corticosteroids therapy was unnecessary. Aseptic meningitis related to NSAIDs reported in lupus patients should be considered because of their specific modality of care and their favourable outcome. PMID- 20541296 TI - Developing a service user designed tool for the assessment of student mental health nurses in practice: a collaborative process. AB - In this article we describe and critically analyse the process of developing an assessment tool designed by users of mental health services to assess student nurses in practice. The developmental process raised a number of complex and unexpected issues. The findings suggest that rather than "assess" student nurses in practice, service users should have a role in reviewing student's practice. Whilst there was a consensus amongst stake-holders that engaging in this feedback process is beneficial to both the student and service user, it is the manner in which it is sought which requires further investigation. PMID- 20541297 TI - Muscle activity and acceleration during whole body vibration: effect of frequency and amplitude. AB - BACKGROUND: Whole body vibration may improve muscle and bone strength, power and balance although contradictory findings have been reported. Prolonged exposure may result in adverse effects. We investigated the effects of high (5.5 mm) and low (2.5mm) amplitude whole body vibration at various frequencies (5-30 Hz) on muscle activity and acceleration throughout the body. METHODS: Surface electromyographic activity was recorded from 6 leg muscles in 12 healthy adults (aged 31.3 (SD 12.4) years). The average rectified acceleration of the toe, ankle, knee, hip and head was recorded from 15 healthy adults (36 (SD 12.1) years) using 3D motion analysis. FINDINGS: Whole body vibration increased muscle activity 5-50% of maximal voluntary contraction with the greatest increase in the lower leg. Activity was greater with high amplitude at all frequencies, however this was not always significant (P<0.05-0.001). Activation tended to increase linearly with frequency in all muscles except gluteus maximus and biceps femoris. Accelerations throughout the body ranged from approximately 0.2 to 9 g and decreased with distance from the platform. Acceleration at the head was always < 0.33 g. The greatest acceleration of the knee and hip occurred at approximately 15 Hz and thereafter decreased with increasing frequency. INTERPRETATION: Above the knee at frequencies > 15 Hz acceleration decreased with distance from the platform. This was associated with increased muscle activity, presumably due to postural control and muscle tuning mechanisms. The minimal acceleration at the head reduces the likelihood of adverse reactions. The levels of activation are unlikely to cause hypertrophy in young healthy individuals but may be sufficient in weak and frail people. PMID- 20541298 TI - Acute and chronic toxicity of Roundup Weathermax and Ignite 280 SL to larval Spea multiplicata and S. bombifrons from the Southern High Plains, USA. AB - Pesticides have been implicated in widespread amphibian declines. We assessed acute and chronic toxicity of two widely used herbicides to larval New Mexico (Spea multiplicata) and Plains (S. bombifrons) spadefoots from cropland and native grassland playas. Roundup WeatherMAX (WM) toxicity estimates (48- and 216 h LC(50); 48-h LC(1)) for both species were similar to environmental concentrations expected from accidental overspray. Chronic (30-day) exposure to WM at predicted environmental concentrations (2.0 and 2.8 mg glyphosate acid equivalents/L) reduced survival of both species. Ignite 280 SL (IG) toxicity estimates (48-h LC(50) and LC(1)) for both species were above predicted environmental concentrations of 1.0 mg glufosinate/L. Chronic exposure to predicted environmental concentrations of IG did not reduce survival of either species. Toxicity test results suggest that at predicted environmental concentrations IG would not cause extensive mortalities among larval New Mexico and Plains spadefoots. However, WM may cause extensive mortality among larvae of these species. PMID- 20541299 TI - Severe renovascular hypertension in a patient with Takayasu arteritis. PMID- 20541300 TI - Use of a prostate symptom score to identify men at risk of future kidney failure: insights from the HUNT II Study. AB - BACKGROUND: Chronic kidney disease (CKD) screening beyond patients with diabetes mellitus or hypertension increasingly is discussed. Some guidelines recommend kidney function testing of patients with benign prostatic hyperplasia; however, the significance of extending this to general population screening is unclear. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 30,466 men from the HUNT II (Second Health Study in Nord-Trondelag; 1995-1997) representing 66.8% of the entire adult male population in Nord-Trondelag County, Norway. PREDICTOR: The International Prostate Symptom Score was used to detect the presence and severity of lower urinary tract symptoms (LUTS), a surrogate measure of benign prostate hyperplasia suitable for use in general practice. OUTCOMES: Kidney failure was defined as starting renal replacement therapy or CKD death with a documented stable estimated glomerular filtration rate<15 mL/min/1.73 m2. RESULTS: During 10.5 years of follow-up, 78 men developed kidney failure. Kidney failure risks were 2.60 (95% CI, 1.47-4.58) and 4.08 (95% CI, 1.74-9.53) times higher for men with moderate and severe LUTS compared with men with no/mild LUTS, respectively. However, age-stratified analysis showed that the incidence rate ratio for moderate/severe LUTS versus no/mild LUTS was 1.27 (95% CI, 0.76-2.13), and multivariable Cox analysis showed no significant association between LUTS and risk of kidney failure. Screening effectiveness was improved only slightly by including men with moderate/severe LUTS in addition to patients with diabetes, hypertension, or cardiovascular disease. Better effectiveness was achieved by simply including all men older than 60 years. LIMITATIONS: The ability of the International Prostate Symptom Score to predict the presence and severity of obstruction is only moderate. Ascertainment of severe CKD (estimated glomerular filtration rate, 30-15 mL/min/1.73 m2) was not possible. CONCLUSION: LUTS were not significantly associated with future kidney failure after adjusting for age and therefore in isolation are not a basis for kidney failure screening. PMID- 20541301 TI - Effect of N-acetylcysteine on serum creatinine and kidney function: results of a randomized controlled trial. AB - BACKGROUND: Evidence for a protective effect of N-acetylcysteine (NAC) on acute and chronic kidney disease is equivocal, and controversy persists about whether NAC affects creatinine level independently of actual kidney function. Study objectives are to investigate whether NAC affects serum creatinine level independently of alterations in other measures of kidney function. STUDY DESIGN: Double-blind randomized controlled trial. SETTING & PARTICIPANTS: Patients with stage 3 chronic kidney disease (n = 60), Canada, 2007-2008. INTERVENTION: Participants were randomly allocated to receive 4 doses of oral NAC (each 1,200 mg) or placebo, administered at 12-hour intervals. OUTCOME: The primary outcome was change in serum creatinine level between baseline and 4 hours after the last treatment dose. In addition, changes in other parameters of kidney function were measured between baseline and 4, 24, or 48 hours after the last treatment dose. MEASUREMENTS: Serum creatinine, cystatin C, 24-hour urine protein and creatinine excretion, and creatinine clearance. RESULTS: 60 patients, mean age of 70 years, 75% men, 50% had diabetes, with mean creatinine clearance of 43.7 +/- 18.8 (SD) mL/min were enrolled. Between baseline and 4 hours posttreatment, serum creatinine level decreased by 0.044 +/- 0.15 mg/dL in the NAC group and 0.040 +/- 0.18 mg/dL in the placebo group (95% CI for difference, -0.09 to 0.08; P = 0.9). No significant differences between groups were observed for change in serum creatinine, cystatin C, urine protein, urine creatinine, or creatinine clearance values at any time. LIMITATIONS: Blinding patients to orally administered liquid NAC is difficult and it is possible that patients receiving NAC were not sufficiently blinded. Effects of NAC beyond 48 hours of treatment were not evaluated. CONCLUSIONS: In this randomized controlled trial, NAC had no short term effect on creatinine level and did not decrease urine protein excretion within 48 hours of treatment. PMID- 20541302 TI - Lower retinol levels as an independent predictor of mortality in long-term hemodialysis patients: a prospective observational cohort study. AB - BACKGROUND: Malnutrition, inflammation, and oxidative stress are inter-related mechanisms linked to the progression of cardiovascular disease and prognosis of long-term hemodialysis (HD) patients. In this study, we focus on antioxidant vitamins and trace elements and the relationship of their serum levels to the prognosis of long-term HD patients. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 261 long-term HD patients prospectively followed up for 5 years (2003-2008). The control group consisted of 66 healthy participants. PREDICTORS: Retinol, alpha-tocopherol, retinol-binding protein 4 (RBP-4), and the trace elements zinc and selenium. OUTCOMES: Mortality and cardiovascular mortality. During follow-up, 146 patients (56%) died, and for 71 of these, death was due to cardiovascular causes. MEASUREMENTS: Retinol, alpha tocopherol, RBP-4, zinc, selenium, and basic nutritional and inflammatory parameters measured at the beginning of the study. RESULTS: Retinol and RBP-4 levels were significantly increased, whereas retinol:RBP-4 ratio and alpha tocopherol, selenium, and zinc levels were decreased in HD patients compared with controls (retinol, 168.1 +/ 64.4 microg/dL in HD patients vs 99.1 +/-23.3 [corrected] microg/dL in controls; P<0.001). Lower retinol level was found to be a significant independent predictor of overall and cardiovascular mortality in multivariate Cox analysis (HR, 0.733 [95% CI, 0.599-0.896], P=0.002, and 0.694 [95% CI, 0.511-0.942], P=0.02, per 1 SD, respectively). The worst prognoses for patients with lower retinol levels were observed when these were combined with low albumin levels. LIMITATIONS: Sample size, investigation of prevalent, not incident, dialysis patients. CONCLUSIONS: This is the first study showing a lower retinol level as an independent predictor of overall and cardiovascular mortality in HD patients. It has to be elucidated whether the beneficial effects of higher serum retinol levels should be attributed to only better nutritional support or also to retinol's role in immune response and differentiation. PMID- 20541304 TI - Rural male suicide in Australia. AB - The rate of suicide amongst Australia's rural men is significantly higher than rural women, urban men or urban women. There are many explanations for this phenomenon including higher levels of social isolation, lower socio-economic circumstances and ready access to firearms. Another factor is the challenge of climate transformation for farmers. In recent times rural areas of Australia have been subject to intense climate change events including a significant drought that has lingered on for over a decade. Climate variability together with lower socio-economic conditions and reduced farm production has combined to produce insidious impacts on the health of rural men. This paper draws on research conducted over several years with rural men working on farms to argue that attention to the health and well-being of rural men requires an understanding not only of these factors but also of the cultural context, inequitable gender relations and a dominant form of masculine hegemony that lauds stoicism in the face of adversity. A failure to address these factors will limit the success of health and welfare programs for rural men. PMID- 20541303 TI - Is neighborhood racial/ethnic composition associated with depressive symptoms? The multi-ethnic study of atherosclerosis. AB - The racial/ethnic composition of a neighborhood may be related to residents' depressive symptoms through differential levels of neighborhood social support and/or stressors. We used the Multi-Ethnic Study of Atherosclerosis to investigate cross-sectional associations of neighborhood racial/ethnic composition with the Center for Epidemiologic Studies-Depression (CES-D) scale in adults aged 45-84. The key exposure was a census-derived measure of the percentage of residents of the same racial/ethnic background in each participant's census tract. Two-level multilevel models were used to estimate associations of neighborhood racial/ethnic composition with CES-D scores after controlling for age, income, marital status, education and nativity. We found that living in a neighborhood with a higher percentage of residents of the same race/ethnicity was associated with increased CES-D scores in African American men (p < 0.05), and decreased CES-D scores in Hispanic men and women and Chinese women, although these differences were not statistically significant. Models were further adjusted for neighborhood-level covariates (social cohesion, safety, problems, aesthetic quality and socioeconomic factors) derived from survey responses and census data. Adjusting for other neighborhood characteristics strengthened protective associations amongst Hispanics, but did not change the significant associations in African American men. These results demonstrate heterogeneity in the associations of race/ethnic composition with mental health and the need for further exploration of which aspects of neighborhood environments may contribute to these associations. PMID- 20541305 TI - "These are not good things for other people to know": how rural Tanzanian women's experiences of pregnancy loss and early neonatal death may impact survey data quality. AB - Little research in low-income countries has compared the social and cultural ramifications of loss in childbearing, yet the social experience of pregnancy loss and early neonatal death may affect demographers' ability to measure their incidence. Ninety-five qualitative reproductive narratives were collected from 50 women in rural southern Tanzania who had recently suffered infertility, miscarriage, stillbirth or early neonatal death. An additional 31 interviews with new mothers and female elders were used to assess childbearing norms and social consequences of loss in childbearing. We found that like pregnancy, stillbirth and early neonatal death are hidden because they heighten women's vulnerability to social and physical harm, and women's discourse and behaviors are under strong social control. To protect themselves from sorcery, spiritual interference, and gossip--as well as stigma should a spontaneous loss be viewed as an induced abortion--women conceal pregnancies and are advised not to mourn or grieve for "immature" (late-term) losses. Twelve of 30 respondents with pregnancy losses had been accused of inducing an abortion; 3 of these had been subsequently divorced. Incommensurability between Western biomedical and local categories of reproductive loss also complicates measurement of losses. Similar gender inequalities and understandings of pregnancy and reproductive loss in other low resource settings likely result in underreporting of these losses elsewhere. Cultural, terminological, and methodological factors that contribute to inaccurate measurement of stillbirth and early neonatal death must be considered in designing surveys and other research methods to measure pregnancy, stillbirth, and other sensitive reproductive events. PMID- 20541307 TI - Beyond body counts: a qualitative study of lives and loss in Burkina Faso after 'near-miss' obstetric complications. AB - Averting women's pregnancy-related death is today recognised as an international health and development priority. Maternal survival is, in this sense, a success story. There is, however, little research into what happens to the women who survive the severe obstetric complications that are the main causes of maternal mortality. This paper examines findings from repeated in-depth interviews with 64 women who survived a clinically defined 'near-miss.' These interviews were conducted as part of a prospective longitudinal study of women who 'nearly died' of pregnancy-related complications in Burkina Faso, a poor country in West Africa. Drawing on sociological and anthropological perspectives that consider the defining characteristics of 'loss' to be social as much as biomedical, the paper seeks to understand loss as disruption of familiar forms and patterns of life. Women's accounts of their lives in the year following the near-miss event show that such events are not only about blood loss, seizures or infections, but also about a household crisis for which all available resources were mobilised, with a train of physical, economic and social consequences. The paper argues that near-miss events are characterised by the near-loss of a woman's life, but also frequently by the loss of the baby and by further significant disruptions in three overlapping dimensions of women's lives. These include disruption of bodily integrity through injury, ongoing illness and loss of strength and stamina; disruption of the household economy through high expenditure, debts and loss of productive capacity; and disruption of social identity and social stability. Maternal health policy needs to be concerned not only with averting the loss of life, but also with preventing or ameliorating others losses set in motion by an obstetric crisis. PMID- 20541306 TI - Child obesity associated with social disadvantage of children's neighborhoods. AB - Evidence suggests variability in adult obesity risk at a small-scale geographic area is associated with differences in neighborhood socioeconomic status (SES). However, the extent to which geographic variability in child obesity is associated with neighborhood SES is unknown. The objective of this paper was to estimate risk of child obesity associated with multiple census tract SES measures and race within a large urban U.S. county. Height, weight, age, sex, medical insurance type and census tract residence were obtained for 6-18 year old children (n=8616) who received medical care at a health plan in King County, Washington, in 2006. Spatial analyses examined the individual risk of obesity (BMI > or = 95th percentile) with 2000 US census tract measures of median household income, home ownership, adult female education level, single parent households, and race as predictors. Conditional autoregressive regression models that incorporated adjacent census tracts (spatial autocorrelation) were applied to each census tract variable, adjusting for individual variables. We found that in adjusted spatial models, child obesity risk was significantly associated with each census tract variable in the expected direction: lower household income, lower home ownership, and for each 10% increase in less educated women, and single parent households, as well as non-white residents. In a spatial model including all variables, the SES/race variables explained approximately 24% of geographic variability in child obesity. Results indicated that living in census tracts with social disadvantage defined by multiple different measures was associated with child obesity among insured children in a large U.S. urban county. These results contribute new information on relationships between broader social and economic context and child obesity risk using robust spatial analyses. PMID- 20541308 TI - "You feel like you can't live anymore": suicide from the perspectives of Canadian men who experience depression. AB - Severe depression is a known risk factor for suicide, yet worldwide men's suicide rates continue to outnumber reported rates of men's depression. While acknowledging that the pathways to suicide are diverse, and being mindful of the complex challenges inherent to studying suicide, we interviewed men who experienced depression as a means to better understanding the processes they used to counter and contemplate suicide. This novel qualitative study provides insights on how masculine roles, identities and relations mediate depression related suicidal ideation in a cohort of 38 men in Canada, ranging in age from 24 to 50 years-old. Constant comparative analyses yielded the core category of reconciling despair in which men responded to severe depression and suicidal ideation by following two pathways. To counter suicide actions, connecting with family, peers and health care professionals and/or drawing on religious and moral beliefs were important interim steps for quelling thoughts about suicide and eventually dislocating depression from self-harm. This pathway revealed how connecting with family through masculine protector and father roles enabled men to avoid suicide while positioning help-seeking as a wise, rational action in re establishing self-control. The other pathway, contemplating escape, rendered men socially isolated and the overuse of alcohol and other drugs were often employed to relieve emotional, mental and physical pain. Rather than providing respite, these risky practices were the gateway to men's heightened vulnerability for nonfatal suicidal behaviour. Men on this pathway embodied solitary and/or risk taker identities synonymous with masculine ideals but juxtaposed nonfatal suicidal behaviours as feminine terrain. PMID- 20541309 TI - The natural history of hereditary angioedema and the impact of treatment with human C1-inhibitor concentrate during pregnancy: a long-term survey. AB - OBJECTIVE: The course of hereditary angioedema (HAE) and the efficacy and safety of human C1-INH concentrate were appraised during pregnancy and the postpartum period, in patients with HAE. STUDY DESIGN: Retrospective analysis of clinical data on 118 pregnancies (82 full-term and 36 abortions) in 41 female patients, extracted from the National HAE Registry, medical charts and patient diaries. RESULTS: HAE attack frequency increases in 48% of pregnancies, whereas 33% of pregnancies were associated with mitigation of clinical signs and 19% of the pregnancies had no influence on the course of HAE, as compared to disease severity seen during the 2-year period preceding the pregnancy. During 46 full term pregnancies, 26 patients reported attacks; 52% of these occurred in the third trimester. Abdominal attacks are the most common presentation of HAE during pregnancy. Attack number was significantly higher in patients who had sustained their initial attack before 8 years of age. Attack number increased during the third trimester if the fetus was afflicted by HAE. During the postpartum period, attacks occurred in 6/82 pregnancies. Patients received 91 vials of C1-INH concentrate altogether for the relief of acute attacks and for short- or long term prophylaxis during pregnancy. This therapy was effective in all instances; no adverse effects were observed. CONCLUSIONS: Pregnancy can either aggravate or mitigate edematous attacks, or alternatively, it may have no influence on the severity of the disease. According to our experience, C1-INH concentrate is an effective and safe therapeutic option during pregnancy. PMID- 20541310 TI - Environmental management framework for wind farm siting: methodology and case study. AB - This paper develops an integrated framework to evaluate land suitability for wind farm siting that combines multi-criteria analysis (MCA) with geographical information systems (GIS); an application of the proposed framework for the island of Lesvos, Greece, is further illustrated. A set of environmental, economic, social, and technical constraints, based on recent Greek legislation, identifies the potential sites for wind power installation. Furthermore, the area under consideration is evaluated by a variety of criteria, such as wind power potential, land cover type, electricity demand, visual impact, land value, and distance from the electricity grid. The pair-wise comparison method in the context of the analytic hierarchy process (AHP) is applied to estimate the criteria weights in order to establish their relative importance in site evaluation. The overall suitability of the study region for wind farm siting is appraised through the weighted summation rule. Results showed that only a very small percentage of the total area of Lesvos could be suitable for wind farm installation, although favourable wind potential exists in many more areas of the island. PMID- 20541311 TI - Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution? AB - BACKGROUND: The need for and intensity of follow-up to detect disease recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) remains a matter for debate. OBJECTIVE: To determine whether diagnosis of asymptomatic recurrence after RC by routine follow-up investigations confers a survival benefit versus symptomatic recurrence. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 479 patients with nonmetastatic bladder TCC receiving no neoadjuvant chemotherapy/radiation therapy and prospectively followed with a standardised protocol for a median 4.3 yr (range: 0.3-20.9) after RC at an academic tertiary referral centre. INTERVENTION: RC and extended pelvic lymph node dissection with ileal orthotopic bladder substitution. MEASUREMENTS: Cancer specific survival (CSS) and overall survival (OS) probability for asymptomatic and symptomatic recurrent patients were estimated using the Kaplan-Meier method. The effects of age, nerve-sparing surgery, pathologic tumour stage, lymph node status, adjuvant chemotherapy, mode of recurrence diagnosis, and recurrence site on survival were assessed with multivariable Cox regression models. RESULTS AND LIMITATIONS: Of the 174 of 479 patients (36.3%) with tumour recurrence, 87 were diagnosed by routine follow-up investigations and 87 by symptoms. Routine follow up mostly detected lung metastases and urethral recurrences, while symptoms were predominantly the result of bone metastases and concomitant pelvic/distant recurrences. Of 24 patients with urethral recurrences, 13 had carcinoma in situ (CIS). Of these, 12 were successfully managed with urethra-sparing treatment, and 6 are still alive with no evidence of disease. Most other recurrent long-term survivors had lung and extrapelvic lymph node metastases. Cumulative 5-yr survival rates of the entire cohort were 69.8% (95% confidence interval [CI], 65.5-74.3%) for CSS and 61.9% (95% CI, 57.4-66.7%) for OS. In multivariable analysis, mode of recurrence diagnosis and site of initial recurrence were the only independent predictors of CSS and OS. Patients with recurrences detected by routine follow-up investigations and with secondary urothelial tumours as site of recurrence had a slightly but significantly higher survival probability. CONCLUSIONS: Patients diagnosed with asymptomatic recurrences during our routine follow-up after RC had a slightly higher survival than patients with symptomatic recurrences. Routine follow-up appears particularly effective in early detection of urethral CIS, which can be treated conservatively. In addition, the predominance of lung and extrapelvic lymph node metastases in survivors may justify the use of routine cross-sectional imaging. PMID- 20541312 TI - Reply from author re: Oliver Reich. What do we know (or think we know) about erectile dysfunction following laser treatments for lower urinary tract symptoms? Eur Urol 2010;58:212-3 and Rocco Damiano, Riccardo Autorino. Sexual outcome following photoselective vaporization of the prostate: is there enough evidence? Eur Urol 2010;58:214-5. PMID- 20541314 TI - Metal immobilization in hazardous contaminated minesoils after marble slurry waste application. A field assessment at the Tharsis mining district (Spain). AB - A one-year field trial was conducted at the abandoned mine site of Tharsis (Spain) in order to assess the potential value of waste sludge generated during the processing of marble stone, as an additive for assisting natural remediation of heavily contaminated acid mine soils. An amendment of 22 cmol(c) of lime per kilogram of soil was applied to raise the pH level from 3.2 to above 6. The amendment application was effective in reducing concentrations of Al, Fe, Mn, sulfate and potentially hazardous trace elements (mainly Cu, Pb, Zn and Cd) in the most labile metal pools (water-soluble and EDTA-extractable fractions). Geochemical equilibrium calculations indicate that sulfate complexes and free metal ions were the dominant aqueous species in the soil solution. Metal coprecipitation with nanocrystalline ferric oxyhydroxides may be the major chemical mechanism of amendment-induced immobilization. The alleviating effect of the soil amendment on the metal bioavailability and phytotoxicity showed promise for assisting natural revegetation of the mine land. PMID- 20541313 TI - Homogeneous prostate cancer mortality in the Nordic countries over four decades. AB - BACKGROUND: Incidence of prostate cancer (PCa) has greatly increased in the Nordic region over the past two decades, following the advent of prostate specific antigen (PSA) screening. Consequently, interpreting temporal trends in PCa has become difficult, and the impact of changes in exposure to causal factors is uncertain. OBJECTIVE: To reveal geographic differences and temporal trends in PCa in the Nordic countries. Because the recorded incidence of PCa has been profoundly influenced by PSA screening, we focused our analyses primarily on PCa mortality. DESIGN, SETTING, AND PARTICIPANTS: We analyzed national PCa incidence and mortality data from Denmark, Finland, Norway, and Sweden from 1965 to 2006 using the PC-NORDCAN software program and the online NORDCAN database. MEASUREMENTS: Cumulative incidence and cumulative mortality from PCa were calculated for selected calendar years during four decades, along with age standardized mortality rates. Incidence data in NORDCAN come from individual countries' cancer registries, and mortality data come from national mortality registries. RESULTS AND LIMITATIONS: From 1965 to 2006, 172 613 deaths from PCa were reported in the four Nordic countries. A substantial rise in incidence was observed across the region, with some geographic variation, since the late 1980s. In contrast, both disease-specific mortality rates and cumulative risk of PCa mortality lacked consistent temporal trends over the same period. Cumulative mortality from PCa ranged between 3.5% and 7.5% in the region over four decades, whereas cumulative incidence jumped from about 9% to >20%. Mortality has remained fairly constant among the countries, with a minimally lower risk in Finland. CONCLUSIONS: Unlike most malignancies, the occurrence of lethal PCa showed minimal geographic variation and lacked consistent temporal trends over four decades. These findings may guide our search for important causes of PCa, a malignancy with etiology that is still largely unknown. PMID- 20541315 TI - Effects of Ni2+ on the characteristics of bulking activated sludge. AB - This study investigated effects of the continuous addition of a high concentration of Ni(2+) on the characteristics of bulking activated sludge as well as on the variety and recovery of their ability removing organic pollutants and ammonia in a sequencing batch reactor (SBR). To the knowledge of the authors, this is the first study to examine the changes in quantity and composition of the extracellular polymeric substances (EPS) in bulking activated sludge before and after the addition of a high-concentration of Ni(2+). The correlation between these changes and the sludge characteristics was also investigated. The results showed that after a 40-day acclimation to the addition of 60 mg/L Ni(2+), the ability to remove organic pollutants was recovered; but the ability to remove ammonia was not. The addition of Ni(2+) made a great change in the quantity and composition of the EPS in bulking sludge, including both exterior soluble EPS (EPS(S)) and interior bound EPS (EPS(b)), showing a slight increase followed by a large decrease before reaching a steady state. The difference between the change in the amounts of EPS(S) and EPS(b) was not significant. However, among the component fractions, the change in protein content was obvious than that of polysaccharide and humic acid. PMID- 20541316 TI - Synergistic effects of arbuscular mycorrhizal fungi and phosphate rock on heavy metal uptake and accumulation by an arsenic hyperaccumulator. AB - The effects of arbuscular mycorrhizal (AM) fungi and phosphate rock on the phytorextraction efficiency of a hyperaccumulator (Pteris vittata) and a non hyperaccumulator (Cynodon dactylon) plant were studied. Both seedlings were planted in As contaminated soil under different treatments [(1) control (contaminated soil only), (2) indigenous mycorrhizas (IM), (3) mixed AM inoculum [indigenous mycorrhiza + Glomus mosseae (IM/Gm)] and (4) IM/Gm + phosphate rock (P rock)] with varying intensities (40%, 70% and 100%) of water moisture content (WMC). Significant As reduction in soil (23.8% of soil As reduction), increase in plant biomass (17.8 g/pot) and As accumulation (2054 mg/kg DW) were observed for P. vittata treated with IM/Gm + PR at 100% WMC level. The overall results indicated that the synergistic effect of mycorrhiza and P rock affected As subcellular distribution of the hyperaccumulator and thereby altered its As removal efficiency under well-watered conditions. PMID- 20541317 TI - Equilibrium, kinetic and thermodynamic studies of the biosorption of textile dye (Reactive Red 195) onto Pinus sylvestris L. AB - This study investigated the biosorption of Reactive Red 195 (RR 195), an azo dye, from aqueous solution by using cone biomass of Pinus sylvestris Linneo. To this end, pH, initial dye concentration, biomass dosage and contact time were studied in a batch biosorption system. Maximum pH for efficient RR 195 biosorption was found to be 1.0 and the initial RR 195 concentration increased with decreasing percentage removal. Biosorption capacity increased from 6.69 mg/g at 20 degrees C to 7.38 mg/g at 50 degrees C for 200mg/L dye concentration. Kinetics of the interactions was tested by pseudo-first-order and pseudo-second-order kinetics, the Elovich equation and intraparticle diffusion mechanism. Pseudo-second-order kinetic model provided a better correlation for the experimental data studied in comparison to the pseudo-first-order kinetic model and intraparticle diffusion mechanism. Moreover, the Elovich equation also showed a good fit to the experimental data. Freundlich and Langmuir adsorption isotherms were used for the mathematical description of the biosorption equilibrium data. The activation energy of biosorption (Ea) was found to be 8.904 kJ/mol by using the Arrhenius equation. Using the thermodynamic equilibrium coefficients obtained at different temperatures, the study also evaluated the thermodynamic constants of biosorption (DeltaG(o), DeltaH(o) and DeltaS). The results indicate that cone biomass can be used as an effective and low-cost biosorbent to remove reactive dyes from aqueous solution. PMID- 20541318 TI - Synthesis of alpha'L-C2S cement from fly-ash using the hydrothermal method at low temperature and atmospheric pressure. AB - The objective of this study was the synthesis of alpha'(L)-C(2)S (Ca(2)SiO(4)) belite cement, starting from fly-ash of system CaO-SiO(2)-Al(2)O(3)-SO(3), and using the hydrothermal method in alkaline solution. The lime deficit in these ashes was compensated by the addition of slaked lime from lime bagging workshops. The hydrothermal treatment of the mixture was carried out in demineralized water, NaOH or KOH solution, continually stirred at a temperature below 100 degrees C and atmospheric pressure. The dehydration and calcination of the mixtures at temperatures between 800 and 1100 degrees C allowed alpha'(L)-C(2)S-rich cement to be obtained. The optimization of the synthesis parameters (temperature and time of stirring, pH of solution, temperature and duration of mixture burning) was also studied. The phase formation during various synthesis stages was studied by X-ray diffraction (XRD). Other techniques, such as SEM and EDX, were used to characterize the cement minerals. The results obtained showed that these ashes could form belite cement composed of only one dicalcium silicate phase (alpha'(L) C(2)S). PMID- 20541320 TI - How building an underwater pipeline connecting Libya to Sicilian coast is affecting environment: polycyclic aromatic hydrocarbons (PAHs) in sediments; monitoring the evolution of the shore approach area of the Gulf of Gela (Italy). AB - The purpose of this study was to determine the variation of concentrations and distribution of PAHs in the sediments of the Gela coastal area (Italy) caused by the construction of an underwater pipeline connecting Libya to Sicilian coast. The receiving terminal of offshore pipeline, crossing the Mediterranean Sea, 516 Km long, up to 1127 meters deep, is located in Gela (Sicily, Italy). No bibliographic data regarding hydrocarbons are available for this area. In this paper we report the results of analysis on the water and organic along PAHs.The total concentrations of 16 PAHs in the sediments, analyzed during five surveys, ranged from 2.4 to 434 microg/kg of dry weight. The highest concentrations of total PAHs were found in sediments during the monitoring campaign immediately following the laying of the pipeline. A progressive decrease during the subsequent surveys was observed: The found concentrations was in the direction of restoring the initial situation. Highest levels of PAHs concentration have been often observed in sample stations endowed with highest organic matter content. PMID- 20541319 TI - Heavy metal concentrations in roadside soils and correlation with urban traffic in Beijing, China. AB - A detailed investigation was conducted to study the heavy metal concentrations in roadside soils of Beijing. The concentrations of Cd, Cu, Pb and Zn showed a decreasing trend with increasing distance from the road while such trend was not identified in As, Cr and Ni. In addition, the concentrations of Cd, Cu, Pb and Zn significantly positively correlated with black carbon (BC) and TOC (p<0.01). The soil samples from West 2nd Ring Road with the highest traffic volume had the highest heavy metal concentrations of the 10 roads, and Pb concentration was significantly positively correlated with traffic volumes (p<0.05). According to the soil guideline values of China, Cd was considered to have considerable contamination in roadside soils, while Cu, Pb and Zn less, but As, Ni, Cr none. The concentrations of heavy metals in roadside soils of Beijing were considered medium or low in comparison with those in other cities; this may be due to the windy and dry climate in Beijing. The heavy metals could move with wind along the wind direction and the soil samples had higher heavy metal concentrations at the downwind direction. PMID- 20541321 TI - Presence of naturally occurring radioactive materials in sludge samples from several Spanish water treatment plants. AB - Sludge samples from eleven potable water treatment plants (PWTP), three waste water treatment plants (WWTP) and an industrial water treatment plant (IWTP), located in different areas of Spain, mainly in Catalonia, were analyzed for their radiological content in order to determine whether they could be considered as industries affected by naturally occurring radioactive material (NORM). In general, samples from the PWTPs showed higher activity values for the alpha and gamma emitting isotopes than the WWTPs and the IWTP. For example, samples from the area located in the north of Catalonia show values of (234)U, (235)U and (238)U in the range of 84.4-792.1 Bq/kg, 3.3-26.8 Bq/kg and 63.8-585.9 Bq/kg, respectively. In general, for PWTP, the values obtained for the gamma emitter and alpha emitter isotopes showed that both the geology and the industrial activities correlate with the values measured. The magnitude of these results demonstrates the need to measure the radionuclide content of these samples before reaching a decision about their final disposal. PMID- 20541322 TI - Ehrlichia ewingii infection and exposure rates in dogs from the southcentral United States. AB - We used PCR and a novel serologic assay to determine infection and exposure rates to Ehrlichia ewingii in dogs from an area of northeast Oklahoma and northwest Arkansas where Amblyomma americanum ticks are abundant. Of 143 dogs assayed, 13 (9.1%) harbored E. ewingii by PCR and 64 (44.8%) had antibodies to E. ewingii detected using a peptide-based microtiter plate ELISA. Dogs were more likely (P=0.001) to be positive by PCR if sampled in August (30.8%) but no association was found between seropositive status and month of collection of sample (P>0.05). Additional testing revealed PCR evidence of Ehrlichia chaffeensis (4/143; 2.8%) and Anaplasma platys (5/143; 3.5%) as well as antibodies reactive to E. chaffeensis (25/143; 17.5%), Ehrlichia canis (2/143; 1.4%), and Anaplasma spp. (8/143; 5.6%). Testing of another 200 dogs from the area revealed additional PCR and/or serologic evidence of E. ewingii, E. canis, E. chaffeensis, and A. platys. None of the 343 dogs evaluated had evidence of Borrelia burgdorferi exposure. These data support the interpretation that E. ewingii may be the primary agent of canine ehrlichiosis in this region, and suggest that diagnostic evaluation of dogs suspected to have a tick-borne disease should include assays targeting this organism. PMID- 20541323 TI - Effect of Ascaris suum infection on performance of fattening pigs. AB - Scientific investigations of production losses in pigs due to roundworms are rarely conducted in commercial farms, despite the fact that this information is needed to decide whether anthelmintic treatment is cost-effective or not. Therefore, the aim of our study was to compare performance in fattening pigs treated or not treated for Ascaris suum infections. Two Danish pig farms producing fatteners and showing A. suum-induced liver white spot prevalences of 10-33% were selected for the study. In each farm, pens with fattening pigs were randomly assigned to either treatment with an anthelmintic (Flubenol, Janssen Animal Health), or a placebo. Pigs were treated by administering anthelmintic or placebo mixed in the feed for five consecutive days (5mg/kg body weight) on day 2 6 and day 36-40 after introduction to the finishing unit. Fecal egg excretion before first shipment, liver lesion scores (white spots), lean meat percentage at slaughter, average daily gain, and feed conversion were recorded weekly per pen and evaluated for the entire fattening period (30-100kg). A. suum egg excretion was detected in none of the 57 pens where pigs were treated with anthelmintic compared to 18.2% of 57 pens in the placebo group. Pen floor fecal sampling underestimated the prevalence of A. suum in the fattening units compared to individual rectal sampling; only 22% of pens where A. suum was present were diagnosed correctly by both sampling methods. The prevalence of white spots did not differ significantly between pigs treated with anthelmintic (26.7%) and pigs treated with placebo (23.7%), but considerable variation between batches and over time was observed. Liver lesion scores (none, few, moderate, many) were not significantly influenced by de-worming twice during the fattening period. There were no significant differences in average daily gain, feed conversion and lean meat percentage between pigs treated with anthelmintic or placebo. This lack of effect may be explained in part by a rather low infection intensity, as measured by fecal egg counts, but in contrast, white spot numbers were moderate to high. A possible negative influence of other disease, mainly diarrhea due to Lawsonia intracellularis, on performance could not be excluded. Treatment with flubendazole twice during fattening prevented A. suum egg excretion but did not reduce the occurrence of liver white spots. To improve performance significantly, repeated treatments over several consecutive rounds might be necessary. PMID- 20541324 TI - Effect of different pressure magnitudes on hypertrophic scar in a Chinese population. AB - INTRODUCTION: This study aimed to investigate the effect of different pressure magnitudes on treatment outcomes of hypertrophic scars, and determine pressure loss over time. METHODS: A randomized clinical trial was adopted. 53 hypertrophic scar samples from 17 Chinese participants were recruited and randomly assigned into a high pressure group (20-25 mmHg) and low pressure group (10-15 mmHg) for a five-month intervention program. The scars were assessed objectively before intervention and monthly after intervention for thickness, color (redness, yellowness and lightness) and scar pliability. Pressure magnitude at each assessment was also measured. Two-way repeated ANOVA was used to compare for differences between groups. RESULTS: The results showed that both levels of pressure produced reduction in scar thickness and redness, but the improvement in the high pressure group was statistically better than that of the counterpart (both p<0.05). Monthly pressure measurement revealed that pressure loss in the high pressure group was more severe. However, no major changes in other color parameters and pliability were observed for both the groups. CONCLUSION: High pressure was demonstrated to be more effective for scar management, but it was also more prone to higher pressure loss. Pressure therapy integrated with regular monitoring of the interface pressure is suggested to improve its therapeutic efficacy. PMID- 20541325 TI - Meat standards and grading: a world view. AB - This paper addresses the principles relating to meat standards and grading of beef and advances the concept that potential exists to achieve significant desirable change from adopting more consumer focused systems within accurate value-based payment frameworks. The paper uses the definitions that classification is a set of descriptive terms describing features of the carcass that are useful to those involved in the trading of carcasses, whereas grading is the placing of different values on carcasses for pricing purposes, depending on the market and requirements of traders. A third definition is consumer grading, which refers to grading systems that seek to define or predict consumer satisfaction with a cooked meal. The development of carcass classification and grading schemes evolved from a necessity to describe the carcass using standard terms to facilitate trading. The growth in world trade of meat and meat products and the transition from trading carcasses to marketing individual meal portions raises the need for an international language that can service contemporary needs. This has in part been addressed by the United Nations promoting standard languages on carcasses, cuts, trim levels and cutting lines. Currently no standards exist for describing consumer satisfaction. Recent Meat Standards Australia (MSA) research in Australia, Korea, Ireland, USA, Japan and South Africa showed that consumers across diverse cultures and nationalities have a remarkably similar view of beef eating quality, which could be used to underpin an international language on palatability. Consumer research on the willingness to pay for eating quality shows that consumers will pay higher prices for better eating quality grades and generally this was not affected by demographic or meat preference traits of the consumer. In Australia the MSA eating quality grading system has generated substantial premiums to retailers, wholesalers and to the producer. Future grading schemes which measure both carcass yield and eating quality have the potential to underpin the development and implementation of transparent value-based payment systems which will encourage improved production efficiency throughout the supply chain. PMID- 20541326 TI - The effects of core suture purchase on the biomechanical characteristics of a multistrand locking flexor tendon repair: a cadaveric study. AB - PURPOSE: To determine the effects of suture purchase on work of flexion (WOF), 2 mm gap force, and load to failure on the combination cross-locked cruciate interlocking horizontal mattress (CLC-IHM) flexor tendon repair in zone II. METHODS: A total of 33 fresh-frozen cadaveric fingers were mounted in a custom jig, and the flexor digitorum profundus of each finger was fixed to the mobile arm of a tensile strength machine. Initial measurements of WOF were obtained. Each tendon was repaired with the CLC core suture, randomly assigned to placement of 3, 5, 7 or 10 mm from the cut edge of the tendon, and completed with the IHM circumferential suture. After the repair was completed, measurements of WOF were repeated. Each finger was cycled 1000 times. After each 250 cycles, gapping was recorded, and WOF was measured again. Change in WOF (WOF after repair - WOF of intact tendon) was calculated. Tendons were then dissected from the fingers and linearly tested for 2-mm gap force and ultimate load to failure. RESULTS: The group repaired at 10 mm had the lowest percent increase in WOF (5.2%), the highest 2-mm gap force (89.8 N), and the highest ultimate load to failure (111.5 N). The group repaired at 3 mm had the highest percent increase in WOF (22.1%), the lowest 2-mm gap force (54.6 N), and the lowest ultimate load to failure (84.6 N). CONCLUSIONS: A 10-mm suture purchase is the recommended distance for optimal performance for the CLC-IHM combination repair method. This method with a 10-mm suture purchase has a low increase in WOF, high strength, and high resistance to gapping, and it should be strong enough to tolerate early motion. PMID- 20541327 TI - Osseocutaneous integration of an intraosseous transcutaneous amputation prosthesis implant used for reconstruction of a transhumeral amputee: case report. AB - Exoprosthetic replacement with an artificial limb is the main option for reconstruction after traumatic amputation of an upper limb. Direct skeletal attachment using an osseointegrated implant improves the ease of fixation of the exoprosthesis to the amputation stump. We now report the use of an intraosseous transcutaneous amputation prosthesis that is designed to achieve osseocutaneous integration. Osseocutaneous integration differs from osseointegration because the aim is to create a stable interface among the implant, the bone, and the soft tissues. This reduces the risk of soft tissue infection and troublesome discharge, which are problems encountered with current osseointegrated implants that focus largely on the bone-implant interface. We describe our experience with an intraosseous transcutaneous amputation prosthesis in a case of transhumeral amputation with 2 years of follow-up. PMID- 20541328 TI - Effects of synovial interposition on healing in a canine tendon explant culture model. AB - PURPOSE: To investigate whether synovium interposition between repaired tendon ends can integrate into the tendon repair and improve tendon healing strength in a canine tendon explant culture model. METHODS: We used 80 flexor digitorum profundus tendons from 10 mixed-breed dogs for this study. The flexor digitorum profundus tendons were assigned to 2 groups: repaired tendons with synovium implanted between the cut tendon ends and repaired tendons without any implantation between the tendon ends. The repaired tendons were cultured for either 2 or 4 weeks and then assessed mechanically for rupture strength and histology. RESULTS: The strength of the repaired tendons with the synovium interposition was significantly higher (p < .001) than the repaired tendons without interposition at both 2 and 4 weeks. The strength of the repaired tendons at 4 weeks was significantly higher than that at 2 weeks in both groups. CONCLUSIONS: Interpositional synovial grafts have the potential to accelerate tendon healing when they are implanted at the repair site. The exact mechanism of this effect remains to be elucidated. PMID- 20541329 TI - Oblique pedicled paraumbilical perforator-based flap for reconstruction of complex proximal and mid-forearm defects: a report of two cases. AB - Reconstruction of complex proximal and mid-forearm wounds can be challenging. Free tissue transfer might not be feasible in certain patients or at institutions lacking microsurgical expertise and equipment. Traditional pedicled flaps are either insufficient in length to reach more proximal forearm defects or are used sparingly due to donor site complications and extremity stiffness. We present a novel technique to reconstruct forearm defects using the oblique pedicled paraumbilical perforator (PUP) based flap. This flap is simple to harvest, has low donor site morbidity, and allows elbow and shoulder range of motion during the interval between flap transfer and pedicle division. PMID- 20541330 TI - Resection of heterotopic ossification of the elbow: a comparison of ankylosis and partial restriction. AB - PURPOSE: This study tests the hypothesis that the results of release of elbow stiffness related to heterotopic ossification (HO) are comparable whether there is partial or complete restriction (ankylosis) of flexion and extension. METHODS: Eighteen patients who had surgical release of complete bony ankylosis between the humerus and ulna were retrospectively compared to 27 matched patients who had surgical release of partial restriction of elbow flexion and extension related to HO. Patients were evaluated a minimum of 10 months after surgery, using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Broberg and Morrey rating system. RESULTS: An average of 22 months after surgery (range, 10 to 62 mo), the arc of flexion and extension averaged 95 degrees in the ankylosis cohort and 93 degrees in the partial HO cohort. Forearm rotation averaged 131 degrees versus 134 degrees ; the mean Disabilities of the Arm, Shoulder, and Hand score was 28 versus 30 points; and the mean Broberg and Morrey score was 81 versus 84 points, respectively. CONCLUSIONS: After controlling for other factors, patients with elbow stiffness related to HO can recover comparable motion after surgical release at short-term follow-up whether they have complete ankylosis or only partial restriction of motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 20541331 TI - Nerve-sparing dorsal and volar approaches to the radiocarpal joint. AB - Surgical approaches to the wrist joint have traditionally been focused on providing wide exposure to allow adequate access to the carpus. In light of recent investigations on the innervation and proprioception of the wrist joint, one should also take into consideration not to denervate the wrist capsule and ligaments. In this manuscript, we propose 2 surgical approaches to the dorsal and volar radiocarpal joint, intended to minimize damage to the innervation of the capsule while providing ample access to the wrist. PMID- 20541332 TI - Osteochondritis dissecans of the elbow. PMID- 20541333 TI - Effect of risperidone on acute methamphetamine-induced hyperthermia in rats. AB - The abuse of methamphetamine (METH) is popular in many parts of the world. The number of fatal cases related to METH-induced hyperthermia is increasing, but no definitive therapy has yet been found. In the present study, we investigated the ability of risperidone to attenuate acute METH-induced hyperthermia and the mechanism of its action. When administered before and after a single high METH dose (10 mg/kg), risperidone significantly suppressed acute METH-induced hyperthermia in a dose-dependent manner. The same effect was produced by dopamine 1 (DA(1)) and serotonin-2A (5-HT(2A)) receptor blockers, but not by D2, 5-HT(1A), 5-HT(2B/2C), or 5-HT(2C) receptor blockers, demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D(1) and 5-HT(2A) receptors. A microdialysis study showed that when METH (10 mg/kg) was subcutaneously injected into rats, the levels of DA, 5-HT, glutamate, and the nitric oxide (NO) metabolites NOx (NO2-+ NO3-) in the anterior hypothalamus increased. Risperidone pretreatment significantly attenuated increases in the levels of DA, 5-HT, glutamate, and NOx. The present study indicates that risperidone may be an effective drug for treating METH-induced hyperthermia in humans and that METH influences the DA and 5-HT neuron systems as well as other neuron systems, including the glutamate and NO systems. PMID- 20541334 TI - Protective efficacy of a Classical swine fever virus C-strain deletion mutant and ability to differentiate infected from vaccinated animals. AB - Classical swine fever (CSF) continues to be the most economically damaging pig disease in the world. The disease can be effectively controlled by vaccination with the live C-strain vaccine. This vaccine, however, does not enable the serological differentiation between infected and vaccinated animals (DIVA) and its use can therefore impose severe trade restrictions. CSF-specific diagnostic ELISAs detect antibodies directed against the conserved and immunodominant A domain of the E2 structural glycoprotein. We previously reported the production of a C-strain virus in which the immunodominant TAVSPTTLR epitope of the A domain is stably mutated with the aim to render the virus suitable as a DIVA vaccine. We here report that a single vaccination with this vaccine virus protected pigs from a lethal challenge dose of the highly virulent Brescia strain. Analysis of the sera, however, demonstrated that a commercially available E2 ELISA was unsuitable as an accompanying DIVA test. PMID- 20541335 TI - Changing profile of the bovine rotavirus G6 population in the south of Ireland from 2002 to 2009. AB - Bovine group A rotavirus is one of the main causes of neonatal diarrhoea in calves. This study examined the different G and P genotypes circulating in the bovine population, from 2002-2009, in the south of Ireland. Rotavirus positive bovine faecal samples (n=332) were collected from the Cork Regional Veterinary Laboratory, between 2002 and 2009 and subjected to RNA extraction, PAGE analysis, and G and P genotyping. Genotyping analysis identified G6, G10, P[5], and P[11] to be the predominant G and P genotypes in the present study, with G6 rotavirus responsible for 70-80% of rotavirus infections. The highest combination of G and P types found was G6 P[5], followed by G6 P[5+11] mixed infection. The prevalence of G6 and G10 has shifted over the years, with an increase in the amount of G10 P[11] being detected. Novel combinations (G6+G10P[11], G6+G10P[5+11] and G10P[5+11]) were also detected for the first time. In addition to this, sequence analysis of the VP7 RT-PCR amplicons has revealed that Irish G6 strains are falling within three different lineages, III-V. During this study, two samples, initially genotyped as G8P[11] were identified through sequence analysis as being true G6, lineage III with a high nucleotide identity to Hun4, a G6 human sample from Hungary. The increase in novel G and P type combinations, as well as changes seen in G6 samples could have an impact on rotavirus vaccination programmes, as the current vaccine available may not offer protection against all of these circulating types. PMID- 20541336 TI - Disseminated Mycobacterium avium subsp. avium infection in a cat, the Netherlands. PMID- 20541337 TI - Incidence of long-term ipsilateral and contralateral ototoxicity following radiotherapy for nasopharyngeal carcinoma. AB - OBJECTIVE: To characterize the long-term adverse effects of radiotherapy on the ears in patients with nasopharyngeal carcinoma (NPC), we investigated ipsilateral and contralateral ototoxicities in the external, middle, and inner ear. METHODS: The records of 48 ears in 24 radiotherapy-treated NPC patients were retrospectively analyzed. Radiotherapy doses varied between 60 and 70 Gy in 2-Gy fractions at 5 fractions/week. Ototoxicities were identified by otoscope and pure tone audiograms conducted at 2-3 month intervals for >=12 months. The relationship between radiation dosage and sensorineural threshold deterioration was statistically compared using the Mann-Whitney U-test. RESULTS: Post radiotherapy, 50% of all ears (3 of 6) that developed severe otitis externa were on the contralateral side. There was a post-radiotherapy increase in contralateral otitis media with effusion (OME) (1-7 ears), but a decrease in ipsilateral cases (16-12 ears), with 2 ears on either side subsequently developing chronic otitis media (COM). All ears that showed sensorineural hearing loss (SNHL) before radiotherapy exhibited a further threshold deterioration of more than 15 dB. No statistically significant difference (p=0.086) in average radiation dose was seen between ears with sensorineural threshold deterioration (50.0 Gy) and those without (48.2 Gy). CONCLUSION: Long-term ototoxicity following radiotherapy for NPC can occur in either the ipsilateral or contralateral ears. Pathophysiology varies between and within each side. The post therapy increase in OME on the contralateral side was thought to be due to radiotherapy-induced Eustachian tube damage, and the sensorineural threshold deterioration in at least 4 ears was thought to be due to chronic cochlea damage secondary to COM. PMID- 20541338 TI - MRI-guided breast biopsy at 3T using a dedicated large core biopsy set: feasibility and initial results. AB - OBJECTIVE: The increasing importance of breast MRI in the diagnostic processes concerning breast cancer yield often lesions that are visible on MRI only. To assess the nature of these lesions, pathologic analysis is necessary. Therefore, MR-guided biopsy should be available. Breast MRI at 3T has shown advantage over 1.5T. Unfortunately, current equipment for MR-guided biopsy is better suited for intervention at 1.5T due to the danger of heating titanium co-axial sleeves and large susceptibility artifacts. We evaluated a dedicated 3T breast biopsy set that uses plastic coaxial needles to overcome these problems. MATERIALS AND METHODS: We performed MRI-guided breast biopsy in 23 women with 24 MRI-only visible breast lesions at 3T. Biopsy procedures were performed with plastic coaxial needles in a closed bore 3T clinical MR system on a dedicated phased array breast coil with a commercially available add-on stereotactic biopsy device. RESULTS: Width of the needle artifact was 2mm in all 24 cases. Biopsy procedure was completed between 35 and 67 min. The procedure was judged moderately easy in 12 and normal in 10 cases. One procedure was judged difficult and there was one technical failure. CONCLUSION: MRI-guided breast biopsy at 3T is a fast and accurate procedure. The plastic coaxial needles reduce the susceptibility artifact largely and do not increase the difficulty of the procedure. The diagnostic yield is at least equal to the diagnostic yield of the same procedure at 1.5T. Therefore, this technique can be safely used for lesions only visible at 3T MRI. PMID- 20541339 TI - Correlations between aorto-popliteal bolus transit speed and aortic and popliteal bolus transit time during CT angiography of aortoiliac and lower extremity arteries. AB - PURPOSE: The purpose of this study was to investigate correlations between the aorto-popliteal bolus transit speed and aortic and popliteal bolus transit time in order to evaluate the possibility for prediction of bolus transit speed by single test injection technique. MATERIALS AND METHODS: Approval was obtained from our institutional review board for this study, which included 42 patients, from all of whom written informed consent was obtained. Low-dose serial CT scanning after injection of 12 ml contrast material (300 mg/ml) at a rate of 3 ml/s followed by saline flush was performed twice, first at the level of the upper abdomen and second at the level of the knee joint. The times needed to reach peak enhancement of the upper abdominal aorta (T-aorta) and bilateral popliteal arteries (T-popliteal) were obtained, and aorto-popliteal bolus transit speeds between the abdominal aorta and popliteal arteries were calculated. ABI was recorded for the bilateral feet. The Pearson's product-moment correlation coefficient was used to investigate the correlation between the bolus transit speed and T-aorta, T-popliteal, ABI, and patient age. RESULT: The respective correlation coefficients for bolus transit speed on the one hand and T-aorta, T popliteal, ABI, patient age on the other were -0.50, -0.84, 0.36, and -0.52. CONCLUSION: The time to peak enhancement for popliteal arteries showed the strongest correlation with aorto-popliteal bolus transit speeds, and was considered to be the most accurate predictor for aorto-popliteal bolus transit speeds. PMID- 20541340 TI - Determination of voriconazole in human serum and plasma by micellar electrokinetic chromatography. AB - The micellar electrokinetic capillary chromatography (MEKC) separation and analysis of voriconazole and UK 115794 (internal standard) were examined and an assay for determination of voriconazole in human plasma and serum was developed. The MEKC medium comprises a 2:15 (v/v) mixture of methanol and a pH 9.3 buffer composed of 5mM Na(2)B(4)O(7), 7 mM Na(2)HPO(4) and 54 mM SDS. Sample preparation is based upon liquid/liquid extraction with ethylacetate and dichloromethane (75%/25%) at physiological pH. Using this approach with 250 microl serum or plasma and reconstitution of the dried extract into 100 microl of a buffer composed of 0.5mM Na(2)B(4)O(7) and 0.7 mM Na(2)HPO(4) (pH 9.3), the detection and quantitation limits were determined to be 0.1 and 0.2 microg/ml, respectively, a sensitivity that is suitable for therapeutic drug monitoring of voriconazole (provisional therapeutic range: 1-6 microg/ml) in human plasma and serum samples. The method was validated and compared to an HPLC method, showing excellent agreement between the two for a set of 91 samples that stemmed from patients being treated with voriconazole. The MEKC assay is also demonstrated to be suitable to explore pharmacokinetic data of voriconazole. PMID- 20541341 TI - Poor outcomes with cryoplasty for lower extremity arterial occlusive disease. AB - OBJECTIVES: Cryoplasty has been proposed as a different therapy to address the problems of recurrent lesions. We reviewed our experience with cryoplasty to determine its outcome treating patients with lesions in native vessels and within stents. METHODS: A retrospective review of all patients undergoing cryotherapy between 2004 and 2008 was conducted. Patency was defined by at least one of the following criteria: flow through the vessel demonstrated by angiography or duplex ultrasonography, maintenance of an ankle-brachial index (ABI) greater than 0.10 above the preprocedural value, or maintenance of a palpable pedal pulse that was absent before the procedure in an asymptomatic patient. Patency, limb salvage, symptomatic improvement, and freedom from surgical bypass were determined with Kaplan-Meier survival analysis and compared by log-rank testing. Multivariate analysis was performed by Cox proportional-hazards regression. RESULTS: Eighty eight cryoplasty procedures were performed in 71 patients, with 35 procedures for in-stent restenosis and 37 for native vessel disease. Sixteen of 88 procedures in grafts were excluded from analysis secondary to combined disease process and/or bypass graft stenosis. Lesions treated with cryoplasty had an average of 2.9 prior endovascular interventions. Eighty-five percent of the lesions were described as complex (multifocal, diffuse, or occlusion) and the mean lesion length was 15 +/- 10 cm. Initial cryoplasty technical success rate was 68% (25 of 37) for native vessels and 71% (25 of 35) for in-stent procedures. One year primary patency for the native vs stent group was 17% vs 28%, respectively (P = .18). The 1-year primary assisted patency for the native vs stent group was 28% vs 47%, respectively (P = .33). The 1-year secondary patency for the native vs stent group was 41% vs 57% (P = .42), respectively. Freedom from claudication at 1 year for the native vs stent group was 32% vs 21% (P = .80). Compared to balloon angioplasty, cryoplasty has an averaged up-cost of $1851.50 per procedure. CONCLUSION: Cryoplasty was used in patients with extensive disease and multiple prior interventions. Cryoplasty provided poor patency rates and poor relief from claudication at 1 year in this population. Overall, cryoplasty seems to be an expensive endovascular tool with marginal clinical improvement in our experience. PMID- 20541342 TI - Endovascular repair of extent I thoracoabdominal aneurysms with landing zone extension into the aortic arch and mesenteric portion of the abdominal aorta. AB - Thoracic endovascular aortic repair (TEVAR) has emerged as an alternative for patients at prohibitive risk for open thoracic or thoracoabdominal surgery, decreasing perioperative morbidity and mortality. Aneurysms that involve both the left subclavian artery (LSA) proximally and the celiac artery (CA) distally present a unique challenge to the use of TEVAR. We report a series of six high risk patients presenting with extent I thoracoabdominal aortic aneurysms who were successfully treated with TEVAR including coverage of the LSA and the CA. PMID- 20541343 TI - A typical case of nutcracker phenomenon. PMID- 20541344 TI - The effects of systemic hypothermia on a murine model of thoracic aortic ischemia reperfusion. AB - INTRODUCTION: Hypothermia is widely used to mediate ischemia-reperfusion injury associated with repair of the thoracoabdominal aorta. Experiments were designed in a murine model of thoracic aortic ischemia-reperfusion (TAR) to evaluate the effect of moderate systemic hypothermia on neurologic function, spinal cord morphology, and indices of inflammation in critical organs. METHODS: C57BL/6 mice were subjected to TAR under hypothermic (34 degrees C) or normothermic (38 degrees C) conditions, followed by 24 or 48 hours of normothermic reperfusion. Neurologic functions were assessed during reperfusion. Spinal cords were examined at 24 and 48 hours after reperfusion, and the degree of injury qualified by counting the number of viable motor neurons within the anterior horns. Keratinocyte chemokine, interleukin-6, and myeloperoxidase levels were measured from lung, liver, and kidney at 24 and 48 hours. RESULTS: Normothermic TAR resulted in a dense neurologic deficit in all mice throughout the reperfusion period. Mice subjected to TAR under hypothermic conditions had transient, mild neurologic deficit during the initial periods of reperfusion. Between 24 and 48 hours, delayed paralysis developed in half of these mice, whereas the other half remained neurologically intact. Spinal cord histology showed a graded degree of injury that correlated with neurologic function. There was no correlation between markers of inflammation in various organs and neurologic outcomes following TAR. CONCLUSION: Systemic moderate hypothermia was protective against immediate paralysis after TAR in all cases and was associated with delayed paralysis in 50% of mice. This study suggests that delayed-onset paralysis may be the result of a local insult, rather than a systemic inflammatory event, precipitating spinal cord injury. PMID- 20541345 TI - Outcomes of reinterventions after subintimal angioplasty. AB - OBJECTIVE: With increased use of subintimal angioplasty (SIA), the role of reintervention after recurrence is currently unknown. To more clearly define the technical feasibility, patency, and clinical outcomes of reinterventions after SIA, we reviewed our cumulative experience. METHODS: A retrospective review of patient information (including demographics, indications, procedures, noninvasive arterial studies, and postprocedural events) was performed on those patients undergoing reintervention after a primary subintimal angioplasty in the infrainguinal vessels. Continuous and noncontinuous data were compared using the Student t-test and the z test, respectively. Patency was calculated by Kaplan Meier analysis. Survival curves were compared using log-rank and Wilcoxon testing for univariate analysis and Cox hazard-regression analysis for multivariate analysis. RESULTS: From December 2002, through July 2006, 495 SIAs were performed for infrainguinal disease in 482 patients. Of this cohort, 121 patients (25%) required 188 consecutive reinterventions. Each patient underwent an average of 1.5 +/- 0.8 (range, 1-7) reinterventions during this study. We analyzed only the outcomes of 124 consecutive, first reinterventions. Mean interval time between primary SIA and the first reintervention was 7.8 +/- 6.8 months (range, 1 day-31 months). Indications for reintervention were clinical only (recurrence of symptoms or worsening exam), diagnostics only (recurrence based on peripheral vascular lab studies), or both in 18%, 25%, and 52% of patients, respectively. Technical success was achieved in 94% (n = 117) of the procedures. Repeat SIA technique was utilized in 68% (n = 84) of reinterventions and other endovascular therapies (32%; n = 40), of which the majority were transluminal angioplasty, for the remaining reinterventions. Mean follow-up was 8.6 months (range, 0-34 months). The patency rate at 1 year for the first reintervention was 33%. One year patency rates for reinterventions performed within 3 months of the primary SIA were worse than those performed after 3 months (22% vs 34%; P = .04). In addition, patients treated for claudication had better 1-year patency than those treated for critical limb ischemia (37% vs 27%; P = .03). Other demographic or procedural variables did not significantly affect patency. In patients with critical limb ischemia (CLI), limb salvage rate at 1 year was 71%. CONCLUSION: Endovascular reintervention after SIA is a safe and technically feasible procedure for recurrences and offers good limb salvage rate. Early reinterventions performed within 3 months of the original SIA portend a worse outcome. In addition, reinterventions are less durable in patients with CLI compared with claudication. Finally, by identifying a recurrent stenosis instead of an occlusion, close surveillance may contribute to improved overall outcome. PMID- 20541346 TI - The spectrum of arterial compression at the thoracic outlet. AB - OBJECTIVE: In the absence of ischemic events, arterial pathology at the thoracic outlet (TO) is rarely identified because findings of chronic arterial pathology may be masked by symptoms of neurogenic compression. This study describes the clinical presentations and significance of arterial compression at the TO. METHODS: This was a retrospective analysis of the clinical records and imaging studies of 41 patients with objective findings of arterial compression at the TO. Sixteen were diagnosed from 1990 to 2003, during which 284 patients underwent surgery for TO decompression with selective arterial imaging; 25 were diagnosed from 2003 to 2009, and 62 underwent TO surgical decompressions. RESULTS: Subclavian artery stenosis, with or without poststenotic dilatation (PSD), was found in 26 patients (63%), subclavian artery aneurysms in 12 (29%), chronic subclavian occlusion in 1(2.4%), and axillary artery compression in 2 (5%). Chronic symptoms difficult to discern from neurogenic compression were present in 27 patients (66%; 24 had subclavian stenoses or PSD, or both, 1 had subclavian occlusion, and 2 had axillary artery compression); 13 (32%) presented with acute ischemia (11 had aneurysms and 2 had PSDs), and 1 asymptomatic patient had a subclavian aneurysm. Osteoarticular anomalies were found in 27 patients (66%), including 19 cervical ribs, 4 first rib anomalies, and 4 clavicular or first rib fractures, or both. Among 27 patients with subclavian aneurysms or PSD, 21 (78%) had a bone anomaly. Arterial pathology was deemed significant in 30 patients (73%) and mild or moderate in 11 (21%). Symptoms in 23 of these patients were compatible with neurogenic compression without clinical suspicion of arterial pathology, but 13 (56%) harbored a significant arterial anomaly. CONCLUSIONS: The incidence of arterial pathology secondary to compression at the TO may be underestimated, and in the absence of obvious ischemia, significant arterial pathology may not be suspected. Two-thirds of patients with arterial compression have associated bone anomalies. Therefore, routine arterial imaging seems advisable for patients evaluated for TO syndrome in the presence of a bone anomaly at the TO or an examination that shows an arterial abnormality. In the absence of these signs, however, arterial pathology may be overlooked in patients with symptoms suggestive of neurogenic compression. Further study is needed to elucidate the incidence, natural history, and clinical relevance of arterial compression and PSD at the TO. PMID- 20541347 TI - A further meta-analysis of population-based screening for abdominal aortic aneurysm. AB - PURPOSE: It remains unclear whether population-based screening for abdominal aortic aneurysm (AAA) in men reduces all-cause long-term mortality. We performed an updated meta-analysis of randomized controlled trials of AAA screening for prevention of long-term mortality in men. METHODS: To identify all randomized controlled trials of population-based AAA screening with long-term (>= 10 year) follow-up in men, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched through June 2009. Data regarding AAA-related and all-cause mortality (including Cox regression hazard ratios [HRs] and 95% confidence intervals [CIs]) were abstracted from each individual study. For each study, data regarding mortality in both the screening and control groups were used to generate odds ratios (ORs) and 95% CIs. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic ORs or HRs (or risk ratios where no HR was reported) in both fixed- and random-effects models. RESULTS: Our search identified four randomized controlled trials of population based AAA screening with long-term follow-up in men aged >= 65 years. Pooled analysis demonstrated a statistically significant reduction in AAA-related mortality (random-effects OR, 0.55; 95% CI, 0.36 to 0.86; P = .008; P for heterogeneity = .01; absolute risk reduction [ARR], 4 per 1000; number needed to screen [NNS], 238; random-effects HR, 0.55; 95% CI, 0.35 to 0.86; P = .009; P for heterogeneity = .009) and revealed a statistically nonsignificant reduction (but a strong trend toward a significant reduction) in all-cause mortality (fixed effects OR, 0.98; 95% CI, 0.95 to 1.00 [1.001]; P = .06; P for heterogeneity = .93; ARR, 5 per 1000; NNS, 217; fixed-effects HR, 0.98; 95% CI, 0.96 to 1.00 [1.0001]; P >= .05 [P = .052]; P for heterogeneity = .74) with AAA screening relative to control. CONCLUSION: The results of our analysis suggest that population-based screening for AAA reduces AAA-related long-term mortality by 4 per 1000 over control in men aged >= 65 years. Whereas, screening for AAA shows a strong trend toward a significant reduction in all-cause long-term mortality by 5 per 1000, which does not narrowly reach statistical significance. PMID- 20541348 TI - Incidence, follow-up, and outcomes of incidental abdominal aortic aneurysms. AB - BACKGROUND: Incidental abdominal aortic aneurysms (AAAs) are identified during imaging for other reasons. Incidental AAAs are important findings because they require monitoring and surgical treatment, when indicated, to prevent rupture. The prevalence of incidental AAAs and their management has not been extensively studied. METHODS: We electronically screened a 25% simple random sample of abdominal computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI) studies conducted between 1996 and 2008 at one academic medical center. Screen-positive reports were manually reviewed to determine if they showed an incidental AAA. We reviewed the medical records of all in-patients to determine whether the incidental AAA was documented, a treatment plan was identified, and whether it was communicated to the patient's family physician through the discharge summary. We used evidence-based recommended schedules to determine the adequacy of AAA monitoring for each person. RESULTS: In 79,121 abdominal images, we identified 812 incidental AAAs (1.0% of all studies) or 364 incidental AAAs annually (95% confidence interval [CI], 349-379). Patients were elderly (mean age, 74 years), and AAAs were a mean diameter of 4.0 cm. For 174 inpatients, AAAs were noted in only 51 patients (29%) and only 25 (15%) were communicated to the family physician. Of 329 patients who were observed beyond their first recommended follow-up scan, only 51 (16%) were monitored appropriately throughout their entire follow-up; the median proportion of follow up time with recommended monitoring was 56% (interquartile range, 32%-82%). Elective AAA repair was done in 98 patients (13%), the probability of which was significantly increased when AAA monitoring frequency was compliant with that recommended in practice guidelines. Six patients (0.8%) were admitted with aortic rupture, the probability of which was independent of AAA monitoring. CONCLUSION: Incidental AAAs are common and appear to be poorly monitored. Our data suggested that improved monitoring of incidental AAAs was independently associated with elective AAA repair. Population-based analyses are required to determine the influence that monitoring has on incidental AAA rupture and patient mortality. PMID- 20541349 TI - Below knee bare nitinol stent placement in high-risk patients with critical limb ischemia is still durable after 24 months of follow-up. AB - BACKGROUND: This study evaluated the durability of nitinol stent placement in high-risk patients with chronic critical limb ischemia (CLI) and infrapopliteal lesions after suboptimal balloon angioplasty. METHODS: Between January 2006 and January 2009, 53 high-risk patients (24 women; mean age, 71.8 +/- 5.1 years) with CLI underwent infragenicular stent placement with a 4F sheath-compatible self expanding nitinol stent. Patients had three or more serious cardiopulmonary comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, coronary artery occlusive disease, American Society of Anesthesiologists score >/=3, previous myocardial infarction, coronary stent or bypass, or infection after peripheral revascularization. Endovascular therapy was performed in 30 stenoses and 23 occlusions in 53 patients. The mean stenosis length was 5.5 +/- 1.9 cm. The mean occlusion length was 6.5 +/- 2.9 cm. The mean follow-up was 24.1 +/- 7.3 months and consisted of clinical examination, ankle-brachial index (ABI) measurements, and duplex ultrasound imaging. Digital subtraction angiography was performed if restenosis or reocclusion was suspected. RESULTS: The technical success rate was 98.1%. The 24-month cumulative primary patency rate was 75.5%. During the follow-up, two patients underwent successful repeat angioplasty, and four patients required crural bypass. The 24-month secondary patency and freedom from amputation rates were 88.7% and 88.7%, respectively. The mean ABI increased significantly at 12 and 24 months (P < .001). Risk stratification to detect predictors that influenced the patency rate showed that proximal lesions had significant better patency than distal crural lesions (83.3% vs 65.2%, P = .04). The morphology of the lesions (stenoses vs occlusions, P = .88) did not seem to influence primary patency. Four patients died from nonprocedure-related causes during the follow-up, including lung cancer, myocardial infarction, and glioblastoma multiforme. No procedure-related deaths were recorded. CONCLUSIONS: The 2-year outcome of our series underscores the value of infrapopliteal nitinol stent placement as a durable bailout treatment option in high-risk CLI patients with suboptimal angioplasty. PMID- 20541350 TI - Urinary bladder injuries during vascular surgery. AB - Urologic complications related to vascular surgery involving the ureter have been well recognized. These include ureteral compression from aneurysms, congenital anomalies such as retrocaval ureter, obstruction from retroperitoneal fibrosis, iatrogenic injury, and ureteric fistulas. Complications involving the bladder are more infrequent. Most of these bladder-related complications involve the use of tunneling devices for synthetic bypass grafts. We report an unusual case of a transvesically placed femoral-femoral bypass graft with delayed presentation. We also reviewed the English literature for experience with diagnosis and treatment of bladder injuries during vascular surgical procedures. PMID- 20541351 TI - Estimation of blood alcohol concentration by horizontal attenuated total reflectance-Fourier transform infrared spectroscopy. AB - Numerous methods like distillation followed by iodometric titrations, gas chromatograph (GC)-flame ionization detector, gas chromatograph-mass spectrophotometer, GC-Headspace, Breath analyzer, and biosensors including alcohol dehydrogenase (enzymatic) have been used to determine blood alcohol concentration (BAC). In the present study, horizontal attenuated total reflectance-Fourier transform infrared spectroscopy had been used to determine BAC in whole blood. The asymmetric stretching frequency of C-C-O group of ethanol in water (1,045 cm(-1)) had been used to calculate BAC using Beer's Law. A seven point calibration curve of ethanol was drawn in the concentration range 24-790 mg dL(-1). The curve showed good linearity over the concentration range used (r(2)=0.999, standard deviation=0.0023). The method is accurate, reproducible, rapid, simple, and nondestructive in nature. PMID- 20541352 TI - Risk of invasive breast cancer after lobular intra-epithelial neoplasia: review of the literature. AB - OBJECTIVE: Lobular intra-epithelial neoplasia (LIN) is a rare breast disease that has been regarded alternately as a risk factor for invasive breast cancer in both breasts or a true breast cancer precursor. The controversy is largely dependent on the estimation of the IBC (Invasive Breast Cancer) risk after LIN; however a systematic review of the published data has not been previously performed. We aimed to review the IBC after LIN and the characteristics of those cancers. METHODS: A PubMed search was performed to identify the published articles in English addressing the breast cancer risk after LIN. RESULTS: There was a wide range in the figures estimating the risk of the breast cancer among the 22 studies that form the basis of this review. The cumulative average risk of invasive breast cancer (IBC) was 8.7% (range 0-33). It was 4.7% (range 0-25) for the ipsilateral and 4.2% (range 0-16) for the contralateral breast. 52% of the breast cancers occurred more than 10 years after the initial LIN. A lobular histotype was present in 30% (range 0-67%) of all IBC. CONCLUSIONS: LIN should be considered both as a risk factor (low and similar level of IBC risk for both breasts, long delay between LIN and IBC) and a precursor for IBC (over representation of lobular histotype). PMID- 20541353 TI - [Activity and the available human resources working in 66 French Southern intensive care units]. AB - BACKGROUND: The aim of the study was to determine the activity and the available human resources working in 66 intensive care unit (ICU). METHODS: One-day audit performed between January 2009 and May 2009 by trained residents. RESULTS: Among 710 beds, 695 (98%) beds were available for 626 patients (occupation rate=90%). The two most frequent causes of admission were shock and pneumonia. On admission, the median SAPS II was 46. More than 75% of patients had at least two organ dysfunctions within their ICU stay (respiratory failure=80%, circulatory failure=67%). At the moment of the audit, the median SOFA score was 3, and 549 (88%) patients had required a billing procedure with an admission SAPS II greater or equal to 15. Twenty seven percent of ICUs had a ratio patients/nurses or patients/aid nurse greater than 2.5 and 4, respectively whereas 58% ICUs had a ratio open beds/nurse greater than 2.5 or open beds/aid nurse greater than 4. CONCLUSION: In this study, more than 75% patients had at least two organ dysfunctions within their ICU stay and 88% required a billing procedure and had an admission SAPS II greater or equal to 15. Nevertheless, the staff resource remained below the 2002 decree in 27% ICUs. PMID- 20541354 TI - [Does the second cycle of French medical studies prepare students to be future anesthesiologists and intensivists?]. AB - OBJECTIVE: To analyze the factors influencing the choice of the specialty "anesthesiology and intensive care" by medical students at the end of the second cycle of the French medical curriculum. This study had three aims: to measure the attraction of students for this specialty, to assess the perception of this specialty at this stage of the medical studies, and to study the influence of the teaching of "anesthesiology and intensive care" during this second cycle on student perceptions of the specialty. STUDY DESIGN: Descriptive study. MATERIAL AND METHODS: We conducted an anonymous survey among 407 medical students who were at the end of their sixth year of their medical studies, and who were enrolled in one of the four schools of medicine in Lyon, France, for the university year 2007 2008. RESULTS: Three hundred and twenty-eight surveys were analyzed. The specialty "anesthesiology and intensive care" was ranked third overall in terms of preferred specialties. Intensive care was rated the most attractive component, and respondents in particular noted its multisystem perspective and perceived utility. Anesthesiology was in general seen as highly technical and potentially lucrative, but holding increased medicolegal risk. The hospital training courses were highly rated by the students, who believed these to be the best way to learn about this specialty. However, respondents indicated that not enough hospital training courses were available, and only training courses in the intensive care units and the prehospital care department led the students towards this specialty. Accordingly, the nature and practice of anesthesiology were less well known by students. CONCLUSION: Numerous medical students want to become intensivists. Anesthesiology is less well-known at this stage of the medical studies. The teaching of the "anesthesiology and intensive care" specialty needs to be optimized. PMID- 20541355 TI - [Incidence of cryptorchidism at birth: a prospective study at the University Hospital of Nice]. PMID- 20541356 TI - Second-generation locking mechanisms and ethylene oxide sterilization reduce tibial insert backside damage in total knee arthroplasty. AB - This study evaluated the effects of polyethylene quality and locking mechanism on damage to the nonarticulating (backside) surface of retrieved tibial inserts in total knee arthroplasty. Inserts with peripheral capture (PC) locking mechanisms and ethylene oxide (EtO)-sterilized polyethylene were hypothesized to prevent major backside damage. A total of 156 inserts were sorted by locking mechanism and sterilization method and analyzed by damage scoring methods. Ninety-seven specimens exhibited burnishing. Significant positive linear correlations were observed between damage score and age in vivo for all combinations, but damage occurred at a significantly lower rate for second-generation PC implants with EtO sterilization. Most specimens in this group were undamaged (46/72), with others exhibiting only burnishing. Sex, body mass index, and weight did not influence backside damage. PMID- 20541358 TI - Unicondylar knee retrieval analysis. AB - Unicondylar knee arthroplasty (UKA) is considered an alternative to total knee arthroplasty for patients who have arthritis limited to one compartment of the knee. This study examined surface damage of 3 contemporary UKA designs that were retrieved at revision surgery. Two of the UKA designs were fixed bearing and one was mobile bearing. Demographic information was collected, as well as information about the implants used at revision surgery. Articular surface damage was greater in the fixed-bearing designs as compared to the mobile bearing, although the mobile-bearing implants had significantly shorter length of implantation. Backside damage was also graded for the mobile bearing and when combined with articular wear resulted in overall damage scores higher than both fixed-bearing designs. The fixed-bearing designs showed delamination and surface deformation, whereas the mobile bearing had no evidence of these damage modes. However, mobile bearing components showed other types of wear, and significant wear damage was present on the bearing surfaces of the mobile-bearing implants despite a short time of implantation. At the time of conversion to a total knee arthroplasty, more than 50% of cases required the use of stems, augments, or constrained inserts for the tibial reconstruction. In conclusion, wear modes differed among UKA prosthesis designs. Revision of a UKA to a total knee arthroplasty remains complex with the tibial preparation more complicated than in the primary setting. PMID- 20541357 TI - Five- to eight-year results of a prospective study in 118 arthroplasties using posterior-stabilized rotating-platform knee implants. AB - We prospectively enrolled 118 patients (133 knees) whose arthroplasties were performed using posterior-stabilized rotating-platform knee implants. Introduced in year 2000, this implant's performance beyond 5 years is not reported on, to date. We present 5- to 8-year (average, 6.5 years) results of 118 posterior stabilized rotating-platform knee arthroplasties. Kaplan-Meier survival rate was 100%, considering revision or the need for it as the end point. Mean Knee Society Score improved from 27 (range, 1-54) to 96 (range, 54-100). Mean function score improved from 51 (range, 5-81) to 83 (range, 0-100). No patient had spin-out of rotating bearing or osteolysis. Postoperatively, knee flexion averaged 120 degrees (range, 80 degrees -155 degrees ), 34% patients achieved more than 130 degrees flexion, and 67% patients could sit cross legged. Only 5% patients presented with patellofemoral symptoms. PMID- 20541359 TI - Kneeling is safe for patients implanted with medial-pivot total knee arthroplasty designs. AB - Nine ADVANCE (Wright Medical Technology, Arlington, TN)) Medial-Pivot (MP) and 9 ADVANCE Double-High total knee arthroplasties were analyzed under radiographic surveillance at standing, mid kneeling, and full kneeling. In vivo tibiofemoral contact positions were obtained using the 3- to 2-dimensional image registration technique. The contact in Double-High knee was always more posterior than that in the MP knee presumably because of the presence of the posterior cruciate ligament. The contact positions in both the designs moved anterior from standing to mid kneeling, moved posterior from mid kneeling to full kneeling, and remained within the intended articulation range of the implants. This study indicates that kneeling is safe in MP total knee arthroplasty even in the absence of a cam-post or posterior cruciate ligament. PMID- 20541360 TI - Quality of life outcomes in revision versus primary total knee arthroplasty. AB - The purpose of this study was to evaluate and compare the quality of life and satisfaction outcomes of patients undergoing primary and revision total knee arthroplasty (TKA). Sixty revision and 199 primary TKA patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford-12 Knee Score, Short Form-12, and patient-reported satisfaction. Baseline preoperative scores demonstrate that revision TKA patients have inferior quality of life across all measures (WOMAC, Oxford-12, and Short Form-12) in comparison with primary TKA patients (P < .05). At follow-up revision, TKA patients continue to have inferior outcomes (P < .05) in comparison with primary TKA patients. When adjusting for confounding factors in regression analyses, revisions are inferior to primary TKA by 8.6 (95% confidence interval, 2.7-14.6) normalized WOMAC units. PMID- 20541361 TI - The relationship between body composition and selected metabolic syndrome markers in black adolescents in South Africa: the PLAY study. AB - OBJECTIVE: To determine the relationship between body composition and selected markers of the metabolic syndrome in black adolescents. METHODS: The group consisted of 232 adolescent boys and girls aged 15-19 y attending two secondary schools in a low socio-economic status area of Potchefstroom, South Africa. Body mass (kg), stature (cm), and waist (WC) and hip circumferences were measured using standard methods. Body mass index and waist:hip ratio were calculated. Percentage body fat and lean body mass were measured by air displacement plethysmography. Fasting plasma insulin, fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP), and diastolic blood pressure were measured. RESULTS: Children with a high body fat percentage (boys >20%, girls >25%) had significantly higher serum leptin concentration than children with normal body fat percentage (boys, P = 0.005; girls, P < 0.0001). Girls with a high body fat percentage also reported significantly higher SBP (P = 0.004), diastolic blood pressure (P = 0.03), plasma insulin (P = 0.004), and HOMA-IR (P = 0.004) than girls with normal body fat percentage. Body fat percentage had a significant positive association with HOMA IR (P = 0.02) and SBP (P = 0.02), respectively. A significant positive correlation was also found between plasma leptin concentration and body mass index (P < 0.0001), WC (P < 0.0001), body fat percentage (P < 0.0001), and fat:height index (P < 0.001). CONCLUSION: A significant positive association was found between body fat percentage and both SBP and HOMA-IR, respectively. Girls with a high body fat percentage had significantly higher BP, plasma insulin, and HOMA-IR than girls with normal body fat percentage, indicating risk of non communicable diseases. PMID- 20541362 TI - Relation between degree of obesity and site-specific adipose tissue fatty acid composition in a Mediterranean population. AB - OBJECTIVE: Obesity itself could be a key factor determining fatty acid (FA) composition of adipose tissue (AT). A Mediterranean diet influences this relationship. However, a relation between different overweight and obesity levels (including morbidly obese subjects) and AT FA pattern has not been fully established. The objective of the present study was to analyze potential differences in AT FA composition attending to degree of obesity in patients who follow a Mediterranean dietary pattern. METHODS: Our study comprises 60 patients classified as overweight, obese, or morbidly obese (20 subjects in each group). Dietary composition was assessed by a 7-d record, and visceral and subcutaneous AT FAs were analyzed by gas chromatography. Cardiometabolic risk-related parameters were also assessed. RESULTS: Our results showed that dietary habits were similar among groups, although palmitic intake was higher and palmitoleic intake was lower in the morbidly obese group. Concerning AT, we observed significant differences in the visceral depot. Concretely, both total monounsaturated FA (P = 0.039) and palmitoleic acid (P = 0.008) were higher in overweight subjects. Most differences were found in the subcutaneous tissue. Among them, n-9 and total monounsaturated FA (P < 0.001) were significantly higher again in overweight subjects, while 22:6n-3 was higher in morbidly obese subjects. Subcutaneous adipose dihommo-gamma-linolenic content and dietary palmitic and palmitoleic acids were independent predictors of body mass index. CONCLUSIONS: We confirm the relationship between degree of obesity and dietary and AT FA composition in this Mediterranean population. Despite a similar dietary pattern among groups, overweight and morbidly obese patients have a less detrimental FA profile than obese patients, probably due to differences in adipose tissue metabolism. PMID- 20541363 TI - Beneficial effects of oligopeptides from marine salmon skin in a rat model of type 2 diabetes. AB - OBJECTIVE: This study aimed at investigating whether treatment with oligopeptides from marine salmon skin (OMSS) could modulate type 2 diabetes mellitus (T2DM) related hyperglycemia and beta-cell apoptosis in rats induced by high fat diet and low doses of streptozotocin and its therapeutic mechanisms. METHODS: Groups of T2DM rats were treated with OMSS or bovine serum albumin (3.0 g/kg/d) for 4 wk and their blood samples, together with those of normal control rats, were collected before and 4 wk after treatment. The levels of fasting blood glucose (FBG) and insulin, serum superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH), tumor necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) in rats were determined. The islet cell apoptosis and Fas/FasL expression were detected by TUNEL and immunohistochemistry. RESULTS: In comparison with control rats, higher levels of FBG and frequency of apoptotic islet cells were detected in the bovine serum albumin group of diabetic rats, accompanied by higher levels of Fas expression in the pancreatic islets, serum TNFalpha, IFNgamma, and MDA, but lower levels of SOD and GSH. However, the levels of FBG and frequency of apoptotic islet cells were significantly reduced in OMSS treated rats. Lower levels of Fas expression were observed in the pancreatic islets of OMSS-treated rats. Significantly reduced levels of serum TNFalpha, IFNgamma, and MDA, but increased levels of SOD and GSH, were detected in OMSS treated rats. CONCLUSIONS: Treatment with OMSS significantly reduced FBG in diabetic rats. This antidiabetic activity may be mediated by down-regulating T2DM related oxidative stress and inflammation, protecting the pancreatic beta-cells from apoptosis. PMID- 20541364 TI - Fasting blood glucose levels in patients presenting for elective surgery. AB - OBJECTIVE: The incidence of diabetes mellitus (DM) is increasing worldwide; however, its diagnosis is often delayed. Identifying patients with abnormal fasting blood glucose (FBG) levels preoperatively may have important implications for immediate and long-term outcomes. The aim of the present study was to determine the prevalence of impaired fasting glucose (IFG) and provisional diagnosis of DM (PDD) with potential risk factors in patients presenting for elective surgery. METHODS: We measured FBG in consecutive adult patients undergoing elective non-cardiac surgery from September 2006 to August 2007. Patient age, sex, body mass index, and FBG were collected in the morning of their scheduled intervention. FBG was classified according to the World Health Organization categorization. Patients with a history of DM were excluded from the final analysis. The prevalence of IFG and PDD and odds ratio for risk factors were calculated. RESULTS: Four hundred ninety-three patients without a prior diagnosis of DM were sampled; 19.3% (95 of 493) had IFG and 6.5% (32 of 493) had PDD. Male subjects had a greater risk of PDD than female subjects (odds ratio 2.5, 95% confidence interval 1.2-5.5, P = 0.017). Increased body mass index was not a risk factor for IFG or PDD. The prevalence of IFG but not of PDD had a tendency to increase with age after 40 y. CONCLUSION: More than 25% of patients without a prior diagnosis of DM presenting for elective surgery had increased FBG levels. Obtaining this information may initiate not only an earlier detection of DM in some patients but also affect acute perioperative management and outcomes. PMID- 20541365 TI - Methodology for adding glycemic index values to 24-hour recalls. AB - OBJECTIVE: To describe a standardized method to assign glycemic index (GI) values to food items, obtained from 3 x 24-h recalls among Aboriginal and Torres Strait Islander and non-Indigenous Australian children, which can be adapted for use with simple food composition databases. METHODS: Four published GI databases were used as the source of GI values. Changes were made to a previously published methodology for GI value assignment to accommodate the needs of the Many Rivers Diabetes Prevention Project. RESULTS: There were 1132 food items in the recall database. Two hundred nineteen (19.3%) food items were directly linked to the FoodWorks GI database and 545 (48.1%) items were assigned the GI value of a "closely related" food item in the four GI databases used. Among the top carbohydrate contributors, 113 (35.3%) items have a direct linkage with the FoodWorks GI database. The mean +/- SEM dietary GI and glycemic load (GL) of the study population resulting from this methodology are 57.5 +/- 0.3 and 143.4 +/- 2.6, respectively. CONCLUSION: This simple method provides opportunities for countries without food composition database that are comprehensive for GI/GL but which contain accurate information on carbohydrates in foods to assign high quality GI values to food items in epidemiological studies based on 24-h recalls. PMID- 20541366 TI - beta-Hydroxy-beta-methylbutyrate modifies human peripheral blood mononuclear cell proliferation and cytokine production in vitro. AB - OBJECTIVE: The main objective was to investigate the potential immunomodulatory effects of beta-hydroxy-beta-methylbutyrate (HMB) in human cells. METHODS: Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). RESULTS: Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-alpha concentration in the culture medium was reduced by ~35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-alpha production, but not on proliferation and cell cycle progression. CONCLUSION: HMB may be a useful agent to consider for modulation of immune function in specific situations. PMID- 20541367 TI - Consumption of polyphenol concentrate with dietary fructo-oligosaccharides enhances cecal metabolism of quercetin glycosides in rats. AB - OBJECTIVE: We verified the hypothesis that the consumption of polyphenol concentrate (PC), rich in quercetin and its glycosides (36 g/100 g), in association with different dietary fiber matrices, that is, an easily fermentable fructo-oligosaccharides (FOS) or non-fermentable cellulose (CEL), causes a disparate adaptive response of the cecal microbial activity in rats. This in turn facilitates further utilization of biologically active polyphenolic compounds, which are not, as usual, digested in the foregut. METHODS: Four-week experimental feeding of male Wistar rats consisted of diets containing 5% FOS or CEL, as a source of dietary fiber, with or without 0.3% addition of PC. RESULTS: Positive changes in rat cecum were observed resulting from the ingestion of an FOS containing diet, such as decreased pH and increased the production of short-chain fatty acids in the digesta, compared with a CEL-containing diet. The addition of PC to the FOS diet did not eliminate the positive effects of the latter, except for a slight increase in cecal pH and a decrease in microbial glycolytic activity. However, a simultaneous increase in the cecal butyrate pool was also observed. An adaptation process of the microflora enzymatic system to dieting with PC and FOS was proven in further enhanced susceptibility of rutin (quercetin 3-O-glucorhamnoside), hyperoside (quercetin 3-O-galactoside), and quercitrin (quercetin 3-O-rhamnoside) to hydrolysis by the cecal digesta solution. CONCLUSION: Especially when consumed together, PC and FOS are important dietary factors affecting the susceptibility of quercetin glycosides to microbial metabolism in the cecum. The intensification of the hydrolysis of quercetin glycosides by dietary treatments leads also to the increased metabolism of quercetin itself. PMID- 20541368 TI - Isoflavonoids and peptides from meju, long-term fermented soybeans, increase insulin sensitivity and exert insulinotropic effects in vitro. AB - OBJECTIVE: Although soybeans have been shown to alleviate metabolic syndromes, fermented soybeans may have even greater effects. We investigated the antidiabetic effects of meju, a soy food that is fermented up to 2 mo, and the mechanism by which it exerts its effects. METHODS: Meju was prepared by a traditional fermentation process: soybeans were fermented outdoors for 20 or 60 d. Methanol (M-60) and water (W-60) extracts from meju that had fermented for 60 d contained mostly isoflavonoid aglycones and small peptides, respectively, as opposed to mostly glycosylated isoflavonoids and proteins in the original soybeans. RESULTS: Daidzein, M-60, and W-60 had better insulin-sensitizing actions by activating peroxisome proliferator-activated receptor-gamma in 3T3-L1 adipocytes than did unfermented soybeans. In addition, Min6 insulinoma cells treated with genistein, M-60, and W-60 had greater glucose-stimulated insulin secretion capacity and greater beta-cell viability than those treated with unfermented soybeans. This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression. Furthermore, genistein, daidzein, and M-60 stimulated glucagon-like peptide-1 secretion in enteroendocrine NCI-H716 cells, which generated insulinotropic actions. CONCLUSION: The compositional changes in isoflavonoids and peptides that occurred during a longer fermentation period, without the use of salt, enhanced the antidiabetic effect of soybeans. PMID- 20541369 TI - Long-term results of trismus release in noma patients. AB - Noma, also known as cancrum oris, is an infectious disease that results in a loss of orofacial tissue, due to gangrene of soft and bony tissue. It is especially seen in young children in the sub-Saharan region. Among the sequelae of patients who survive noma, trismus is one of the most disabling. This retrospective research studied the long-term results of trismus release in noma patients. Thirty-six patients could be traced in the villages and were included in the study. The mean mouth opening in this group was 10.3mm (95% CI: 7.0; 13.6mm) and the mean period after discharge from hospital was 43 months. Better mouth opening was observed in patients who continued physiotherapy after discharge, were older, and those with a 'soft' (vs. 'hard') inner and outer cheek on palpation. The result of trismus release in noma patients in the long term was extremely poor in this study. PMID- 20541370 TI - Resequencing of the vesicular glutamate transporter 2 gene (VGLUT2) reveals some rare genetic variants that may increase the genetic burden in schizophrenia. AB - OBJECTIVES: Vesicular glutamate transporters (VGLUT1-3) package glutamate into vesicles in the presynaptic terminal and regulate the release of glutamate. In mesencephalic dopamine neuron culture, the majority of isolated dopamine neurons express VGLUT2, but not VGLUT1 or 3, have been demonstrated. As related to the dysregulated glutamatergic hypothesis of schizophrenia, the gene encoding VGLUT2 is the most plausible candidate involved in the pathogenesis of this illness. METHODS: We searched for genetic variants in the promoter region and 12 exons (including UTR ends) of the VGLUT2 gene using direct sequencing in a sample of Han Chinese schizophrenic patients (n=375) and non-psychotic controls (n=366) from Taiwan, and conducted a case-control association study. RESULTS: We identified 8 common SNPs in the VGLUT2 gene. SNP and haplotype-based analyses showed no association with schizophrenia. Besides, we identified 9 rare variants in 13 out of 375 patients, including 3 variants located at the promoter region, 2 synonymous variants located at protein coding regions, and 4 variants located at UTR ends. No rare variants were found in the control subjects. Collectively, these rare variants were significantly overrepresented in the patient group (3.5% versus 0, p value of Fisher's exact test=2.3x10(-5)), suggesting they may contribute to the pathogenesis of schizophrenia. CONCLUSION: Although the functional significance of these rare variants remains to be characterized, our study may lend support to the multiple rare mutations hypothesis of schizophrenia, and may provide genetic clues to indicate the involvement of the glutamate transmission pathway in the pathogenesis of schizophrenia. PMID- 20541371 TI - Childhood trauma and genetic factors in familial schizophrenia associated with the NOS1AP gene. AB - There is some evidence that childhood adversity may be associated with the expression of schizophrenia but whether genetic risk affects this finding is unknown. We investigated the history of early trauma in 194 subjects from 24 multiply affected families where schizophrenia was previously shown to be associated with a functional allele in the NOS1AP gene. In subjects with schizophrenia (n=79), only events prior to the onset of psychosis were considered. Generalized estimating equation models that adjusted for familial clustering were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Subjects with narrowly defined schizophrenia were more likely than their unaffected family members to have a history of early trauma (adjusted OR=4.17, 95% CI=1.52, 11.44). The results were similar after adjusting for the NOS1AP risk genotype (adjusted OR=3.57, 95% CI=1.32, 9.65) and for maternal or paternal history of schizophrenia (adjusted ORs=3.27, 95% CI=1.45, 7.38; 4.38, 95% CI=1.61, 11.91, respectively). The results suggest that childhood trauma is associated with expression of schizophrenia independent of measured genetic susceptibility and may be a candidate for gene-environment research using genetic variants. PMID- 20541372 TI - Subsequent higher education after adolescent depression: a 15-year follow-up register study. AB - BACKGROUND: Adolescent depression has been shown to have a range of adverse outcomes. We used longitudinal data to investigate subsequent higher education in former depressed adolescents. METHOD: A Swedish population-based investigation of depression in 16-17-year-olds was followed up in national registers 15 years later. Adolescents with depression (n=361, 78% females) were compared to a group of non-depressed peers of the same age (n=248, 77% females). The main outcome was graduation from higher education by age 30. RESULTS: The adolescent with depression were less likely than their non-depressed peers to have graduated from higher education by age 30, both regarding females (27.7% vs. 36.4%, p<.05) and males (12.7% vs. 28.6%, p<.05). After adjustment for early school performance, socioeconomic status and maternal education, the decreased likelihood of subsequent graduation from higher education remained for depressed males (OR, 0.27; 95% CI, 0.08-0.93) but not for depressed females (OR, 0.93; 95% CI, 0.58 1.49). CONCLUSION: Contrary to what previous research has suggested, adolescent depression and its consequences might be particularly destructive to subsequent higher education in males. PMID- 20541373 TI - Change in psychiatrists' attitudes towards the physical health care of patients with schizophrenia coinciding with the dissemination of the consensus on physical health in patients with schizophrenia. AB - PURPOSE: To evaluate the impact of the "Spanish Consensus on Physical Health in Patients with Schizophrenia" on psychiatrists' evaluations of the physical health of patients with schizophrenia. METHOD: Epidemiological, non-interventional, national, multicentre study, with two retrospective, cross-sectional data collection stages in which 229 psychiatrists evaluated 1193 clinical records of patients with schizophrenia (ICD-10) seen in January and September of 2007. RESULTS: Mean age of the patients was 39.7+/-11.6 years, 65.5% were men, diagnosed for schizophrenia 14.0+/-10.3 years ago. Forty percent of the patients suffer from a concomitant disease, the most prevalent being hypercholesterolemia (46.3%), hypertriglyceridaemia (33.5%) and arterial hypertension (26.0%). The difference in the number of patients who had all the physical measurements taken between the two cross-sectional evaluations was 13.8% (CI: 11.8%, 15.7%). The differences for each parameter were: weight 13.7% (CI: 11.7%, 15.6%), BMI 13.58% (CI: 11.6%, 15.5%), waist circumference 14.0% (CI: 12.0%, 15.39%), lipid profile 2.9% (CI: 1.9%, 3.9%) and glycaemia 2.6% (CI: 1.7%, 3.5%). CONCLUSIONS: These results imply that the dissemination of the "Consensus on Physical Health in Schizophrenia Patients", and possibly other actions, has made psychiatrists more aware of an integral approach to patients with schizophrenia, promoting increased monitoring of the physical health of these patients. PMID- 20541374 TI - The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia. AB - The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimer's dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE epsilon4 alleles in MCI and mild AD, while there was no association of APOE epsilon4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD. PMID- 20541375 TI - Cationic nanoemulsions as non-viral vectors for plasmid DNA delivery. AB - Non-viral gene carriers have been extensively investigated as alternatives to viral vectors for therapeutic gene delivery. Many cationic lipid carriers including liposomes, emulsions, and solid lipid nanoparticles are used to transfer plasmid DNA. Stable nanoemulsions were prepared and modified by conjugating fatty acids with cationic amino acids including lysine, arginine, and histidine with the help of carbodiimide. Concentrations of crosslinker and amino acids were optimized to obtain the maximal surface potential. The zeta potential and size distribution of the cationic nanoemulsions were measured using photon correlation spectroscopy. The morphology of nanoemulsion-DNA complexes was examined by transmission electron microscopy. The transfection efficiencies and cytotoxicity of three cationic nanoemulsions were evaluated using 3T3 fibroblast cells. The maximal zeta potentials of lysine-, arginine-, and histidine-modified nanoemulsions were 50, 43, and 7 mV, respectively. The transfection efficiencies of amino acid-modified nanoemulsions were in the order of lysine > arginine > histidine. Low cytotoxicities of these three amino acid-modified nanoemulsions were observed. A facile and inexpensive in situ modification for producing cationic nanoemulsions was developed. The results show the potential of amino acid-modified cationic nanoemulsions as non-viral vectors for gene delivery. PMID- 20541376 TI - [Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome]. AB - We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome. PMID- 20541377 TI - [Acute renal failure following Chlamydia pneumoniae pneumonia in a child]. AB - Acute renal failure (ARF) following Chlamydia pneumoniae pneumonia is rarely reported in adults. We present an observation in a 10-year-old child, who had C. pneumoniae pneumonia treated with roxithromycin for a period of 10 days, without any other nephrotoxic drug, in particular nonsteroidal anti-inflammatory drugs. At the end of antibiotic treatment, he presented with asthenia, polyuria, polydipsia, increased plasma creatinine, metabolic acidosis, hypokalemia, and markers of tubular damage. The etiological investigations showed positive C. pneumoniae antibodies, increased serum concentrations of C3 and C4 complement, IgA, and IgG. No uveitis was noted. The diagnosis was tubulointerstitial nephropathy after C. pneumoniae pneumonia. C. pneumoniae pneumonia should be considered a differential diagnosis of community-acquired pneumonia, especially in cases of poor response to conventional antibiotic therapy. It may be associated with tubulointerstitial nephropathy and/or rapidly progressive glomerulonephritis whose severity varies in children as in adults. Early and effective treatment of C. pneumoniae infection with macrolide antibiotics usually provides favorable progression of renal function. PMID- 20541378 TI - UK Fourth National Colorectal Cancer Consensus Meeting 2009. PMID- 20541379 TI - RITA--Registry of Industrial Toxicology Animal data: the application of historical control data for Leydig cell tumors in rats. AB - Historical data for Leydig cell tumors from untreated or vehicle treated rats from carcinogenicity studies collected in the RITA database are presented. Examples are given for analyses of these data for dependency on variables considered to be of possible influence on the spontaneous incidence of Leydig cell tumors. In the 7453 male rats available for analysis, only one case of a Leydig cell carcinoma was identified. The incidence of Leydig cell adenomas differed markedly between strains. High incidences of close to 100% have been found in F344 rats, while the mean incidence was 4.2% in Sprague-Dawley rats and 13.7% in Wistar rats. Incidences in Wistar rats were highly variable, primarily caused by different sources of animals. Mean incidences per breeder varied from 2.8 to 39.9%. Analyses for the dependency on further parameters have been performed in Wistar rats. In breeders G and I, the Leydig cell tumor incidence decreased over the observation period and with increasing mean terminal body weight. The incidence of Leydig cell tumors increased with mean age at necropsy and was higher in studies with dietary admixture compared to gavage studies. These parameters had no effect on Leydig cell tumor incidence in breeders A and B. Animals from almost all breeders had a considerably higher mean age at necropsy when bearing a Leydig cell adenoma than animals without a Leydig cell adenoma. Studies with longitudinal trimming of the testes had a higher incidence than studies with transverse trimming. The observed dependencies and breeder differences are discussed and explanations are given. Consequences for the use of historical control data are outlined. With the retrospective analyses presented here we were able to confirm the published features of Leydig cell adenomas and carcinomas. This indicates that the RITA database is a valuable tool for analyses of tumors for their biological features. Furthermore, it demonstrates that the RITA database is highly beneficial for the definition of reliable historical control data for carcinogenicity studies on a scientifically solid basis. PMID- 20541380 TI - Genetic influences on Chronic Obstructive Pulmonary Disease - a twin study. AB - BACKGROUND: Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted. METHODS: Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20-71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45-108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects. RESULTS: The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population. After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2-15.8, p = 0.03) in Danish twins and 3.4 (1.5-7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46-77%) of the individual COPD-susceptibility in the Danish population and 61% (48-72%) in the Swedish population. CONCLUSION: The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors. PMID- 20541381 TI - Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients. AB - NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD. This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (>or=40 years; smoking history >or=10 pack-years) with stable moderate-to-severe COPD (post bronchodilator FEV(1) >or= 30% and <80% predicted, FEV(1)/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 microg, placebo, or tiotropium 18 microg once-daily for 7 days. The primary endpoint was mean trough (23-24 h post-dose) FEV(1) on Day 7. Secondary endpoints included mean trough FEV(1) on Day 1, and FEV(1) and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV(1) 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV(1) on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 microg, 100 microg and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV(1) was significantly higher (p < 0.05) with NVA237 50 and 100 microg versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated. NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852). PMID- 20541382 TI - A proposal of a new model for long-term weaning: respiratory intensive care unit and weaning center. AB - BACKGROUND: Respiratory intermediate care units (RICU) are hospital locations to treat acute and acute on chronic respiratory failure. Dedicated weaning centers (WC) are facilities for long-term weaning. AIM: We propose and describe the initial results of a long-term weaning model consisting of sequential activity of a RICU and a WC. METHODS: We retrospectively analysed characteristics and outcome of tracheostomised difficult-to wean patients admitted to a RICU and, when necessary, to a dedicated WC along a 18-month period. RESULTS: Since February 2008 to November 2009, 49 tracheostomised difficult-to wean patients were transferred from ICUs to a University-Hospital RICU after a mean ICU length of stay (LOS) of 32.6 +/- 26.6 days. The weaning success rate in RICU was 67.3% with a mean LOS of 16.6 +/- 10.9 days. Five patients (10.2%) died either in the RICU or after being transferred to ICU, 10 (20.4%) failed weaning and were transferred to a dedicated WC where 6 of them (60%) were weaned. One of these patients was discharged from WC needing invasive mechanical ventilation for less than 12h, 2 died in the WC, 1 was transferred to a ICU. The overall weaning success rate of the model was 79.6%, with 16.3% and 4.8% in-hospital and 3-month mortality respectively. The model resulted in an overall 39 845 +/- 22 578 euro mean cost saving per patient compared to ICU. CONCLUSION: The sequential activity of a RICU and a WC resulted in additive weaning success rate of difficult-to wean patients. The cost-benefit ratio of the program warrants prospective investigations. PMID- 20541383 TI - Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations. AB - Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. METHODS: A multicentre study was carried out in 121 COPD patients (92% males, 63 +/- 11 yr, FEV(1), 49 +/- 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. RESULTS: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR = 6.8, p < 0.01; PI(max), OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. CONCLUSIONS: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction. PMID- 20541384 TI - Airway dimensions in COPD: relationships with clinical variables. AB - BACKGROUND: COPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease. METHODS: Fifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than -950 Hounsfield units. CT measures were related to clinical features of COPD. RESULTS: Thicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; beta = 0.20, p = 0.003, Frequent Exacerbations; beta = 0.14, p = 0.017, Total St George's Score; beta = 0.50, p = 0.001 and body mass index [BMI]; beta = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (beta = -0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = -0.30, p = 0.025 and r = -0.32, p = 0.015). CONCLUSIONS: CT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema. PMID- 20541386 TI - The role of indoleamine 2,3 dioxygenase in the induction of immune tolerance in organ transplantation. AB - The aim of this review is to present current information on transplantation research regarding the role of indoleamine 2,3 dioxygenase in immune regulation. We present the basic mechanisms by which the enzyme is expressed, followed by tryptophan catabolism that leads to midg1 phase arrest and apoptosis. Other effects proposed, although not yet completely proven and generally accepted, include T-cell development suppression, secretion of regulatory cytokines such as IL10, and generation of new T regulatory cells. Clinical studies are being performed worldwide; thus, our goal is to focus on the clinical potential relevance of the enzyme rather than a presentation on a molecular basis so that health care providers concerning transplantation are aware of this promising field in immunology and therapeutics. We do emphasize the fact that information regarding the role of indoleamine 2,3 dioxygenase in human beings is still scarce. PMID- 20541385 TI - T regulatory cells and transplantation tolerance. AB - Despite the development of successful immunosuppression protocols and tremendous improvement in short-term graft survival rates, the problem of chronic graft loss remains the bane of clinical transplantation. The induction and maintenance of transplantation tolerance is the "Holy Grail" of transplantation. The recent identification and characterization of regulatory T cells has opened up exciting opportunities for tolerance induction, immunotherapy, and immunomodulation in transplantation. This review focuses on current understanding of regulatory T cells and their role in transplantation tolerance. PMID- 20541387 TI - Hypertension in the kidney transplant recipient. AB - Elevated arterial blood pressure is common after kidney transplantation and contributes to shortened patient and allograft survivals and increased fatal and nonfatal cardiovascular events. Unfortunately, current evidence indicates that arterial blood pressure remains poorly controlled in kidney transplant recipients. One concern is how best to evaluate treated levels of arterial pressure in transplant recipients as office and clinic measurements often differ from blood pressure readings obtained using ambulatory blood pressure monitoring. Some antihypertensive drugs interact with immunosuppressive medications and adversely affect electrolyte balance and kidney function, which complicates the management of kidney transplant patients. Target blood pressure readings have been suggested by different guidelines, but patient-specific management plan is still lacking. Understanding the basic mechanisms responsible for the persistent hypertension after kidney transplantation is helpful in drafting patient-directed management plan that includes both pharmacologic and nonpharmacologic interventions to achieve target blood pressure control. In this review, we propose a multilayered treatment plan that addresses hypertension in both the early and late posttransplant periods, bearing in mind complications of antihypertensive medications, interactions with immunosuppressive drugs, patient comorbidities, and patient-specific cardiovascular risk factors in the posttransplant period. PMID- 20541388 TI - Characterization and recycling of cadmium from waste nickel-cadmium batteries. AB - A severe threat was posed due to improper and inefficient recycling of waste batteries in China. The present work considered the fundamental aspects of the recycling of cadmium from waste nickel-cadmium batteries by means of vacuum metallurgy separation in scale-up. In the first stage of this work, the characterization of waste nickel-cadmium batteries was carried out. Five types of batteries from different brands and models were selected and their components were characterized in relation to their elemental chemical composition and main phase. In the second stage of this work, the parameters affecting the recycling of cadmium by means of vacuum metallurgy separation were investigated and a L(16) (4(4)) orthogonal design was applied to optimize the parameters. With the thermodynamics theory and numerical analysis, it can be seen that the orthogonal design is an effective tool for investigating the parameters affecting the recycling of cadmium. The optimum operating parameters for the recycling of cadmium obtained by orthogonal design and verification test were 1073 K (temperature), 2.5h (heating time), 2 wt.% (the addition of carbon powder), and 30 mm (the loaded height), respectively, with recycling efficiency approaching 99.98%. The XRD and ICP-AES analyzed results show that the condensed product was characterized as metallic cadmium, and cadmium purity was 99.99% under the optimum condition. PMID- 20541389 TI - Seismic analysis for translational failure of landfills with retaining walls. AB - In the seismic impact zone, seismic force can be a major triggering mechanism for translational failures of landfills. The scope of this paper is to develop a three-part wedge method for seismic analysis of translational failures of landfills with retaining walls. The approximate solution of the factor of safety can be calculated. Unlike previous conventional limit equilibrium methods, the new method is capable of revealing the effects of both the solid waste shear strength and the retaining wall on the translational failures of landfills during earthquake. Parameter studies of the developed method show that the factor of safety decreases with the increase of the seismic coefficient, while it increases quickly with the increase of the minimum friction angle beneath waste mass for various horizontal seismic coefficients. Increasing the minimum friction angle beneath the waste mass appears to be more effective than any other parameters for increasing the factor of safety under the considered condition. Thus, selecting liner materials with higher friction angle will considerably reduce the potential for translational failures of landfills during earthquake. The factor of safety gradually increases with the increase of the height of retaining wall for various horizontal seismic coefficients. A higher retaining wall is beneficial to the seismic stability of the landfill. Simply ignoring the retaining wall will lead to serious underestimation of the factor of safety. Besides, the approximate solution of the yield acceleration coefficient of the landfill is also presented based on the calculated method. PMID- 20541390 TI - PolyshrinkTM based microfluidic chips and protein microarrays. AB - A new approach for the rapid production of microfluidic chips integrating protein spots is described. The technology, called "Print-n-Shrink", is based on the screen-printing of a microfluidic design (using a dielectric ink) onto PolyshrinkTM polystyrene sheets. The initial printing which have a minimum size of 15 MUm (height)*230 MUm (width) was thermally treated (30s, 163 degrees C) to shrink and generate features of 85 MUm (height)*100 MUm (width). Protein spots were also demonstrated to be shrinkable and arrays of 50 MUm-size spots with density up to 6400 spots/cm(2) were achieved. Proteins such as monoclonal antibodies or cellular adhesion proteins were thus spotted onto the PolyshrinkTM sheets and shrunk together with the microfluidic design, creating complete biochips integrating both complex microfluidic designs and protein spots for bioanalytical applications. These shrunk spots were shown to host enough active proteins to enable the achievement of both sensitive sandwich immunoassays (Brain Natriuretic Peptide, C-Reactive Protein and c-Troponin I) and localized cell culture. PMID- 20541391 TI - Highly sensitive Escherichia coli O157:H7 detection in a large volume sample using a conical polymer tube chamber consisting of micro-glass beads. AB - In this study, we developed a method for the highly sensitive detection of viable pathogenic bacteria in a large volume sample by performing RNA concentration, amplification, and using fluorescently tagged capture probes in a single polymer chamber without transferring RNA samples from one chamber to another. Nucleic acids were extracted from Escherichia coli O157:H7 and loaded into glass micro beads embedded in a conical polymer tube chamber. Nucleic acids were concentrated in the micro-tube in a low pH buffer (pH 5). The mRNA, which was adsorbed to the glass micro-beads, was amplified by Nucleic Acid Sequence Based Amplification in the same chamber at a relatively high pH (pH 8.9). The products amplified were measured using the hair-loop type detection probe with FAM and DABCYL, which was pre-mixed in the NASBA mater mixture. As a result, high sensitivity (100% for rain water and 60% for river water) with less than 10 viable E. coli O157:H7 in 100ml could be achieved within 4h using the simple method proposed in this study. PMID- 20541392 TI - Development of D-allose sensor on the basis of three strategic enzyme reactions. AB - Rare sugars are defined as monosaccharides and their derivatives that rarely exist in nature, according to the International Society of Rare Sugars. D-Allose (3-epi d-glucose) is one of the rare sugars, for which various physiological activities have recently been found, with increasing attention to its applications to bio-industry. Until now, however, there is no convenient method of measuring these sugars in a specific manner. For detecting D-allose, three consecutive enzyme reactions were devised by fabricating of a reaction batch chamber packed with L-rhamnose isomerase (LRI), D-tagatose 3-epimerase (DTE) and a screen-printed electrode, on which D-fructose dehydrogenase (DFDH) was immobilized. To obtain a substantial sensing system, extensive experimental parameters were optimized. These included the concentration of photo crosslinkable poly (vinyl alcohol) bearing stilbazolium groups (PVA-SbQ), reaction ratios, and temperature of the batch chamber. By adopting the three consecutive enzyme reactions, an undesirable reverse reaction was minimized. As a result, the developed sensor system exhibited a good linear response on D-allose in the range from 0.1 to 50 mM (r(2)=0.998). The system has an apparent advantage over the previous chromatography approach in terms of simplicity and inexpensiveness. PMID- 20541393 TI - Site-selective dual modification of periplasmic binding proteins for sensing applications. AB - We have developed three sensitive and specific amino acid sensors based on bacterial periplasmic solute binding proteins. A site-specific amino-terminal transamination reaction provides a useful complement to cysteine chemistry for the covalent modification of biomolecules in this application. We demonstrate this combination to attach two different chromophores to a single biomolecule in two locations. The periplasmic glutamine binding protein from E. coli was modified with a pair of dyes suitable for fluorescence resonance energy transfer, and this conjugate exhibited an l-glutamine dependent optical response. Two periplasmic binding proteins from the thermophilic organism Thermotoga maritima, for arginine and aliphatic amino acids, were modified and evaluated similarly. All three conjugates manifested signal changes mediated by resonant energy transfer upon binding their respective ligands, with nanomolar dissociation constants and stereochemical specificity. This represents a readily generalizable method for construction of reagentless biosensors. The double-labeling strategy was also exploited for the surface attachment of a dye-labeled glutamine binding protein via a biotin-streptavidin interaction. PMID- 20541394 TI - Postoperative intensity modulated radiation therapy in high risk prostate cancer: a dosimetric comparison. AB - The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT. PMID- 20541395 TI - Availability of palliative care services for children with cancer in economically diverse regions of the world. AB - PURPOSE: We assessed the availability and quality of palliative care for children with cancer according to national income per capita. METHODS: We surveyed physicians who care for children with cancer using the Cure4Kids website (http://www.cure4kids.org). Queries addressed oncology practice site; reimbursement; specialised palliative care, pain management and bereavement care; location of death; decision-making support and perceived quality of care. Responses were categorised by low-, middle- and high-income country (LIC, MIC and HIC). RESULTS: Of 262 completed questionnaires from 58 countries (response rate, 59.8%), 242 were evaluable (55%). Out-of-pocket payment for oncology (14.8%), palliative care (21.9%) and comfort care medications (24.3%) was most likely to be required in LIC (p<0.001). Availability of specialised palliative care services, pain management, bereavement care and institutional or national decision-making support was inversely related to income level. Availability of high-potency opioids (p=0.018) and adjuvant drugs (p=0.006) was significantly less likely in LIC. Physicians in LIC were significantly less likely than others to report high-quality pain control (p<0.001), non-pain symptom control (p=0.003) and emotional support (p=0.001); bereavement support (p=0.035); interdisciplinary care (p<0.001) and parental participation in decisions (p=0.013). CONCLUSION: Specialised palliative care services are unavailable to children with cancer in economically diverse regions, but particularly in LIC. Access to adequate palliation is associated with national income. Programme development strategies and collaborations less dependent on a single country's economy are suggested. PMID- 20541396 TI - MGMT expression levels predict disease stabilisation, progression-free and overall survival in patients with advanced melanomas treated with DTIC. AB - Metastatic melanoma responds poorly to systemic treatment. We report the results of a prospective single institution study evaluating O(6)-methylguanine-DNA methyltransferase (MGMT) status as a potential predictive and/or prognostic marker among patients treated with dacarbazine (DTIC) 800-1000 mg/m(2) monotherapy administered as a 3-weekly schedule for advanced malignant melanomas. The study was approved by the Regional Ethical Committee. Surgical biopsies from metastatic or loco-regional deposits obtained prior to DTIC treatment were snap frozen immediately upon removal and stored in liquid nitrogen up to processing. Median time from enrolment to end of follow-up was 67 months. MGMT expression levels evaluated by qRT-PCR correlated significantly to DTIC benefit (CR/PR/SD; p=0.005), time to progression (TTP) (p=0.005) and overall survival (OS) (p=0.003). MGMT expression also correlated to Breslow thickness in the primary tumour (p=0.014). While MGMT promoter hypermethylation correlated to MGMT expression, MGMT promoter hypermethylation did not correlate to treatment benefit, TTP or OS, suggesting that other factors may be critical in determining MGMT expression levels in melanomas. In a Cox proportional regression analysis, serum lactate dehydrogenase (LDH, p<0.001), MGMT expression (p=0.022) and p16(INK4a) expression (p=0.037) independently predicted OS, while TTP correlated to DTIC benefit after 6 weeks only (p=0.001). Our data reveal MGMT expression levels to be associated with disease stabilisation and prognosis in patients receiving DTIC monotherapy for advanced melanoma. The role of MGMT expression as a predictor to DTIC sensitivity versus a general prognostic factor in advanced melanomas warrants further evaluation. PMID- 20541397 TI - An organic solvent-stable protease from organic solvent-tolerant Bacillus cereus WQ9-2: purification, biochemical properties, and potential application in peptide synthesis. AB - An extracellular solvent-stable protease producing bacterium WQ9-2 was isolated and identified taxonomically as Bacillus cereus. The protease from strain WQ9-2 was purified to homogeneity with an estimated molecular mass of 37 kDa. The purified protease showed maximum activity at 50 degrees C and pH 8.0. The protease may be classified as a metalloprotease since it was strongly inhibited by EDTA and 1,10-phenanthroline. The protease showed extreme activity and stability in the presence of both 50% (v/v) hydrophilic or hydrophobic solvents. The synthesis of the precursor (Cbz-Ala-Phe-NH2) of a bitter dipeptide could be catalyzed by the protease in the presence of 50% dimethylsulfoxide with the product crystals separating directly. The protease displayed broad catalysis specificity for carboxyl component and different substrate preferences in various solvent media, thus confirming its potential application in peptide synthesis. PMID- 20541398 TI - Bioprocessing papaya processing waste for potential aquaculture feed supplement- economic and nutrient analysis with shrimp feeding trial. AB - Papaya processing waste (PPW), a major fruit processing waste in the Hawaii islands, served as substrate for yeast (Saccharomyces cerevisiae) growth. The fermented PPW products containing nutrients of 45% crude protein and various fat, fiber, lignin, cellulose, and minerals were advantages to nutrients of yeast alone. Three experimental diets controlled at 35% protein formulation containing different levels of inclusion of PPW products and a commercial control diet were fed to shrimps for 8 weeks. The 50% inclusion of PPW diets were comparable to commercial feed in weight, growth, feed conversion ratio (FCR) and survival rate. Such bioprocess treatment system would be economically feasible with the control of annual cost and increase of the amount of PPW treated. The selling price of PPW products and annual operation and maintenance cost were the most influential factors to additional profits. This study presented a promising alternative for environmental-friendly treatment of organic wastes as well as the sustainability of local agriculture and aquaculture industries. PMID- 20541399 TI - Immobilization of silver nanoparticles synthesized using Curcuma longa tuber powder and extract on cotton cloth for bactericidal activity. AB - The present study reports the synthesis of silver (Ag) nanoparticles from silver precursor using plant biomaterials, Curcuma longa tuber powder and extract. Water soluble organics present in the plant materials were mainly responsible for the reduction of silver ions to nano-sized silver particles. pH played a major role in size control of the particles. Silver nanoparticle synthesis was higher in tuber extract compared to powder, which was attributed to the large and easy availability of the reducing agents in the extract. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The minimum bactericidal concentration (MBC) for Escherichia coli BL-21 strain was found to be 50 mg/L. Immobilization of silver nanoparticles on cotton cloth using sterile water showed better bactericidal activity when compared to polyvinylidene fluoride (PVDF) immobilized cloth, but on consecutive washing the activity reduced drastically in sterile water immobilized cloth. PMID- 20541400 TI - Characterization and pulp refining activity of a Paenibacillus campinasensis cellulase expressed in Escherichia coli. AB - The Cel-BL11 gene from Paenibacillus campinasensis BL11 was cloned and expressed in Escherichia coli as a His-tag fusion protein. Zymographic analysis of the recombinant protein revealed cellulase activity corresponding to a protein with a 38-kDa molecular weight. The optimum temperature and pH for purified cellulase were 60 degrees C and pH 7.0, respectively. The enzyme retained more than 80% activity after 8h at 60 degrees C at pH 6 and 7. The cellulase has a Km of 11.25 mg/ml and a Vmax of 1250 MUmol/min/mg with carboxylmethyl cellulose (CMC). Then enzyme was active on Avicel, swollen Avicel, CMC, barley beta-glucan, laminarin in the presence of 100 mM acetate buffer. It was inhibited by Hg2+, Cu2+ and Zn2+. Significant kraft pulp refining energy saving, 10%, was exhibited by the pretreatment of this cellulase applied at 2 IU per gram of oven-dried pulp. Broad pH and temperature stability render this cellulase a convenient applicability toward current mainstream biomass conversion and other industrial processes. PMID- 20541401 TI - Sludge palm oil as a renewable raw material for biodiesel production by two-step processes. AB - In this study, biodiesel was produced from sludge palm oil (SPO) using tolune-4 sulfonic monohydrate acid (PTSA) as an acid catalyst in different dosages in the presence of methanol to convert free fatty acid (FFA) to fatty acid methyl ester (FAME), followed by a transesterification process using an alkaline catalyst. In the first step, acid catalyzed esterification reduced the high FFA content of SPO to less than 2% with the different dosages of PTSA. The optimum conditions for pretreatment process by esterification were 0.75% (w/w) dosage of PTSA to SPO, 10:1 M ratio, 60 degrees C temperature, 60 min reaction time and 400 rpm stirrer speed. The highest yield of biodiesel after transesterification and purification processes was 76.62% with 0.07% FFA and 96% ester content. The biodiesel produced was favorable as compared to EN 14214 and ASTM 6751 standard. This study shows a potential exploitation of SPO as a new feedstock for the production of biodiesel. PMID- 20541402 TI - Synthesis of two marine farnesylacetones that dilate the basilar arteries of rabbits. AB - We have synthesized novel vasodilatation farnesylacetones 1 and 2, which are major active constituents of Sargassum siliquastrum collected from the coast of the East Sea in Korea, in 9 steps. A test of the vasodilatation effect of synthetic intermediates and their deprotected compounds on the basilar arteries of rabbits revealed that 14 and 14-1 have a similar dilation effect as their target marine natural products 1 and 2. PMID- 20541403 TI - Efficient synthesis of 5'-O-laurate of 1-beta-D-arabinofuranosylcytosine via highly regioselective enzymatic acylation in binary solvent mixtures. AB - Regioselective enzymatic acylations of 1-beta-D-arabinofuranosylcytosine (ara-C) with vinyl laurate (VL) in binary organic solvents were explored for the preparation of 5'-O-laurate of ara-C. Among the nine kinds of enzymes, Novozym 435 showed the highest regioselectivity (>99.9%) towards the 5'-OH of ara-C. This lipase showed higher catalytic activity in hexane-pyridine than in other tested solvent mixtures. The most suitable VL to ara-C molar ratio, initial water activity, and reaction temperature were shown to be 15:1, 0.07, and 50 degrees C, respectively, under which the initial reaction rate and the maximum substrate conversion were as high as 84.0 mmol L(-1) h(-1) and 98.1%, respectively. The product of Novozym 435-catalyzed acylation was characterized by (13)C NMR and confirmed to be 5'-O-laurate of ara-C. PMID- 20541404 TI - Diazinones as P2 replacements for pyrazole-based cathepsin S inhibitors. AB - A pyridazin-4-one fragment 4 (hCatS IC(50)=170 microM) discovered through Tethering was modeled into cathepsin S and predicted to overlap in S2 with the tetrahydropyridinepyrazole core of a previously disclosed series of CatS inhibitors. This fragment served as a template to design pyridazin-3-one 12 (hCatS IC(50)=430 nM), which also incorporates P3 and P5 binding elements. A crystal structure of 12 bound to Cys25Ser CatS led to the synthesis of the potent diazinone isomers 22 (hCatS IC(50)=60 nM) and 27 (hCatS IC(50)=40 nM). PMID- 20541405 TI - Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease: exploration of P2 quinazoline substituents. AB - Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8 methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. PMID- 20541406 TI - AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect. AB - AMP-activated protein kinase (AMPK) is a potential therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. As part of an ongoing search for new AMPK activators from plants, this study found that the total extract of Myristica fragrans (nutmeg) activated the AMPK enzyme in differentiated C2C12 cells. As active constituents, seven 2,5-bis-aryl-3,4 dimethyltetrahydrofuran lignans, tetrahydrofuroguaiacin B (1), saucernetindiol (2), verrucosin (3), nectandrin B (4), nectandrin A (5), fragransin C(1) (6), and galbacin (7) were isolated from this extract. Among the isolates, compounds 1, 4, and 5 at 5 microM produced strong AMPK stimulation in differentiated C2C12 cells. In addition, the preventive effect of a tetrahydrofuran mixture (THF) on weight gain in a diet-induced animal model was further examined. These results suggest that nutmeg and its active constituents can be used not only for the development of agents to treat obesity and possibly type-2 diabetes but may also be beneficial for other metabolic disorders. PMID- 20541407 TI - Eudistomidin G, a new beta-carboline alkaloid from the Okinawan marine tunicate Eudistoma glaucus and structure revision of eudistomidin B. AB - A new beta-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the (1)H NMR data, CD spectra, [alpha](D) values, and HPLC analysis of 2b, 2c, and natural eudistomidin B. PMID- 20541408 TI - Segregation in a mycorrhizal fungus alters rice growth and symbiosis-specific gene transcription. AB - Arbuscular mycorrhizal fungi (AMF) form symbioses with the majority of plants, improving plant nutrition and diversity. Evidence exists suggesting that AMF contain populations of genetically different nucleotypes coexisting in a common cytoplasm. This potentially has two important consequences for their genetics. First, by random distribution of nuclei at spore formation, new offspring of an AMF could receive different complements of nucleotypes compared to the parent or siblings-we consider this as segregation. Second, genetic exchange between AMF would allow the mixing of nuclei, altering nucleotype diversity in new spores. Because segregation was assumed not to occur and genetic exchange has only recently been demonstrated, no attempts have been made to test whether this affects the symbiosis with plants. Here, we show that segregation occurs in the AMF Glomus intraradices and can enhance the growth of rice up to five times, even though neither parental nor crossed AMF lines induced a positive growth response. This process also resulted in an alteration of symbiosis-specific gene transcription in rice. Our results demonstrate that manipulation of AMF genetics has important consequences for the symbiotic effects on plants and could be used to enhance the growth of globally important crops. PMID- 20541409 TI - Clock and cycle limit starvation-induced sleep loss in Drosophila. AB - Neural systems controlling the vital functions of sleep and feeding in mammals are tightly interconnected: sleep deprivation promotes feeding, whereas starvation suppresses sleep. Here we show that starvation in Drosophila potently suppresses sleep, suggesting that these two homeostatically regulated behaviors are also integrated in flies. The sleep-suppressing effect of starvation is independent of the mushroom bodies, a previously identified sleep locus in the fly brain, and therefore is regulated by distinct neural circuitry. The circadian clock genes Clock (Clk) and cycle (cyc) are critical for proper sleep suppression during starvation. However, the sleep suppression is independent of light cues and of circadian rhythms as shown by the fact that starved period mutants sleep like wild-type flies. By selectively targeting subpopulations of Clk-expressing neurons, we localize the observed sleep phenotype to the dorsally located circadian neurons. These findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food. PMID- 20541410 TI - Determinants of myosin II cortical localization during cytokinesis. AB - Myosin II is an essential component of the contractile ring that divides the cell during cytokinesis. Previous work showed that regulatory light chain (RLC) phosphorylation is required for localization of myosin at the cellular equator. However, the molecular mechanisms that concentrate myosin at the site of furrow formation remain unclear. By analyzing the spatiotemporal dynamics of mutant myosin subunits in Drosophila S2 cells, we show that myosin accumulates at the equator through stabilization of interactions between the cortex and myosin filaments and that the motor domain is dispensable for localization. Filament stabilization is tightly controlled by RLC phosphorylation. However, we show that regulatory mechanisms other than RLC phosphorylation contribute to myosin accumulation at three different stages: (1) turnover of thick filaments throughout the cell cycle, (2) myosin heavy chain-based control of myosin assembly at the metaphase-anaphase transition, and (3) redistribution and/or activation of myosin binding sites at the equator during anaphase. Surprisingly, the third event can occur to a degree in a Rho-independent fashion, gathering preassembled filaments to the equatorial zone via cortical flow. We conclude that multiple regulatory pathways cooperate to control myosin localization during mitosis and cytokinesis to ensure that this essential biological process is as robust as possible. PMID- 20541411 TI - The function of bilateral odor arrival time differences in olfactory orientation of sharks. AB - The direction of an odor signal source can be estimated from bilateral differences in signal intensity and/or arrival time. The best-known examples of the use of arrival time differences are in acoustic orientation. For chemoreception, animals are believed to orient by comparing bilateral odor concentration differences, turning toward higher concentrations. However, time differences should not be ignored, because odor plumes show chaotic intermittency, with the concentration variance several orders of magnitude greater than the concentration mean. We presented a small shark species, Mustelus canis, with carefully timed and measured odor pulses directly into their nares. They turned toward the side stimulated first, even with delayed pulses of higher concentration. This is the first conclusive evidence that under seminatural conditions and without training, bilateral time differences trump odor concentration differences. This response would steer the shark into an odor patch each time and thereby enhance its contact with the plume, i.e., a stream of patches. Animals with more widely spaced nares would be able to resolve smaller angles of attack at higher swimming speeds, a feature that may have contributed to the evolution of hammerhead sharks. This constitutes a novel steering algorithm for tracking odor plumes. PMID- 20541412 TI - Transient frictional slip between integrin and the ECM in focal adhesions under myosin II tension. AB - BACKGROUND: The spatiotemporal regulation of adhesion to the extracellular matrix is important in metazoan cell migration and mechanosensation. Although adhesion assembly depends on intracellular and extracellular tension, the biophysical regulation of force transmission between the actin cytoskeleton and extracellular matrix during this process remains largely unknown. RESULTS: To elucidate the nature of force transmission as myosin II tension is applied to focal adhesions, we correlated the dynamics of focal adhesion proteins and the actin cytoskeleton to local traction stresses. Under low extracellular tension, newly formed adhesions near the cell periphery underwent a transient retrograde displacement preceding elongation. We found that myosin II-generated tension drives this mobility, and we determine the interface of differential motion, or "slip," to be between integrin and the ECM. The magnitude and duration of both adhesion slip and associated F-actin dynamics is strongly modulated by ECM compliance. Traction forces are generated throughout the slip period, and adhesion immobilization occurs at a constant tension. CONCLUSIONS: We have identified a tension dependent, extracellular "clutch" between integrins and the extracellular matrix; this clutch stabilizes adhesions under myosin II driven tension. The current work elucidates a mechanism by which force transmission is modulated during focal adhesion maturation. PMID- 20541413 TI - A new method for synchronization of motion capture and plantar pressure data. AB - A common plantar pressure analysis technique requires dividing the pressure distribution into regions based on key landmarks of the foot. Typically, this is done using visual inspection of the footprint and is subject to error when there is abnormal foot contact. A novel, robust method of synchronizing motion capture and plantar pressure data was created that allows for motion capture markers to be projected onto the plantar pressure mat for accurate subdivision of the foot. Validation studies showed that spatial synchronization of the plantar pressure and motion capture systems was determined to be accurate within 1 sensel. PMID- 20541414 TI - Repeatability of a new protocol for gait analysis in adult subjects. AB - The reliability of kinematic measurements has a top priority in gait analysis. The aim of the present work was to assess the inter-trial, inter-session and inter-examiner variability of an anatomical-based protocol by an established method. The gait of two young adult volunteers was analyzed by four examiners with different degrees of experience in three sessions 1 week apart. The data of five trials of level walking were collected and the rotations in the three anatomical planes of the pelvis, hip, knee and ankle were calculated. The mean value over the gait cycle of the standard deviation of these rotations was calculated for each of the 24 groups of five trials (inter-trial), the eight groups of five trials multiplied by three sessions (inter-session), and the two groups of five trials multiplied by three sessions multiplied by four examiners (inter-examiner). For each rotation, the inter-examiner variability was larger than the inter-session, and the latter larger than the inter-trial. The present ratio between inter-examiner and inter-trial variability was found to be smaller than that of the conventional protocol for each of the gait variables. PMID- 20541415 TI - Extra-temporal involvement in herpes simplex encephalitis. PMID- 20541416 TI - Minimal access keyhole surgery for mesial temporal lobe epilepsy. AB - A keyhole surgical approach for the treatment of medically intractable temporal lobe epilepsy is described. Additionally, patients who had keyhole surgery are contrasted with individuals who underwent a non-keyhole approach for outcome parameters of seizure freedom, complications, and speed of recovery. Patients who had a keyhole approach for temporal lobe epilepsy with over 2 years follow-up were compared with all patients who had selective amygdalohippocampectomy performed in a non-keyhole fashion over the same time period. Rates of seizure freedom were comparable in the 17 patients with keyhole surgery and the 34 individuals who had a non-keyhole approach. However, patients treated with keyhole surgery were discharged from the hospital earlier than non-keyhole patients (p=0.04), and with a shorter operative time (p=0.0001). The restricted keyhole surgical exposure has not limited the ability to perform surgery for temporal lobe epilepsy with favorable results on reducing the seizure tendency, and patients may be benefited by a minimal access technique with a more rapid recovery from surgery. PMID- 20541417 TI - Efficacy of the American Heart Association/American Stroke Association guidelines for ultra-early, intentional antihypertensive therapy in intracerebral hemorrhage. AB - Whether the intentional antihypertensive therapy recommended by the American Heart Association/American Stroke Association (AHA/ASA) guidelines has clinical benefit for patients who have acute spontaneous intracerebral hemorrhage (ICH) has yet to be proven. We retrospectively reviewed the clinical charts of 175 patients with putaminal or thalamic ICH with acute hypertension to examine the correlation between the efficacy of antihypertensive therapy within 3 hours of onset, hematoma expansion (HE) after hospitalization and clinical outcome. The aim of the antihypertensive therapy was to achieve and maintain a systolic blood pressure of 120 mm Hg to 160 mm Hg until the second CT scan. The mean arterial pressure (MAP) after admission was the average MAP values measured every hour for the first 3 hours of hospitalization or until the second CT scan, if this was performed within the same timeframe. Thirty-two (18.3%) patients were found to have HE. Prior to the second CT scan, antihypertensive medications were administered to all patients without any major complications. A multiple logistic regression analysis revealed that a MAP of >110 mm Hg after admission was the only variable independently associated with HE (odds ratio [OR] = 3.455; 95% confidence interval [CI] = 1.510-8.412; p = 0.004). Modified Rankin Scale scores of < or = 3 on day 30 were significantly more common in those patients without HE (p = 0.002). Our findings suggest that there are clinical benefits, by the prevention of subsequent HE, in maintaining a MAP level lower than that recommended by the AHA/ASA (110 mm Hg) after hospitalization for patients who have ICH. PMID- 20541418 TI - Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment. AB - Circadian and sleep disturbances are common behavioural and psychological symptoms of dementia; circadian rhythm-related molecules may be altered in dementia patients. This study investigated the expression of the period 1 clock gene product (PER1), which is involved in circadian rhythms, and inducible nitric oxide synthase (iNOS), thought to generate nitric oxide, important in rapid eye movement (REM) sleep regulation. Specifically, we investigated the difference in expression of these two genes between patients with cognitive impairment and controls. We studied iNOS and PER1 mRNA expression using real-time polymerase chain reaction in peripheral leukocytes during REM sleep, non-REM sleep and wake stages in patients with Alzheimer's disease (AD, n=5), patients with mild cognitive impairment (MCI, n=8) and controls (n=9) during polysomnography examination. Expression of iNOS significantly increased during REM sleep in AD patients compared to MCI patients and controls. There were no significant differences in PER1 expression between the three groups, but an increase in PER1 expression during the wake stage was observed for all participants. Increased expression of iNOS during REM sleep of patients with AD might be a compensation mechanism for maintaining REM sleep. However, the precise role of nocturnal expression of iNOS in patients with AD requires further investigation. PMID- 20541419 TI - Sensitivity and specificity of in vivo diffusion-weighted MRI in acute spinal cord injury. AB - The aim of this study was to test the sensitivity and specificity of diffusion weighted MRI for the detection of acute spinal cord injury. Forty female New Zealand white rabbits were randomly divided into four groups: the mild, moderate and severe injury groups, and the control (sham operation) group. Contusion of the spinal cord was induced using a weight-drop impactor. All animals were imaged using T1-weighted, T2-weighted, and diffusion-weighted imaging (DWI) sequences at 30 minutes, 6 hours, and 24 hours after injury. One animal from each group was killed at each time point for histologic examination of the spinal cord. DWI had a sensitivity of 100% at all time points, whereas T2-weighted MRI had a sensitivity of 43.33% at 30 minutes after injury, 81.48% at 6 hours after injury, and 95.83% at 24 hours after injury. Conversely, the specificity of DWI was lower than that of T2-weighted MRI at all time points. One animal in the control group had a non-specific high signal on DWI. Significant systematic differences were seen between DWI and T2-weighted MRI at both 30 minutes and 6 hours after injury. The apparent diffusion coefficient values of the lesion were lower than those of adjacent unaffected regions in the mild and moderate injury groups, but higher than adjacent unaffected regions in the severe injury group. The histological findings were reliably correlated with the magnetic resonance findings. We found that DWI has a higher sensitivity, but a lower specificity, than conventional MRI for the detection of early pathological changes after contusive injury. PMID- 20541420 TI - Inhibition of inducible nitric oxide synthase expression and cell death by (-) epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. AB - The aim of this study was to investigate the involvement of inducible nitric oxide synthase (iNOS) in the action of (-)-epigallocatechin-3-gallate (EGCG), a potential neuroprotective agent against Parkinson's disease (PD), and to test for toxicity resulting from high doses of EGCG. EGCG was administered to 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice at two different doses (10mg/kg and 50mg/kg). EGCG treatment reduced the neuronal death rate to less than 50%. The level of iNOS expression in the MPTP group was 20% higher than that seen in the control group, but in the EGCG groups, iNOS expression was reduced to the level observed in the negative control group. The two doses of EGCG were equally beneficial for cell rescue, and no toxicity was observed with the higher dose. Inhibition of iNOS may be an important mechanism underlying the prevention of MPTP toxicity, and EGCG may potentially be a neuroprotective agent against PD. PMID- 20541421 TI - Carboplatin and etoposide combined with bevacizumab for the treatment of recurrent glioblastoma multiforme. AB - Relapsed glioblastoma multiforme (GBM) responds poorly to standard therapies. Vascular endothelial growth factor (VEGF) is implicated in the development of GBM and the anti-VEGF monoclonal antibody bevacizumab has shown early clinical promise against malignant glioma. We treated six patients with recurrent GBM using bevacizumab combined with carboplatin and etoposide chemotherapy (ACE regimen). Toxicity was that expected for carboplatin and etoposide alone, except for an ischemic stroke in one patient. We observed partial responses in five patients and one responding patient developed extensive tumour necrosis after 2 cycles of treatment. Median progression-free and overall survival was 19 and 29.9weeks, respectively. Four responding patients developed recurrence, which was characterized by markedly less peri-tumoral edema, mass effect and necrosis compared with tumours at baseline. Two patients developed local extracranial extension. In conclusion, ACE was active in recurrent GBM and was mostly well tolerated. PMID- 20541422 TI - Leaving the structural ivory tower, assisted by interactive 3D PDF. AB - The ability to embed interactive three-dimensional (3D) models into electronic publications in portable document format (PDF) greatly enhances the accessibility of molecular structures. Here, we report advances in this procedure and discuss what is needed to develop this format into a truly useful tool for the structural biology community as well as for readers who are less well trained in molecular visualization. PMID- 20541423 TI - The 26S proteasome: assembly and function of a destructive machine. AB - The heart of the ubiquitin-mediated degradation pathway, the 26S proteasome, endoproteolytically cleaves most intracellular proteins, thereby maintaining biological homeostasis and regulating many crucial processes in the cell. This hydrolyzing machine comprises more than 30 different subunits, which perform different functions including the recognition, unfolding, translocating and cleavage of protein substrates. Thus, careful assemblage and regulation of the 26S proteasome is essential to ensure correct positioning and function of each subunit, thereby preserving the delicate cellular balance between protein synthesis and degradation. Here, we review the most current research on the 26S proteasome assembly pathway, and describe the mechanism used by the cell to manage the complex structure and functions of the proteasome. PMID- 20541424 TI - Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents. AB - Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D- and L-phenylglycine were found to be effective inhibitors, with a slight preference for the d-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (approximately 35 nM), potencies which were retained on mutant variants of the protease. PMID- 20541425 TI - Synthesis and biological study of 3-(phenylsulfonyl)thieno[2,3 e][1,2,3]triazolo[1,5-a]pyrimidines as potent and selective serotonin 5-HT6 receptor antagonists. AB - A number of 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines were prepared and their 5-HT6 receptor binding affinity and ability to inhibit the functional cellular responses to serotonin were evaluated. 3-[(3 chlorophenyl)sulfonyl]-N-(tetrahydrofuran-2-ylmethyl)thieno[2,3 e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{5,26} appeared to be the most active in a functional assay (IC50=29.0 nM) and 3-(phenylsulfonyl)-N-(2-thienylmethyl) thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{1,28} demonstrated the greatest affinity in a 5-HT6 receptor radioligand binding assay (Ki=1.7 nM). A screening of 5-HT2A and 5-HT2B receptor affinity revealed that 3 (phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines are highly selective 5-HT6 receptor ligands. PMID- 20541426 TI - Synthesis and structure-activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor. AB - 4-((1H-imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The piperazine derivatives were found to have low (or no) affinity for human histamine H3 receptor, whereas the piperidine derivatives showed moderate to high affinity, and their agonistic activity was greatly influenced by substituents on the aromatic ring. Among the piperidine-containing compounds, 17d and 17h were potent human histamine H3 receptor agonists with high selectivity over the closely related human H4 receptor. Our results indicate that appropriate conformational restriction, that is, by the piperidine spacer moiety, favors specific binding to the human histamine H3 receptor. PMID- 20541427 TI - New antimalarials with a triterpenic scaffold from Momordica balsamina. AB - Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of three new cucurbitane-type triterpenoids, balsaminols C-E (1 3). Their structures were elucidated on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY). Balsaminols C-E, together with ten cucurbitacins isolated from the same plant (4-13), were evaluated for their antimalarial activity against the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Most of the compounds displayed antimalarial activity. Compounds 9 and 12 revealed the highest antiplasmodial effects against both strains (IC50 values: 4.6, and 7.4 microM, 3D7, respectively; 4.0, and 8.2 microM, Dd2, respectively). Structure activity relationships are discussed. Furthermore, the preliminary toxicity toward human cells of compounds 1-5 and 9 was investigated in breast cancer cell line (MCF-7). Compounds were inactive or showed weak toxicity (IC50 values>19.0). PMID- 20541428 TI - In situ SEM, TEM and AFM studies of the antimicrobial activity of lemon grass oil in liquid and vapour phase against Candida albicans. AB - Inhibition of Candida albicans growth was shown by lemon grass oil (LGO) and lemon grass oil vapour (LGO vapour) at 288microg/ml and 32.7microg/ml concentration, respectively. The assessment of cell damage by LGO and LGO vapour was done through scanning electron microscope (SEM), transmission electron microscope (TEM) and atomic force microscope (AFM) observations. SEM analysis showed complete rupture of C. albicans cells treated with LGO vapour while in those treated with LGO in broth, only shrinkage was observed. TEM study showed the alterations in morphology upon treatment with LGO while complete degradation of the Candida cells was observed in case of LGO vapour. Further three dimensional morphological changes and roughness of the cells have also been evaluated with AFM after the treatment with LGO & LGO vapour. Roughness (root mean square value) was significantly higher in control C. albicans cells (211.97nm) than LGO (143nm) and LGO vapour (5.981nm) treated cells. The results for the first time demonstrate relatively higher efficacy of LGO vapours for inhibition and cellular damage of C. albicans cells as compared to the LGO in liquid phase. This suggests the potential application of LGO vapour phase against infections caused by C. albicans. PMID- 20541429 TI - Parry-Romberg syndrome: volumetric regeneration by structural fat grafting technique. AB - The use of adipose tissue transfer for correction of maxillo-facial defects was reported for the first time at the end of the 19th century and has since been the subject of numerous studies. Structural Fat Grafting (SFG) differs from other fat grafting techniques in both the harvesting and placement of the fat. The main indications for SFG are for the restoration and rejuvenation of the face. Recent applications include the correction of localised tissue atrophy, loss of substance due to trauma, post-tumour, congenital complex craniofacial deformities, burns, and hemifacial atrophy. The authors describe a case of a 20 year-old woman with right Parry-Romberg syndrome (PRS) treated over many years with many different surgical reconstructive techniques with poor results. After five SFG (three complete procedures and two minor revisions) over three years, the authors obtained a good aesthetic result with complete patient satisfaction. SFG can be an excellent technique for facial reconstruction and re-contouring, with natural and long-lasting results. PMID- 20541430 TI - Surgical pericardioscopy with rigid endoscope: a risky technique for an incomplete result. PMID- 20541431 TI - Venovenous malformation: a common finding after Kawashima operation. AB - OBJECTIVES: It has been reported that systemic venovenous malformation (VVM) can develop in patients with interrupted inferior vena cava (IVC) and univentricular type of congenital heart disease who undergo superior vena cava to pulmonary artery connection (Kawashima operation). These malformations can lead to profound systemic desaturation postoperatively. However, there have been few reports that characterise the prevalence, anatomic details and clinical correlations of these systemic VVM arising after Kawashima operation. In this study, we describe our experience with VVM after Kawashima operation, and discuss issues regarding their evaluation and postoperative management. METHODS: Eight patients with median age 19 months (range: 5-238) who underwent Kawashima operation were subjected to postoperative angiography, prospectively. Sites of VVM origin and entry, as well as their course, were documented. The presence of pulmonary arteriovenous malformations (AVMs) was also documented. RESULTS: At median follow-up of 31 months (range: 16-72 months), a total of 14 VVM were found in different supra- and infra-diaphragmatic sites in six patients (75%); four of them had concomitant pulmonary AVM while the remaining two patients had only pulmonary AVM. CONCLUSIONS: Our findings suggest that systemic VVM can occur frequently after Kawashima operation and can produce significant desaturation postoperatively, and hence we support hepatic incorporation. Performing detailed angiographic studies of the supra- and infra-diaphragmatic systemic veins in routine assessment of patients before Kawashima operation is, probably, warranted. PMID- 20541432 TI - Freedom SOLO valve: early- and intermediate-term results of a single centre's first 100 cases. AB - OBJECTIVE: The Freedom SOLO aortic valve is a bovine pericardial stentless valve, which requires only one suture line. The aim of our single-centre retrospective study was to assess postoperative and intermediate-term haemodynamic results of the first 100 consecutively implanted valves. METHODS: One hundred patients (39 male and 61 female) underwent aortic valve replacement with a Freedom SOLO from November 2006 to January 2008. Their clinical, operative, platelet levels, echocardiography and follow-up data were prospectively recorded. All but two patients were available for follow-up (98% completeness), which averaged 12.6 +/- 5.06 months. RESULTS: Associated procedures were performed in 38 patients (38%): 27 coronary artery bypass grafting (CABG), 11 mitral valve replacement, 11 septal myectomy and one ablation for atrial fibrillation. The mean age at the time of surgery was 77.2 +/- 6.43 years. The mean European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 8.05 +/- 2.07. Mean cross-clamp time of isolated valve replacements was 51.27 +/- 4.7 min and 63.18 +/- 21.7 min with associated procedures. The mean implanted valve size was 23.5 +/- 1.9 mm. One patient was re operated for bleeding, two for pericardial effusion and 39 were transfused. The overall hospital mortality was 3%. One patient died suddenly postoperatively, and a second due to a fatal atrio-ventricular block. A third patient died following a subdural bleed. Three patients required a pacemaker before hospital discharge. The overall patient survival was 97 +/- 2.26% at 1 year. Echocardiographic results preoperative, 8 days postoperative and 12 months after surgery showed mean transvalvular gradients of 50.6 +/- 15.3, 15.6 +/- 5.2 and 11.5 +/- 3.8 mm Hg, respectively, and mean left ventricular ejection fractions of 37.9 +/- 10.2%, 44 +/- 15.2% and 53.6 +/- 10.4%. Effective orifice area index for valve sizes 19, 21, 23, 25 and 27 were 0.91 +/- 0.08, 0.97 +/- 0.1, 1.08 +/- 0.07, 1.53 +/- 0.12 and 1.57 +/- 0.1cm(2)m(-2), respectively. There were three early non-structural dysfunctions (grade 1) of regurgitation, which remained stable at 12 months. CONCLUSIONS: Freedom SOLO valve has very good early- and intermediate-term results. Short implantation times and its haemodynamic performances, particularly in small diameters, allow us to use it by first intention in older and often sicker patients. These results must be confirmed by long-term outcomes. PMID- 20541433 TI - Photoinactivation of different human tumor cell lines and sheep red blood cells in vitro by liposome-bound Zn(II) Phthalocyanine: Effects of cholesterol. AB - The in vitro photoinactivation of human tumor cell lines and sheep red blood cells (SRBC) by Zinc (II) Phthalocyanine (ZnPc) was investigated using unilamellar liposome (LUV) as delivery system, in the presence and absence of cholesterol (CHOL) in the formulation. The presence of CHOL improves the stability of the system showing to be essential for the photodynamic action of ZnPc. LUVs prepared without CHOL did not present any antiproliferative effects neither induced significant photohaemolysis. The presence of ZnPc in the culture medium caused total cell growth inhibition (TGI) only at concentrations higher than 250 micromol dm(-3). For ZnPc in LUV/CHOL (mass ratio=3:1), the mean TGI values for almost all studied cells were around 80 micromol dm(-3), and 14 micromol dm(-3) for human ovarian carcinoma (NIH: OVCAR-3) cells. The cytoplasmic components of OVCAR-3 and SRBC when irradiated in presence of ZnPc in LUV/CHOL were completely destroyed, culminating in cell swelling, lysis and death by necrosis. PMID- 20541434 TI - Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract. AB - We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract. PMID- 20541435 TI - Relative, label-free protein quantitation: spectral counting error statistics from nine replicate MudPIT samples. AB - Nine replicate samples of peptides from soybean leaves, each spiked with a different concentration of bovine apotransferrin peptides, were analyzed on a mass spectrometer using multidimensional protein identification technology (MudPIT). Proteins were detected from the peptide tandem mass spectra, and the numbers of spectra were statistically evaluated for variation between samples. The results corroborate prior knowledge that combining spectra from replicate samples increases the number of identifiable proteins and that a summed spectral count for a protein increases linearly with increasing molar amounts of protein. Furthermore, statistical analysis of spectral counts for proteins in two- and three-way comparisons between replicates and combined replicates revealed little significant variation arising from run-to-run differences or data-dependent instrument ion sampling that might falsely suggest differential protein accumulation. In these experiments, spectral counting was enabled by PANORAMICS, probability-based software that predicts proteins detected by sets of observed peptides. Three alternative approaches to counting spectra were also evaluated by comparison. As the counting thresholds were changed from weaker to more stringent, the accuracy of ratio determination also changed. These results suggest that thresholds for counting can be empirically set to improve relative quantitation. All together, the data confirm the accuracy and reliability of label-free spectral counting in the relative, quantitative analysis of proteins between samples. PMID- 20541437 TI - Digital asymmetric waveform isolation (DAWI) in a digital linear ion trap. AB - Traditionally, in a quadrupole mass filter, ion isolation is achieved by scanning the rf and DC voltages with a fixed ratio. In this paper, we describe an innovative procedure implemented in a digitally driven linear ion trap termed digital asymmetric waveform isolation (DAWI) in which ion isolation is obtained by manipulation of the duty cycle of the rectangular waveforms. Variation of the waveform duty cycle allows introduction of a precisely defined DC quadrupole component into the main trapping field of the quadrupole ion filter. The DAWI method is completely controlled at software level and does not require any hardware modification. PMID- 20541438 TI - Quality control based on isotopic distributions for high-throughput MALDI-TOF and MALDI-FTICR serum peptide profiling. AB - In this study, we have implemented a new quality control (QC) parameter for peptide profiling based on isotopic distributions. This QC parameter is an objective measure and facilitates automatic sorting of large numbers of peptide spectra. Peptides in human serum samples were enriched using reversed-phase C(18) functionalized magnetic beads using a high-throughput robotic platform. High resolution MALDI-TOF and ultrahigh resolution MALDI-FTICR mass spectra were obtained and a workflow was developed for automated analysis and evaluation of these profiles. To this end, the isotopic distributions of multiple peptides were quantified from both MALDI-TOF and MALDI-FTICR spectra. Odd peptide isotope distributions in TOF spectra could be rationalized from ultrahigh resolution FTICR spectra that showed overlap of different peptides. The comparison of isotope patterns with estimated polyaveragine distributions was used to calculate a QC value for each single mass spectrum. Sorting these QC values enabled the best MALDI spectrum to be selected from replicate spots. Moreover, using this approach spectra containing high intensities of polymers or other contaminants and lacking peptides of interest can be efficiently removed from a clinical dataset. In general, this method simplifies the exclusion of low quality spectra from further statistical analysis. PMID- 20541439 TI - Postural control and thigh muscle activity in men with knee osteoarthritis. AB - The aim of this study was to examine the standing balance and the function of vastus medialis (VM) and biceps femoris (BF) muscles with surface electromyography (EMG). Fifty-four subjects with uni- or bilateral knee osteoarthritis (OA) (aged 50-69 years) and 53 age-matched randomly selected clinically and radiologically healthy men participated in this study. Postural control was assessed on a force platform with a bipedal stance with eyes open (EO) and closed (EC) and a monopedal stance with EO. The balance parameters, mean sway velocity, velocity along AP and ML axes, elliptical area, standard deviation of center of pressure, average radial displacement, mean frequency and frequency domain balance parameters and different power spectral density frequency bands were determined. Root mean square (RMS) for EMG amplitude, mean EMG frequency (f(EMG,mean)) and median EMG frequency (f(EMG,med)) of motor unit activity were calculated from the normalized EMG data. During bipedal stance with EC and EO, there were no significant differences in balance parameters between groups, but during bipedal stance with EO, the RMS in VM was about 56% higher (p<0.05) in subjects with knee OA than in the control subjects and the values of f(EMG,mean) and f(EMG,med) were about 48% higher (p<0.05) in control subjects than subjects with knee OA. It is concluded that subjects with knee OA do not have any standing balance deficit, but they do exhibit increased muscle activity in VM muscle compared to control subjects. PMID- 20541440 TI - Concomitant pulmonary infection with Nocardia transvalensis and Aspergillus ustus in lung transplantation. AB - Lung infections with Nocardia and Aspergillus spp in lung transplant recipients (LTRs) create diagnostic and therapeutic challenges. The present case illustrates the difficulties in identifying these pathogens in LTRs. A high degree of clinical suspicion and aggressive early management are required to ensure good outcomes. Although prospective data on treating these conditions are scarce, the empiric use of combination broad-spectrum anti-microbials initially seems prudent. PMID- 20541441 TI - Ceiling effects make Hughes and Nicholson's data analyses and conclusions inconclusive. AB - Hughes and Nicholson (2010) suggest that recognizing oneself is easier from face vs. voice stimuli, that a combined presentation of face and voice actually inhibits self-recognition relative to presentation of face or voice alone, that the left hemisphere is superior in self-recognition to the right hemisphere, and that recognizing self requires more effort than recognizing others. A re examination of their method, data, and analyses unfortunately shows important ceiling effects that cast doubts on these conclusions. PMID- 20541442 TI - The temporal organization of functional brain connectivity is abnormal in schizophrenia but does not correlate with symptomatology. AB - Previous work employing graph theory and nonlinear analysis has found increased spatial and temporal disorder, respectively, of functional brain connectivity in schizophrenia. We present a new method combining graph theory and nonlinear techniques that measures the temporal disorder of functional brain connections. Multichannel electroencephalographic data were windowed and functional networks were reconstructed using the minimum spanning trees of correlation matrices. Using a method based on Shannon entropy, we found elevated connection entropy in gamma activity of patients with schizophrenia; however, gamma connection entropy remained elevated in patients with schizophrenia even after a reduction in symptoms due to treatment with antipsychotics. Our results are consistent with several possibilities: (1) aberrant functional connectivity is epiphenomenal to schizophrenia, (2) aberrant functional connectivity is a central feature but antipsychotics reduce symptoms by an independent mechanism, or (3) connection entropy is not an appropriately sensitive measure of brain abnormalities in schizophrenia. PMID- 20541443 TI - Transition of adolescents with HIV to adult care: characteristics and current practices of the adolescent trials network for HIV/AIDS interventions. AB - The transition process from pediatric to adult health care for adolescents with chronic diseases is always challenging and can be even more so for adolescents with HIV disease. The purpose of this study was to describe characteristics and current practices surrounding the transition of adolescents from the clinics of the Adolescent Trials Network for HIV/AIDS Interventions to adult medical care. This report focuses on the processes of transition, perceived barriers and facilitators, and anecdotal reports of successes and failures. Practice models used to assist adolescents during transition to adult medical care are described. Interviews were conducted with 19 key informants from 14 Adolescent Trials Network clinics. Findings revealed no consistent definition of "successful" transition, little consensus among the sites regarding specific elements of a transition program, and a lack of mechanisms to assess outcomes. Sites that viewed transition as a process rather than an event consistently described more structured program elements. PMID- 20541444 TI - Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. AB - The novel analgesic tapentadol combines mu-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule and shows potent analgesia in various rodent models of pain. We analyzed the contribution of opioid and monoaminergic mechanisms to the activity of tapentadol in rat models of nociceptive and neuropathic pain. Antinociceptive efficacy was inferred from tail withdrawal latencies of experimentally naive rats using a tail flick test. Antihypersensitive efficacy was inferred from ipsilateral paw withdrawal thresholds toward an electronic von Frey filament in a spinal nerve ligation model of mononeuropathic pain. Dose-response curves of tapentadol (intravenous) were determined in combination with vehicle or a fixed dose (intraperitoneal) of the mu-opioid receptor antagonist naloxone (1mg/kg), the alpha2-adrenoceptor antagonist yohimbine (2.15 mg/kg), or the serotonin 5-HT(2A) receptor antagonist ritanserin (0.316 mg/kg). Tapentadol showed clear antinociceptive and antihypersensitive effects (>90% efficacy) with median effective dose (ED(50)) values of 3.3 and 1.9 mg/kg, respectively. While the antinociceptive ED(50) value of tapentadol was shifted to the right 6.4-fold by naloxone (21.2mg/kg) and only 1.7-fold by yohimbine (5.6 mg/kg), the antihypersensitive ED(50) value was shifted to the right 4.7-fold by yohimbine (8.9 mg/kg) and only 2.7-fold by naloxone (5.2mg/kg). Ritanserin did not affect antinociceptive or antihypersensitive ED(50) values of tapentadol. Activation of both mu-opioid receptors and alpha2-adrenoceptors contribute to the analgesic effects of tapentadol. The relative contribution is, however, dependent on the particular pain indication, as mu-opioid receptor agonism predominantly mediates tapentadol's antinociceptive effects, whereas noradrenaline reuptake inhibition predominantly mediates its antihypersensitive effects. PMID- 20541445 TI - Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast. AB - We describe and demonstrate a system to generate hyperpolarized water in the 0.35 T fringe field of a clinical 1.5 T whole-body magnetic resonance imaging (MRI) magnet. Once generated, the hyperpolarized water is quickly and continuously transferred from the 0.35 T fringe to the 1.5 T center field of the same magnet for image acquisition using standard MRI equipment. The hyperpolarization is based on Overhauser dynamic nuclear polarization (DNP), which effectively and quickly transfers the higher spin polarization of free radicals to nuclear spins at ambient temperatures. We visualize the dispersion of hyperpolarized water as it flows through water-saturated systems by utilizing an observed -15-fold DNP signal enhancement with respect to the unenhanced (1)H MRI signal of water at 1.5 T. The experimental DNP apparatus presented here is readily portable and can be brought to and used with any conventional unshielded MRI system. A new method of immobilizing radicals to gel beads via polyelectrolyte linker arms is described, which led to superior flow Overhauser DNP performance compared to previously presented gels. We discuss the general applicability of Overhauser DNP of water and aqueous solutions in the fringe field of commercially available magnets with central fields up to 4.7 T. PMID- 20541446 TI - Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. AB - A major concern in the antiretroviral (ARV) treatment of HIV infections with protease inhibitors (PI) is the emergence of resistance, which results from the selection of distinct mutations within the viral protease (PR) gene. Among patients who do not respond to treatment with the PI nelfinavir (NFV), the D30N mutation is often observed. However, several reports have shown that D30N emerges with different frequencies in distinct HIV-1 genetic forms or subtypes. In the present work, we analyzed the binding of NFV and the Gag substrate CA/p2 to PR from HIV-1 subtypes B and C through molecular dynamics (MD) simulations. The wild type and drug-resistant D30N mutants were investigated in both subtypes. The compensatory mutations N83T and N88D, observed in vitro and in vivo when subtype C acquires D30N, were also studied. D30N appears to facilitate conformational changes in subtype B PR, but not in that from subtype C, and this could be associated with disestablishment of an alpha-helical region of the PR. Furthermore, the total contact areas of NFV or the CA/p2 substrate with the mutant PR correlated with changes in the resistance patterns and replicative capacity. Finally, we observed in our MD simulations that mutant PR proteins show different patterns for hydrophobic/van der Waals contact. These findings suggest that different molecular mechanisms contribute to resistance, and we propose that a single mutation has distinct impacts on different HIV-1 subtypes. PMID- 20541447 TI - Analysis of aberrantly spliced HRPT2 transcripts and the resulting proteins in HPT-JT syndrome. AB - The risk for parathyroid carcinoma is high in those with the HPT-JT syndrome. Parafibromin is a protein derived from HRPT2 gene and its inactivation has been coupled to familial form of parathyroid malignancy. We previously identified altered transcripts resulting from splice site mutation of the HRPT2 gene in a family with this syndrome. In the present work, we investigated the stability of the altered HRPT2 transcripts and translation products produced in the HPT-JT syndrome. We quantified the differentially expressed HRPT2 mRNAs using real-time RT-PCR and developed a novel monoclonal parafibromin antibody to study the expression of parafibromin in the HPT-JT syndrome. The relative quantification ratios of the wild type HRPT2 mRNA, 23 bp deleted HRPT2 mRNA, and 70 bp deleted HRPT2 mRNA in the HPT-JT syndrome were 0.68, 0.17 and 0.15, respectively. But endogenous parafibromin expression was not detectable in the HPT-JT syndrome carcinoma. The altered HRPT2 mRNAs resulting from the splice site mutation in the HPT-JT syndrome were stable, but their parafibromin translation products from the HPT-JT syndrome carcinoma were probably degraded rapidly. Additional studies that aim to fully characterize the consequences of altered HRPT2 mRNAs in HPT-JT syndrome are required to explore these possibilities. PMID- 20541449 TI - Generational patterns of alcohol consumption: Continuity and change. AB - In most contemporary western societies there is growing concern about rising levels of alcohol consumption, particularly by young people, even in countries, such as France, which have previously been assumed to have 'sensible' drinking cultures. Recent popular and policy debates about British drinking cultures have hinted at a shift in generational attitudes towards alcohol, as well as patterns of consumption. Previous intergenerational studies of work and care have found that in particular historical periods different normativities develop, reflecting both social and economic conditions. In this paper, we draw on a research project about alcohol consumption conducted in an urban and rural area - including intergenerational interviews with case study families - to identify the different normativities in terms of attitudes towards and consumption of alcohol experienced by three cohort generations in their youth. The paper then goes on to explore the patterns of both change and continuity that are evident in the interviewees' experiences. The conclusion reflects on drivers of intergenerational change and associated health policy implications. PMID- 20541448 TI - Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. AB - MLL1 fusion proteins activate HoxA9 gene expression and cause aggressive leukemias that respond poorly to treatment, but how they recognize and stably bind to HoxA9 is not clearly understood. In a systematic analysis of MLL1 domain recruitment activity, we identified an essential MLL1 recruitment domain that includes the CXXC domain and PHD fingers and is controlled by direct interactions with the PAF elongation complex and H3K4Me2/3. MLL1 fusion proteins lack the PHD fingers and require prebinding of a wild-type MLL1 complex and CXXC domain recognition of DNA for stable HoxA9 association. Together, these results suggest that specific recruitment of MLL1 requires multiple interactions and is a precondition for stable recruitment of MLL1 fusion proteins to HoxA9 in leukemogenesis. Since wild-type MLL1 and oncogenic MLL1 fusion proteins have overlapping yet distinct recruitment mechanisms, this creates a window of opportunity that could be exploited for the development of targeted therapies. PMID- 20541450 TI - Three-dimensional geometric morphometrics for studying floral shape variation. AB - Variation in floral shape is of major interest to evolutionary and pollination biologists, plant systematists and developmental geneticists. Quantifying this variation has been difficult due to the three-dimensional (3D) complexity of angiosperm flowers. By combining 3D geometric representations of flowers obtained by micro-computed tomography scanning with geometric morphometric methods, well established in zoology and anthropology, floral shape variation can be analyzed quantitatively, allowing for powerful interpretation and visualization of the resulting patterns of variation. PMID- 20541452 TI - Assembly of the flagellum and its role in cell morphogenesis in Trypanosoma brucei. AB - Eukaryotic flagella are microtubule-based structures required for a variety of functions including cell motility and sensory perception. Most eukaryotic flagella grow out from a cell into the surrounding medium, but when the flagellum of the protozoan parasite Trypanosoma brucei exits the cell via the flagellar pocket, it is attached along the length of the cell body by a cytoskeletal structure called the flagellum attachment zone (FAZ). The exact reasons for flagellum attachment have remained elusive, but evidence is emerging that the attached flagellum plays a major role in cell morphogenesis in this organism. In this review we discuss evidence published in the past four years that is unravelling the role of the flagellum in organelle segregation, inheritance of cell shape and cytokinesis. PMID- 20541451 TI - Genetic perspectives on crop domestication. AB - The process of crop domestication has long been a topic of active research for biologists, anthropologists and others. Genetic data have proved a powerful resource for drawing inferences on questions regarding the geographical origins of crops, the numbers of independent domestication events for a given crop species, the specific molecular changes underlying domestication traits, and the nature of artificial selection during domestication and subsequent crop improvement. We would argue that these genetic inferences are fundamentally compatible with recent archaeological data that support a view of domestication as a geographically diffuse, gradual process. In this review, we summarize methodologies ranging from quantitative trait locus mapping to resequencing used in genetic analyses of crop evolution. We also highlight recent major insights regarding the timing and spatial patterning of crop domestication and the distinct genetic underpinnings of domestication, diversification and improvement traits. PMID- 20541453 TI - Ligational, analytical and biological applications on oxalyl bis(3,4 dihydroxybenzylidene) hydrazone. AB - The molecular modeling and parameters have been calculated to confirm the geometry of oxalyl bis(3,4-dihydroxybenzylidene) hydrazone, H(6)L. The metal complexes of Cr(3+), VO(2+), ZrO(2+), HfO(2+), UO(2)(2+) and MoO(2)(2+) with H(6)L have been prepared and characterized by partial elemental analysis, spectral studies (electronic; IR), thermal analysis and magnetic measurements. The data suggest the formation of polymer complexes with a unit [Cr(H(4)L)(H(2)O)(3)Cl].H(2)O, [VO(H(4)L)(H(2)O)(2)], [Hf(H(4)L)(H(2)O)].H(2)O [UO(2)(H(4)L)(H(2)O)(2)].2H(2)O [MoO(2)(H(4)L)] and [(ZrO)(2)(H(2)L) (C(2)H(5)OH)(2)]. The ligand behaves as a dibasic bidentate in all complexes except ZrO(2+) which acts as a tetrabasic tetradentate with the two ZrO(2+) ions. An octahedral geometry was proposed for the Cr(3+), HfO(2+), MoO(2)(2+)and UO(2)(2+) complexes and square pyramid for VO(2+). The Cr(3+) is necessary to degrade the DNA of eukaryotic subject completely; the other complexes have little effect. H(6)L was found suitable as a new reagent for the separation and preconcentration of ZrO(2+) ions from different water samples using flotation technique with satisfactory results. PMID- 20541454 TI - Study on the resonance nonlinear scattering spectra of the interactions of promethazine hydrochloride and chlorpromazine hydrochloride with 12 tungstophosphoric acid and their analytical applications. AB - In pH 1.0 HCl medium, 12-tungstophosphoric acid (TP) reacted with promethazine hydrochloride (PMZ) and chlorpromazine hydrochloride (CPZ) to form ion association complexes, which led to a great enhancement of the resonance nonlinear scattering such as second-order scattering (SOS) and frequency doubling scattering (FDS). Their maximum SOS and FDS peaks were located at 585 nm (TP PMZ), 584 nm (TP-CPZ) and 388 nm (TP-PMZ), 329 nm (TP-CPZ), respectively. These results provided some indication for the determination of PMZ and CPZ by SOS and FDS methods. The linear range of TP-PMZ and TP-CPZ systems were 0.0069-2.5 microg mL(-1), 0.102-5.0 microg mL(-1) (SOS) and 0.079-6.0 microg mL(-1), 0.0133-5.0 microg mL(-1) (FDS), respectively. The detection limits (3sigma) of PMZ and CPZ were 2.08 ng mL(-1), 3.07 ng mL(-1) (SOS) and 2.22 ng mL(-1), 3.98 ng mL(-1) (FDS), respectively. In this work, the optimum reaction conditions, the influences of coexisting substances and ionic strength and analytical application have been investigated. The methods have been successfully applied to the determination of PMZ and CPZ in tablets. In addition, the composition of ion association complexes and the reaction mechanism are also discussed. PMID- 20541455 TI - Synthesis, characterization, photophysical and oxygen-sensing properties of a novel europium(III) complex. AB - In this paper, we report the synthesis, characterization, crystal structure, and photophysical properties of a novel Eu(3+) complex of Eu(DBM)(3)IPD, where DBM=1,3-diphenyl-propane-1,3-dione and IPD=4-(1H-imidazo[4,5 f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline. Its elementary application for oxygen-sensing application is also investigated by doping it into a silica matrix of MCM-41. Experimental data suggest that the 20mg/g doped Eu(DBM)(3)IPD/MCM-41 system exhibits a high sensitivity of 3.6 towards molecular oxygen with a good linear relationship of R(2)=0.9987. In addition, the 20 mg/g doped Eu(DBM)(3)IPD/MCM-41 system owns a quick response of 8 s towards oxygen, along with its excellent atmosphere insensitivity and photobleaching resistance. All these results suggest that both Eu(DBM)(3)IPD and Eu(DBM)(3)IPD/MCM-41 systems are promising candidates for oxygen-sensing optical sensors. PMID- 20541456 TI - Synthesis and spectroscopic properties of novel asymmetric Schiff bases. AB - Three novel diimine Schiff bases including two asymmetric imines (2-OH)R-CHN C(6)H(4)-CHN-R'(2-OH) type [where R=R'=phenyl for H(2)L(1); R=naphthyl, R'=phenyl for H(2)L(2) and R=R'=naphthyl for H(2)L(3)] have been synthesized with a new two step method. For this purpose, the starting Schiff bases 4-nitrobenzylidene-2 hydroxyaniline (SB(1)-NO(2)) and 4-nitrobenzylidene-2-hydroxy-3-naphthylamine (SB(2)-NO(2)) have been synthesized, previously. Nitro groups of them have been reduced into their amino derivatives (SB(1)-NH(2) and SB(2)-NH(2)) with sodium dithionite as selective reductant and the other imino groups have been formed by adding salicylaldehyde or 2-hydroxy-1-naphthaldehyde to the same solutions. The structures of the diimine Schiff bases were confirmed by elemental analyses, ESI MS, FT-IR, (1)H NMR and (13)C NMR spectroscopy. The phenol-imine and keto-amine tautomerism of the Schiff bases were investigated by FT-IR, (1)H NMR, (13)C NMR techniques and UV-vis spectra in different solvents (DMSO, methanol, chloroform, toluene and cyclohexane). The effects of acidic and basic media on the tautomeric equilibria were discussed. PMID- 20541457 TI - Effect of nano-clay platelets on the J-aggregation of thiacyanine dye organized in Langmuir-Blodgett films: a spectroscopic investigation. AB - In this paper we report the effect of the incorporation of nano-dimensional clay platelets, laponite, on the J-aggregation of a thiacyanine dye N,N'-dioctadecyl thiacyanine perchlorate (NK) assembled into Langmuir-Blodgett (LB) monolayers. pi A isotherms and atomic force microscopic studies confirm the successful incorporation of clay platelets into the Langmuir monolayer of NK. J-aggregates of NK remain present in LB films lifted at lower as well as higher surface pressures in the absence of laponite clay platelets. However, with the incorporation of clay platelets, J-aggregates are formed only in LB films lifted at higher surface pressure of 30 mN/m and totally absent in the films lifted at lower surface pressures of 10 and 15 mN/m. This may be due to the formation of nano-trapping level by overlapping of clay platelets at higher surface pressure. NK molecules may get squeezed to these nano-trapping to form J-aggregates. PMID- 20541458 TI - Theoretical studies of EPR spectra and defect structure for Er3+ center in lithium niobate. AB - The optical and EPR spectra of octahedral Er(3+) center in LiNbO(3) have been studied by diagonalizing 364 x 364 complete energy matrices. The new set of crystal-field parameters that can well account for the Stark levels and EPR parameters have been obtained for Er(3+) ions in LiNbO(3). Simultaneously, by simulating the most reliable six-order parameter B(60) obtained, we have presented the evidence that the Er(3+) ions do not occupy the actual Li(+) site, but have a displacement along the C(3)-axis away from the Li(+) center by about 0.0454 nm. The conclusion is well in accord with that drawn by earlier workers. PMID- 20541459 TI - Flower cells in patients with infective dermatitis associated with HTLV-1. AB - BACKGROUND: Infective dermatitis associated with HTLV-1 (IDH) is a severe childhood form of eczema that may progress to adult T-cell leukemia/lymphoma (ATL). OBJECTIVE: In this study, the presence of clinical and laboratory parameters suggestive of ATL was evaluated in a cohort of 30 patients with IDH. STUDY DESIGN: Over a period of 33 months, the patients were submitted to three monthly clinical evaluations, routine laboratory exams, full blood count and blood smears, and to six-monthly blood sampling for HTLV-1 proviral load determination. HTLV-1 proviral load was quantified using real-time TaqMan PCR assay. RESULTS: Abnormal cells (Ably) were found in the peripheral blood smears of nine patients (30%), flower cells being detected in five of these cases (16.6%). The presence of Ably and flower cells was not associated with a higher proviral load in those patients. CONCLUSIONS: This is the first report on the presence of flower cells in HTLV-1-infected children and adolescents. Furthermore, these cells have not previously been reported in IDH patients. The cases with flower cells probably represent precursory ATL cases, these patients being at a greater risk of developing ATL. PMID- 20541460 TI - Effects of repetition rate of bone-conducted vibration on ocular and cervical vestibular-evoked myogenic potentials. AB - OBJECTIVE: This study applied bone-conducted vibration (BCV) stimuli at various repetition rates to investigate the effects of repetition rate on both ocular and cervical vestibular-evoked myogenic potentials (oVEMPs and cVEMPs). METHODS: Twenty-five healthy subjects underwent oVEMP tests in BCV mode at repetition rates of 1, 5, 10, 20, 30 and 40Hz. The optimal repetition rates (5, 10 and 20Hz) for oVEMPs were also adopted to elicit cVEMPs, and 20Hz stimuli were further evaluated in pathological ears. RESULTS: At repetition rates of 1, 5, 10, 20, 30 and 40Hz, the prevalence of clear oVEMPs were 100% in groups of 5, 10 and 20Hz, with no significant differences in the mean nI latency, but the mean nI-pI amplitude of the 20Hz group showed significantly larger. For the BCV-cVEMPs, 5, 10 and 20Hz stimuli yielded similar information. Clinically, the BCV mode at 20Hz stimuli was also appropriate for evaluating VEMPs in ears of vestibular schwannoma. CONCLUSIONS: The BCV mode at a repetition rate of 20Hz is recommended for the mass detection of VEMPs. SIGNIFICANCE: Eliciting VEMPs in BCV mode using 20Hz stimuli takes a short time and may trigger a high prevalence with large amplitude. PMID- 20541461 TI - Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: an EEG study. AB - OBJECTIVE: Locked-in syndrome (LIS) is a state of complete paralysis, except for ocular movements, which results from ventral brainstem lesions. Patients typically are fully conscious. Here we tested the hypothesis that electroencephalographic (EEG) rhythms are abnormal in LIS patients, possibly due to an impaired neural synchronization between brainstem and cerebral cortex. METHODS: Resting state eyes-closed EEG data were recorded in 13 LIS subjects and 15 cognitively normal control subjects. With reference to the individual alpha frequency (IAF), the bands of interest were delta (IAF-8 to IAF-6Hz), theta (IAF 6 to IAF-4Hz), alpha 1 (IAF-4 to IAF-2Hz), alpha 2 (IAF-2 to IAFHz), and alpha 3 (IAF to IAF+2Hz). Furthermore, beta 1 (13-20Hz) and beta 2 (20-30Hz) bands were also considered. Cortical EEG sources were estimated by low-resolution electromagnetic tomography (LORETA). RESULTS: The power of alpha 2 and alpha 3 sources in all regions was lower in patients with LIS compared to controls. The power of delta sources in central, parietal, occipital and temporal regions was higher in patients with LIS compared to controls. CONCLUSIONS: These results suggest that cortical sources of resting state eyes-closed alpha and delta rhythms are abnormal in LIS patients. SIGNIFICANCE: LIS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition. PMID- 20541462 TI - Changes in movement-related beta-band EEG signals in human spinal cord injury. AB - OBJECTIVE: The purpose of this study was to characterize differences in movement related beta-band signals of the brain between people with chronic spinal cord injury (SCI) and neurologically intact volunteers. METHODS: A 64 channel EEG system was used to record EEG while subjects attempted brisk toe plantar flexion in response to auditory cues. Change in amplitude in beta-band frequencies during times of event-related desynchronization and synchronization (ERD and ERS) and topography of ERD and ERS were compared across groups and correlated to ASIA motor and sensory impairment scores for SCI subjects. RESULTS: ERS amplitude immediately following the movement attempt was significantly smaller (t-test; p<0.001) in SCI subjects as compared to controls. The ERD change tended to be greater and the topography was more widespread in SCI subjects. Incomplete SCI subjects with more severe neurological injury (lesser ASIA motor score) had lower peak ERS amplitude and a significant correlation was observed between sensorimotor impairments and ERS amplitude (r(2)=0.79; p=0.02). CONCLUSIONS: Our results suggest that motor processing in the brain is altered after SCI, and that it occurs in proportion to the severity of neurological injury. SIGNIFICANCE: These results are important for brain computer interface applications that rely on ERD and ERS pattern recognition. PMID- 20541463 TI - Epithelioid angiosarcoma of the lung with pleural metastases: a rare cause of haemoptysis clinicopathological conference. AB - Angiosarcomas are a rare type of malignant vascular tumour characterised by proliferation of tumour cells with vascular endothelial features. These tumours are usually very aggressive and overall mortality is very high. Pulmonary angiosarcomas are usually secondary tumours, and only a few primary cases have been reported. We present a case of a 56 year-old male with persistent haemoptysis secondary to lung epithelioid angiosarcoma with pleural metastases. PMID- 20541464 TI - Male hypogonadism associated with advanced cancer: a systematic review. AB - Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life. PMID- 20541465 TI - Lung cancer after treatment for breast cancer. AB - Breast cancer is the most common cancer in women, and the second most common cause of cancer death after lung cancer. Improvements in the outcome of breast cancer mean that more patients are living longer and are, therefore, at risk of developing a second malignancy. The aim of this review is to present the current understanding of the risk of lung cancer arising in patients previously treated for early stage breast cancer. We review data on the effect of treatment factors (ie, surgery type, radiotherapy technique, and adjuvant chemotherapy) and patient factors (ie, age and smoking) on the risk of developing a subsequent lung cancer. The evidence suggests that older radiotherapy techniques were associated with a substantially increased risk of developing lung cancer in the ipsilateral lung, but there is no clear evidence of an increased risk with modern techniques. Smoking is an important risk factor, and increases the risk of lung cancer in those receiving radiotherapy. Adjuvant chemotherapy is not significantly associated with an increased risk. The risk of developing lung cancer increases with time elapsed since treatment, but any effect of age at treatment is unclear. PMID- 20541466 TI - MiRNAs as biomarkers and therapeutic targets in cancer. AB - The knowledge that miRNA expression is frequently dysregulated in cancer has uncovered an entirely new repertoire of molecular factors upstream of gene expression, with exciting potential as novel biomarkers and therapeutic targets in cancer. Exploiting the unique characteristics of these molecules including their stability, tissue specificity, ease of detection and manipulation, will bring clinicians ever closer to achieving the goal of individualized cancer treatment. We present a comprehensive and timely review of the role of miRNAs in cancer. Herein we address briefly miRNA biogenesis, the putative role of miRNAs as oncogenes or tumor suppressors, and their potential as sensitive and specific tumor markers with particular emphasis on the commonest cancers; breast, prostate, lung and colorectal. We also discuss circulating tumor-associated miRNAs which are emerging as clinically useful tools for early detection, prognostication and management of various cancers. Finally we explore their potential therapeutic applications in the field of cancer and highlight some of the potential challenges that need to be overcome in order to bring miRNAs from bench to bedside. Given the evidence to date, we envisage a pivotal role for miRNAs in the future individualized management of cancer patients. PMID- 20541467 TI - Successful birth following transfer of frozen-thawed embryos produced from in vitro matured oocytes. AB - It is well established that ovarian hyperstimulation syndrome (OHSS) is more frequent in patients with polycystic ovarian syndrome. In-vitro maturation (IVM) of immature oocytes presents a potential alternative for the fertility treatment and prevention of OHSS for these patients. This report describes the case of a 26 year old woman with a successful pregnancy and delivery following the transfer of frozen-thawed embryos derived from in-vitro matured oocytes. She had three failed cycles of ovarian stimulation (using low-dose step-up gonadotrophin protocol) with or without intrauterine insemination cycles, an ovulation-induction cycle with luteal long protocol, two fresh IVM cycle and one frozen-thawed IVM cycle. During the IVF cycle, she developed moderate OHSS and required hospitalization for 3 weeks. Following four unsuccessful IVF or IVM cycles, 15 months after the last cryopreservation, six fertilized oocytes were thawed for a scheduled embryo transfer. Following thawing, four fertilized oocytes survived and cleaved. Four frozen-thawed embryos were transferred. Six weeks after embryo transfer an ongoing intrauterine single pregnancy with fetal heartbeat was confirmed by transvaginal ultrasound. An uneventful pregnancy and delivery via Caesarean section at 39 weeks resulted in the birth of a normal healthy infant. PMID- 20541468 TI - Hysteroscopic findings in women with two and with more than two first-trimester miscarriages are not significantly different. AB - The purpose of this study was to analyse hysteroscopic results in patients with recurrent miscarriages and to compare the frequency of uterine anomalies in women with a history of exactly two and with more than two consecutive miscarriages. A retrospective analysis of 206 patients undergoing hysteroscopy for repeated early pregnancy losses was performed at two university centres. Late miscarriages were excluded, terminations of pregnancy were not counted. Eighty-seven patients had suffered from exactly two early miscarriages and 119 from more than two. Both groups were comparable with respect to age at admission (32.95+/-4.46 versus 34.06+/-5.02 years) and at first miscarriage (30.43+/-4.24 versus 29.08+/-5.38 years). The prevalence of acquired (adhesions, polyps, fibroids) and congenital uterine anomalies (septate or bicornuate uterus, etc.) did not differ significantly (acquired: 28.7 versus 27.7%; congenital: 9.2 versus 16.8%). The rates of uterine anomalies did not differ significantly overall (36.8 versus 42.9%). In conclusion, uterine anomalies are frequently found in patients with two and with more than two early miscarriages. Due to the high rate of anomalies, their risk for adverse pregnancy outcome and a possible therapeutic approach, hysteroscopy might be a diagnostic option even after two early miscarriages. PMID- 20541469 TI - Successful application of preimplantation genetic diagnosis for hypokalaemic periodic paralysis. AB - Hypokalaemic periodic paralysis is a rare dominant inherited disease where a person suffers sudden falls of circulating potassium concentrations, producing muscle weakness and sometimes severe paralysis. Attacks can occur as frequently as several times a day or once in a year. The age of onset is usually adolescence but symptoms can appear as early as 10 years of age. Muscle weakness can compromise vital functions such as breathing or swallowing and heart arrhythmias are also frequent during attacks. Preimplantation genetic diagnosis, an early form of prenatal diagnosis for couples at risk of transmitting inherited diseases, was used to prevent the transmission of this disease. Six polymorphic short tandem repeat or microsatellite markers (STR) closely linked to the CACNA1S gene were tested. Three fully informative markers were chosen to establish the disease-bearing haplotype in the family and to determine the genetic status of five embryos by multiplex fluorescent heminested PCR. Four of the five embryos tested were diagnosed as non-affected and one as affected. Two embryos were transferred resulting in a singleton pregnancy and the birth of a healthy girl. PMID- 20541470 TI - Dutch technical specification (NTA 8070) on devices for assisted reproductive technologies. AB - In 2006 the Dutch Society for Clinical Embryologists (KLEM) approached the Netherlands Standardisation Institute (NEN) for advice regarding the lack of safety and quality specifications for medical devices used in assisted reproductive technology. A project plan was drafted in accordance with NEN standardized methods for the development of norms and Dutch technical specifications (NTA) and a working group was launched consisting of all interested parties. A framework was then set up to develop an NTA that focused on the safety of gametes, embryos and the unborn offspring. The three main parts of the NTA describe the classification of medical devices, the requirements for new and existing devices and testing methods. The content of the NTA can be considered mainly as a consensus of the participants in the working group from both industry and clinical embryologists (KLEM). A final draft was sent to representatives from or allied to the government and to a notified body, and NTA 8070, entitled Devices for Assisted Reproductive Technologies (ART), was issued in March 2008. PMID- 20541471 TI - HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation. AB - The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. PMID- 20541472 TI - Erythropoietic differentiation of a human embryonic stem cell line harbouring the sickle cell anaemia mutation. AB - Herein is reported efficient erythropoietic differentiation of a human embryonic stem cell (ESC) line derived from a preimplantation genetic diagnosis (PGD) screened embryo that harbours the homozygous sickle cell disease (SCD) haemoglobinopathy mutation. This human ESC line possesses typical pluripotency characteristics and forms multilineage teratomas in vivo. SCD-human ESC efficiently differentiated to the haematopoietic lineage under serum-free and stromal co-culture conditions and gave rise to robust primitive and definitive erythrocytes. Expression of embryonic, fetal and adult sickle globin genes in SCD PGD-derived human ESC-derived erythrocytes was confirmed by quantitative real time PCR, intracytoplasmic fluorescence-activated cell sorting and in-situ immunostaining of PGD-derived human ESC teratoma sections. These data introduce important methodologies and paradigms for using patient-specific human ESC to generate normal and haemoglobinopathic erythroid progenitors for biomedical research. PMID- 20541474 TI - Re: Harry Fisch et al.: Rising hypospadia rates: disproving a myth. (Journal of Pediatric Urology 2010; 6: 37-39). PMID- 20541473 TI - Penile ischemic injury in the exstrophy/epispadias spectrum: new insights and possible mechanisms. AB - OBJECTIVE: Partial or complete penile loss following bladder exstrophy and/or epispadias repair has been reported in the literature progressively more frequently. PATIENTS AND METHODS: The authors report new cases of penile injury following bladder exstrophy and/or epispadias repair referred to their centers and not previously published. They review the literature on this subject and offer an explanation as to the likely mechanism for the penile injury and recommendations to avoid this complication. RESULTS: Seven new cases of partial or complete penile loss following bladder exstrophy or epispadias repair have been recently referred to the authors' institutions. Twenty-one patients have previously been reported in the literature. Altogether, 24 cases occurred after bladder exstrophy closure: 23 after complete primary repair of exstrophy (Mitchell repair) and one after first-stage radical soft-tissue mobilization (Kelly repair). Nineteen of 24 patients did not have a pelvic osteotomy at the time of primary closure. Four cases occurred after epispadias repair: two following the second-stage radical soft-tissue mobilization (Kelly repair) and two following penile disassembly epispadias repair (Mitchell repair). CONCLUSION: Exstrophy closure combined with epispadias repair can be followed by ischemic penile injury, particularly when osteotomy is not performed. Compression of the pudendal vessels after pubic apposition and/or direct injury to the pudendal vessels play an important role in the pathogenesis of this complication. PMID- 20541475 TI - Laparoscopic orchiopexy for non-palpable testes: outcome of two techniques. AB - OBJECTIVE: To assess the outcome of laparoscopic orchiopexy and the two-stage Fowler Stephens technique for managing patients with impalpable testis in terms of safety, feasibility and efficacy. PATIENTS AND METHODS: This study included 78 patients who presented with 88 non-palpable testes to the outpatient clinic of Sohag university hospital in 2005-2009, and underwent laparoscopy by the same surgeon. Intra-abdominal testes were managed by laparoscopic orchiopexy if low, two-stage Fowler-Stephens technique if high, and orchiectomy if atrophic. Children were evaluated postoperatively to check the location and size of the testicle and to exclude any other complication. RESULTS: Median age at presentation was 16 months (range 11-42 months). Four testes were absent while inguinal exploration was necessary for six testes with the vas entering the internal ring. Of the 78 intra-abdominal testes, 45 were identified as high (Fowler-Stephens in 43; orchiectomy in two atrophic testes) and 33 as low (orchiopexy). Follow up was 3-55 months (mean 34 months). Twelve patients (12 testes) were lost to follow up (7 Fowler-Stephens; 5 orchiopexy). On follow up, the testes were normal sized and well positioned in the scrotum in 28/28 and 32/36 testes in the orchiopexy and Fowler-Stephens groups with an overall success rate of 100% and 88.8%, respectively. Two testes showed testicular displacement and two showed testicular atrophy in patients of the Fowler-Stephens group. CONCLUSION: Laparoscopy provides a safe and accurate modality for diagnosing and managing patients with non-palpable testes, with excellent outcomes. PMID- 20541476 TI - Back disorders among Israeli youth: a prevalence study in young military recruits. AB - BACKGROUND CONTEXT: Back problems are reported with increasing frequency in adults and adolescents. Most information is from self-reported questionnaires or studies with small sample sizes. Reports were usually focused on specific diseases and biased toward overdiagnosis. PURPOSE: To assess the prevalence of common back disorders among a large cohort of 17-year-old males and females recruited by the Israel Defense Forces (IDF). STUDY DESIGN: A retrospective cross sectional prevalence study. PATIENT SAMPLE: Seventeen-year-old Israeli male and female military recruits reporting as directed by the IDF for preinduction medical examination between January 01, 1998 and December 31, 2006. OUTCOME MEASURES: Military functional limitation Grades 1 to 7 per diagnosis category. METHODS: Military recruits were examined and classified based on medical and orthopedic diagnoses. They were referred for orthopedic consultation as necessary. Four orthopedic classifications were used: spinal deformity (including kyphosis and scoliosis), back pain (including neck and radicular syndromes), spondylolysis/olisthesis, and limitations resulting from trauma or spinal surgery. Data were coded into a central database, and descriptive statistics are presented. RESULTS: The overall prevalence of back disorders among 828,171 17 year-old military recruits (61.5% male) was 16.8%. Back disorders resulting in significant functional limitation were diagnosed in 0.8% of recruits. The most prevalent diagnoses were spinal deformities (kyphosis and scoliosis, females 11.9%, males 11.5%) and back pain (females 3.0%, males 5.6%). Most of these diagnoses were rated as mild. CONCLUSIONS: When using objective criteria, overall back disorders in a large population of 17-year-old recruits were 17%, considerably lower than most reports. Back morbidity severe enough to prevent combat duty occurred at a rate of less than 1%, suggesting that serious back morbidity is not a frequent finding in this age group. LEVEL OF EVIDENCE: Symptom prevalence study, Level III. PMID- 20541478 TI - A promising biosensing-platform based on bismuth oxide polycrystalline-modified electrode: characterization and its application in development of amperometric glucose sensor. AB - Nano-structured bismuth oxide (nano-BiOx) is a suitable material for enzyme immobilization owing to its attractive properties, such as large specific surface area, suitable permeability of the resulting film, the high biocompatibility, and as well as photovoltaic effect from semiconductor nanoparticles. Thus, a new type of amperometric glucose biosensor based on nano-BiOx was constructed. The amperometric detection of glucose was assayed by potentiostating the GOD/nano BiOx electrode at 0.5 V to oxidize the enzymatically generated hydrogen peroxide. The proposed biosensor provided a linear response to glucose over a concentration range of 1 x 10(-6) M to 1.5 x 10(-3) M with a sensitivity of 51.0+/-0.4 mA/(M cm(2)) and a detection limit of 4 x 10(-7) M based on S/N=3. The apparent Michaelis-Menten constant was calculated to be 2.9 x 10(-3) M. In addition, characterization of nano-BiOx and modified electrode was performed by FT-IR spectroscopy, Raman spectroscopy, scanning electron microscope (SEM) and rotating disk electrode (RDE) voltammetry. PMID- 20541479 TI - Determination of haloacetic acids in human urine by headspace gas chromatography mass spectrometry. AB - Haloacetic acids (HAAs) are water disinfection byproducts (DBPs) formed by the reaction of chlorine oxidizing compounds with natural organic matter in water containing bromine. HAAs are second to trihalomethanes as the most commonly detected DBPs in surface drinking water and swimming pools. After oral exposure (drinking, showering, bathing and swimming), HAAs are rapidly absorbed from the gastrointestinal tract and excreted in urine. Typical methods used to determine these compounds in urine (mainly from rodents) only deal with one or two HAAs and their sensitivity is inadequate to determine HAA levels in human urine, even those manual sample preparation protocols which are complex, costly, and neither handy nor amenable to automation. In the present communication, we report on a sensitive and straightforward method to determine the nine HAAs in human urine using static headspace (HS) coupled with GC-MS. Important parameters controlling derivatisation and HS extraction were optimised to obtain the highest sensitivity: 120 microl of dimethylsulphate and 100 microl of tetrabutylammonium hydrogen sulphate (derivatisation regents) were selected, along with an excess of Na(2)SO(4) (6 g per 12 ml of urine), an oven temperature of 70 degrees C and an equilibration time of 20 min. The method developed renders an efficient tool for the precise and sensitive determination of the nine HAAs in human urine (RSDs ranging from 6 to 11%, whereas LODs ranged from 0.01 to 0.1 microg/l). The method was applied in the determination of HAAs in urine from swimmers in an indoor swimming pool, as well as in that of non-swimmers. HAAs were not detected in the urine samples from non-swimmers and those of volunteers before their swims; therefore, the concentrations found after exposure were directly related to the swimming activity. The amounts of MCAA, DCAA and TCAA excreted from all swimmers are related to the highest levels in the swimming pool water. PMID- 20541477 TI - The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. AB - MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the polymerase associated factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates posttranslational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knockdown of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is downregulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis. PMID- 20541480 TI - Disentangling nutritional factors and household characteristics related to child stunting and maternal overweight in Guatemala. AB - The aim of this study was to identify nutritional factors and households characteristics associated with child stunting, maternal overweight and the familial coexistence of both types of malnutrition. In Guatemala, 2000, with nationally representative data, we selected 2261 households with at least one child aged 12-60 months and his/her mother. Nutritional status was assessed in children (e.g., stunting as height-for-age Z-score<-2) and mothers (e.g., overweight as body mass index > or =25 kg/m(2)) and identified the presence of both, child stunting and maternal overweight in the same household (SCOM). With logistic regression models we assessed the association of the malnutrition indicators with individual and household socio-economic and health characteristics. SCOM was identified in 18% of households. Socio-economic status (SES) of SCOM households was significantly lower than SES of households with non stunted children. SCOM households, compared to those with normal-stature children and normal weight mothers, were more likely to have mothers of short stature (adjusted odds ratio-OR+/-95% CI=3.1 (2.1-4.7)), higher parity (1.2 (1.1-1.3)), currently working (1.7 (1.1-2.6), and self-identified as indigenous (2.0 (1.3 3.1)). Factors associated with stunting in children such as poverty, maternal short stature and indigenousness, were predictors of SCOM. These findings support the notion that SCOM is an extension of the malnutrition spectrum in the most disadvantaged population groups in countries that are in the middle of their nutrition transitions such as Guatemala. At the same time it revealed that these populations are already in the stage of chronic, nutrition related diseases associated with less physical activity and more access to highly processed foods of low cost, high dietary energy and low nutrient density in important population groups. The challenge for the decision makers and service deliverers is to guide SCOM households to deal equally with both extremes of the malnutrition continuum. PMID- 20541481 TI - [New diagnostic criteria for gestational diabetes mellitus after the HAPO study. Are they valid in our environment?]. PMID- 20541482 TI - [Acquired hypogonadotropic hypogonadism in a man with primary empty sella turcica]. PMID- 20541483 TI - Adolescents with and without a facial difference: The role of friendships and social acceptance in perceptions of appearance and emotional resilience. AB - This study investigated the role of friendships and social acceptance in self perceptions of appearance and depressive symptoms, comparing adolescents with and without a facial difference. Adolescents with a visible cleft (n=196) were compared with adolescents with a non-visible cleft (n=93), and with a comparison group (n=1832). Boys with a visible difference reported significantly more positive perceptions of friendships and less depressive symptoms than the comparison group. These results were interpreted in the context of indicators of emotional resilience. The objective measure of facial difference did not explain levels of depressive symptoms, while subjective measures did. Subjective ratings of appearance mediated the association between social acceptance and depressive symptoms in all samples. Gender did not contribute in explaining the paths between friendships, appearance, and depressive symptoms. The associations between perceptions of social acceptance, appearance, and emotional distress, support the possible utility of strengthening social experiences in preventing and treating appearance-concerns. PMID- 20541484 TI - Brief report: The use of dermal autograft for fascial repair of TRAM flap donor sites. AB - Reconstruction of the breast and other tissues by the transverse rectus abdominis myocutaneous (TRAM) flap is an accepted, reliable technique with a high success rate. Closure of the anterior rectus sheath defect that results from this flap has been the subject of debate, since hernia formation is considered a risk. We have reviewed 20 patients from a consecutive series of free TRAM and pedicled TRAM flaps using dermal autograft removed from zone IV of the flap and 117 patients using mesh, and assessed the complication of these techniques. Average follow-up time was 21.7 months (ranged 5 months to 4 years). There was one wound infection (5%) and one bulging (5%) in the dermal autograft group and 2 (1.7) bulgings, 3 (0.85) hernias and 2 (1.7) infections in the mesh group. There was no significant difference in the complication rate between the two techniques though. We conclude that the principal advantages of the dermal autograft in TRAM flap donor site closure are ease of use, economy and the benefit of using an autologous, biological material. PMID- 20541485 TI - Using pharmacy data to screen for look-alike, sound-alike substitution errors in pediatric prescriptions. AB - OBJECTIVE: The aim of this study was to pilot test a screening approach to detect potential look-alike, sound-alike (LASA) errors in pediatric outpatient prescriptions. METHOD: Medicaid pharmacy claims from one state were reviewed. From a list of LASA drug pairs, we identified candidate pairs meeting the following criteria: 1) one drug was commonly prescribed in children; 2) the paired drug was uncommonly prescribed for children; and 3) both drugs were available as oral preparations only, resulting in 11 LASA pairs. We identified patients who usually received one drug in a pair, then presented with a first dispensing of the paired drug, representing a "screening alert" for potential LASA error. We determined a "true error" as any patient who triggered a screening alert, received only one dispensing of the paired drug in the subsequent 6 months, and had no diagnoses supporting the dispensing of the paired drug. RESULTS: Among the 22 test drugs, there were 1 420 091 prescriptions to 173 005 subjects. There were 395 screening alerts generated, representing a screening alert frequency of 0.28 screening alerts per 1000 prescriptions. We identified 43 true LASA errors. In the dataset, the overall LASA error rate is estimated to be approximately 0.00003%, or 0.03 LASA errors per 1000 prescriptions. CONCLUSION: Prescription dispensing patterns can be used to screen for LASA errors in pediatric prescriptions. The rates of pediatric LASA errors appear to be much lower than other types of pediatric medication errors and may be best addressed by automated processes. PMID- 20541486 TI - Gastric adenocarcinoma and Helicobacter pylori: correlation with p53 mutation and p27 immunoexpression. AB - INTRODUCTION: Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27(KIP1) is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations. GOALS: To verify the relationship among H. pylori infection, p53 mutations and p27(Kip1) Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression. RESULTS: From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(-), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations. CONCLUSIONS: The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer. PMID- 20541487 TI - A non-blood pressure-measuring student of hypertension looks at blood pressure variability. PMID- 20541488 TI - The scuttle fly. PMID- 20541489 TI - Motor learning. AB - Although learning a motor skill, such as a tennis stroke, feels like a unitary experience, researchers who study motor control and learning break the processes involved into a number of interacting components. These components can be organized into four main groups. First, skilled performance requires the effective and efficient gathering of sensory information, such as deciding where and when to direct one's gaze around the court, and thus an important component of skill acquisition involves learning how best to extract task-relevant information. Second, the performer must learn key features of the task such as the geometry and mechanics of the tennis racket and ball, the properties of the court surface, and how the wind affects the ball's flight. Third, the player needs to set up different classes of control that include predictive and reactive control mechanisms that generate appropriate motor commands to achieve the task goals, as well as compliance control that specifies, for example, the stiffness with which the arm holds the racket. Finally, the successful performer can learn higher-level skills such as anticipating and countering the opponent's strategy and making effective decisions about shot selection. In this Primer we shall consider these components of motor learning using as an example how we learn to play tennis. PMID- 20541490 TI - The shadow of the future affects cooperation in a cleaner fish. AB - Humans show great flexibility in adjusting their levels of cooperation to account for current and future circumstances. For example, levels of cooperation are higher if there is more competition at the level of the whole population than with interacting partners and when individuals are likely to gain social prestige. Humans also show the capacity to increase current levels of cooperation to account for future payoffs if it is likely that repeated interactions will occur with the same partner (known as 'the Shadow of the Future'). Here, we provide the first evidence for this capacity in a non-human animal, the cleaner fish Labroides bicolor. L. bicolor individuals show uneven frequency of use of different areas within a large home range, which should in turn affect the delay between repeated interactions with individual reef fish 'clients'. In areas where the frequency of clients encountering cleaners is higher, cleaners are more likely to experience future costs of cheating, so future payoffs are of more concern for current decisions. In line with this, we found a negative correlation between cheating and the frequency of clients encountering cleaners in L. bicolor home ranges. PMID- 20541491 TI - Sexual behavior: dietary food switch induced by sex. AB - Pregnancy in humans induces cravings for special food: the same occurs in Drosophila females. New work now shows that mating throws a nutritional switch in favor of a high-protein diet and that modulation of nutritional balance depends on the sex peptide receptor and involves neuronal TOR-S6 kinase signaling. PMID- 20541492 TI - Musical consonance: the importance of harmonicity. AB - A recent study suggests that musical consonance is based on harmonicity, a preference that reflects the central role of harmonicity in auditory perception. PMID- 20541493 TI - Intergroup empathy: how does race affect empathic neural responses? AB - How does race affect the human ability to share and respond to the suffering of others? Recent evidence provides novel insight into how and why race alters empathic neural response. PMID- 20541494 TI - Epigenetic switching: bacteria hedge bets about staying or moving. AB - Growing populations of Bacillus subtilis exhibit bistability: motile cells co exist with long chains of sessile cells. An epigenetic switch has been characterized that controls the transition between the two cell types. PMID- 20541495 TI - Mating-system evolution: rise of the irresistible males. AB - Mating-system models have struggled to account for the high frequency of males found with hermaphrodites in a common Mediterranean shrub. The discovery of its unusual self-incompatibility system now provides an elegant and unexpected solution to the puzzle. PMID- 20541496 TI - Cytokinesis: ER keeps Mid1 in the middle. AB - How cells mark the region of the plasma membrane where the cleavage furrow will assemble is a classic question in cell biology. A new study has shown an unexpected role for cortically associated endoplasmic reticulum in positioning the site of cell division. PMID- 20541497 TI - Retinal processing: global players like it local. AB - A recent study of a specific type of retinal amacrine cell shows how a single interneuron can implement a large number of parallel feedback circuits, illustrating how highly complex circuits can be generated by a small number of neurons. PMID- 20541498 TI - Plasmodesmata formation: poking holes in walls with ise. AB - Secondary plasmodesmata are cytoplasmic channels connecting adjacent plant cells that arise after cell division. How membrane-delimited channels penetrate cell walls is unknown, but now two genes, ISE1 and ISE2, are shown to be required for pathways that limit their formation. PMID- 20541499 TI - Working memory: the importance of theta and gamma oscillations. AB - Working memory is the ability to actively hold information in the mind. Recent results demonstrate that working memory is organized by oscillatory processes in the theta and gamma frequency range. PMID- 20541500 TI - The lighter side of a sweet reaction. AB - The unique advantage of neutrons as biological probes is the ability to visualize hydrogen atoms in macromolecules. In this issue, Kovalevsky et al. (2010) solved an ensemble of xylose isomerase structures by neutron crystallography, and the determination of hydrogen atom rearrangements during the catalytic cycle provides insight into the enzyme's mechanism. PMID- 20541501 TI - Fibronectin structure: a new piece of the puzzle emerges. AB - In the structure of the gelatin binding domain (GBD) of fibronectin reported by Graille et al. (2010), both the zinc-mediated dimerization and the rearrangement of 8F(I) from the canonical F(I) fold are unexpected, suggesting interesting new directions for researchers in the field. PMID- 20541502 TI - Topoisomerase IB-DNA interactions: X marks the spot. AB - The observation made twenty years ago that type IB topoisomerases bound DNA helix helix juxtapositions was unexpected, given the controlled helical rotation mechanism of the enzyme. In this issue, Patel et al. (2010) provide an elegant structural explanation for this interaction. PMID- 20541503 TI - From poor resolution to rich insight. AB - In a recent Nature paper, the stability and convergence radius of low-resolution crystal structure refinement is improved by the addition of a deformable elastic network energy, which brings in higher-resolution information and preserves local interactions (Schroder et al., 2010). PMID- 20541504 TI - An approach for de novo structure determination of dynamic molecular assemblies by electron cryomicroscopy. AB - Single-particle electron cryomicroscopy is a powerful method for three dimensional (3D) structure determination of macromolecular assemblies. Here we address the challenge of determining a 3D structure in the absence of reference models. The 3D structures are determined by alignment and weighted averaging of densities obtained by native cryo random conical tilt (RCT) reconstructions including consideration of missing data. Our weighted averaging scheme (wRCT) offers advantages for potentially heterogeneous 3D densities of low signal-to noise ratios. Sets of aligned RCT structures can also be analyzed by multivariate statistical analysis (MSA) to provide insights into snapshots of the assemblies. The approach is used to compute 3D structures of the Escherichia coli 70S ribosome and the human U4/U6.U5 tri-snRNP under vitrified unstained cryo conditions, and to visualize by 3D MSA the L7/L12 stalk of the 70S ribosome and states of tri-snRNP. The approach thus combines de novo 3D structure determination with an analysis of compositional and conformational heterogeneity. PMID- 20541505 TI - Three-dimensional structure of TspO by electron cryomicroscopy of helical crystals. AB - The 18 kDa TSPO protein is a polytopic mitochondrial outer membrane protein involved in a wide range of physiological functions and pathologies, including neurodegeneration and cancer. The pharmacology of TSPO has been extensively studied, but little is known about its biochemistry, oligomeric state, and structure. We have expressed, purified, and characterized a homologous protein, TspO from Rhodobacter sphaeroides, and reconstituted it as helical crystals. Using electron cryomicroscopy and single-particle helical reconstruction, we have determined a three-dimensional structure of TspO at 10 A resolution. The structure suggests that monomeric TspO comprises five transmembrane alpha helices that form a homodimer, which is consistent with the dimeric state observed in detergent solution. Furthermore, the arrangement of transmembrane domains of individual TspO subunits indicates a possibility of two substrate translocation pathways per dimer. The structure provides the first insight into the molecular architecture of TSPO/PBR protein family that will serve as a framework for future studies. PMID- 20541506 TI - Metal ion roles and the movement of hydrogen during reaction catalyzed by D xylose isomerase: a joint x-ray and neutron diffraction study. AB - Conversion of aldo to keto sugars by the metalloenzyme D-xylose isomerase (XI) is a multistep reaction that involves hydrogen transfer. We have determined the structure of this enzyme by neutron diffraction in order to locate H atoms (or their isotope D). Two studies are presented, one of XI containing cadmium and cyclic D-glucose (before sugar ring opening has occurred), and the other containing nickel and linear D-glucose (after ring opening has occurred but before isomerization). Previously we reported the neutron structures of ligand free enzyme and enzyme with bound product. The data show that His54 is doubly protonated on the ring N in all four structures. Lys289 is neutral before ring opening and gains a proton after this; the catalytic metal-bound water is deprotonated to hydroxyl during isomerization and O5 is deprotonated. These results lead to new suggestions as to how changes might take place over the course of the reaction. PMID- 20541507 TI - Evolution in action: N and C termini of subunits in related T = 4 viruses exchange roles as molecular switches. AB - The T = 4 tetravirus and T = 3 nodavirus capsid proteins undergo closely similar autoproteolysis to produce the N-terminal beta and C-terminal, lipophilic gamma polypeptides. The gamma peptides and the N termini of beta also act as molecular switches that determine their quasi equivalent capsid structures. The crystal structure of Providence virus (PrV), only the second of a tetravirus (the first was NomegaV), reveals conserved folds and cleavage sites, but the protein termini have completely different structures and the opposite functions of those in NomegaV. N termini of beta form the molecular switch in PrV, whereas gamma peptides play this role in NomegaV. PrV gamma peptides instead interact with packaged RNA at the particle two-folds by using a repeating sequence pattern found in only four other RNA- or membrane-binding proteins. The disposition of peptide termini in PrV is closely related to those in nodaviruses, suggesting that PrV may be closer to the primordial T = 4 particle than NomegaV. PMID- 20541508 TI - Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding. AB - Fibronectin is a modular extracellular matrix protein involved in cell adhesion, cell motility, wound healing, and maintenance of cell morphology. It is composed of multiple repeats of three distinct modules: F(I), F(II), and F(III). Various combinations of these modules create fragments able to interact with different constituents of the extracellular matrix. Here, we present the 2.5-A resolution crystal structure of its 45-kDa gelatin-binding domain (GBD; 6F(I)-1F(II)-2F(II) 7F(I)-8F(I)-9F(I)), which also corresponds to the C-terminal half of the migration stimulating factor, a Fn splice variant expressed in human breast cancers. GBD forms a very compact zinc-mediated homodimer, in stark contrast with previous structures of fibronectin fragments. Most remarkably, 8F(I) no longer adopts the canonical F(I) fold but is composed of two long strands that associate with 7F(I) and 9F(I) into a large beta-sheet superdomain. Binding studies in solution confirmed that Zn induces conformational rearrangements and causes loss of binding of Fn-GBD to high-affinity collagen peptides. These data suggest the Zn may play a regulatory role for the cellular functions of fibronectin. PMID- 20541509 TI - Structure of the 100S ribosome in the hibernation stage revealed by electron cryomicroscopy. AB - In the stationary growth phase of bacteria, protein biosynthesis on ribosomes is suppressed, and the ribosomes are preserved in the cell by the formation of the 100S ribosome. The 100S ribosome is a dimer of the 70S ribosome and is formed by the binding of the ribosome modulation factor and the hibernation promoting factor. However, the binding mode between the two 70S ribosomes and the mechanism of complex formation are still poorly understood. Here, we report the structure of the 100S ribosome by electron cryomicroscopy and single-particle image analysis. The 100S ribosome purified from the cell in the stationary growth phase is composed of two transfer RNA-free 70S ribosomes, has two-fold symmetry, and is formed through interactions between their 30S subunits, where interactions between small subunit proteins, S2, S3 and S5, appear to be critical for the dimerization. PMID- 20541510 TI - Crystal structure of a bacterial topoisomerase IB in complex with DNA reveals a secondary DNA binding site. AB - Type IB DNA topoisomerases (TopIB) are monomeric enzymes that relax supercoils by cleaving and resealing one strand of duplex DNA within a protein clamp that embraces a approximately 21 DNA segment. A longstanding conundrum concerns the capacity of TopIB enzymes to stabilize intramolecular duplex DNA crossovers and form protein-DNA synaptic filaments. Here we report a structure of Deinococcus radiodurans TopIB in complex with a 12 bp duplex DNA that demonstrates a secondary DNA binding site located on the surface of the C-terminal domain. It comprises a distinctive interface with one strand of the DNA duplex and is conserved in all TopIB enzymes. Modeling of a TopIB with both DNA sites suggests that the secondary site could account for DNA crossover binding, nucleation of DNA synapsis, and generation of a filamentous plectoneme. Mutations of the secondary site eliminate synaptic plectoneme formation without affecting DNA cleavage or supercoil relaxation. PMID- 20541511 TI - Unusual target site disruption by the rare-cutting HNH restriction endonuclease PacI. AB - The crystal structure of the rare-cutting HNH restriction endonuclease PacI in complex with its eight-base-pair target recognition sequence 5'-TTAATTAA-3' has been determined to 1.9 A resolution. The enzyme forms an extended homodimer, with each subunit containing two zinc-bound motifs surrounding a betabetaalpha-metal catalytic site. The latter is unusual in that a tyrosine residue likely initiates strand cleavage. PacI dramatically distorts its target sequence from Watson-Crick duplex DNA base pairing, with every base separated from its original partner. Two bases on each strand are unpaired, four are engaged in noncanonical A:A and T:T base pairs, and the remaining two bases are matched with new Watson-Crick partners. This represents a highly unusual DNA binding mechanism for a restriction endonuclease, and implies that initial recognition of the target site might involve significantly different contacts from those visualized in the DNA bound cocrystal structures. PMID- 20541512 TI - Crystal structure of an intracellular subtilisin reveals novel structural features unique to this subtilisin family. AB - The intracellular subtilisin proteases (ISPs) are the only known members of the important and ubiquitous subtilisin family that function exclusively within the cell, constituting a major component of the degradome in many Gram-positive bacteria. The first ISP structure reported herein at a spacing of 1.56 A reveals features unique among subtilisins that has enabled potential functional and physiological roles to be assigned to sequence elements exclusive to the ISPs. Unlike all other subtilisins, ISP from B. clausii is dimeric, with residues from the C terminus making a major contribution to the dimer interface by crossing over to contact the partner subunit. A short N-terminal extension binds back across the active site to provide a potential novel regulatory mechanism of intrinsic proteolytic activity: a proline residue conserved throughout the ISPs introduces a kink in the polypeptide backbone that lifts the target peptide bond out of reach of the catalytic residues. PMID- 20541513 TI - Tsetse fly blood meal modification and trypanosome identification in two sleeping sickness foci in the forest of southern Cameroon. AB - The blood meal origins of 222 tsetse flies (213 Glossina palpalis palpalis, 7 Glossina pallicera pallicera, one Glossina nigrofusca and one Glossina caliginea) caught in 2008 in two Human African trypanosomiasis foci (Bipindi and Campo) of south Cameroon were investigated. 88.7% of tsetse flies blood meals were identified using the heteroduplex method and the origin of the remaining blood meals (11.3%) was identified by sequencing the cytochrome B gene. Most of the meals were from humans (45.9%) and pigs (37.4%), 16.7% from wild animals. Interestingly, new tsetse fly hosts including turtle (Trionyx and Kinixys) and snake (Python sebae) were identified. Significant differences were recorded between Bipindi where the blood meals from pigs were predominant (66.7% vs 23.5% from humans) and Campo where blood meals from humans were predominant (62.9% vs 22.7% from pigs). Comparison with the data recorded in 2004 in the same foci (and with the same molecular approach) demonstrated significant modifications of the feeding patterns: increase in blood meals from pigs in Bipindi (66.7% in 2008 vs 44.8% in 2004) and in Campo (20.5% in 2008 vs 6.8% in 2004), decrease in that from human (significant in Bipindi only). 12.6%, 8.1% and 2.7% of the flies were, respectively, Trypanosoma congolense forest type, Trypanosoma congolense savannah type and Trypanosoma brucei gambiense infected. These results demonstrate that tsetse fly feeding patterns can be specific of a given area and can evolve rapidly with time. They show an active circulation of a variety of trypanosomes in sleeping sickness foci of southern Cameroon. PMID- 20541514 TI - Simplified cysteine dioxygenase activity assay allows simultaneous quantitation of both substrate and product. AB - A high-performance liquid chromatography (HPLC) method for enzyme activity assays using a hydrophilic interaction liquid chromatography (HILIC) column in combination with an evaporative light scattering detector was developed. The method was used to measure the activity of the non-heme mono-iron enzyme cysteine dioxygenase. The substrate cysteine and the product cysteine sulfinic acid are very weak chromophores, making direct ultraviolet (UV) detection without derivatization rather insensitive; moreover, derivatization of cysteine is often not efficient. Using the system described, underivatized substrate and product in samples from cysteine dioxygenase activity assays could be separated and analyzed. Furthermore, it was possible to quantify cysteic acid, the noncatalytic oxidation product of cysteine sulfinic acid. Acetone was used both to stop the enzymatic reaction by protein precipitation and as an organic mobile phase, making sample preparation very easy and the assay highly reproducible. PMID- 20541515 TI - Polyamidoamine dendrimer as a spacer for the immobilization of glucose oxidase in capillary enzyme microreactor. AB - Polyamidoamine dendrimer (PAMAM) is one of a number of dendritic polymers with precise molecular structure, highly geometric symmetry, and a large number of terminal groups. In this study, different generations of PAMAM (G0-G4) were introduced onto the inner wall of fused-silica capillaries by microwave irradiation and a new type of glucose oxidase (GOx) capillary enzyme microreactor was developed based on enzyme immobilization in the prepared PAMAM-grafted fused silica capillaries. The optimal enzymolysis conditions for beta-d-glucose in the microreactor were evaluated by capillary zone electrophoresis. In addition, the enzymolysis efficiencies of different generations of PAMAM-GOx capillary enzyme microreactor were compared. The results indicate that enzymolysis efficiency increased with increasing generations of PAMAM. The experimental results provide the possibility for the development and application of an online immobilized capillary enzyme microreactor. PMID- 20541516 TI - Enzymatic preparation of high-specific-activity beta-D-[6,6'-3H]fructose-2,6 bisphosphate: Application to a sensitive assay for fructose-2,6-bisphosphatase. AB - beta-D-Fructose-2,6-bisphosphate (Fru-2,6-P(2)) is an important regulator of eukaryotic glucose homeostasis, functioning as a potent activator of 6 phosphofructo-1-kinase and inhibitor of fructose-1,6-bisphosphatase. Pharmaceutical manipulation of intracellular Fru-2,6-P(2) levels, therefore, is of interest for the treatment of certain diseases, including diabetes and cancer. [2-(32)P]Fru-2,6-P(2) has been the reagent of choice for studying the metabolism of this effector molecule; however, its short half-life necessitates frequent preparation. Here we describe a convenient, economical, one-pot enzymatic preparation of high-specific-activity tritium-labeled Fru-2,6-P(2). The preparation involves conversion of readily available, carrier-free d-[6,6' (3)H]glucose to [6,6'-(3)H]Fru-2,6-P(2) using hexokinase, glucose-6-phosphate isomerase, and 6-phosphofructo-2-kinase. The key reagent in this preparation, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from human liver, was produced recombinantly in Escherichia coli and purified in a single step using an appendant C-terminal hexa-His affinity tag. Following purification by anion exchange chromatography using triethylammonium bicarbonate as eluant, radiochemically pure [6,6'-(3)H]Fru-2,6-P(2) having a specific activity of 50 Ci/mmol was obtained in yields averaging 35%. [6,6'-(3)H]Fru-2,6-P(2) serves as a stable, high-specific-activity substrate in a facile assay capable of detecting fructose-2,6-bisphosphatase in the range of 10(-14) to 10(-15) mol, and it should prove to be useful in many studies of the metabolism of this important biofactor. PMID- 20541517 TI - Adaptation of an enzymatic polyfructosan assay to clinical practice. AB - Inulin or polyfructosan clearance is regarded as the most accurate method of assessing the glomerular filtration rate. We propose an enzymatic method of polyfructosan determination based on the hydrolysis of polyfructosan into fructose by inulinase and the elimination of the interfering quantity of glucose by glucose oxidase. This spectrophotometric microplate formatted assay, which demonstrated very good specificity and reproducibility (within-run precision <1% and between-run precision <3.5%), is cheap and simple to perform and can be used by all analytical laboratories and in all clinical conditions. PMID- 20541518 TI - A cautionary note on using N-acetylcysteine as an antagonist to assess isothiocyanate-induced reactive oxygen species-mediated apoptosis. AB - N-Acetylcysteine (NAC) has been widely used in cell culture-based studies for the role of reactive oxygen species (ROS) generation in apoptosis induction by isothiocyanates (ITCs). Here we have demonstrated, using [(14)C]phenethyl ITC and [(14)C]sulforaphane, that NAC pretreatment significantly reduces ITC cellular uptake by conjugating with ITCs in the medium, suggesting that reduced uptake of ITCs, rather than the antioxidant activity of NAC itself, is responsible for the diminished downstream apoptotic effects. The study provides a cautionary note on the assay in studying mechanisms of apoptosis by ITCs and other electrophilic and thiol-reactive compounds. PMID- 20541519 TI - Base pair opening kinetics and dynamics in the DNA duplexes that specifically recognized by very short patch repair protein (Vsr). AB - In Escherichia coli, the very short patch (VSP) repair system is a major pathway for removal of T.G mismatches in Dcm target sequences. In the VSP repair pathway, the very short patch repair (Vsr) endonuclease selectively recognizes a T.G mismatch in Dcm target sequences and hydrolyzes the 5'-phosphate group of the mismatched thymine. The hydrogen exchange NMR studies here revealed that the T5.G18 mismatch in the Dcm target sequence significantly stabilizes own base pair but destabilizes the two neighboring G4.C19 and A6.T17 base pairs compare to other T.G mismatches. These unusual patterns of base pair stability in the Dcm target sequence can explain how the Vsr endonuclease specifically recognizes the mismatched Dcm target sequence and intercalates into the DNA. PMID- 20541520 TI - Sterol metabolism and SREBP activation. AB - Cholesterol is one of the major components of membrane lipids. Adjustment of the membrane cholesterol balance is, therefore, pivotal in the maintenance of cellular homeostasis. Cholesterol biosynthesis and uptake are tightly regulated at the transcriptional level through a negative feedback control. The transcription factor family known as sterol regulatory element-binding proteins (SREBPs) is in charge of this feedback control. In particular, SREBP-2 is activated in a cholesterol-dependent manner, and hence is deeply involved in regulation of the expression of genes closely related to cholesterol metabolism. Sterol metabolites, including cholesterol, 24,25-dihydrolanosterol and oxysterols, strongly participate in the regulation of sterol metabolism via binding to its particular proteins. PMID- 20541521 TI - High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2. AB - The diverse biological activities of the insulin-like growth factors (IGF-1 and IGF-2) are mediated by the IGF-1 receptor (IGF-1R). These actions are modulated by a family of six IGF-binding proteins (IGFBP-1-6; 22-31 kDa) that via high affinity binding to the IGFs (K(D) approximately 300-700 pM) both protect the IGFs in the circulation and attenuate IGF action by blocking their receptor access. In recent years, IGFBPs have been implicated in a variety of cancers. However, the structural basis of their interaction with IGFs and/or other proteins is not completely understood. A critical challenge in the structural characterization of full-length IGFBPs has been the difficulty in expressing these proteins at levels suitable for NMR/X-ray crystallography analysis. Here we describe the high-yield expression of full-length recombinant human IGFBP-2 (rhIGFBP-2) in Escherichia coli. Using a single step purification protocol, rhIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern. The protein retained full biologic activity. This study represents the first high yield expression of wild-type recombinant human IGFBP-2 in E. coli and first structural characterization of a full-length IGFBP. PMID- 20541522 TI - Non-polymerizing long-pitch actin dimers that interact with myosin. AB - The production of a soluble actomyosin complex would be a significant step toward elucidating molecular interactions responsible for biological movement. We took a systematic approach to producing soluble long-pitch actin dimers that are polymerization-deficient yet retain biological protein-protein interactions, including myosin binding. Actin mutant proteins and chemical crosslinking were combined with different polymerization inhibition strategies, including ADP ribosylation, or the use of a polymerization-deficient actin mutant protein. While all of the long-pitch actin dimers retained interactions reflective of F actin activity, each displayed different interactions with myosin. Myosin did not interact productively with long-pitch actin dimers capped with DNase-I, and led to filament formation of unmodified long-pitch actin dimers or dimers possessing a polymerization-deficient actin subunit. However, ADP-ribosylated long-pitch actin dimers interacted with myosin, giving this dimer great potential for producing a soluble actomyosin complex, which could greatly improve our understanding of the molecular basis of movement in cells, tissues, and organisms. PMID- 20541523 TI - Structural polymorphism of non-covalent peptide-based delivery systems: highway to cellular uptake. AB - During the last two decades, delivery has become a major challenge for the development of new therapeutic molecules for the clinic. Although, several strategies either viral or non viral have been proposed to favor cellular uptake and targeting of therapeutics, only few of them have reach preclinical evaluation. Amongst them, cell-penetrating peptide (CPP) constitutes one of the most promising strategy and has applied for systemic in vivo delivery of a variety of therapeutic molecules. Two CPP-strategies have been described; using peptide carriers either covalently-linked to the cargo or forming non-covalent stable complexes with cargo. Peptide-based nanoparticle delivery system corresponds to small amphipathic peptides able to form stable nanoparticles with either proteins/peptides or nucleic acids and to enter the cell independently of the endosomal pathway. Three families of peptide-based nanoparticle systems; MPG, PEP and CADY have been successfully used for the delivery of various biologically active cargoes both ex vivo and in vivo in several animal models. This review will focus on the mechanism of the peptide-based nanoparticles; PEP, MPG and CADY in a structural and biophysical context. It will also highlight the major parameters associated to particle formation/stabilization and the impact of the carrier structural polymorphism in triggering cellular uptake. PMID- 20541524 TI - The structure of Aspergillus niger phytase PhyA in complex with a phytate mimetic. AB - Phytases hydrolyse the phosphomonoesters of phytate (myo-inositol-1,2,3,4,5,6 hexakis phosphate) and thus find uses in plant and animal production through the mobilisation of phosphorus from this source. The structure of partially deglycosylated Aspergillus niger PhyA is presented in apo form and in complex with the potent inhibitor myo-inositol-1,2,3,4,5,6-hexakis sulfate, which by analogy with phytate provides a snapshot of the Michaelis complex. The structure explains the enzyme's preference for the 3'-phosphate of phytate. The apo-and inhibitor-bound forms are similar and no induced-fit mechanism operates. Furthermore the enzyme structure is apparently unaffected by the presence of glycosides on the surface. The new structures of A. niger PhyA are discussed in the context of protein engineering studies aimed at modulating pH preference and stability. PMID- 20541525 TI - Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress. AB - The exposure to acute or chronic endoplasmic reticulum (ER) stress has been known to induce dysfunction of islets, leading to apoptosis. The reduction of ER stress in islet isolation for transplantation is critical for islet protection. In this study, we investigated whether tauroursodeoxycholate (TUDCA) could inhibit ER stress induced by thapsigargin, and restore the decreased glucose stimulation index of islets. In pig islets, thapsigargin decreased the insulin secretion by high glucose stimulation in a time-dependent manner (1h, 1.35+/-0.16; 2h, 1.21+/ 0.13; 4h, 1.17+/-0.16 vs. 0h, 1.81+/-0.15, n=4, p<0.05, respectively). However, the treatment of TUDCA restored the decreased insulin secretion index induced by thapsigargin (thapsigargin, 1.25+/-0.12 vs. thapsigargin+TUDCA, 2.13+/-0.19, n=5, p<0.05). Furthermore, the culture of isolated islets for 24h with TUDCA significantly reduced the rate of islet regression (37.4+/-5.8% vs. 14.5+/-6.4%, n=12, p<0.05). The treatment of TUDCA enhanced ATP contents in islets (27.2+/ 3.2pmol/20IEQs vs. 21.7+/-2.8pmol/20IEQs, n=9, p<0.05). The insulin secretion index by high glucose stimulation is also increased by treatment of TUDCA (2.42+/ 0.15 vs. 1.92+/-0.12, n=12, p<0.05). Taken together, we suggest that TUDCA could be a useful agent for islet protection in islet isolation for transplantation. PMID- 20541526 TI - Functional analysis of the honeybee (Apis mellifera L.) salivary system using proteomics. AB - In insects, specific proteins and physiologically active molecules whose functions are related to their lifestyles are secreted from the salivary system. To investigate proteins/molecules related to the sociality of the European honeybee (Apis mellifera L.), we performed a proteomic analysis of the honeybee salivary system. The honeybee salivary system comprises two secretory glands: the postcerebral gland (PcG) and the thoracic gland (TG), both of which are connected to a common duct that opens in the mouthpart. Although most (31 out of 35) of the major proteins identified from the PcG and TG were housekeeping proteins, the spot intensities for aldolase and acetyl-CoA acyltransferase 2 were stronger in the PcG than in the TG in the 2-dimensional gel electrophoresis. Immunoblotting confirmed that the expression of these proteins was stronger in the PcG than in the TG, whereas expression was almost not detectable in the hypopharyngeal gland (HpG), suggesting that carbohydrate metabolism is enhanced in the honeybee PcG. In addition, imaginal disc growth factor 4 (IDGF4) was synthesized in the honeybee salivary system. Immunoblotting indicated IDGF4 expression was very strong in the PcG, moderate in the TG, and very weak in the HpG. A considerable amount of IDGF4 was detected in the royal jelly, while less was detected in honey, strongly suggesting that the honeybee salivary system secretes IDGF4 into the royal jelly and honey. The secreted IDGF4 might therefore affect growth and physiology of the other colony members. PMID- 20541527 TI - In vitro dissection revealed that the kinase domain of wheat RNA ligase is physically isolatable from the flanking domains as a non-overlapping domain enzyme. AB - Wheat RNA ligase contains 5'-hydroxyl kinase, 2',3'-cyclic phosphate 3' phosphodiesterase, and 5'-phosphate 2'-phosphate-3'-hydroxyl RNA ligase activities in a 110-kDa polypeptide. Taking advantage of a wheat cell-free protein production system, we prepared various fragments containing a part of the enzyme. The method allowed us to check the activities of the fragments rapidly, eliminating the time-consuming cloning and sequencing steps for the expression of the fragment proteins. The results showed that each of the three activities can be assigned to a non-overlapping domain that does not require the presence of the other part(s) of the enzyme for its activity. This contrasts to the case of yeast tRNA ligase, in which the central kinase domain has been suggested to require to be tethered to one of the flanking domains for its activity. PMID- 20541528 TI - Access to gram scale amounts of functional globular adiponectin from E. coli inclusion bodies by alkaline-shock solubilization. AB - The adipose tissue derived protein adiponectin exerts anti-diabetic, anti inflammatory and anti-atherosclerotic effects. Adiponectin serum concentrations are in the microgram per milliliter range in healthy humans and inversely correlate with obesity and metabolic disorders. Accordingly, raising circulating adiponectin levels by direct administration may be an intriguing strategy in the treatment of obesity-related metabolic disorders. However production of large amounts of recombinant adiponectin protein is a primary obstacle so far. Here, we report a novel method for large amount production of globular adiponectin from E. coli inclusion bodies utilizing an alkaline-shock solubilization method without chaotropic agents followed by precipitation of the readily renaturing protein. Precipitation of the mildly solubilized protein capitalizes on advantages of inclusion body formation. This approach of inclusion body protein recovery provides access to gram scale amounts of globular adiponectin with standard laboratory equipment avoiding vast dilution or dialysis steps to neutralize the pH and renature the protein, thus saving chemicals and time. The precipitated protein is readily renaturing in buffer, is of adequate purity without a chromatography step and shows biological activity in cultured MCF7 cells and significantly lowered blood glucose levels in mice with streptozotocin induced type 1 diabetes. PMID- 20541529 TI - Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. AB - Recently, salidroside (p-hydroxyphenethyl-beta-d-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB 231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment. PMID- 20541530 TI - Voltage-dependent anion channel in mammalian spermatozoa. AB - Voltage-dependent anion channel (VDAC) is a multi-functional channel protein in the mitochondrial outer membrane of all eukaryotes. It is involved in extensive physiological and pathophysiological processes. However there is only scant information about VDAC in mammalian reproduction, fertility and development in the past. It is now recognized through recent studies that VDAC is present in male mammalian germinal tissues and cells, and plays crucial roles in spermatogenesis, sperm maturation and fertilization. This review will discuss the presence, localization and function of VDAC in mammalian spermatozoa. PMID- 20541531 TI - EID1-induces brown-like adipocyte traits in white 3T3-L1 pre-adipocytes. AB - PPARgamma and pRB play an important role in the development of adipose cells, and functional modification of these proteins may lead to beneficial changes in adipose cell physiology. In the present work, we show that over-expression of EID1 (E1A-like inhibitor of differentiation), an inhibitor of muscle cell differentiation, reduces PPARgamma ligand-dependent transactivation and decreases triglyceride stores in pre-adipocytes (3T3-L1 cells). Additionally, we found that EID1 binds to pRB at the onset of adipocyte differentiation and may act to reduce pRB levels. Over-expression of EID1 in 3T3-L1 cells leads to increased expression of UCP1 and PGC-1alpha, both of which are involved in caloric dissipation and thermogenesis, in brown adipose tissue. These results indicate that EID1 is able to reduce fat accumulation in adipose cells and induce expression of brown fat genes in pre-adipocytes (3T3-L1 cells) normally destined to become white fat cells. The functional reduction of PPARgamma and pRB mediated by EID1 in adipose cells may play an important role in insulin resistance and the metabolic syndrome. PMID- 20541532 TI - Redox status affects the catalytic activity of glutamyl-tRNA synthetase. AB - Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in tetrapyrrole biosynthesis is not known. Previous studies have shown that GluRS1, one of two GluRSs from the extremophile Acidithiobacillus ferrooxidans, is inactivated when intracellular heme is elevated suggesting a specific role for GluRS1 in the regulation of tetrapyrrole biosynthesis. We now show that, in vitro, GluRS1 activity is reversibly inactivated upon oxidation by hemin and hydrogen peroxide. The targets for oxidation-based inhibition were found to be cysteines from a SWIM zinc-binding motif located in the tRNA acceptor helix binding domain. tRNA(Glu) was able to protect GluRS1 against oxidative inactivation by hemin plus hydrogen peroxide. The sensitivity to oxidation of A. ferrooxidans GluRS1 might provide a means to regulate tetrapyrrole and protein biosynthesis in response to extreme changes in both the redox and heme status of the cell via a single enzyme. PMID- 20541533 TI - Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice. AB - Understanding dendritic cell (DC) subset functions should lead to the development of novel types of vaccine. Here we characterized expression of XC chemokine receptor 1 (XCR1) and its ligand, XCL1. Murine XCR1 was the only chemokine receptor selectively expressed in CD8alpha(+) conventional DCs. XCL1 was constitutively expressed in NK cells, which contribute to serum XCL1 levels. NK and CD8(+) T cells increased XCL1 production upon activation. These expression patterns were conserved in human blood cells, including the BDCA3(+) DC subset. Thus, in human and mice, certain DC subsets should be chemotactic towards NK or activated CD8(+) T cells through XCR1. PMID- 20541534 TI - Role of a PAS sensor domain in the Mycobacterium tuberculosis transcription regulator Rv1364c. AB - The Mycobacterium tuberculosis transcriptional regulator Rv1364c regulates the activity of the stress response sigma factor sigma(F). This multi-domain protein has several components: a signaling PAS domain and an effector segment comprising of a phosphatase, a kinase and an anti-anti-sigma factor domain. Based on Small Angle X-ray Scattering (SAXS) data, Rv1364c was recently shown to be a homo-dimer and adopt an elongated conformation in solution. The PAS domain could not be modeled into the structural envelope due to poor sequence similarity with known PAS proteins. The crystal structure of the PAS domain described here provides a structural basis for the dimerization of Rv1364c. It thus appears likely that the PAS domain regulates the anti-sigma activity of Rv1364c by oligomerization. A structural comparison with other characterized PAS domains reveal several sequence and conformational features that could facilitate ligand binding - a feature which suggests that the function of Rv1364c could potentially be governed by specific cellular signals or metabolic cues. PMID- 20541535 TI - Small-molecule FRET probes for protein kinase activity monitoring in living cells. AB - In this study, the applicability of fluorescently labeled adenosine analogue oligoarginine conjugates (ARC-Photo probes) for monitoring of protein kinase A (PKA) activity in living cells was demonstrated. ARC-Photo probes possessing subnanomolar affinity towards the catalytic subunit of PKA (PKAc) and competitive with the regulatory subunit (PKAr), penetrate cell plasma membrane and associate with PKAc fused with yellow fluorescent protein (PKAc-YFP). Detection of inter molecular Forster resonance energy transfer (FRET) efficiency between the fluorophores of the fusion protein and ARC-Photo probe can be used for both the evaluation of non-labeled inhibitors of PKAc and for monitoring of cAMP signaling via detection of changes in the activity of PKA as a cAMP downstream effector. PMID- 20541536 TI - APOBEC-1 complementation factor (ACF) forms RNA-dependent multimers. AB - Limited proteolysis of APOBEC-1 complementation factor (ACF) and computational secondary structure modeling were used to guide the construction of a well folded, truncation protein spanning residues 1-320 and containing three RNA recognition motifs (RRMs). ACF320 bound preferentially to apoB mRNA and supported APOBEC-1 dependent editing at 40% of the activity of full length ACF. Live cell FRET and immunoprecipitation assays revealed that ACF320 formed homomultimers in situ that were bridged by RNA. Our study predicted that the C to U editosome may be assembled on the mooring sequence of apoB mRNA as a dimer of ACF bound to a dimer of APOBEC-1. PMID- 20541537 TI - Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression. AB - Protein X from hepatitis B virus (HBV) appears to play a critical role in the development of hepatocellular carcinoma (HCC). The hepatoma upregulated protein (HURP) is also upregulated in a majority of HCC cases, therefore suggesting that HURP represents an oncogene. In this study, we describe a link between the viral protein HBx, HURP, and the establishment of cisplatin chemoresistance in HCC cells. Hep3B cells which express HBx displayed increased levels of HURP mRNA and protein, and showed resistance to cisplatin-induced apoptosis. Knockdown of HURP in HBx-expressing cells reversed this effect and sensitized Hep3B cells to cisplatin. Interestingly, SATB1, a global gene regulator which is often overexpressed in malignant breast cancer, was also induced following expression of HBx. The anti-apoptotic effect of HBx was shown to require activation of the p38/MAPK pathway in Hep3B cells. In addition, the expression of survivin, an anti apoptotic protein, was also upregulated by HBx in an HURP-dependent manner. Taken together, these results indicate that HBx activates the expression of HURP via the p38/MAPK pathway and the SATB1 protein, culminating with the accumulation of the anti-apoptotic protein survivin. Our findings illustrate the role of the viral protein HBx in preventing apoptosis during cancer progression and establishment of chemoresistance. PMID- 20541538 TI - Carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase: biological activities and selective toxicities. AB - Toxoplasma gondii adenosine kinase (EC 2.7.1.20) is the major route of adenosine metabolism in this parasite. The enzyme is significantly more active than any other enzyme of the purine salvage in T. gondii and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Several 6 benzylthioinosines have already been identified as subversive substrates of the T. gondii but not human adenosine kinase. Therefore, these compounds are preferentially metabolized to their respective nucleotides and become selectively toxic against the parasites but not its host. In the present study, we report the testing of the metabolism of several carbocyclic 6-benzylthioinosines, as well as their efficacy as anti-toxoplasmic agents in cell culture. All the carbocyclic 6 benzylthioinosine analogues were metabolized to their 5'-monophosphate derivatives, albeit to different degrees. These results indicate that these compounds are not only ligands but also substrates of T. gondii adenosine kinase. All the carbocyclic 6-benzylthioinosine analogues showed a selective anti toxoplasmic effect against wild type parasites, but not mutants lacking adenosine kinase. These results indicate that the oxygen atom of the sugar is not critical for substrate binding. The efficacy of these compounds varied with the position and nature of the substitution on their phenyl ring. Moreover, none of these analogues exhibited host toxicity. The best compounds were carbocyclic 6-(p methylbenzylthio)inosine (IC(50)=11.9 microM), carbocyclic 6-(p methoxybenzylthio)inosine (IC(50)=12.1 microM), and carbocyclic 6-(p methoxycarbonylbenzylthio)inosine (IC(50)=12.8 microM). These compounds have about a 1.5-fold better efficacy relative to their corresponding 6 benzylthioinosine analogues (Rais et al., Biochem Pharmacol 2005;69:1409-19 [29]). The results further confirm that T. gondii adenosine kinase is an excellent target for chemotherapy and that carbocyclic 6-benzylthioinosines are potential anti-toxoplasmic agents. PMID- 20541540 TI - Analysis of MMP2 promoter polymorphisms in patients with pseudoxanthoma elasticum. AB - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder predominantly affecting the skin, the eyes and the cardiovascular system. The disease is caused by mutations in the ABCC6 gene and characterized by ectopic calcification and extracellular matrix (ECM) alterations. Matrix metalloproteinases (MMPs) play a pivotal role in the process of ECM remodeling and are likely implied in PXE pathology. The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter of the MMP2 gene, and PXE. METHODS: We evaluated the allelic distribution of five SNPs in the MMP2 promoter in DNA samples from 168 German patients affected by PXE and in 168 healthy, age- and sex-matched control subjects using restriction fragment length polymorphism analysis. RESULTS: The alleles c.-1575G, c.-1306C, and c.-790T were more abundant in the PXE patients' group. Furthermore, the haplotype GCTCG was significantly associated with PXE (OR 1.56, 95% CI 1.14-2.12, P(corrected)=0.026). CONCLUSIONS: Our results may indicate an involvement of MMP2 in the pathology of PXE. The promoter polymorphisms associated with PXE may lead to increased MMP2 expression and thereby contribute to the elevated proteolytic activity observed in PXE in vitro and in vivo. PMID- 20541539 TI - Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC ESI-QTOFMS-based metabolomics. AB - Ifosfamide (IF) and cyclophosphamide (CP) are common chemotherapeutic agents. Interestingly, while the two drugs are isomers, only IF treatment is known to cause nephrotoxicity and neurotoxicity. Therefore, it was anticipated that a comparison of IF and CP drug metabolites in the mouse would reveal reasons for this selective toxicity. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), and the results analyzed by multivariate data analysis. Of the total 23 drug metabolites identified by UPLC-ESI-QTOFMS for both IF and CP, five were found to be novel. Ifosfamide preferentially underwent N-dechloroethylation, the pathway yielding 2-chloroacetaldehyde, while cyclophosphamide preferentially underwent ring-opening, the pathway yielding acrolein (AC). Additionally, S-carboxymethylcysteine and thiodiglycolic acid, two downstream IF and CP metabolites, were produced similarly in both IF- and CP treated mice. This may suggest that other metabolites, perhaps precursors of thiodiglycolic acid, may be responsible for IF encephalopathy and nephropathy. PMID- 20541541 TI - Expression levels of a LAR-like receptor protein tyrosine phosphatase correlate with neuronal branching and arbor density in the medicinal leech. AB - LAR-like receptor protein tyrosine phosphatases (RPTPs), which are reported to be highly expressed in the nervous systems of most bilaterian animals, have been implicated in the regulation of critical developmental processes, such as neuronal pathfinding, cell adhesion and synaptogenesis. Here we report that two LAR-like RPTPs in the medicinal leech, HmLAR1 and HmLAR2, play roles in regulating the size and density of neuronal arbors within the developing nervous system and in the body wall. Employing single-cell RNAi knockdown and transgene expression techniques, we demonstrate that the expression level of HmLAR1 is directly correlated with the density of an identified neuron's arborization. Knocking down HmLAR1 mRNA levels in the mechanosensory pressure (P) neurons produces a reduced central arbor and a smaller arbor in the peripheral body wall, with fewer terminal branches. By contrast, overexpression of this receptor in a P cell leads to extensive neuronal sprouting, including many supernumerary neurites and terminal branches as well as, in some instances, the normal monopolar morphology of the P cell becoming multipolar. We also report that induced neuronal sprouting requires the expression of the receptor's membrane tethered ectodomain, including the NH(2)-Ig domains, but not of the intracellular phosphatase domains of the receptor. Interestingly, sprouting could be elicited upon ectopic expression of HmLAR1 and the related RPTP, HmLAR2 in the P and other neurons, including those that do not normally express either RPTP, suggesting that the substrates involved in HmLAR-induced sprouting are present in most neurons irrespective of whether they normally express these LAR-like RPTPs. Our data are consistent with the hypothesis that the receptors' ectodomains promote an adhesive interaction that enhances the maintenance of new processes. PMID- 20541542 TI - Regulation of axonal development by the nuclear protein hindsight (pebbled) in the Drosophila visual system. AB - The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. PMID- 20541543 TI - Inhibitory effect on protein kinase Ctheta by Crocetin attenuates palmitate induced insulin insensitivity in 3T3-L1 adipocytes. AB - Epidemiologic and experimental studies have pointed to an etiologic role of elevated plasma free fatty acids in insulin resistance, which is frequently associated with a state of low-grade inflammation. In this study, we investigated the effects of Crocetin, a unique carotenoid, on insulin resistance induced by palmitate in 3T3-L1 adipocytes. Exposure of palmitate led to an increase in insulin receptor substrate-1 (IRS-1) serine(307) phosphorylation as well as activation of c-Jun NH(2)-terminal kinase (JNK) and inhibitor kappaB kinase beta (IKKbeta), concomitantly with reductions of IRS-1 function and glucose metabolism. Interestingly, pretreatment with Crocetin almost reversed all of these abnormalities in a dose-dependent manner. IRS-1 serine(307) phosphorylation was significantly reduced by JNK or IKKbeta inhibitor, especially by combination of these two inhibitors. Moreover, palmitate treatment induced activation of protein kinase Ctheta (PKCtheta) while blocking PKCtheta significantly inhibited JNK and IKKbeta activation induced by palmitate or phorbol 12-myristate 13 acetate (PKC activator, PMA), and attenuated the palmitate-induced defects in insulin action. Crocetin demonstrated an impressive suppression in the activation of PKCtheta induced not only by palmitate but also by PMA in a dose-dependent manner. Taken together, Crocetin inhibited JNK and IKKbeta activation via suppression of PKCtheta phosphorylation, attenuating insulin insensitivity induced by palmitate in 3T3-L1 adipocytes. PMID- 20541545 TI - Promoter-proximal pausing and its release: molecular mechanisms and physiological functions. AB - For a long time, not much attention had been paid to post-initiation steps in transcription, because it was widely believed that transcriptional control was brought about almost entirely through the regulation of transcription initiation. However, it has become clear that the process of elongation is also tightly controlled by a collection of regulatory factors called transcription elongation factors and contributes, for example, to rapid induction of immediate-early genes and to the control over the viral life cycle. Transcription elongation has attracted attention also because this process is coupled with various RNA processing events. In this review, we discuss biochemical and physiological aspects of elongation control, particularly focusing on the role of the negative elongation factor NELF. PMID- 20541544 TI - Requirement of NF-kappaB signalling pathway for modulation of the cholinergic muscarinic M3 receptor expression by INGAP-PP in insulin-producing cells. AB - The pentadecapeptide comprising the 104-118 amino acid sequence of the ilotropin derived Reg3-related islet neogenesis-associated protein (INGAP-PP) has been implicated in beta cell neogenesis and enhancement of insulin secretion in pancreatic islets. The aim of this study was to investigate intracellular pathways by which INGAP-PP signals in insulin-producing cells. Treatment with INGAP-PP increased insulin secretion and intracellular calcium levels in MIN6 cells. INGAP-PP exposure activated c-Myc, serum and particularly nuclear factor kappaB (NF-kappaB) response elements in insulin-producing cells (1.7+/-0.1, 1.8+/ 0.1, 2.4+/-0.3 for RINm5F, and 1.3+/-0.1, 1.3+/-0.1 and 1.6+/-0.1 fold for MIN6 cells compared to controls, respectively). There was an increase in the proliferation rate of viable cells (162+/-17% for RINm5F and 155+/-13% for MIN6) that was accompanied by an increase in proliferating cell nuclear antigen (PCNA) protein expression (187+/-19% and 170+/-8% for RINm5F and MIN6 cells respectively) following INGAP-PP treatment. INGAP-PP increased the expression of the muscarinic M(3) receptor subtype (169+/-4% for RINm5F and 222+/-20% for MIN6 cells). Activation of multiple serum response elements by foetal calf serum also increased muscarinic M(3) receptor expression (173+/-9% for RINm5F and 140+/-7% for MIN6 cells). The blockade of NF-kappaB signalling pathway strongly decreased muscarinic M(3) receptor expression in response to both stimuli. In summary, a network of intracellular signals that includes activation of c-Myc signalling pathway and increased PCNA expression might be related to the increased proliferation rate of insulin-producing cells following incubation with INGAP-PP. NF-kappaB signalling plays an essential role in controlling the expression of the muscarinic M(3) receptor. PMID- 20541546 TI - Lauroylethanolamide is a potent competitive inhibitor of lipoxygenase activity. AB - The lipoxygenase (LOX) pathway was proposed to compete with hydrolysis and be partly responsible for the metabolism of polyunsaturated N-acylethanolamines (PU NAEs). Treatment of Arabidopsis seedlings with lauroylethanolamide (NAE 12:0) resulted in elevated levels of PU-NAE species, and this was most pronounced in plants with reduced NAE hydrolase activity. Enzyme activity assays revealed that NAE 12:0 inhibited LOX-mediated oxidation of PU lipid substrates in a dose dependent and competitive manner. NAE 12:0 was 10-20 times more potent an inhibitor of LOX activities than lauric acid (FFA 12:0). Furthermore, treatment of intact Arabidopsis seedlings with NAE 12:0 (but not FFA 12:0) substantially blocked the wound-induced formation of jasmonic acid (JA), suggesting that NAE 12:0 may be used in planta to manipulate oxylipin metabolism. PMID- 20541547 TI - Curdlan-mediated regulation of human phagocyte-specific chitotriosidase. AB - Human phagocyte-specific chitotriosidase is part of innate immunity and shows anti-fungal activity towards chitin-containing fungi. We investigated the effect of stimulation of the C-type lectin receptor dectin-1 by beta-1,3-glucan (curdlan) on chitotriosidase expression and release by human phagocytes. We observed that curdlan triggers chitotriosidase release from human neutrophils. In addition, we show that curdlan impairs chitotriosidase induction in monocytes. Finally, curdlan temporarily induces chitotriosidase in enzyme-expressing monocyte-derived macrophages, followed by reduction of chitotriosidase expression after prolonged stimulation. These data on regulation of phagocyte-specific chitotriosidase following curdlan recognition support an important role of chitotriosidase in the elimination of chitin-containing pathogens. PMID- 20541548 TI - Bacillus subtilis SSE4 produces subtulene A, a new lipopeptide antibiotic possessing an unusual C15 unsaturated beta-amino acid. AB - Subtulene A, a new cyclic lipopeptide, was isolated from the culture broth of Bacillus subtilis SSE4. This antibiotic compound contained the seven common alpha amino acids, L-Asn-1, D-Tyr-2, D-Asn-3, L-Gln-4, L-Pro-5, D-Asn-6, L-Ser-7 and the unique beta-amino acid-8 present in the iturin family. 1D and 2D NMR, as well as MS analyses, identified the beta-amino acid as 3-amino-13-methyltetradec-8 enoic acid, an Iso C15 long chain beta-amino acid. B. subtilis SSE4 was also found to produce iturin A. B. subtilis SSE4 culture filtrate exhibited both antifungal and antibacterial activities. PMID- 20541549 TI - Domain compatibility in Ire1 kinase is critical for the unfolded protein response. AB - The unfolded protein response is a mechanism to cope with endoplasmic reticulum stress. In Saccharomyces cerevisiae, Ire1 senses the stress and mediates a signaling cascade to upregulate responsive genes through an unusual HAC1 mRNA splicing. The splicing requires interconnected activity (kinase and endoribonuclease (RNase)) of Ire1 to cleave HAC1 mRNA at the non-canonical splice sites before translation into Hac1 transcription factor. Analysis of the truncated kinase domain from Ire1 homologs revealed that this domain is highly conserved. Characterization by domain swapping indicated that a functional ATP/ADP binding domain is minimally required. However the overall domain compatibility is critical for eliciting its full RNase function. PMID- 20541550 TI - Aloe emodin glycosides stimulates glucose transport and glycogen storage through PI3K dependent mechanism in L6 myotubes and inhibits adipocyte differentiation in 3T3L1 adipocytes. AB - The present study discusses the efficacy of Aloe emodin-8-O-glycoside (AEG), a plant derived anthroquinone, on alleviating insulin resistance and augmenting glycogen synthesis in L6 myotubes and 3T3L1 adipocytes. Dose-dependent increase in glucose uptake activity (GUA) was observed in both cell lines. Immunoblot analysis revealed an insulin-like glucose transporting mechanism of AEG by activating key markers involved in the insulin signaling cascade such as insulin receptor beta IRbeta, insulin receptor substrate1, 85 phosphatidyl inositol 3' kinase (PI3K) and PKB. Glucose transporter 4 translocation was confirmed by determining the uptake of glucose in the presence of insulin receptor tyrosine kinase and PI3K inhibitors. AEG was found to enhance glycogen synthesis through the inhibition of glycogen synthase kinase 3beta. In conclusion, AEG enhances glucose transport by modulating the proximal and distal markers involved in glucose uptake and its transformation into glycogen. PMID- 20541551 TI - The role of enoyl-CoA hydratase short chain 1 and peroxiredoxin 3 in PP2-induced apoptosis in human breast cancer MCF-7 cells. AB - We show that 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) induces apoptosis and down-regulates the expression of enoyl-CoA hydratase short chain 1 (ECHS1) and peroxiredoxin 3 (PRDX3) in human breast cancer MCF-7 cells. The decrease of ECHS1 and PRDX3 was validated by Western blot and quantitative real-time reverse transcription-PCR in MCF-7 and other carcinoma cells. Knockdown and over-expression of ECHS1 and/or PRDX3 further supported the key role of ECHS1 and PRDX3 in regulation of PP2-induced apoptosis. These results suggest a possible apoptotic pathway whereby down-regulation of ECHS1 and PRDX3 potentiates PP2-induced apoptosis in MCF-7 cells. PMID- 20541552 TI - Weird fingers: functional analysis of WIP domain proteins. AB - WIP proteins form a plant specific subfamily of C2H2 zinc finger (ZF) proteins. In this study, we functionally characterized the WIP domain, which consists of four ZF motifs, and discuss molecular functions for WIP proteins. Mutations in each of the ZFs lead to loss of function of the TT1/WIP1 protein in Arabiopsis thaliana. SV40 type nuclear localisation signals were detected in two of the ZFs and functionally characterized using GFP fusions as well as new mutant alleles identified by TILLING. Promoter swap experiments showed that selected WIP proteins are partially able to take over TT1 function. Activity of the AtBAN promoter, a potential TT1 target, could be increased by the addition of TT1 to the TT2-TT8-TTG1 regulatory complex. PMID- 20541553 TI - Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. AB - Neutrophil interaction with activated endothelial cells (EC) is required for transmigration. We examined consequences of this interaction on NETosis. Co culture of activated EC with neutrophils induced neutrophil extracellular trap (NET) formation, which was partially dependent on production of IL-8 by activated EC. Extended neutophil/EC co-culture resulted in EC damage, which could be abrogated by inclusion of either diphenyleneiodonium to inhibit the NAPDH oxidase pathway required for NETosis, or DNAse to disrupt NETs. These findings offer new insight into mechanisms whereby NETs trigger damage to the endothelium in sepsis, small vessel vasculitis and possibly the villous trophoblast in preeclampsia. PMID- 20541555 TI - The effect of mild agitation on in vitro erythroid development. AB - The cultivation of erythroid cells at large scale would have to be performed in suitable bioreactors which would most likely employ some mode of agitation to ensure optimal mass and gas transfer and prevent culture inhomogeneity. The effect of low agitation at 15-20 rpm on ex vivo erythropoiesis of PB CD34+ derived cultures was investigated and found to have significant impact on erythroid development. Agitated cultures showed a reduced lag phase and increased cell expansion during the early stages of culture. Additionally, agitation accelerated erythroid differentiation as seen by the loss of early development markers, acquisition of late erythroid markers and premature cell cycle arrest, although not yielding higher fractions of terminally differentiated cells in comparison to stationary culture. However, agitation at 20 rpm led to significantly increased loss of cell viability after day 15 in culture, an effect that could be reduced by decreasing the agitation rate to 15 rpm. On the one hand these results imply that agitation may improve cell yields and reduce expensive cytokine-dependent early culture stages but on the other hand it might introduce the risk of increased cell death in large scale culture. PMID- 20541554 TI - Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance. AB - The hypothalamic neuropeptide orexin mediates arousal, sleep, and naturally rewarding behaviors, including food intake. Male sexual behavior is altered by orexin receptor-1 agonists or antagonists, suggesting a role for orexin-A in this naturally rewarding behavior. However, the specific role of endogenous orexin-A or B in different elements of male sexual behavior is currently unclear. Therefore, the current studies utilized markers for neural activation and orexin cell-specific lesions to test the hypothesis that orexin is critical for sexual motivation and performance in male rats. First, cFos expression in orexin neurons was demonstrated following presentation of a receptive or non-receptive female without further activation by different elements of mating. Next, the functional role of orexin was tested utilizing orexin-B conjugated saporin, resulting in orexin cell body lesions in the hypothalamus. Lesions were conducted in sexually naive males and subsequent sexual behavior was recorded during four mating trials. Lesion males showed shortened latencies to mount and intromit during the first, but not subsequent mating trials, suggesting lesions facilitated initiation of sexual behavior in sexually naive, but not experienced males. Likewise, lesions did not affect sexual motivation in experienced males, determined by runway tests. Finally, elevated plus maze tests demonstrated reduced anxiety-like behaviors in lesioned males, supporting a role for orexin in anxiety associated with initial exposure to the female in naive animals. Overall, these findings show that orexin is not critical for male sexual performance or motivation, but may play a role in arousal and anxiety related to sexual behavior in naive animals. PMID- 20541556 TI - Activities of natural methyl farnesoids on pupariation and metamorphosis of Drosophila melanogaster. AB - Methyl farnesoate (MF) and juvenile hormone (JH III), which bind with high affinity to the receptors USP and MET, respectively, and bisepoxy JH III (bisJH III) were assessed for several activities during Drosophila larval development, and during prepupal development to eclosed adults. Dietary MF and JH III were similarly active, and more active than bisJH III, in lengthening larval development prior to pupariation. However, the order of activity was changed (JH III>bisJH III>MF) with respect to preventing prepupae from eclosing as normal adults, whether administered in the larval diet or as topically applied at the white puparium stage. If endogenous production of all three larval methyl farnesoids was suppressed by a strongly driven RNAi against HMGCR in the corpora allata cells, most larvae did not attain pupariation. Farnesol (which has no demonstrated life-necessary function in larval life except in corpora allata cells as a precursor to methyl farnesoid biosynthesis) when incorporated into the diet rescued attainment of pupariation in a dose-dependent manner, presumably by rescuing endogenous production of all three hormones. A more mild suppression of endogenous methyl farnesoid production enabled larval attainment of pupariation. However, in this background dietary MF had increased activity in preventing puparia from attaining normal adult eclosion. The physiological relevance of using exogenous methyl farnesoids to block prepupal development to normally eclosed adults was tested by, instead, protecting in prepupae the endogenous titer of methyl farnesoids. JH esterase normally increases during the mid-late prepupal stage, presumably to clear endogenous methyl farnesoids. When JH esterase was inhibited with an RNAi, it prevented attainment of adult eclosion. Cultured adult corpora allata from male and female Aedes aegypti released both MF and JH III, and the A. aegypti nuclear receptor USP bound MF with nanomolar affinity. These A. aegypti data support the use of Drosophila as a model for mosquitoes of the binding of secreted MF to USP. PMID- 20541557 TI - Multiple unfolding events during native folding of the Tetrahymena group I ribozyme. AB - Despite the ubiquitous nature of misfolded intermediates in RNA folding, little is known about their physical properties or the folding transitions that allow them to continue folding productively. Folding of the Tetrahymena group I ribozyme includes sequential accumulation of two intermediates, termed I(trap) and misfolded (M). Here, we probe the structure and folding transition of I(trap) and compare them to those of M. Hydroxyl radical and dimethyl sulfate footprinting show that both I(trap) and M are extensively structured and crudely resemble the native RNA. However, regions of the core P3-P8 domain are more exposed to solvent in I(trap) than in M. I(trap) rearranges to continue folding nearly 1000-fold faster than M, and urea accelerates folding of I(trap) much less than M. Thus, the rate-limiting transition from I(trap) requires a smaller increase in exposed surface. Mutations that disrupt peripheral tertiary contacts give large and nearly uniform increases in re-folding of M, whereas the same mutations give at most modest increases in folding from I(trap). Intriguingly, mutations within the peripheral element P5abc give 5- to 10-fold accelerations in escape from I(trap), whereas ablation of P13, which lies on the opposite surface in the native structure, near the P3-P8 domain, has no effect. Thus, the unfolding required from I(trap) appears to be local, whereas the unfolding of M appears to be global. Further, the modest effects from several mutations suggest that there are multiple pathways for escape from I(trap) and that escape is aided by loosening nearby native structural constraints, presumably to facilitate local movements of nucleotides or segments that have not formed native contacts. Overall, these and prior results suggest a model in which the global architecture and peripheral interactions of the RNA are achieved relatively early in folding. Multiple folding and re-folding events occur on the predominant pathway to the native state, with increasing native core interactions and cooperativity as folding progresses. PMID- 20541558 TI - The unfolded state of the murine prion protein and properties of single-point mutants related to human prion diseases. AB - The prion protein can exist both in a normal cellular isoform and in a pathogenic conformational isoform. The latter is responsible for the development of different neurodegenerative diseases, for example Creutzfeldt-Jakob disease or fatal familial insomnia. To convert the native benign state of the protein into a highly ordered fibrillar aggregate, large-scale rearrangements of the tertiary structure are necessary during the conversion process and intermediates that are at least partially unfolded are present during fibril formation. In addition to the sporadic conversion into the pathogenic isoform, more than 20 familial diseases are known that are caused by single point mutations increasing the probability of aggregation and neurodegeneration. Here, we demonstrate that the chemically denatured states of the mouse and human prion proteins have very similar structural and dynamic characteristics. Initial studies on the single point mutants E196K, F198S, V203I and R208H of the oxidized mouse construct, which are related to human prion diseases, reveal significant differences in the rate of aggregation. Aggregation for mutants V203I and R208H is slower than it is for the wild type, and the constructs E196K and F198S show accelerated aggregation. These differences in aggregation behaviour are not correlated with the thermal stability of the mutants, indicating different mechanisms promoting the conformational conversion process. PMID- 20541559 TI - Computational experiments reveal plausible mechanisms for changing patterns of hepatic zonation of xenobiotic clearance and hepatotoxicity. AB - No concrete, causal, mechanistic theory is available to explain how different hepatic zonation patterns of P450 isozyme levels and hepatotoxicity emerge following dosing with different compounds. We used the synthetic method of modeling and simulation to discover, explore, and experimentally challenge concrete mechanisms that show how and why biomimetic zonation patterns can emerge and change within agent-based analogues, expecting that those mechanisms may have counterparts in rats. Mobile objects map to compounds. One analogue represents a cross-section through a lobule. It is comprised of 460 identical, quasi autonomous functional units called sinusoidal segments (SSs). SSs detect and respond to compound-generated response signals and the local level of an endogenous gradient. Each SS adapts by using those signals to adjust (or not) the probability that it will clear a detected compound during the next simulation cycle. The adjustment decision is based on the value of a biomimetic algorithm that is based on an assumed, evolution imposed, genetic mandate that normal hepatocytes resist increasing the cost of their actions. The algorithm estimates the long-term, discounted cost to a given SS of continuing to use its current clearance effort. Upon compound exposure, lobular analogues developed a variety of clearance and hepatotoxicity patterns that were strikingly similar to those reported in the literature. A degree of quantitative validation was achieved against data on hepatic zonation of CYP1A2 mRNA expression caused by three different doses of TCDD (2,3,7,8-tetracholorodibenzo-p-dioxone). PMID- 20541561 TI - Novel tumor growth inhibition mechanism by cell cycle regulator cdk2ap1 involves antiangiogenesis modulation. AB - We evaluated the effect of expressing the cell cycle regulator protein cdk2 associating protein1 (cdk2ap1) in inhibiting growth of squamous cell carcinoma (SCC). Expression of cdk2ap1 correlated with reduction in several SCC malignant cell phenotypes, including reduced angiogenesis. We observed several alterations in gene expression consistent with classical functions of cdk2ap1, including upregulation of cell cycle inhibitory genes, and an upregulation in expression of genes belonging to both intrinsic and extrinsic apoptotic cascades. Interestingly, we also uncovered a profile of gene expression and activation of signaling pathways that may suggest new tumor-suppressive functions for cdk2ap1 through downregulation of invasion/metastasis and modulation of antiangiogenesis by upregulation of the TGFbeta signaling pathway. Blocking of the TGFbeta1 pathway resulted in inhibition of the cdk2ap1 antiangiogenesis phenotype. In combination, these data support the role of cdk2ap1 as a tumor suppressor gene that can regulate SCC tumor growth in a cell autonomous manner through decreases in invasiveness and a non-cell autonomous manner through decreases in angiogenesis phenotypes, and these are novel phenotypes induced by cdk2ap1. PMID- 20541560 TI - PECAM-1: conflicts of interest in inflammation. AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a cell adhesion and signaling receptor that is expressed on hematopoietic and endothelial cells. PECAM-1 is vital to the regulation of inflammatory responses, as it has been shown to serve a variety of pro-inflammatory and anti-inflammatory functions. Pro inflammatory functions of PECAM-1 include the facilitation of leukocyte transendothelial migration and the transduction of mechanical signals in endothelial cells emanating from fluid shear stress. Anti-inflammatory functions include the dampening of leukocyte activation, suppression of pro-inflammatory cytokine production, and the maintenance of vascular barrier integrity. Although PECAM-1 has been well-characterized and studied, the mechanisms through which PECAM-1 regulates these seemingly opposing functions, and how they influence each other, are still not completely understood. The purpose of this review, therefore, is to provide an overview of the pro- and anti-inflammatory functions of PECAM-1 with special attention paid to mechanistic insights that have thus far been revealed in the literature in hopes of gaining a clearer picture of how these opposing functions might be integrated in a temporal and spatial manner on the whole organism level. A better understanding of how inflammatory responses are regulated should enable the development of new therapeutics that can be used in the treatment of acute and chronic inflammatory disorders. PMID- 20541562 TI - Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters. AB - Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine (epsilondA), and 3,N4-etheno-2'-deoxycytidine (epsilondC), markers for LPO derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model, in O. viverrini infected hamsters that had received N-nitrosodimethylamine (NDMA, 12.5 ppm in dw) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method, from 21 up to 180 days post O. viverrini-infection. In inflamed areas of the liver, etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct. Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters, treated with or w/o NDMA when compared with untreated controls. Levels were found highest in the liver of O. viverrini infected plus NDMA-treated hamsters. Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development. Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase (ALP) activity, bile duct hyperplasia, dysplasia, precancerous lesions, and CCA appearance. Also elevated expression of alkyladenine DNA glycosylase (AAG), which excises 1,N6-ethenoadenine (epsilonA) was linked to higher adduct formation, suggesting imbalanced repair. Our results implicate accumulation of inflammation related, promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis. PMID- 20541563 TI - Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA. AB - Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p<0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types. PMID- 20541564 TI - Somatostatin and nociceptin inhibit neurons in the central nucleus of amygdala that project to the periaqueductal grey. AB - The central nucleus of amygdala (CeA) plays an important role in modulation of the descending antinociceptive pathways. Using whole-cell patch clamp recordings from brain slices, we found that CeA neurons responded to the endogenous ligands somatostatin (SST) and nociceptin/orphanin FQ (OFQ) via an increased K conductance. Co-application with selective antagonists suggested that SST and OFQ act on SSTR2 and ORL1 receptors, respectively. Taking account of anatomical localisation of recorded neurons, the present study showed that many responsive neurons were located within the medial subdivision of CeA and all CeA projection neurons to the midbrain periaqueductal grey invariably responded to these peptides. Randomly selected agonist-responsive neurons in CeA predominantly classified physiologically as low-threshold spiking neurons. The similarity of SST, OFQ and, as previously reported, opioid responsiveness in a sub-population of CeA neurons suggests converging roles of these peptides to inhibit the activity of projections from CeA to vlPAG, and potentially similar antinociceptive actions in this pathway. PMID- 20541565 TI - Effects of Salmonella on spatial-temporal processes of jejunal development in chickens. AB - To study effects of Salmonella enteritidis on morphological and functional changes in chicken jejunal development, we analysed gene expression profiles at seven points post-infection in 1-21 day-old broiler chickens. Nine clusters with different gene expression patterns were identified, and the genes in each cluster were further analyzed by a functional annotation clustering method (DAVID). Functional and morphological developmental processes dominated in all the nine clusters. Salmonella infection caused delays in several intestinal-morphological processes, whereas functional metabolic processes occurred in a similar spatial temporal frame compared to normal jejunum development. A clear difference between normal developing- and Salmonella disturbed jejunum was the higher expression of genes involved in cell turn-over at early stages in the infected jejunum. Surprisingly, we found no clustered immune related processes in the infected birds. To compare the immunological processes between control and Salmonella infected chickens, the gene expression data was superimposed on known immunological KEGG pathways. Furthermore an in-depth analysis on the immune gene level was performed. As expected, we did find immunological processes in the Salmonella infected jejunum. Several of these processes could be verified by immunohistochemistry measurements of different immunological cell types. However, the well-ordered spatial-temporal development of the immune system, as observed in control non-infected animals, was completely abolished in the infected animals. Several immunological processes started much earlier in time, whereas other processes are disorganised. These data indicate that normal morphological and immunological development of jejunum is changed dramatically by a disturbance due to Salmonella infection. Due to the disturbance, the well-organized spatial temporal development of morphological processes are delayed, those of the immunological development are scattered, whereas metabolic functional processes are almost not affected. This demonstrates the flexibility of developmental processes in the broiler chicken intestine. PMID- 20541566 TI - Tissue culture drug resistance analysis of a novel HIV-1 protease inhibitor termed PL-100 in non-B HIV-1 subtypes. AB - PL-100 is a novel HIV-1 protease inhibitor (PI) that maintains activity against viruses that are resistant to other PIs. To further characterize this compound, we used it to select for drug resistance in tissue culture, using two non-B HIV-1 subtypes, viz. subtype C and a CRF01_AE recombinant virus. PL-100 selected for both minor and major PI resistance mutations along either of two distinct pathways. One of these involved the V82A and L90M resistance mutations while the other involved a mutation at position T80I, with other mutations being observed at positions M46I/L, I54M, K55R, L76F, P81S and I85V. The resistance patterns in both subtype C and CRF01_AE were similar and an accumulation of at least three mutations in the flap and active sites were required in each case for high-level resistance to occur, demonstrating that PL-100 has a high genetic barrier against the development of drug resistance. PMID- 20541567 TI - Odor cues from tumor-bearing mice induces neuroimmune changes. AB - Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion. PMID- 20541568 TI - Biochemical characterization of serine acetyltransferase and cysteine desulfhydrase from Leishmania major. AB - Cysteine metabolism exhibits atypical features in Leishmania parasites. The nucleotide sequence annotated as LmjF32.2640 encodes a cysteine desulfhydrase, which specifically catalyzes the breakdown of cysteine into pyruvate, NH(3) and H(2)S. Like in other pathogens, this capacity might be associated with regulatory mechanisms to control the intracellular level of cysteine, a highly toxic albeit essential amino acid, in addition to generate pyruvate for energy production. Besides, our results provide the first insight into the biochemical properties of Leishmania major serine acetyltransferase (SAT), which is likely involved in the two routes for de novo synthesis of cysteine in this pathogen. When compared with other members of SAT family, the N-terminal region of L. major homologue is uniquely extended, and seems to be essential for proper protein folding. Furthermore, unlike plant and bacterial enzymes, the carboxy-terminal-C(10) sequence stretch of L. major SAT appears not to be implicated in forming a tight bi-enzyme complex with cysteine synthase. PMID- 20541569 TI - Importance of lipid-exposed residues in transmembrane segment four for family B calcitonin receptor homo-dimerization. AB - Dimerization of the prototypic family B G protein-coupled secretin receptor is determined by the lipid-exposed face of transmembrane segment four (TM4), and has substantial functional importance, facilitating G protein coupling. Recently, we demonstrated that the human secretin receptor elicits an inter-receptor bioluminescence resonance energy transfer (BRET) signal with most other human family B peptide receptors, except for the calcitonin receptor. In this study we have explored the occurrence and importance of calcitonin receptor oligomerization. Static and saturation receptor BRET were utilized to demonstrate that, unlike the human calcitonin receptor that does not yield a significant homomeric BRET signal, the rabbit calcitonin receptor exhibits strong resonance energy transfer. Within the lipid-exposed face of TM4, rabbit and human calcitonin receptors differ by a single amino acid (Arg236 in human; His in rabbit), while Thr253 that occurs in human and rabbit calcitonin receptors is unique across family B receptors. Mutating Arg236 or Thr253 of the human calcitonin receptor to residues found in the rabbit calcitonin receptor or the human secretin receptor (R236H, R236Y and T253A) resulted in generation of significant BRET signals. Similarly, mutation of Val250 of the human calcitonin receptor to another key lipid-facing residue found in the secretin receptor (V250I) also increased the receptor BRET signal. These data support the consistent theme of lipid-exposed residues of TM4 being important for the dimerization of the calcitonin receptor. However, rabbit and human calcitonin receptor constructs bound calcitonin and stimulated cAMP similarly, suggesting that differences in BRET could reflect differences in orientation or in the stability of homo-dimeric receptor complexes, which were nevertheless similarly effective in eliciting the functions attributed to that complex. The likelihood of human calcitonin receptor dimerization, even in the absence of a significant BRET signal, was further supported by data demonstrating that the peptide representing TM4 of this receptor that disrupts the rabbit receptor BRET signal, produced a right shift in the cAMP concentration-response curves for both rabbit and human receptors. PMID- 20541570 TI - Hydrolysis of softwood by Aspergillus mannanase: role of a carbohydrate-binding module. AB - Endo beta-1,4-mannanases (beta-mannanases, EC 3.2.1.78), belonging to CAZy GH5 and GH26 families, catalyze the hydrolysis of structurally different mannans. In this study, the mannanase encoding gene of Aspergillus aculeatus VN was expressed in Aspergillus niger D15#26 using pAN 52-4 vector, under the control of PgpdA promoter and TtrpC terminator. In order to improve the hydrolytic capacity of this GH5 on lignocellulosic substrate, the family 1 carbohydrate-binding module (CBM1) of Aspergillus niger cellobiohydrolase B was artificially fused at the C terminal end of this enzyme with a natural linker. Both mannanase and mannanase CBM genes were successfully expressed in A. niger D15#26, producing proteins with molecular masses of 54 and 79 kDa, respectively. The Michaelis-Menten constants, pH activity profiles and temperature optima of three enzymes (wild-type mannanase, recombinant mannanase and recombinant mannanase-CBM) were similar, but the fused mannanase-CBM enzyme was more thermostable. Cross-comparison of the three enzymes for softwood hydrolysis in association with Trichoderma reesei enzymatic cocktail showed that mannanase-CBM improved the glucose yield compared to wild-type and recombinant mannanases. PMID- 20541571 TI - Rice ragged stunt virus segment S6-encoded nonstructural protein Pns6 complements cell-to-cell movement of Tobacco mosaic virus-based chimeric virus. AB - The protein(s) that support intercellular movement of Rice ragged stunt virus (RRSV) have not yet been identified. In this study, the role of three nonstructural proteins Pns6, Pns7 and Pns10 in cell-to-cell movement were determined with a movement-deficient Tobacco mosaic virus (TMV) vector. The results showed that only the Pns6 could complement the cell-to-cell movement of the movement-deficient TMV in Nicotiana tabacum Xanthi nc and N. benthamiana plants, and both N- and C-terminal 50 amino acids of Pns6 were essential for the cell-to-cell movement. Transient expression in epidermal cells from N. benthamiana showed that the Pns6-eGFP fusion protein was present predominantly along the cell wall as well as a few punctate sites perhaps indicating plasmodesmata. Taken together with previous finding that the Pns6 has nucleic acid-binding activity (Shao et al., 2004), the possible role of Pns6 in cell-to cell movement of RRSV were discussed. PMID- 20541572 TI - Repeated taste exposure increases liking for vegetables by low-income elementary school children. AB - Children's food preferences play a major role in their food choices and consumption. The objective of the present study was to examine if repeated tastings of selected vegetables in a school setting increased children's liking of these items. A total of 360 fourth- and fifth-grade students attending four low-income, public elementary schools in southeastern Louisiana volunteered to participate. During the spring of 2008, children were offered a taste of carrots, peas, tomatoes, and bell peppers once a week for 10 weeks. At each tasting session children recorded whether they swallowed each of the vegetables, spit it into the napkin, or did not put it in their mouth and indicated their liking for each vegetable using a Likert-type response scale. Approximately one-half of the children tasted eight of ten times during the program (46.5% for those who began disliking and 68.5% for those who began liking the vegetables). Proc Glimmix analyses indicated that for children who began the program disliking the vegetables, repeated tasting improved liking scores for carrots, peas, and tomatoes; liking for bell peppers did not change. The number of children who reported liking or liking a lot for previously disliked vegetables was greater after eight or nine taste exposures. Repeated tasting of less-liked vegetables by children in a cafeteria-based setting is a strategy to promote liking of these items and is effective in approximately half of the participants. PMID- 20541573 TI - Impact of restraint and disinhibition on PYY plasma levels and subjective feelings of appetite. AB - The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait. PMID- 20541574 TI - Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS stimulated cytokines by antimicrobial peptides. AB - Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered. PMID- 20541576 TI - Biomonitoring Equivalents for bisphenol A (BPA). AB - Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline. BE values are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for bisphenol A (BPA) from Health Canada, the United States Environmental Protection Agency (USEPA) and the European Food Safety Authority (EFSA). BE values were derived based on data on BPA urinary excretion in humans. The BE value corresponding to the oral provisional tolerable daily intake (pTDI) of 25 microg/kg-d from Health Canada is 1mg/L (1.3mg/g creatinine); value corresponding to the US EPA reference dose (RfD) and EFSA tolerable daily intake (TDI) estimates (both of which are equal to 50 microg/kg-d) is 2mg/L (2.6 mg/g creatinine). These values are estimates of the 24-h average urinary BPA concentrations that are consistent with steady-state exposure at the respective exposure guidance values. These BE values may be used as screening tools for evaluation of central tendency measures of population biomonitoring data for BPA in a risk assessment context and can assist in prioritization of the potential need for additional risk assessment efforts for BPA relative to other chemicals. PMID- 20541575 TI - Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema. AB - Intracerebral hemorrhage (ICH) can cause secondary brain damage through inflammation-related pathways. Thrombin and one of its receptors, protease activated receptor-1 (PAR-1); matrix metalloproteinase (MMP)-9; and aquaporin (AQP)-4 are stroke-related inflammatory mediators that have been implicated in ICH pathology. To further characterize the inflammatory response after ICH, we studied the temporal profile of the expression of these inflammatory mediators and assessed their potential correlation with brain edema formation after brain hemorrhage in rats. ICH was modeled by infusing autologous blood into the striatum. Then mRNA and protein expression was assessed over the course of 5 days. We found that the mRNA and/or protein expression of thrombin, PAR-1, AQP-4, and MMP-9 was upregulated between 2h and 5 days after ICH. Each reached a maximal level at day 2, except for AQP-4 protein, which peaked at day 5. Brain water content after ICH presented a similar trend; it was increased at 2h, peaked at day 2, and then decreased but remained elevated at day 5. Our data provide novel evidence that upregulation of these selected inflammatory mediators occurs very early and persists for several days after ICH, and that temporal patterns of expression of thrombin and AQP-4 are associated with brain edema formation. These findings have important implications for efforts to reduce secondary brain damage after ICH. PMID- 20541577 TI - Biomonitoring Equivalents for triclosan. AB - Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite(s) in a biological medium (blood, urine, or other medium) consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for triclosan based on recent evaluations from the United States Environmental Protection Agency (US EPA), the European Commission's Scientific Committee on Consumer Products (EC SCCP) and the Australian National Industrial Chemicals Notification and Assessment Scheme (NICNAS). BE values corresponding to the reference dose (RfD) or margin of safety (MOS) targets from these agencies were derived based on kinetic data (urinary excretion and plasma clearance) from human studies and measured blood concentration data in animal studies. Estimated BE values for urinary total triclosan (free plus conjugates) corresponding to the US EPA RfD and the EC-identified margin of safety target from the NOAEL are 6.4 and 2.6 mg/L, respectively (corresponding to 8.3 and 3.3mg/g creatinine, respectively). Plasma BE values corresponding to the US EPA, EC, and Australian NICNAS values are 0.3, 0.9, and 0.4 mg/L, respectively. These values may be used as screening tools for evaluation of population biomonitoring data for triclosan in a risk assessment context. PMID- 20541578 TI - Clozapine-induced persistent paroxysmal perceptual alteration. PMID- 20541579 TI - Induction of subcutaneous adipose proliferation by olanzapine in rodents. AB - Weight gain induced by atypical antipsychotics causes a serious health concern in the treatment of schizophrenic patients. In the present study chronic treatment of female Wistar rats with olanzapine caused weight gain, but limited effect on food intake. A dramatic drug-induced morphological change of the subcutaneous adipose tissue was observed, i.e. development of a pinkish coloration with the appearance of a "fish egg"-like texture. Histological examination revealed a massive increase in the proliferation of undifferentiated adipocytes. Such proliferation was detected as early as the third day after olanzapine treatment. The changes progressed in a time- and dose-dependent manner. The proliferation of adipose tissue was detected in rats treated with olanzapine independent of increases in weight gain. Protein profiles of the adipose tissue were also altered by olanzapine. These results suggest that olanzapine-induced weight gain may be not solely due to an effect on behavioural satiety. The potential involvement of adipose neuronal input and proliferation are discussed. PMID- 20541580 TI - Protection of trivalent inactivated influenza vaccine against hospitalizations among pandemic influenza A (H1N1) cases in Argentina. AB - The aim of this study was to estimate the effectiveness of 2009 seasonal trivalent inactivated vaccine in reducing hospitalizations due to the novel influenza A H1N1 virus among positive cases. Data collected from Argentina's national epidemiological surveillance system were analyzed. All patients had a clinical diagnosis and underwent positive serological tests for pandemic influenza A H1N1. Logistic regression was used to estimate vaccine effectiveness to prevent severe cases of the disease, measured as hospitalizations. The adjusted effectiveness of the vaccine was 50% (95% CI: 40-59%). Vaccination was significantly associated with hospitalizations in all age groups, and within groups that had and had not received antiviral treatment. These results suggest that seasonal influenza vaccine might have conferred partial protection against severe cases due to the novel pandemic influenza. PMID- 20541581 TI - Long-term immunity and immune response to a booster dose following vaccination with the inactivated Japanese encephalitis vaccine IXIARO, IC51. AB - IC51 (IXIARO, JESPECT) is a recently approved prophylactic Japanese encephalitis virus vaccine with a two-vaccine primary immunization regimen. In this phase 3 trial, after primary immunization with a Day 0/28 dose schedule, seroprotection rates were 83%, 58% and 48% at Month 6, Month 12 and Month 24, respectively. A booster dose at Month 11 and/or Month 23 in subjects with neutralizing antibody titers below the limit of detection (defined as a serum dilution giving a 50% reduction of plaque counts in a plaque reduction neutralization test [PRNT50]<1:10) led to 100% seroconversion. After a single-dose immunization (incomplete primary immunization), only 9% of subjects were seroprotected at Month 6; however, a booster dose at Month 11 led to seroconversion in 99% of subjects. Hence, subjects with incomplete primary immunization can complete their schedule within at least 11 months. PMID- 20541582 TI - The potential value of Clostridium difficile vaccine: an economic computer simulation model. AB - Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially, when being used post-CDI treatment to prevent recurrent disease. PMID- 20541584 TI - Selective cell death in neurodegeneration: why are some neurons spared in vulnerable regions? AB - Neurodegenerative diseases exhibit varying and characteristic patterns of regional brain cell death, yet in each disorder there are distinct variations in the relative vulnerability of neurons within targeted brain regions. For example, in Parkinson's disease (PD) up to 90% of dopaminergic neurons of the ventral tier of the substantia nigra pars compacta are lost at post-mortem, while as few as 25% of dopaminergic neurons in the dorsal tier of this nucleus succumb to the disease process. To date the reasons underlying differential vulnerability of similar neurons within a defined cytoarchitectural region has received little attention. We suggest variations in protein distribution underlies this differential vulnerability. Within the substantia nigra pars compacta the more vulnerable neurons exhibit an increased expression of factors that may contribute to vulnerability (D(2) dopamine autoreceptors, GIRK-2 potassium channels, lactotransferrin and the dopamine transporter) while also expressing a relative lack of neuroprotective elements (dopamine vesicle transport protein and a number of trophic and growth factors). Differential distribution of key proteins expressed by individual cells within the same cytoarchitectural brain region may influence the severity and likelihood of common neurodegenerative mechanisms, such as protein aggregation, oxidative stress, neuroinflammation and apoptosis, and thus the eventual fate of individual cells in the disease process. An understanding of how variable protein expression can influence cell survival within the diseased human brain in a range of neurodegenerative disorders may provide avenues for the development of novel strategies to improve the survival of targeted neurons in vivo. PMID- 20541583 TI - Carrageenan as an adjuvant to enhance peptide-based vaccine potency. AB - New innovative therapies are urgently required in order to combat the high mortality and morbidity associated with advanced cancers. Antigen-specific cancer immunotherapy using peptide-based vaccination has emerged as an attractive approach for the control of cancers due to its simplicity and easy preparation. However, such an approach requires the employment of suitable adjuvants. In the current study, we explored the employment of a sulfated polysaccharide compound from red algae, carrageenan (CGN) as an adjuvant for their ability to generate antigen-specific immune responses and antitumor effects in mice vaccinated with human papillomavirus type 16 (HPV-16) E7 peptide vaccine. We found that carrageenan can significantly enhance the E7-specific immune responses generated by E7 peptide vaccination via the TLR4 activation pathway. In addition, carrageenan could enhance the protective and therapeutic antitumor effects generated by E7 peptide vaccination against E7-expressing tumors. Furthermore, the observed enhancement was not restricted to E7 antigen but was also applicable to other antigenic systems. We also found that other structurally similar compounds to CGN, such as dextran, also generated similar immune enhancement. Thus, our data suggest that CGN and its structurally related compounds may serve as innovative adjuvants for enhancing peptide-based vaccine potency. PMID- 20541585 TI - Metabolically exaggerated cardiac reactions to acute psychological stress: the effects of resting blood pressure status and possible underlying mechanisms. AB - The study aimed to: confirm that acute stress elicits metabolically exaggerated increases in cardiac activity; test whether individuals with elevated resting blood pressure show more exaggerated cardiac reactions to stress than those who are clearly normotensive; and explore the underlying mechanisms. Cardiovascular activity and oxygen consumption were measured pre-, during, and post-mental stress, and during graded sub-maximal cycling exercise in 11 young men with moderately elevated resting blood pressure and 11 normotensives. Stress provoked increases in cardiac output that were much greater than would be expected from contemporary levels of oxygen consumption. Exaggerated cardiac reactions were larger in the relatively elevated blood pressure group. They also had greater reductions in total peripheral resistance, but not heart rate variability, implying that their more exaggerated cardiac reactions reflected greater beta adrenergic activation. PMID- 20541586 TI - Induction of pluripotency in human cord blood unrestricted somatic stem cells. AB - OBJECTIVE: Generation of induced pluripotent stem (iPS) cells from human cord blood (CB)-derived unrestricted somatic stem cells and evaluation of their molecular signature and differentiation potential in comparison to human embryonic stem cells. MATERIALS AND METHODS: Unrestricted somatic stem cells isolated from human CB were reprogrammed to iPS cells using retroviral expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC. The reprogrammed cells were analyzed morphologically, by quantitative reverse transcription polymerase chain reaction, genome-wide microRNA and methylation profiling, and gene expression microarrays, as well as in their pluripotency potential by in vivo teratoma formation in severe combined immunodeficient mice and in vitro differentiation. RESULTS: CB iPS cells are very similar to human embryonic stem cells morphologically, at their molecular signature, and in their differentiation potential. CONCLUSIONS: Human CB-derived unrestricted somatic stem cells offer an attractive source of cells for generation of iPS cells. Our findings open novel perspectives to generate human leukocyte antigen-matched pluripotent stem cell banks based on existing CB banks. Besides the obvious relevance of a second generation CB iPS cell bank for pharmacological and toxicological testing, its application for autologous or allogenic regenerative cell transplantation appears feasible. PMID- 20541587 TI - A power-law distribution of inter-spike intervals in renal sympathetic nerve activity in salt-sensitive hypertension-induced chronic heart failure. AB - To assess sympathetic variability in chronic heart failure (CHF), we evaluated a distribution of inter-spike intervals (ISIs) in renal sympathetic nerve activity (RSNA) in salt-sensitive hypertension-induced CHF (DSSH-CHF) rats. Dahl salt sensitive rats were fed an 8% NaCl diet for 9 weeks to induce salt-sensitive hypertension-induced CHF. ISIs in RSNA were obtained from chronically instrumented conscious rats, and counts (frequency) and ranks of ISIs in RSNA were plotted with a histogram. We found that ISIs in RSNA followed a power-law distribution in rats, and the power-law distribution of ISIs for RSNA in DSSH-CHF rats was significantly different from that in normal rats. These results indicated that sympathetic variability may be significantly different between salt-sensitive hypertension-induced CHF and healthy individuals, which suggests that sympathetic variability may be used to predict abnormality of the sympathetic regulatory system. PMID- 20541588 TI - G-protein-independent modulation of P-type calcium channels by mu-opioids in Purkinje neurons of rat. AB - P-type calcium channels play a key role in the synaptic transmission between mammalian central neurons since a major part of calcium entering pre-synaptic terminals is delivered via these channels. Using conventional whole-cell patch clamp techniques we have studied the effect of mu-opioids on P-type calcium channels in acutely isolated Purkinje neurons from rat cerebellum. The selective mu-opioid agonist DAMGO (10nM) produced a small, but consistent facilitation of current through P-type calcium channels (10+/-1%, n=27, p<0.001). The effect of DAMGO was rapid (less than 10s) and fully reversible. This effect was both concentration and voltage-dependent. The EC(50) for the effect of DAMGO was 1.3+/ 0.4nM and the saturating concentration was 100nM. The endogenous selective agonist of mu-opioid receptors, endomorphin-1 demonstrated similar action. Intracellular perfusion of Purkinje neurons with GTPgammaS (0.5mM) or GDPbetaS (0.5mM), as well as strong depolarizing pre-pulses (+50mV), did not eliminate facilitatory action of DAMGO on P-channels indicating that this effect is not mediated by G-proteins. Furthermore, the effect of DAMGO was preserved in the presence of a non-specific inhibitor of PKA and PKC (H7, 10microM) inside the cell. DAMGO-induced facilitation of P-current was almost completely abolished by the selective mu-opioid antagonist CTOP (100nM). These observations indicate that mu-type opioid receptors modulate P-type calcium channels in Purkinje neurons via G-protein-independent mechanism. PMID- 20541589 TI - Caffeine attenuates lipopolysaccharide-induced neuroinflammation. AB - Caffeine is an antagonist at A1 and A2A adenosine receptors and epidemiological evidence suggests that caffeine consumption reduces the risk of Alzheimer's and Parkinson's diseases. Neuroinflammation plays a role in the etiology of these diseases and caffeine may provide protection through the modulation of inflammation. Adenosine has a known role in the propagation of inflammation and caffeine may reduce microglia activation directly by blocking adenosine receptors on microglia. Chronic neuroinflammation is associated with an increase in extracellular levels of glutamate and drugs that limit the effects of glutamate at neuronal receptors have been shown to indirectly reduce the neuroinflammatory response of microglia cells. A1 and A2A receptors have been shown to regulate the pre-synaptic release of glutamate, therefore, caffeine may also reduce neuroinflammation via its ability to regulate glutamate release. Caffeine was administered at various doses to young rats with experimentally induced neuroinflammation by chronic infusion of lipopolysaccharide (LPS) over two or four weeks into the 4th ventricle and to aged rats with naturally elevated levels of microglia activation. Caffeine attenuated the number of activated microglia within the hippocampus of animals with LPS-induced and age-related inflammation. PMID- 20541590 TI - The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates. AB - Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother-infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC. We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter. VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter. Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility. PMID- 20541591 TI - Regulation of post-translational protein arginine methylation during HeLa cell cycle. AB - BACKGROUND: Post-translational arginine methylation which modifies protein arginyl residues by protein arginine methyltransferase (PRMT) was investigated during synchronized HeLa cell cycle. METHODS: The lysates of cells synchronized at each stage were subjected to one and/or two dimensional electrophoresis followed by Western immunoblot using against anti-asymmetric-dimethyl-arginine (ASYM24), anti-symmetric-dimethyl-arginine (SYM10), and subclasses of PRMTs, including PRMT1, PRMT3, PRMT4 (CARM1), PRMT5, PRMT6, and PRMT7 antibodies. RESULTS: Proteins with approximate molecular masses of 80 kDa, 68 kDa, and 64 kDa, containing asymmetric-dimethyl-arginine (aDMA) were increased at G0/G1 to G1, which lasted until S phase. In addition, 25 kDa protein of symmetric-dimethyl arginine (sDMA) was also markedly up-regulated from G0/G1 to G1. The levels of PRMT3, PRMT6 and PRMT7 were concurrently increased during the cell cycle. Two dimensional gel electrophoresis followed by MALDI-TOF-MS was identified as aDMA 80 kDa and aDMA-68 kDa proteins as heterogeneous nuclear ribonucleoprotein R (hnRNPR), aDMA-64 kDa proteins as cleavage stimulation factor 64 kDa subunit (CstF-64), and sDMA-25 kDa protein as triosephosphate isomerase (TPI). The levels of increased aDMA of hnRNPR were reduced, when HeLa cells were transfected with siRNA for PRMT1, and the aDMA of CstF-64 with siRNA for PRMT3, while depletion of PRMT5 down-regulated sDMA of TPI. CONCLUSION: Protein arginine dimethylations of hnRNPR, CstF-64, and TPI were regulated during HeLa cell cycle by respective PRMTs. GENERAL SIGNIFICANCE: These results suggest that regulation of arginine dimethylation of hnRNPR, CstF-64, and TPI at G0/G1 to G1 are most likely to modulate the cellular growth and proliferation in HeLa cell cycle. PMID- 20541592 TI - D-serine treatment reduces cocaine-primed reinstatement in rats following extended access to cocaine self-administration. AB - The most intractable feature of drug addiction is the high rate of relapse, even following extended periods of abstinence from drug-taking. Evidence suggests that allowing rats extended access to cocaine self-administration leads to behavioral characteristics in these animals that are consistent with the development of addiction in humans. In the current study, rats were allowed to self-administer cocaine over a total of 22 daily sessions, the final seven of which were long access (LgA) sessions of 6 h duration. Assessments of reinstatement of drug seeking behavior were made following reintroduction to the drug-taking environment and noncontingent priming with either conditioned stimulus (CS) or cocaine in both extinguished and abstinent subject groups. Three separate groups of rats were treated with either saline or D-serine (100 mg/kg i.p.) administered 2 h prior to, or immediately following, each extinction training session. Saline treated LgA rats were resistant to the effects of extinction training to reduce noncontingent priming of reinstatement of drug-seeking behavior with either CS or cocaine. In contrast, treatment with D-serine either before or immediately following the sessions resulted in a significant enhancement in the ability of extinction training to reduce cocaine-primed reinstatement of drug-seeking behavior. These results suggest that D-serine can act to enhance the consolidation of extinction learning in LgA rats, and is therefore a promising adjunctive agent along with behavioral therapy for the treatment of cocaine addiction. PMID- 20541593 TI - Distribution of NBCn2 (SLC4A10) splice variants in mouse brain. AB - The five known Na-coupled HCO(3)(-) transporters (NCBTs) of the solute carrier 4 (SLC4) family play important roles in pH regulation and transepithelial HCO(3)(-) transport. Nearly all of the NCBTs have multiple splice variants. One particular NCBT, the electroneutral Na/HCO(3)(-) cotransporter NBCn2 (SLC4A10), which is predominantly expressed in brain, has three known splice variants-NBCn2-A, -B, and -C-as well as a potential variant-D. It is important to know the tissue specific expression of the splice variants for understanding the physiological roles of NBCn2 in central nervous system. In the present study, we developed three novel rabbit polyclonal antibodies against NBCn2: (1) anti-ABCD, which recognizes all four variants; (2) anti-BD, which recognizes NBCn2-B and -D; (3) anti-CD, which recognizes NBCn2-C and -D. By western blotting, we examined the expression and distribution of NBCn2 splice variants in five brain regions: cerebral cortex, subcortex, cerebellum, hippocampus, and medulla. The expression pattern revealed with anti-ABCD is distinct from those revealed with anti-BD and anti-CD. Moreover, by using immunoprecipitation in combination with western blotting, we demonstrate that NBCn2-D does indeed exist and that it is predominantly expressed in subcortex, to a lesser extent in medulla, but at very low levels in cortex, cerebellum, and hippocampus. NBCn2-A may be the dominant variant in mouse brain as a whole, and may also dominate in cerebral cortex, cerebellum, and hippocampus. Immunohistochemistry with anti-ABCD shows that NBCn2 is highly expressed in choroid plexus, cortex, molecular layer of cerebellum, hippocampus, and some specific regions of the brainstem. PMID- 20541594 TI - The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions. AB - Non-clustered protocadherins (PCDHs) are calcium-dependent adhesion molecules which have attracted attention for their possible roles in the neuronal circuit formation during development and their implications in the neurological disorders such as autism and mental retardation. Previously, we found that a subset of the non-clustered PCDHs exhibited circuit-dependent expression patterns in thalamo cortical connections in early postnatal rat brain, but such patterns disappeared in adulthood. In this study, we identified that the non-clustered PCDHs showed differential expression patterns along the septotemporal axis in the subregions of adult hippocampus and dentate gyrus with topographical preferences. The expressions of PCDH1, PCDH9, PCDH10 and PCDH20 showed septal preferences, whereas the expressions of PCDH8, PCDH11, PCDH17 and PCDH19 showed temporal preferences, suggesting that they play roles in the formation/maintenance of intrahippocampal circuits. PCDHs also exhibited the region-specific expression patterns in the areas connected to hippocampal formation such as entorhinal cortex, lateral septum, and basolateral amygdaloid complex. Furthermore, the expression levels of three PCDHs (PCDH8, PCDH19 and PCDH20) were regulated by the electroconvulsive shock stimulation of the brain in the adult hippocampus and dentate gyrus. These results suggest that non-clustered PCDHs are involved in the maintenance and plasticity of adult hippocampal circuitry. PMID- 20541595 TI - Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC). AB - Tinnitus is an auditory disorder characterized by perception of internally generated phantom auditory sensations without corresponding mechanical stimuli arising from the body or external environment. Current auditory based treatment approaches, sometimes in conjunction with nonauditory based strategies, such as Tinnitus Retraining Therapy and Cognitive Behavioral Therapy, have been helpful in mitigating symptoms for the majority of patients. Yet there are over 1 million tinnitus sufferers who still endure troublesome chronic, continuous head noises that are debilitating and interfere with activities of daily living. Here we show that application of deep brain stimulation (DBS) therapy to a locus of caudate neurons (area LC) in the body of the nucleus, a subsite of the striatum that is not part of the classical auditory pathway, can decrease or increase tinnitus loudness perception. The DBS lead traversed through or was adjacent to area LC in six Parkinson's disease and essential tremor subjects with concomitant tinnitus who underwent implantation of the subthalamic or ventral intermediate nucleus. In five subjects where the DBS lead tip traversed area LC, tinnitus loudness in both ears was suppressed to a nadir of level 2 or lower on a 0-10 rating scale. In one subject where the DBS lead was outside area LC, tinnitus was not modulated. In three subjects with preoperative and postoperative audiograms, hearing thresholds were unchanged by area LC stimulation. Neuromodulation of area LC may be interrupting perceptual integration of phantom sensations generated in the central auditory system. This new, basal ganglia based approach to tinnitus modulation warrants further investigation and may be ultimately refined to treat patients with refractory symptoms. PMID- 20541596 TI - Oxidative stress, progressive damage in the substantia nigra and plasma dopamine oxidation, in rats chronically exposed to ozone. AB - The purpose of our work was to determine the effects of oxidative stress on the neurodegeneration process in the substantia nigra, and to evaluate dopamine oxidation metabolites in the plasma using a cyclic voltammetry (CV) technique. We have also studied the correlation between the increases in oxidized dopamine species levels with the severity of lipid-peroxidation in the plasma. Sixty-four male Wistar rats were divided into four experimental groups and received air (Group I, control) or ozone (0.25 ppm) daily by inhalation for 4h for 15 (Group II), 30 (Group III), and 60 (Group IV) days. The brains were processed for immunohistochemical location of dopamine and p53 in the substantia nigra. Plasma collected from these animals was assayed for oxidized dopamine products using CV and lipid-peroxidation levels were measured. Our results indicate that chronic exposure to low O(3) doses causes that the number of dopaminergic neurons decreased, and p53-immunoreactive cells increases until 30 days; which was a function of the time of exposure to ozone. Oxidative stress produces a significant increase in the levels of the dopamine quinones (DAQs) that correlated well (r=0.962) with lipid peroxides in the plasma during the study period. These results suggest that DAQ could be a reliable, peripheral oxidative indicator of nigral dopaminergic damage in the brain. PMID- 20541597 TI - Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration. AB - Auditory perceptual 'restoration' occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of 'auditory scene analysis' to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings. PMID- 20541598 TI - Bio and nanotechnological strategies for tumor-targeted gene therapy. AB - Gene therapy is a new medical approach for the treatment of tumors. For safe and efficient gene therapy, therapeutic genes need to be delivered efficiently into the target tumor cells. Development of gene delivery systems to specifically recognize and target tumor cells and to distinguish them from normal cells, especially in the same tissue or organ, is one of the most important issues regarding the present gene delivery methodologies. The enhanced permeability and retention (EPR) effect using the characteristics of angiogenic tumor blood vessels, as well as gene delivery systems recognizing hyperactivated receptors or intracellular signals, is broadly applied to tumor-targeted gene therapy. In addition, bacterial vectors can be a useful means for targeting hypoxic or anoxic regions of a tumor. PMID- 20541599 TI - Cellular responses by stable and uniform ultrafine titanium dioxide particles in culture-medium dispersions when secondary particle size was 100 nm or less. AB - Even though there have been some investigations into cellular responses induced by ultrafine titanium dioxide (TiO(2)) in vitro, the relationship between cellular responses and secondary particle size is still not clear. In this study, a stable and uniform TiO(2)-cell culture-medium dispersion was prepared, and cellular responses prompted by "ultrafine secondary particles" were examined. The TiO(2)-DMEM-FBS dispersion included secondary particles in which the secondary particle size was 100 nm or less. In the present study, a "secondary particle" was defined as a complex aggregate of TiO(2) primary particles, proteins from FBS and other medium components. Secondary particle size did not influence the cell viability. The TiO(2)-DMEM-FBS dispersion introduced to the human keratinocyte HaCaT cells caused weak intracellular oxidative stress and apoptosis. The cellular influence of ultrafine TiO(2)in vitro is caused by the following mechanisms: (1) Secondary particles are formed. Ultrafine TiO(2) particles dispersed in medium immediately form secondary particles with proteins and salts. (2) "Ultrafine" secondary particles are taken up by the cells. The secondary particles reach the cells by diffusion and/or sedimentation and are taken up by the cells, through endocytosis. (3) Intracellular reactive oxygen species (ROS) level increases. Internalized secondary particles induce an increase in intracellular reactive oxygen species levels, although the secondary particles do not break up in the cell. In the case of ultrafine TiO(2), the increase of the intracellular ROS level was minimal. Moreover, the antioxidation system of cells such as glutathione was working. (4) Apoptotic cell death is induced. An accumulation of oxidative stress activates the apoptotic pathway (such as the caspase-3) and subsequently induces apoptotic cell death. After 24h of exposure to TiO(2), the percentage of apoptotic cells was only 6-7%. As a result, although the ultrafine TiO(2) particles induce some cellular responses, these cellular responses to ultrafine TiO(2) are weaker than those of other cytotoxic ultrafine metal oxide particles, such as nickel oxide. PMID- 20541600 TI - Enzyme activity inhibition and secondary structure disruption of nano-TiO2 on pepsin. AB - In this study, the binding and enzyme activity inhibitory effect of nano-TiO(2) on pepsin was explored compared with micro-TiO(2). Nano-TiO(2) was about 60 nm and micro-TiO(2) was about 200 nm, both round in shape. The activity of pepsin was depressed significantly by nano-TiO(2) comparing to micro-ones. The results of UV spectrometry, HPLC, SDS-PAGE and CD assay proved that micro-TiO(2) has only physical absorption effect on pepsin, but no impairment on primary sequences or secondary structure. However, nano-TiO(2) had coordination interaction with pepsin besides physical binding effect. The secondary structure of pepsin was unfolded with the treatment of nano-TiO(2) at pH 6.5 and pH 3.53, which might consequently affect the beta-hairpin loop that protects the active center of pepsin, and then reduce the enzyme activity. Furthermore, the thermodynamic mechanisms of interaction between nano-TiO(2) and pepsin were explored by fluorescence spectrum and ITC analysis. According to the results of thermodynamic analysis, the K value was 3.64x10(6), stoichiometry (N(pepsin:nano-TiO2)) was 3.04x10(3), the total DeltaH was -2277 cal/mol, DeltaS was 22.7 cal/(K mol), therefore the nano-TiO(2)-pepsin interaction is spontaneous. The depression of activity and the unfolding of secondary structure of pepsin were resulted from non-covalent reactions, including electrostatic force and hydrophobic binding. This work studied the different inhibitory effects and revealed mechanisms of the interaction between micro/nano-TiO(2) and pepsin, and provided a useful approach for evaluating the health risk of nano-materials on level of proteins. PMID- 20541601 TI - Neutrophil-mediated oxidation of enkephalins via myeloperoxidase-dependent addition of superoxide. AB - Neutrophils play a major role in acute inflammation in part by generating superoxide and an array of other reactive species. These white blood cells also contribute to protection against inflammatory pain by releasing opioid peptides. The biochemical interactions of enkephalins with neutrophil-derived oxidants are not well understood. In this investigation we reveal that neutrophils use myeloperoxidase to oxidize enkephalins to their corresponding tyrosyl free radicals, which react preferentially with the superoxide to form a hydroperoxide. In methionine enkephalin, rapid intramolecular oxygen transfer from the hydroperoxide to the Met sulfur results in the formation of a sulfoxide derivative. This reaction may occur at sites of inflammation where enkephalins are released and neutrophils generate large amounts of superoxide. Hydroperoxide formation destroys the aromatic character of the Tyr residue by forming a bicyclic structure via conjugate addition of the terminal amine to the phenol ring. As the N-terminal Tyr and its amino group are essential for their opiate activity, we hypothesize that oxidative modification of this residue should affect the analgesic activity of enkephalins. PMID- 20541602 TI - Low vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2. AB - The sodium-dependent vitamin C transporter (SVCT2) is responsible for the transport of vitamin C into cells in multiple organs, from either the blood or the cerebrospinal fluid. Mice null for SVCT2 (SVCT2(-/-)) do not survive past birth but the cause of death has not yet been ascertained. After mating of SVCT2(+/-) males and SVCT2(+/-) females, fewer SVCT2(-/-) and SVCT2(+/-) progeny were observed than would be expected according to Mendelian ratios. Vitamin C levels in SVCT2(-/-), SVCT2(+/-), and SVCT2(+/+) were genotype-dependent. SVCT2( /-) fetuses had significantly lower vitamin C levels than littermates in placenta, cortex, and lung, but not in liver (the site of vitamin C synthesis). Low vitamin C levels in placenta and cortex were associated with elevations in several markers of oxidative stress: malondialdehyde, isoketals, F(2) isoprostanes, and F(4)-neuroprostanes. Oxidative stress was not elevated in fetal SVCT2(-/-) lung tissue despite low vitamin C levels. In addition to the expected severe hemorrhage in cortex, we also found hemorrhage in the brain stem, which was accompanied by cell loss. We found evidence of increased apoptosis in SVCT2( /-) mice and disruption of the basement membrane in fetal brain. Together these data show that SVCT2 is critical for maintaining vitamin C levels in fetal and placental tissues and that the lack of SVCT2, and the resulting low vitamin C levels, results in fetal death and, in SVCT2(-/-) mice that survive the gestation period, in oxidative stress and cell death. PMID- 20541603 TI - Determinants of thromboxane biosynthesis in rheumatoid arthritis: Role of RAGE and oxidant stress. AB - Thromboxane (TX) biosynthesis by platelets and other cells in response to inflammatory triggers may provide a link between chronic inflammatory disease and atherothrombosis in rheumatoid arthritis (RA). In this study, we investigated the determinants of TX biosynthesis in RA, with particular reference to enhanced oxidative stress, receptor for advanced glycation end-products (RAGE) hyperactivity, and anti-tumor necrosis factor (TNF) treatment. Fifty-four patients with RA and 20 healthy subjects were recruited and a cross-sectional comparison of urinary 11-dehydro-TXB(2), 8-iso-PGF(2alpha), and plasma endogenous secretory RAGE (esRAGE) levels was performed between patients and controls. Urinary 11-dehydro-TXB(2) was significantly higher in RA patients than in healthy controls [425 (309-592) vs 233 (158-327) pg/mg creatinine, P<0.0001]. Furthermore, urinary 8-iso-PGF(2alpha) [323 (221-515) vs 172 (91-292) pg/mg creatinine, P<0.0001] and plasma esRAGE [155 (100-240) vs 377 (195-486) pg/ml, P=0.001] were higher and lower, respectively, in patients than in controls. A direct correlation was found between urinary 11-dehydro-TXB(2) and 8-iso PGF(2alpha) only in patients not on anti-TNF therapy (r=0.420, P=0.021). Conversely, patients on anti-TNF therapy showed significantly lower urinary 8-iso PGF(2alpha) [284 (201-373) vs 404 (241-539) pg/mg creatinine, P=0.043] but not 11 dehydro-TXB(2) than anti-TNF-treated subjects, with esRAGE as the only independent predictor of 11-dehydro-TXB(2) in this group of patients (adjusted R(2)=0.496, beta=-0.725, SEM=0.025, P=0.001). In conclusion, we provide biochemical evidence of enhanced TX biosynthesis in patients with RA, driven, at least in part, by lipid peroxidation. Treatment with anti-TNF agents may blunt isoprostane generation in the absence of significant effects on TX biosynthesis. We suggest that RAGE hyperactivity may escape TNF blockade, thus contributing to persistent TX biosynthesis in this setting. PMID- 20541604 TI - Oxidative stress defense in human-skin-derived mesenchymal stem cells versus human keratinocytes: Different mechanisms of protection and cell selection. AB - Stem cells are undifferentiated cells with the capacity for self-renewal and differentiation. Here we have determined the susceptibility to oxidative stress of isolated mesenchymal stem cells from human skin (S-MSCs) in comparison with keratinocytes, which are differentiated cells of the same lineage. To induce pro oxidant conditions, S-MSCs and keratinocytes were exposed to 0.5mM H(2)O(2) for 2 h, with oxidative effects analyzed after 4, 12, 24, and 48 h of recovery, in terms of cell growth, vitality, apoptosis, DNA damage, variations in individual antioxidant defense and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals. The data indicate different abilities across these two cell types to counteract this oxidative stress, which reflects stress that would normally be experienced by these cells under basal conditions. Human keratinocytes seem to have much greater antioxidant defense to counteract the oxidative injury to which they are continuously exposed in the skin. The S-MSCs are surrounded by a complex microenvironment that protects them from external insults, and so they do not have a particularly efficient defense system, and they were generally less responsive to enhanced pro-oxidant challenge. S-MSCs seem particularly prone to apoptotic events, which might thus represent their primary defense mechanism against stress. PMID- 20541605 TI - RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl XL. AB - Bax, a member of Bcl-2 family, plays an essential role in apoptotic pathways induced by a number of apoptotic stimulus. In a search for new potential binding partners of Bax, we identified the receptor for activated C-kinase 1 (RACK1) by a yeast two-hybrid assay. We demonstrated that RACK1 interacts with Bax through its BH3 domain both in vitro and in vivo. Using immunostaining and immunoprecipitation experiments, we found that RACK1 colocalizes with Bax oligomers and promotes Bax oligomerization both in vitro and in vivo. Furthermore, we observed that RACK1 also interacts with Bcl-XL, an anti-apoptotic protein associated with Bax. Interestingly, the Bcl-XL/Bax interaction is decreased when RACK1 is overexpressed, but is increased when RACK1 is depleted, suggesting RACK1 disrupts the association of Bax and Bcl-XL. In addition, we found that overexpression of RACK1 promotes UV-induced apoptosis, while knocking down RACK1 inhibits the effects. Together, these results indicate that RACK1 promotes apoptosis by promoting Bax oligomerization and dissociating the complex of Bax and Bcl-XL. PMID- 20541606 TI - Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans. AB - Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal activity against Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against Candida albicans and Candida parapsilosis, with MICs of 3.9 and 1.9 microg/ml, respectively. The combination of punicalagin and fluconazole showed a synergistic interaction. MIC for fluconazole decreased twofold when combined with the extract. The FIC index was 0.25. The synergism observed in disk diffusion and checkerboard assays was confirmed in time-kill curves. The effect of punicalagin on the morphology and ultrastructure in treated yeast cells was examined by scanning and transmission electron microscopy. An irregular budding pattern and pseudohyphae were seen in treated yeasts. By transmission electron microscopy, treated cells showed a thickened cell wall, changes in the space between cell wall and the plasma membrane, vacuoles, and a reduction in cytoplasmic content. Since the punicalagin concentration effective in vitro is achievable in vivo, the combination of this agent with fluconazole represents an attractive prospect for the development of new management strategies for candidiasis, and should be investigated further in in vivo models. PMID- 20541607 TI - Metabolic regulation of APOBEC-1 complementation factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes. AB - APOBEC-1 Complementation Factor (ACF) is an RNA-binding protein that interacts with apoB mRNA to support RNA editing. ACF traffics between the cytoplasm and nucleus. It is retained in the nucleus in response to elevated serum insulin levels where it supports enhanced apoB mRNA editing. In this report we tested whether ACF may have the ability to regulate nuclear export of apoB mRNA to the sites of translation in the cytoplasm. Using mouse models of obesity-induced insulin resistance and primary hepatocyte cultures we demonstrated that both nuclear retention of ACF and apoB mRNA editing were reduced in the livers of hyperinsulinemic obese mice relative to lean controls. Coincident with an increase in the recovery of ACF in the cytoplasm was an increase in the proportion of total cellular apoB mRNA recovered in cytoplasmic extracts. Cytoplasmic ACF from both lean controls and obese mouse livers was enriched in endosomal fractions associated with apoB mRNA translation and ApoB lipoprotein assembly. Inhibition of ACF export to the cytoplasm resulted in nuclear retention of apoB mRNA and reduced both intracellular and secreted ApoB protein in primary hepatocytes. The importance of ACF for modulating ApoB was supported by the finding that RNAi knockdown of ACF reduced ApoB secretion. An additional discovery from this study was the finding that leptin is a suppressor ACF expression. Dyslipidemia is a common pathology associated with insulin resistance that is in part due to the loss of insulin controlled secretion of lipid in ApoB containing very low density lipoproteins. The data from animal models suggested that loss of insulin regulated ACF trafficking and leptin regulated ACF expression may make an early contribution to the overall pathology associated with very low density lipoprotein secretion from the liver in obese individuals. PMID- 20541608 TI - Recombinant bacterial expression and purification of human fragile X mental retardation protein isoform 1. AB - The loss of expression of the fragile X mental retardation protein (FMRP) leads to fragile X syndrome. FMRP has two types of RNA binding domains, two K-homology domains and an arginine-glycine-glycine box domain, and it is proposed to act as a translation regulator of specific messenger RNA. The interest to produce sufficient quantities of pure recombinant FMRP for biochemical and biophysical studies is high. However, the recombinant bacterial expression of FMRP has had limited success, and subsequent recombinant eukaryotic and in vitro expression has also resulted in limited success. In addition, the in vitro and eukaryotic expression systems may produce FMRP which is posttranslationally modified, as phosphorylation and arginine methylation have been shown to occur on FMRP. In this study, we have successfully isolated the conditions for recombinant expression, purification and long-term storage of FMRP using Escherichia coli, with a high yield. The expression of FMRP using E. coli renders the protein devoid of the posttranslational modifications of phosphorylation and arginine methylation, allowing the study of the direct effects of these modifications individually and simultaneously. In order to assure that FMRP retained activity throughout the process, we used fluorescence spectroscopy to assay the binding activity of the FMRP arginine-glycine-glycine box for the semaphorin 3F mRNA and confirmed that FMRP remained active. PMID- 20541609 TI - X-ray microCT imaging technique reveals corm microstructures of an arctic-boreal cotton-sedge, Eriophorum vaginatum. AB - X-ray computed tomography (CT), a non-destructive imaging technique, has recently been effectively applied to botanical research. In this study an X-ray microCT technique was developed to allow for anatomical study of the overwintering corms of Eriophorum vaginatum, an ecologically important sedge species in arctic tussock-tundra and boreal peatlands. Using a GE Medical MS8X-130 X-ray microCT scanner, optimal imaging parameters included scanning isolated corms at 80 k Vp and 100 microA with a 3500 ms exposure time and an isotropic voxel size of 10 microm. A Gaussian blur image filter with a blur radius (sigma) of two pixels was applied to the optimal dataset to improve visual detection and contrast of tissues while removing 99.2% of image noise. Using the developed X-ray microCT technique several undocumented anatomical characteristics of the corm were identified including the vascular connection between a parent corm and branching cormel and the 3D shape of sclereid clusters. The 3D structure of sclereid clusters was determined whereby the perimeter of their lance shape is greatly reinforced by sclereids with thicker secondary cell walls as compared to those of the interior of the cluster. The structure of sclereid clusters and their association with leaf traces suggests they may be stabilizing the corm-leaf connection to protect vascular tissues from physical damage. The proposed X-ray microCT technique is an excellent tool for determination of the 3D structure of E. vaginatum corms and may be used to detect alterations in tissue structure and chemistry in response to environmental change in this and other Cyperaceous species. PMID- 20541610 TI - High-throughput production of human proteins for crystallization: the SGC experience. AB - Producing purified human proteins with high yield and purity remains a considerable challenge. We describe the methods utilized in the Structural Genomics Consortium (SGC) in Oxford, resulting in successful purification of 48% of human proteins attempted; of those, the structures of approximately 40% were solved by X-ray crystallography. The main driver has been the parallel processing of multiple (typically 9-20) truncated constructs of each target; modest diversity in vectors and host systems; and standardized purification procedures. We provide method details as well as data on the properties of the constructs leading to crystallized proteins and the impact of methodological variants. These can be used to formulate guidelines for initial approaches to expression of new eukaryotic proteins. PMID- 20541611 TI - Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism. AB - People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease. PMID- 20541612 TI - Name that tune: decoding music from the listening brain. AB - In the current study we use electroencephalography (EEG) to detect heard music from the brain signal, hypothesizing that the time structure in music makes it especially suitable for decoding perception from EEG signals. While excluding music with vocals, we classified the perception of seven different musical fragments of about three seconds, both individually and cross-participants, using only time domain information (the event-related potential, ERP). The best individual results are 70% correct in a seven-class problem while using single trials, and when using multiple trials we achieve 100% correct after six presentations of the stimulus. When classifying across participants, a maximum rate of 53% was reached, supporting a general representation of each musical fragment over participants. While for some music stimuli the amplitude envelope correlated well with the ERP, this was not true for all stimuli. Aspects of the stimulus that may contribute to the differences between the EEG responses to the pieces of music are discussed. PMID- 20541613 TI - Malaria parasite sequences from chimpanzee support the co-speciation hypothesis for the origin of virulent human malaria (Plasmodium falciparum). AB - Phylogenetic analyses of the mitochondrial cytochrome b (cytb), apicoplast caseinolytic protease C (clpC), and 18S rRNA sequences of Plasmodium isolates from chimpanzees along with those of the virulent human malaria parasite P. falciparum showed that the common chimpanzee (Pan troglodytes) malaria parasites, assigned by Rich et al. (2009) to P. reichenowi, constitute a paraphyletic assemblage. The assumption that P. falciparum diverged from P. reichenowi as recently as 5000-50,000 years ago would require a rate of synonymous substitution/site/year in cytb and clpC on the order of 10(-5)-10(-6), several orders of magnitude higher than any known from eukaryotic organelle genomes, and would imply an unrealistically recent timing of the most recent common ancestor of P. falciparum mitochondrial genomes. The available data are thus most consistent with the hypothesis that P. reichenowi (in the strict sense) and P. falciparum co-speciated with their hosts about 5-7 million years ago. PMID- 20541614 TI - Phylogeny, historical biogeography and body size evolution in Pacific Island Crocodile skinks Tribolonotus (Squamata; Scincidae). AB - Competition heavily influences the structure of island communities, particularly in species-rich areas. If ecologically similar lineages come into contact following dispersal, selection may favor rapid evolutionary change; if constraints prevent such change, lineage extinction may result. One mechanism for relieving competition among newly sympatric species is the evolution of body size differences, such as through character displacement or size assortment. The Crocodile skinks of the genus Tribolonotus exhibit a threefold variation in body size, and several species occur in sympatry. We use 2252 bp of DNA sequence data spanning two mitochondrial (cyt b and ND2) and three nuclear (C-mos, Rhodopsin and Phosducin) gene regions to reconstruct the phylogeny of Tribolonotus, use it to examine the biogeography of the genus, and test for size assortment or character displacement. We find evidence that Tribolonotus originated on either Greater Bougainville or in New Guinea, and subsequently colonized surrounding islands via multiple colonization events. Our ancestral state reconstructions support multiple instances of parallel and independent change in body size within Tribolonotus. Additionally, we find no evidence for size assortment and conflicting evidence for character displacement, which we argue suggests that character displacement, combined with ecological differences between New Guinean species (T. gracilis and T. novaeguineae), best explains the evolution of body size in the genus Tribolonotus. PMID- 20541615 TI - Detection of a new erm(X)-mediated antibiotic resistance in Egyptian cutaneous propionibacteria. AB - A total of 107 antibiotic-resistant propionibacteria were isolated from the face of 102 Egyptian acne patients, dermatology staff and controls. Erythromycin clindamycin-resistant propionibacteria were chosen to detect erm(X) gene and it was detected in 29 of 107 (27%) strains. However, just 7 strains had IS1249I, 3 of them had also Tn5432. The erm(X) gene which is not carried on Tn5432 confers inducible resistance to telithromycin by erythromycin or clindamycin. The DNA sequences of the PCR amplification products of this new erm(X)-mediated antibiotic resistance showed >99% identity to the erm(X) gene isolated from a Corynebacterium jeikeium. Southern blotting analysis of the erm(X)-specific probe shows that there were two copies of this resistance gene integrated within the chromosomal DNA. This is the first report of erm(X) being carried by Propionibacterium acnes outside Europe. Whilst the gene is associated with Tn5432 in some strains, the data suggests other genetic element carrying erm(X). The high carriage of erm(X) may affect the efficacy of clindamycin and macrolides for acne treatment in Egypt. PMID- 20541616 TI - Characterization of the mating type (MAT) locus in the Phialocephala fortinii s.l. -Acephala applanata species complex. AB - Members of the Phialocephala fortinii sensu lato -Acephala applanata species complex (PAC) are the dominant root endophytes of woody plants in temperate and boreal forests. In the present study, the mating type (MAT) idiomorphs of eight species belonging to the PAC were cloned. Because direct cloning of MAT idiomorphs was not possible, species phylogenetically placed between the PAC and other helotialean species with characterized MAT locus were used for an intermediate cloning step. Whereas A. applanata showed a homothallic organization structure of the MAT locus, all other species either contained the MAT1-1 or MAT1 2 idiomorph indicative of heterothallism. A Tc1-like transposable element was found within the MAT locus of A. applanata. Analysis of A. applanata strains collected over a broad geographical range showed that the transposable element was present in all A. applanata strains, suggesting an ancient transposition event. Moreover, a partial MAT1-1-1 gene was identified within MAT1-2 idiomorphs, a common phenomenon in the order Helotiales. However, this partial gene was not fixed in all populations of the species. The evolution of the MAT locus with regard to different mating systems is discussed for the species complex. PMID- 20541617 TI - Long-term warm or cold acclimation elicits a specific transcriptional response and affects energy metabolism in zebrafish. AB - Organisms are often forced to acclimate to changing environmental temperature. Temperature compensation mechanisms have been reported, which enable organisms to minimize some of the temperature related effects. To investigate this process, zebrafish (Danio rerio) were acclimated to a control (26 degrees C), an increased (34 degrees C) or a decreased (18 degrees C) temperature for 4, 14 and 28 days. In general, warm acclimation depleted energy stores and decreased the condition factor, while cold acclimation increased both. The energy parameters as well as the transcriptional responses (investigated using printed 15k microarrays and real time PCR) indicated that warm acclimation was particularly stressful. However, after 28 days of warm acclimation, energy stores had recovered from the initial depletion. This could have been facilitated by the observed downregulation of transcripts involved in catabolic processes. Transcriptional regulation seemed to be an important means of coordinating the temperature compensation process. We could distinguish an early response which was independent of the direction of the temperature change and a direction specific long-term response. The early response was characterized by the upregulation of defence mechanisms, tissue regeneration and hemopoiesis. In the long-term response there was a strong emphasis on compensating for the altered metabolic rate as well as cell structure and replacement. PMID- 20541618 TI - Perspectives on carbonic anhydrase. AB - In the years since Larimer and Schmidt-Nielsen published their examination of red blood cell (RBC) carbonic anhydrase (CA) activities as a function of body mass in mammals, our knowledge of CA has expanded dramatically. We are now aware of the diversity of CA isoforms and their implication in a wide array of physiological processes. The catalytic mechanism of CA has been described, and numerous compounds that function as activators or inhibitors of CA activity have been identified. CA is investigated as a diagnostic tumor marker, and CA inhibitors are used or emerging as clinical treatments for diseases as diverse as glaucoma, cancer and obesity. Yet despite the intensity of research effort over the last 50years and the wealth of information that has accumulated, the questions asked by Larimer and Schmidt-Nielsen remain relevant today - we still have much to learn about the patterns and physiological significance of interspecific differences in CA expression and activity. PMID- 20541619 TI - Fused in sarcoma/translocated in liposarcoma: a multifunctional DNA/RNA binding protein. AB - The fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene was initially identified as a component of a fusion pro-oncogene resulting from a chromosomal translocation seen in liposarcomas. FUS/TLS belongs to a sub-family of RNA binding proteins, encoding an N-terminal serine-tyrosine-glycine-glutamine (SYGQ) region, an RNA recognition motif (RRM) flanked by glycine rich (G-rich) regions, a cysteine(2)/cysteine(2) zinc finger motif and multiple RGG repeats. The FUS/TLS protein interacts with RNA, single stranded DNA and double stranded DNA, and is involved in unique functions in mRNA processing and transport, transcriptional regulation and maintenance of genomic stability. Recently, several mutations in this gene have been found in amyotrophic lateral sclerosis (ALS) patients. The mutant forms of FUS/TLS exhibit similar pathology to other ALS causative genes, including aberrant cytoplasmic inclusions and an increased FUS/TLS cytoplasmic to nuclear ratio. The FUS/TLS mutations identified in ALS patients suggests that altered RNA metabolism may play a role in ALS pathogenesis. PMID- 20541620 TI - Variations in p53-like cDNA sequence are correlated with mussel haemic neoplasia: A potential molecular-level tool for biomonitoring. AB - Several bivalve species, including mussels (Mytilus spp.) and clams (Mya spp.), are susceptible to a leukemia-like disease called haemic neoplasia that has been known to decimate whole populations. Previous studies of molecular processes associated with late stages of this disease have implicated analogs of the p53 tumour suppressor protein family in disease etiology. We detected synonymous single nucleotide polymorphisms (SNPs) in the coding region sequence of p53-like cDNA from Mytilus trossulus (bay mussel) that differ between normal and neoplastic haemolymph. SNPs were located at positions 182, 392 and 821 bp. Most (94%) of the late leukemic animals sampled from cages in Burrard Inlet (British Columbia, Canada) had the same p53-like genotype, C182T G392G C821T, whereas 75% of the healthy animals were homozygous at positions C182C and T821T, independent of the genotype at the 392 bp position. As well, we detected an increased number of allelic variants in the leukemic animals that may arise from separate somatic mutation events in haemocyte precursors or from additional p53-like gene copies in polyploidy. Therefore, detection of these SNPs may provide a useful genetic biomarker for efficient monitoring of mussel population health. PMID- 20541621 TI - Natural ligand binding and transfer from liver fatty acid binding protein (LFABP) to membranes. AB - Liver fatty acid-binding protein (LFABP) is distinctive among fatty acid-binding proteins because it binds more than one molecule of long-chain fatty acid and a variety of diverse ligands. Also, the transfer of fluorescent fatty acid analogues to model membranes under physiological ionic strength follows a different mechanism compared to most of the members of this family of intracellular lipid binding proteins. Tryptophan insertion mutants sensitive to ligand binding have allowed us to directly measure the binding affinity, ligand partitioning and transfer to model membranes of natural ligands. Binding of fatty acids shows a cooperative mechanism, while acyl-CoAs binding presents a hyperbolic behavior. Saturated fatty acids seem to have a stronger partition to protein vs. membranes, compared to unsaturated fatty acids. Natural ligand transfer rates are more than 200-fold higher compared to fluorescently-labeled analogues. Interestingly, oleoyl-CoA presents a markedly different transfer behavior compared to the rest of the ligands tested, probably indicating the possibility of specific targeting of ligands to different metabolic fates. PMID- 20541622 TI - Involvement of Na+/H+ exchanger and respiratory burst enzymes NADPH oxidase and NO synthase, in Cd-induced lipid peroxidation and DNA damage in haemocytes of mussels. AB - This study investigated cadmium-induced oxidative and genotoxic effects, such as lipid peroxidation and disturbance of DNA integrity (DNA damage) in haemocytes of mussel Mytilus galloprovincialis and the possible involvement of Na+/H+ exchanger (NHE), and/or the main enzymes of respiratory burst, NADPH oxidase and nitric oxide (NO) synthase, in the induction of Cd toxic effects. In order to verify the role of either NHE, or NADPH oxidase and NO synthase in Cd-mediated toxicity, inhibitors such as ethyl-N-isopropyl-amiloride (EIPA), diphenyleneiodonium chloride (DPI) and NG-nitro-L-arginine methyl ester (L-NAME) were used in each case. Moreover, phorbol-myristate acetate (PMA), a well-known protein kinase C (PKC)-mediated NADPH oxidase and NO synthase stimulator, as well as hydrogen peroxide (H2O2), a well-known genotoxic agent, was also used for elucidating the modulation of signaling molecules within cells, thus leading to the induction of lipid peroxidation and DNA damage. The results of the present study showed that micromolar concentrations of Cd (0.05-50 microM) could enhance both lipid peroxidation and DNA damage, possible via a PKC-mediated signaling pathway with the involvement of NHE, thus leading to the induction of NADPH oxidase and NO synthase activity, since inhibition of either NHE, or NADPH oxidase and NO synthase activity, significantly attenuates Cd-induced toxic effects in each case. PMID- 20541623 TI - Reduced de novo synthesis of 5-methyltetrahydrofolate and reduced taurine levels in ethanol-treated chick brains. AB - In previous studies, exogenous ethanol (3 mmol EtOH/kg egg) caused a 1.6-fold increase in chick brain homocysteine (HoCys) levels at 11 days of development and the mixture of 3 mmol EtOH/kg egg and 34 micromol folic acid/kg egg attenuated EtOH-induced increases in chick brain HoCys levels. Because HoCys is converted to methionine utilizing the methyl donor, 5-methyltetrahydrofolate (5-methyl THF), we studied whether exogenous ethanol (3 mmol EtOH/kg egg) or the mixture of 3 mmol EtOH/kg egg and 34 micromol 5-methyl THF/kg egg inhibited chick brain 10 formyltetrahydrofolate dehydrogenase (10-FTHF DH; EC 1.5.1.6) activities and brain N5, N10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) activities at 11 days of development. Three daily dosages of 3 mmol EtOH/kg egg (E0-2) caused approximately a 7-fold reduction in brain 10-FTHF DH activities and approximately a 1.9-fold reduction in brain MTHFR activities as compared to controls at 11 days of development (p30 cc, and the presence of erythema or induration. Trends for consultation remained without discernable pattern when patients were stratified by age, amount of extravasate, or anatomic location. Conservative management was recommended in all cases. This included elevation of the extremity, frequent pulse and sensation exams, local message, and temporary splinting. There were no secondary complications requiring surgical intervention. CONCLUSIONS: Extravasation of non-ionic CT contrast media appears to be innocuous and can be treated with conservative therapy. Plastic surgery consultation should be obtained when there are obvious signs of skin and soft tissue compromise or symptoms of compartment syndrome. PMID- 20541632 TI - Production of nattokinase by batch and fed-batch culture of Bacillus subtilis. AB - Nattokinase was produced by batch and fed-batch culture of Bacillus subtilis in flask and fermentor. Effect of supplementing complex media (peptone, yeast extract, or tryptone) was investigated on the production of nattokinase. In flask culture, the highest cell growth and nattokinase activity were obtained with 50 g/L of peptone supplementation. In this condition, nattokinase activity was 630 unit/ml at 12 h. In batch culture of B. subtilis in fermentor, the highest nattokinase activity of 3400 unit/ml was obtained at 10h with 50 g/L of peptone supplementation. From the batch kinetics data, it was shown that nattokinase production was growth-associated and culture should be harvested before stationary phase for maximum nattokinase production. In fed-batch culture of B. subtilis using pH-stat feeding strategy, cell growth (optical density monitored at 600 nm) increased to ca. 100 at 22 h, which was 2.5 times higher than that in batch culture. The highest nattokinase activity was 7100 unit/ml at 19 h, which was also 2.1 times higher than that in batch culture. PMID- 20541633 TI - Improvement of xylanase production by thermophilic fungus Thermomyces lanuginosus SDYKY-1 using response surface methodology. AB - Response surface methodology (RSM) was employed to optimize medium composition for the production of a thermostable xylanase from T. lanuginosus SDYKY-1 using economical carbon and nitrogen sources (soybean meal and corncobs, respectively). Plackett-Burman (P-B) design was applied to evaluate the effects of nine variables (powdered corncobs, soybean meal, Tween-80, CaCl(2), MgSO(4).7H(2)O, FeSO(4), KH(2)PO(4), initial pH and inoculum culture volume). Corncobs, soybean meal and FeSO(4) were found to significantly influence on the xylanase production. The concentrations of these three factors were therefore optimized using central composite design and RSM. Adjusting the concentration of corncobs to 38.7g/L, soybean meal to 17.5g/L and FeSO(4) to 0.26g/L favored maximum xylanase production. Xylanase activity of 3078U/mL was obtained after optimization, which was a 144% increase that obtained before optimization (1264U/mL). PMID- 20541634 TI - Optimization of laccase production using response surface methodology coupled with differential evolution. AB - In the present study, laccase production from a locally isolated hyperactive strain of Pleurotus sp. under solid state fermentation (SSF) was carried out and the interactions between different parameters of fermentation were studied using response surface methodology. The saddle shaped response surface plots depicting dual conditions for the enhanced production indicated the presence of isozymes with production optima at different conditions which was verified experimentally. Isoelectric focusing of the enzyme extract revealed that two isoforms were found with a widely varying pI of 3.8 and 9.3 emphasizing the capacity of the enzyme to be deployed at both acidic and alkaline conditions. Optimization of production conditions by coupling the regression equation with differential evolution technique yielded over 54,600IU/gds (3,412,500U/L) with a surfactant concentration of 0.016%, pH 7.99, particle size of 0.25cm, liquid to solid ratio of 4.99 and an incubation period of 8 days. In this study, the optimization process yielded highest titer value of laccase reported to date. PMID- 20541635 TI - Methods for the identification of vascular markers in health and disease: from the bench to the clinic. AB - Several diseases are characterized by changes in the molecular composition of vascular structures, thus offering the opportunity to use specific ligands (e.g., monoclonal antibodies) for imaging and therapy application. This novel pharmaceutical strategy, often referred to as "vascular targeting", promises to facilitate the discovery and development of selective biopharmaceuticals for the management of angiogenesis-related diseases. This article reviews novel biomedical applications based on vascular targeting strategies, as well as methodologies which have been used for the discovery of vascular markers of pathology. PMID- 20541636 TI - Modification-specific proteomics in plant biology. AB - Post-translational modifications (PTMs) are involved in the regulation of a wide range of biological processes, and affect e.g. protein structure, activity and stability. Several hundred PTMs have been described in the literature, but relatively few have been studied using mass spectrometry and proteomics. In general, methods for PTM characterization are developed to study yeast and mammalian biology and later adopted to investigate plants. Our point of view is that it is advantageous to enrich for PTMs on the peptide level as part of a quantitative proteomics strategy to not only identify the PTM, but also to determine the functional relevance in the context of regulation, response to abiotic stress etc. Protein phosphorylation is the only PTM that has been studied extensively at the proteome wide level in plants using mass spectrometry based methods. We review phosphoproteomics studies in plants and discuss the redox mediated PTMs (S-nitrosylation, tyrosine nitration and S-glutathionylation), ubiquitylation, SUMOylation, and glycosylation, including GPI anchors, and the quantitative proteomics methods that are used to study these modification in plants. Where appropriate we contrast the methods to those used for mammalian PTM characterization. PMID- 20541637 TI - Murillo's paintings revealed by spectroscopic techniques and dedicated laboratory made micro X-ray diffraction. AB - This paper describes one of the first case studies using micro-diffraction laboratory-made systems to analyse painting cross-sections. Pigments, such as lead white, vermilion, red ochre, red lac, lapis lazuli, smalt, lead tin yellow type I, massicot, ivory black, lamp black and malachite, were detected in cross sections prepared from six Bartolome Esteban Murillo paintings by micro-Raman and micro-XRD combined with complementary techniques (optical microscopy, SEM-EDS, and FT-IR). The use of micro-XRD was necessary due to the poor results obtained with conventional XRD. In some cases, pigment identification was only possible by combining results from the different analytical techniques utilised in this study. PMID- 20541638 TI - High performance liquid chromatography coupled to atomic fluorescence spectrometry for the speciation of the hydride and chemical vapour-forming elements As, Se, Sb and Hg: a critical review. AB - We present the most recent applications of high performance liquid chromatography (HPLC) hyphenated to hydride generation or chemical vapour generation and atomic fluorescence spectrometry (HG/CVG-AFS), for the determination and speciation of the selected hydride-forming elements arsenic (As), selenium (Se) and antimony (Sb) and the chemical vapour-forming metal Hg. The review focuses on sample preparation, post-column treatments and on the applications of this technique to various liquid and solid samples. This review also intends to discuss some limitations associated to HPLC-HG/CVG-AFS due to the necessity on post-column treatments, including the oxidation of organo-element compounds and the pre reduction to a suitable valence. Nevertheless, the hyphenated technique HPLC HG/CVG-AFS remains an efficient, sensitive and affordable approach to perform speciation of the four studied elements as shown by the variety of applications presented and discussed in this review. PMID- 20541639 TI - Gasoline classification using near infrared (NIR) spectroscopy data: comparison of multivariate techniques. AB - Near infrared (NIR) spectroscopy is a non-destructive (vibrational spectroscopy based) measurement technique for many multicomponent chemical systems, including products of petroleum (crude oil) refining and petrochemicals, food products (tea, fruits, e.g., apples, milk, wine, spirits, meat, bread, cheese, etc.), pharmaceuticals (drugs, tablets, bioreactor monitoring, etc.), and combustion products. In this paper we have compared the abilities of nine different multivariate classification methods: linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), regularized discriminant analysis (RDA), soft independent modeling of class analogy (SIMCA), partial least squares (PLS) classification, K-nearest neighbor (KNN), support vector machines (SVM), probabilistic neural network (PNN), and multilayer perceptron (ANN-MLP) - for gasoline classification. Three sets of near infrared (NIR) spectra (450, 415, and 345 spectra) were used for classification of gasolines into 3, 6, and 3 classes, respectively, according to their source (refinery or process) and type. The 14,000-8000 cm(-1) NIR spectral region was chosen. In all cases NIR spectroscopy was found to be effective for gasoline classification purposes, when compared with nuclear magnetic resonance (NMR) spectroscopy or gas chromatography (GC). KNN, SVM, and PNN techniques for classification were found to be among the most effective ones. Artificial neural network (ANN-MLP) approach based on principal component analysis (PCA), which was believed to be efficient, has shown much worse results. We hope that the results obtained in this study will help both further chemometric (multivariate data analysis) investigations and investigations in the sphere of applied vibrational (infrared/IR, near-IR, and Raman) spectroscopy of sophisticated multicomponent systems. PMID- 20541640 TI - Electrochemical characterization of a single-walled carbon nanotube electrode for detection of glucose. AB - We developed glucose biosensing electrodes using single-walled carbon nanotube (SWCNT) films on flexible, transparent poly(ethylene terephthalate). The homogeneous SWCNT films were fabricated by a vacuum filtration method, and the averaged resistivity and transparency of the fabricated flexible SWCNT films were 400 Omega sq(-1) and 80%, respectively. The glucose sensing electrodes were constructed by encapsulating glucose oxidase (GOx) by Nafion binder into the SWCNT film, and the variation in current response as a function of enzyme loading amount, Nafion thickness were investigated. 30 mg mL(-1) GOx and 2% Nafion was optimal for the detection of glucose. When ferrocene monocarboxylic acid (FMCA) was introduced as diffusional electron mediator, the current responses toward glucose of the Nafion/GOx/SWCNT electrodes in glucose solution containing FMCA were dramatically improved, and the developed sensor was independent of oxygen. In the application of GOx immobilized SWCNT films for glucose detection, a linear electrical response was observed for concentrations ranging from 0.25 to 3.0 mM, and the detection limit and the sensitivity were assessed to be 97 microM and 9.32 microA mM(-1) cm(-2), respectively. Moreover, according to the Lineweaver Burk plot, the apparent Michaelis-Menten constant was calculated to be 23.8 mM, and the current responses did not interfere with coexisting electroactive species, indicating that Nafion is an effective permselective polymer barrier. PMID- 20541641 TI - Optimization and validation of liquid-liquid extraction with low temperature partitioning for determination of carbamates in water. AB - Using a 2(3) experimental design, liquid-liquid extraction with low temperature partitioning (LLE-LTP) was optimized and validated for analysis of three carbamates (aldicarb, carbofuran and carbaryl) in water samples. In this method, 2.0 mL of sample is placed in contact with 4.0 mL of acetonitrile. After agitation, the sample is placed in a freezer for 3 h for phase separation. The organic extract is analyzed by high performance liquid chromatography with ultraviolet detection (HPLC-UV). For validation of the technique, the following figures of merit were evaluated: accuracy, precision, detection and quantification limits, linearity, sensibility and selectivity. Extraction recovery percentages of the carbamates aldicarb, carbofuran and carbaryl were 90%, 95% and 96%, respectively. Even though extremely low volumes of sample and solvent were used, the extraction method was selective and the detection and quantification limits were between 5.0 and 10.0 microg L(-1), and 17.0 and 33.0 microg L(-1), respectively. PMID- 20541643 TI - Optimisation of specialty malt volatile analysis by headspace solid-phase microextraction in combination with gas chromatography and mass spectrometry. AB - The objective of this study was to develop a technique for analysing 14 flavour components, relevant for specialty malts. Therefore, a method was developed for the analysis of these components in dry ground malt using headspace solid-phase microextraction coupled with gas chromatography and mass spectrometry. A procedure was optimised for the optimal amount of sample, fibre selection, extraction temperature and extraction time. Afterwards, the method was calibrated and validated by the quantification of the specialty malt flavour components in a colour, a caramel and a roasted malt. PMID- 20541642 TI - Induced lead binding phytochelatins in Brassica juncea and Sesuvium portulacastrum investigated by orthogonal chromatography inductively coupled plasma-mass spectrometry and matrix assisted laser desorption ionization-time of flight-mass spectrometry. AB - The accumulation and transport of lead in Brassica juncea and Sesuvium portulacastrum plants and the possible formation of complexes of this element with bioligands such as phytochelatins was studied in roots and shoots of plants exposed to different amounts of Pb(NO(3))(2). Speciation studies on the plant extracts were conducted using size exclusion liquid chromatography and ion pair liquid chromatography coupled to UV and ICP-MS to monitor lead and sulphur. The identification of the species separated by chromatography was performed by MALDI TOF-MS. In both types of exposed plants it was possible to identify the presence of the phytochelatin isoform PC(3). The results obtained suggest that both types of plants can be useful in studies of phytoremediation but the ability of S. portulacastrum to accumulate and redistribute Pb from root to shoot is more effective than B. juncea. PMID- 20541644 TI - Ultra-trace determination of plutonium in marine samples using multi-collector inductively coupled plasma mass spectrometry. AB - Sources of plutonium isotopes to the marine environment are well defined, both spatially and temporally, which makes Pu a potential tracer for oceanic processes. This paper presents the selection, optimisation and validation of a sample preparation method for the ultra-trace determination of Pu isotopes ((240)Pu and (239)Pu) in marine samples by multi-collector (MC) ICP-MS. The method was optimised for the removal of the interference from (238)U and the chemical recovery of Pu. Comparison of various separation strategies using AG1 X8, TEVA, TRU, and UTEVA resins to determine Pu in marine calcium carbonate samples is reported. A combination of anion-exchange (AG1-X8) and extraction chromatography (UTEVA/TRU) was the most suitable, with a radiochemical Pu yield of 87+/-5% and a U decontamination factor of 1.2 x 10(4). Validation of the method was accomplished by determining Pu in various IAEA certified marine reference materials. The estimated MC-ICP-MS instrumental limit of detection for (239)Pu and (240)Pu was 0.02 fg mL(-1), with an absolute limit of quantification of 0.11 fg. The proposed method allows the determination of ultra-trace Pu, at femtogram levels, in small size marine samples (e.g., 0.6-2.0 g coral or 15-20 L seawater). Finally, the analytical method was applied to determining historical records of the Pu signature in coral samples from the tropical Northwest Pacific and (239+240)Pu concentrations and (240)Pu/(239)Pu atom ratios in seawater samples as part of the 2008 GEOTRACES intercalibration exercise. PMID- 20541645 TI - Enzyme-linked immunosorbent assays for doping control of 5alpha-reductase inhibitors finasteride and dutasteride. AB - Finasteride and dutasteride are 5alpha-reductase inhibitors included in the World Anti-Doping Agency's list of banned substances. Two highly sensitive and selective ELISA assays were developed for these compounds. Polyclonal rabbit antibodies were raised using synthesized haptens and other commercial products. The best immunoassay obtained, based on an antibody-coated format, showed a limit of detection of 0.01 microg L(-1) and an IC(50) of 0.75 microg L(-1) for finasteride (cross-reactivity with dutasteride<4%). The second assay allowed finasteride and dutasteride determination, with limits of detection of 0.013 and 0.021 microg L(-1), and IC(50) values 0.18 and 1.18 microg L(-1), respectively. Both assays were highly selective to a set of anabolic steroids, but they showed 37% and 30% cross-reactivity with the major urinary metabolite of finasteride, allowing its determination. The developed ELISA had better sensitivity than HPLC/MS/MS method and was applied as a screening technique to quantify dutasteride, finasteride, and its main metabolite in human urine without sample pre-treatment. Moreover, the analysis of dutasteride's excretion urines by ELISA was used to obtain its human excretion rate, essential to improve the analytical strategies about this type of drugs (permitted as medicines and prohibited in sport) and to establish an effective anti-doping policy. PMID- 20541646 TI - A colorimetric sensor for determination of cysteine by carboxymethyl cellulose functionalized gold nanoparticles. AB - A simple and sensitive colorimetric method for cysteine detection was established based on the carboxymethyl cellulose-functionalized gold nanoparticles (CMC AuNPs). The nanoparticles were directly synthesized with sodium carboxymethyl cellulose by a simple approach, which would protect particles against salt induced aggregation. Then the CMC-AuNPs solution exhibited a high colorimetric selectivity to cysteine. The assay results indicated that the introduction of cysteine could induce the aggregation of the colloidal solutions at the presence of sodium chloride, displaying changes in color and in UV-vis absorption spectra. Thus an exceptionally simple, rapid method for detecting cysteine was obtained at the linear range of 10.0-100.0 microM with the relative coefficient of 0.997. The proposed method possessed the advantages of simplicity and sensitivity, and was applied to real urine sample detection. The results were satisfying and the proposed method was especially appropriate for detection of cysteine in biological samples. PMID- 20541647 TI - Characterization of the gas sensors based on polymer-coated resonant microcantilevers for the detection of volatile organic compounds. AB - The gas sensors based on polymer-coated resonant microcantilevers for volatile organic compounds (VOCs) detection are investigated. A method to characterize the gas sensors through sensor calibration is proposed. The expressions for the estimation of the characteristic parameters are derived. The effect of the polymer coating location on the sensor's sensitivity is investigated and the formula to calculate the polymer-analyte partition coefficient without knowing the polymer coating features is presented for the first time. Three polymers: polyethyleneoxide (PEO), polyethylenevinylacetate (PEVA) and polyvinylalcohol (PVA) are used to perform the experiments. Six organic solvents: toluene, benzene, ethanol, acetone, hexane and octane are used as analytes. The response time, reversibility, hydrophilicity, sensitivity and selectivity of the polymer layers are discussed. According to the results, highly sensitive sensors for each of the analytes are proposed. Based on the characterization method, a convenient and flexible way to the construction of electric nose system by the polymer coated resonant microcantilevers can be achieved. PMID- 20541648 TI - Printed protein microarrays on unmodified plastic substrates. AB - A key challenge for the generation of protein microarrays is the immobilization of functional capture probe proteins at the chip surfaces. Here, a new concept for a single step production of protein microarrays to unmodified plastic substrates is presented. It is based on the printing of polymer/protein mixtures and the photochemical attachment of the obtained microstructures to the plastic chip surfaces. In the photochemical process three reactions occur simultaneously: transformation of the polymer into hydrogel dots, covalent binding of the forming gel to the substrate, and covalent immobilization of the proteins to the three dimensional hydrogel scaffold. As an example we use anti-bovine serum albumin as a protein (anti-BSA) and a water swellable polymer network based on polydimethylacrylamide as a scaffold, which is photochemically crosslinked using benzophenone as a crosslinking agent. In one series of microarray experiments the probe density of the immobilized proteins was determined by incorporating fluorescence-labeled anti-BSA in the hydrogels. In a typical experiment, the number of immobilized probes was determined to 4 x 10(9) protein molecules per spot. In other experiments, the microarrays were brought into contact with fluorescently labeled BSA. In such analyses signal-to-noise values of more than 200 were obtained and about 9 x 10(7) antigen molecules were bound per spot. This demonstrates that in a very simple way microarrays with large amount of probes per spot can be realized and that antibodies immobilized in the printed hydrogels remain accessible and retain their functionality. PMID- 20541651 TI - The biology underlying molecular imaging in oncology: from genome to anatome and back again. AB - Cancers are complex, evolving, multiscale ecosystems that are characterized by profound spatial and temporal heterogeneity. The interactions in cancer are non linear in that small changes in one variable can have large changes on another. These multiple interacting phenotypes and spatial scales can best be understood with appropriate mathematical and computational models. Imaging is central to this investigation because it can non-destructively and longitudinally characterize spatial variations in the tumour phenotype and environment so that the system dynamics over time can be captured quantitatively. PMID- 20541652 TI - FDG PET/CT in oncology: "raising the bar". AB - Integrated positron-emission tomography/computed tomography (PET/CT) with 2 [(18)F]-fluoro-2-deoxy-D-glucose (FDG) has revolutionized oncological imaging in recent years and now has a firmly established role in a variety of tumour types. There have been simultaneous step-wise advances in scanner technology, which are yet to be exploited to their full potential in clinical practice. This article will review these technological developments and explore how refinements in imaging protocols can further improve the accuracy and efficacy of PET/CT in oncology. The promises, and limitations, of emerging oncological applications of FDG PET/CT in radiotherapy planning and therapy response assessment will be explored. Potential future developments, including the use of FDG PET probes in oncological surgery, advanced data analysis techniques, and the prospect of integrated PET/magnetic resonance imaging (PET/MRI) will be highlighted. PMID- 20541653 TI - Non FDG PET. AB - 2- [(18)F]-fluoro-2-deoxy-D-glucose (FDG) is the radiopharmaceutical most frequently used for clinical positron emission tomography (PET). However, FDG cannot be used for many oncological, cardiological, or neurological conditions, either because the abnormal tissue does not concentrate it, or because the tissues under investigation demonstrate high physiological glucose uptake. Consequently, alternative PET tracers have been produced and introduced into clinical practice. The most important compounds in routine practice are (11)C choline and (18)F-choline, mainly for the evaluation of prostate cancer; (1)C methionine for brain tumours; (118)F-DOPA ((18)F-deoxiphenilalanine) for neuroendocrine tumours and movement disorders; (68)Ga-DOTANOC (tetraazacyclododecanetetraacetic acid-[1-Nal3]-octreotide) and other somatostatin analogues for neuroendocrine tumours; 11C-acetate for prostate cancer and hepatic masses and 18F-FLT (3-deoxy-3-fluorothymidine) for a number of malignant tumours. Another impetus for the development of new tracers is to enable the investigation of biological processes in tumours other than glucose metabolism. This is especially important in the field of response assessment, where there are new agents that are targeted more specifically at angiogenesis, hypoxia, apoptosis and other processes. PMID- 20541650 TI - Molecular imaging: current status and emerging strategies. AB - In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron emission tomography (PET) or single photon-emission computed tomography (SPECT) based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future. PMID- 20541654 TI - Molecular imaging with dynamic contrast-enhanced computed tomography. AB - Dynamic contrast-enhanced computed tomography (DCE-CT) is a quantitative technique that employs rapid sequences of CT images after bolus administration of intravenous contrast material to measure a range of physiological processes related to the microvasculature of tissues. By combining knowledge of the molecular processes underlying changes in vascular physiology with an understanding of the relationship between vascular physiology and CT contrast enhancement, DCE-CT can be redefined as a molecular imaging technique. Some DCE CT derived parameters reflect tissue hypoxia and can, therefore, provide information about the cellular microenvironment. DCE-CT can also depict physiological processes, such as vasodilatation, that represent the physiological consequences of molecular responses to tissue hypoxia. To date the main applications have been in stroke and oncology. Unlike some other molecular imaging approaches, DCE-CT benefits from wide availability and ease of application along with the use of contrast materials and software packages that have achieved full regulatory approval. Hence, DCE-CT represents a molecular imaging technique that is applicable in clinical practice today. PMID- 20541655 TI - An introduction to functional and molecular imaging with MRI. AB - Magnetic resonance imaging (MRI) has been applied to many aspects of functional and molecular imaging. Many of the parameters used to produce image contrast in MRI are influenced by the local chemical environment around the atoms being imaged; these parameters can be exploited to probe the molecular content of tissues and this has been shown to have many applications in radiology. Diffusion weighted imaging is a well-established method for measuring small changes in the molecular movement of water that occurs following the onset of ischaemia and in the presence of tumours. Exogenous contrast agents containing gadolinium or iron oxide have been used to image tissue vascularity, cell migration, and specific biological processes, such as cell death. MR spectroscopy is a technique for measuring the concentrations of tissue metabolites and this has been used to probe metabolic pathways in cancer, in cardiac tissue, and in the brain. Several groups are developing positron-emission tomography (PET)-MRI systems that combine the spatial resolution of MRI with the metabolic sensitivity of PET. However, the application of MRI to functional and molecular imaging is limited by its intrinsic low sensitivity. A number of techniques have been developed to overcome this which utilize a phenomenon termed hyperpolarization; these have been used to image tissue pH, cellular necrosis, and to image the lungs. Although most of these applications have been developed in animal models, they are increasingly being translated into human imaging and some are used routinely in many radiology departments. PMID- 20541657 TI - Consensus statement on the adoption of the COPE guidelines. PMID- 20541656 TI - Molecular ultrasound imaging: current status and future directions. AB - Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic. PMID- 20541658 TI - "en guise d'introduction ...". PMID- 20541660 TI - Impact of the hypothalamic-pituitary-adrenal/gonadal axes on trajectory of age related cognitive decline. AB - Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are declarative and spatial memories. The hippocampus facilitates the formation of declarative and spatial memories. Notably, the hippocampus is particularly vulnerable to aging. Genetic predisposition and lifetime experiences and exposures contribute to the aging process, brain changes and subsequent cognitive outcomes. In this review, two factors to which an individual is exposed, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, will be considered regarding the impact of age on hippocampal-dependent function. Spatial memory can be affected by cumulative exposure to chronic stress via glucocorticoids, released from the HPA axis, and from gonadal steroids (estrogens, progesterone and androgens) and gonadotrophins, released from the HPG axis. Additionally, this review will discuss how these hormones impact age-related hippocampal function. We hypothesize that lifetime experiences and exposure to these hormones contribute to the cognitive makeup of the aged individual, and contribute to the heterogeneous aged population that includes individuals with cognitive abilities as astute as their younger counterparts, as well as individuals with severe cognitive decline or neurodegenerative disease. PMID- 20541659 TI - Glucocorticoid-induced apoptosis of healthy and malignant lymphocytes. AB - Glucocorticoids exert a wide range of physiological effects, including the induction of apoptosis in lymphocytes. The progression of glucocorticoid-induced apoptosis is a multi-component process requiring contributions from both genomic and cytoplasmic signaling events. There is significant evidence indicating that the transactivation activity of the glucocorticoid receptor is required for the initiation of glucocorticoid-induced apoptosis. However, the rapid cytoplasmic effects of glucocorticoids may also contribute to the glucocorticoid-induced apoptosis-signaling pathway. Endogenous glucocorticoids shape the T-cell repertoire through both the induction of apoptosis by neglect during thymocyte maturation and the antagonism of T-cell receptor (TCR)-induced apoptosis during positive selection. Owing to their ability to induce apoptosis in lymphocytes, synthetic glucocorticoids are widely used in the treatment of haematological malignancies. Glucocorticoid chemotherapy is limited, however, by the emergence of glucocorticoid resistance. The development of novel therapies designed to overcome glucocorticoid resistance will dramatically improve the efficacy of glucocorticoid therapy in the treatment of haematological malignancies. PMID- 20541662 TI - DHEA, important source of sex steroids in men and even more in women. AB - A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepiandrosterone (DHEA) by the human adrenal glands coupled with the indroduction of menopause which stops secretion of estrogens by the ovary. Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years. In fact, from the time of menopause, DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus. Intracrinology, a term coined in 1988, describes the local formation, action and inactivation of sex steroids from the inactive sex steroid precursor DHEA. Over the past 25 years most, if not all, the genes encoding the human steroidogenic and steroid-inactivating enzymes have been cloned and sequenced and their enzymatic activity characterized. The problem with DHEA, however, is that its secretion decreases from the age of 30 years and is already decreased, on average, by 60% at time of menopause. In addition, there is a large variability in the circulating levels of DHEA with some post-menopausal women having barely detectable serum concentrations of the steroid while others have normal values. Since there is no feedback mechanism controlling DHEA secretion within 'normal' values, women with low DHEA will remain with such a deficit of sex steroids for their remaining lifetime. Since there is no other significant source of sex steroids after menopause, one can reasonably believe that low DHEA is involved, in association with the aging process, in a series of medical problems classically associated with post-menopause, namely osteoporosis, muscle loss, vaginal atrophy, fat accumulation, hot flashes, skin atrophy, type 2 diabetes, memory loss, cognition loss and possibly Alzheimer's disease. A recent randomized, placebo-controlled study has shown that all the signs and symptoms of vaginal atrophy, a classical problem recognized to be due to the hormone deficiency of menopause, can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens. In addition, the four domains of sexual dysfucntion are improved. For the other problems of menopause, although similar large scale, randomized and placebo-controlled studies usually remain to be performed, the available evidence already strongly suggests that they could be improved, corrected or even prevented by exogenous DHEA. In men, the contribution of adrenal DHEA to the total androgen pool has been measured at 40% in 65-75-year-old men. Such data stress the necessity of blocking both the testicular and adrenal sources of androgens in order to achieve optimal benefits in prostate cancer therapy. On the other hand, the comparable decrease in serum DHEA levels observed in both sexes has less consequence in men who continue to receive a practically constant supply of testicular sex steroids during their whole life. In fact, in men, the appearance of hormone-deficiency symptoms common to women is observed at a later age and with a lower degree of severity. Consequently, DHEA replacement has shown much more easily measurable beneficial effects in women. Most importantly, despite the non-scientific and unfortunate availability of DHEA as a food supplement in the United States, a situation that discourages rigorous clinical trials on the crucial physiological and therapeutic role of DHEA, no serious adverse event related to DHEA has ever been reported in the world literature (thousands of subjects exposed) or in the monitoring of adverse events by the FDA (millions of subjects exposed), thus indicating, as expected from its known physiology, the excellent safety profile of DHEA. With today's knowledge, one can reasonably suggest that DHEA offers the promise of a safe and efficient replacement therapy for the multiple problems related to hormone deficiency after menopause without the risks associated with estrogen-based or any other treatments. PMID- 20541663 TI - Neuroendocrinology of post-traumatic stress disorder. AB - Dysregulation of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-sympathetic nervous system (SNS), is involved in the pathophysiology of post-traumatic stress disorder (PTSD), an anxiety disorder that develops after exposure to traumatic life events. Neuroendocrine studies in individuals with PTSD have demonstrated elevated basal cerebrospinal fluid corticotropin-releasing hormone concentrations and contradictory results from peripheral measurements, exhibiting low 24 hours excretion of urinary free cortisol, low or normal circulating cortisol levels or even high plasma cortisol levels. The direction of HPA axis activity (hyper-/or hypo-activation), as evidenced by peripheral cortisol measures, may depend on variables such as genetic vulnerability and epigenetic changes, age and developmental stage of the individual, type and chronicity of trauma, co-morbid depression or other psychopathology, alcohol or other drug abuse and time since the traumatic experience. On the other hand, peripheral biomarkers of the SNS activity are more consistent, showing increased 24h urinary or plasma catecholamines in PTSD patients compared to control individuals. Chronically disturbed hormones in PTSD may contribute to brain changes and further emotional and behavior symptoms and disorders, as well as to an increased cardiometabolic risk. PMID- 20541661 TI - Menopause and mitochondria: windows into estrogen effects on Alzheimer's disease risk and therapy. AB - Metabolic derangements and oxidative stress are early events in Alzheimer's disease pathogenesis. Multi-faceted effects of estrogens include improved cerebral metabolic profile and reduced oxidative stress through actions on mitochondria, suggesting that a woman's endogenous and exogenous estrogen exposures during midlife and in the late post-menopause might favourably influence Alzheimer risk and symptoms. This prediction finds partial support in the clinical literature. As expected, early menopause induced by oophorectomy may increase cognitive vulnerability; however, there is no clear link between age at menopause and Alzheimer risk in other settings, or between natural menopause and memory loss. Further, among older post-menopausal women, initiating estrogen containing hormone therapy increases dementia risk and probably does not improve Alzheimer's disease symptoms. As suggested by the 'critical window' or 'healthy cell' hypothesis, better outcomes might be expected from earlier estrogen exposures. Some observational results imply that effects of hormone therapy on Alzheimer risk are indeed modified by age at initiation, temporal proximity to menopause, or a woman's health. However, potential methodological biases warrant caution in interpreting observational findings. Anticipated results from large, ongoing clinical trials [Early Versus Late Intervention Trial with Estradiol (ELITE), Kronos Early Estrogen Prevention Study (KEEPS)] will help settle whether midlife estrogen therapy improves midlife cognitive skills but not whether midlife estrogen exposures modify late-life Alzheimer risk. Estrogen effects on mitochondria adumbrate the potential relevance of estrogens to Alzheimer's disease. However, laboratory models are inexact embodiments of Alzheimer pathogenesis and progression, making it difficult to surmise net effects of estrogen exposures. Research needs include better predictors of adverse cognitive outcomes, biomarkers for risks associated with hormone therapy, and tools for monitoring brain function and disease progression. PMID- 20541664 TI - Assisted reproduction and its neuroendocrine impact on the offspring. AB - Assisted reproductive technologies (ARTs) have been widely used during the last three decades and progressively more children are born with the help of such methods. There is now evidence that ARTs may be associated with slight epigenetic modifications in the expression of several genes that could have a long-term impact on the health of the offspring. Also, a clear association between such techniques and genomic imprinting abnormalities has been reported. The neuroendocrine impact of ART on the offspring includes slight elevations of systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as increased circulating triglyceride concentrations, in children born after ART, especially in those with rapid catch-up growth in weight during early childhood. However, the postnatal growth of most children after ART is normal and no increased incidence of the full metabolic syndrome has been observed in these children and adolescents. Moreover, the pace and timing of puberty of such children is normal and no increased incidence of premature adrenarche could be discerned in ART children in the absence of restricted fetal growth. Finally, a slight modification of the set point of thyroid stimulating hormone sensitivity was observed in ART children, without an apparent impact on thyroid hormone secretion. This has been attributed to epigenetic changes. Questions remain to be answered regarding the future reproductive capacity of children born after ART, as well as their cardiovascular risk in later adult life. Long-term prospective studies should be performed to provide robust evidence. PMID- 20541665 TI - Sex hormone and neuroendocrine aspects of the metabolic syndrome. AB - We discuss the recent advances in the knowledge that the sex steroids testosterone (T), estradiol and dehydroepiandrosterone sulphate (DHEA-S) are involved in the development of visceral obesity and of the metabolic syndrome. Cross talk between leptin and the androgen receptor (AR) in the hypothalamus as well as the peripheral conversion of DHEA and T to estrone, estradiol and dihydrotestosterone (DHT) in adipocytes and hepatocytes play important roles in the metabolic syndrome in men. Finally, we discuss the development of new drugs, selective AR modulators, for treating the metabolic syndrome in men. PMID- 20541666 TI - Ghrelin's role as a major regulator of appetite and its other functions in neuroendocrinology. AB - Ghrelin is a circulating growth-hormone-releasing and appetite-inducing brain-gut peptide. It is a known natural ligand of the growth hormone secretagogue receptor (GHS-R). Ghrelin is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT). The acylation is essential for its orexigenic and adipogenic effects. Ghrelin exerts its central orexigenic effect through activation of various hypothalamic and brain stem neurons. Several new intracellular targets/mediators of the appetite-inducing effect of ghrelin in the hypothalamus have recently been identified, including the AMP-activated protein kinase, its upstream kinase calmodulin kinase kinase 2, components of the fatty acid pathway and the uncoupling protein 2. The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment. Ghrelin regulates the function of the anterior pituitary through stimulation of secretion not only of growth hormone, but also of adrenocorticotrophin and prolactin. The implication of ghrelin and its receptor in the pathogenesis of the neuroendocrine tumors will also be discussed in this review. PMID- 20541667 TI - Pathogenesis of pituitary tumors. AB - Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID- 20541668 TI - Molecular genetics of the aip gene in familial pituitary tumorigenesis. AB - Pituitary adenomas usually occur as sporadic tumors, but familial cases are now increasingly identified. As opposed to multiple endocrine neoplasia type 1 and Carney complex, in familial isolated pituitary adenoma (FIPA) syndrome no other disease is associated with the familial occurrence of pituitary adenomas. It is an autosomal dominant disease with incomplete variable penetrance. Approximately 20% of patients with FIPA harbour germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene located on 11q13. Patients with AIP mutations have an overwhelming predominance of somatotroph and lactotroph adenomas, which often present in childhood or young adulthood. AIP, originally identified as a molecular co-chaperone of several nuclear receptors, is thought to act as a tumor suppressor gene; overexpression of wild-type, but not mutant AIP, reduces cell proliferation while knockdown of AIP stimulates it. AIP is shown to bind various proteins, including the aryl hydrocarbon receptor, Hsp90, phosphodiesterases, survivin, RET and the glucocorticoid receptor, but currently it is not clear which interaction has the leading role in pituitary tumorigenesis. This chapter summarizes the available clinical and molecular data regarding the role of AIP in the pituitary gland. PMID- 20541669 TI - Somatostatin and somatostatin receptors: from basic concepts to clinical applications. AB - Somatostatin (SS) and SS receptors (ssts) are broadly expressed in the human body where they exert many physiological actions. Moreover, they can be expressed in many pathological tissues. Particularly, a high density of ssts has been described in human neuroendocrine tumors (NETs). SS and ssts have a therapeutic and diagnostic value in several clinical conditions. For this reason stable SS analogues have been developed. Among SS-analogues, octreotide, octreotide long acting-release (LAR), lanreotide-sustained-release (SR) and lanreotide autogel (ATG) are approved for clinical use and pasireotide is in a late phase of clinical development. Presently, the SS-analogues are the standard treatment option for acromegalic patients and play a prominent role in the symptomatic control of patients with gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). SS-analogues are able to control hormonal hypersecretion and reduce tumoral growth in the majority of cases. However, some patients are resistant to SS analogue treatment and other patients (often GEP-NETs), after a variable period of treatment, develop tachyphylaxis to these compounds. The mechanisms behind this treatment resistance or tachyphylaxis are presently under investigation. The understanding of these mechanisms might help to develop new treatment modalities for patients not responding to the currently available SS-analogues. The high tumoral expression level of ssts, characteristic of many NETs, has been the rational to develop radiolabelled SS-analogues to visualize sst-expressing tumors and to treat unresectable tumors. Indeed, SS-analogues coupled with (111)In are used to perform sst-scintigraphy, which is a very useful first-line imaging technique in the diagnosis and follow-up of GEP-NETs. Moreover, SS-analogues conjugated to (111)In or to other radioisotopes, such as (177)Lu or (90)Y, have promising effects in the treatment of advanced NETs. ssts are expressed in some non-neuroendocrine tumors as well and in some non-tumoral diseases, suggesting that SS-analogues might have a role in the diagnosis and treatment of these pathological conditions as well. The development of novel SS-analogues with new pharmacokinetic and pharmacodynamic characteristics may further improve the clinical applications of such compounds. PMID- 20541670 TI - Somatostatin analogues: treatment of pituitary and neuroendocrine tumors. AB - This chapter summarizes the most recent data on the use of the somatostatin analogues (SSAs), octreotide (OCT) and lanreotide for the treatment of patients with pituitary and neuroendocrine tumors (NETs). These two analogues have a high affinity for somatostatin receptor (SSR) sub-types 2 and 5. The major indications of these compounds are GH- and TSH-secreting pituitary adenomas, secreting NETs and non-functioning NETs in progression. Pasireotide is a new analogue, with a receptor pattern different from previous analogues since it binds with high affinity to SSR types 1, 2, 3 and 5. This analogue will be available to treat patients with ACTH-secreting adenomas in a short time. A recent study has also demonstrated a beneficial effect of OCT long-acting release in patients with non functioning NETs independently from their progression status. These data open the treatment with SSAs in all NET patients. PMID- 20541671 TI - The MENX syndrome and p27: relationships with multiple endocrine neoplasia. AB - In the past 3 years new insight into the etiopathogenesis of hereditary endocrine tumors has emerged from studies conducted on MENX, a rat multiple endocrine neoplasia (MEN) syndrome. MENX spontaneously developed in a rat colony and was discovered by serendipity when these animals underwent complete necropsy, as they were found to consistently develop multiple endocrine tumors with a spectrum similar to both MEN type 1 (MEN1) and MEN2 human syndromes. Genetic studies identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle inhibitor, as the causative mutation for the MENX syndrome. Capitalizing on these findings, we and others identified heterozygous germline mutations in the human homologue, CDKN1B, in patients with multiple endocrine tumors. As a consequence of these observations a novel human MEN syndrome, named MEN4, was recognized which is caused by mutations in p27. Altogether these studies identified Cdkn1b/CDKN1B as a novel tumor susceptibility gene for multiple endocrine tumors in both rats and humans. In this chapter we present the MENX syndrome and its phenotype, and we compare it to the human MEN syndromes; we discuss the current state of knowledge regarding the genes associated to inherited MEN, with a particular focus on CDKN1B; we present recent clinical and basic findings about the MEN4 syndrome and the functional characterization of the CDKN1B mutations identified. These findings are placed in the broader context of how p27 dysregulation might affect neuroendocrine cell function and trigger tumorigenesis. PMID- 20541672 TI - Hormonal therapy of prostate cancer. AB - Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely, especially in the presence of increased AR levels, it becomes important to discover more potent and purely antagonistic blockers of AR. The data obtained with compounds under development are promising. While waiting for this (these) new anti-androgen(s), combined treatment with castration and a pure anti-androgen (bicalutamide, flutamide or nilutamide) is the only available and the best scientifically based means of treating prostate cancer by hormone therapy at any stage of the disease with the optimal chance of success and even cure in localized disease. PMID- 20541674 TI - Controversies in Dermatology: Part II. PMID- 20541675 TI - Actinic keratosis: facts and controversies. AB - Actinic keratoses are common lesions that are generally clinically diagnosed. Although currently most actinic keratoses are treated, whether this is truly necessary is debated. Treatment of all actinic keratoses is advocated because preliminary evidence indicates that actinic keratoses may progress to squamous cell carcinomas. Some also consider actinic keratoses equivalent to squamous cell carcinoma. PMID- 20541676 TI - Keratoacanthoma: facts and controversies. AB - The keratoacanthoma and its variants are clinically and histologically heterogenous. Some consider the keratoacanthoma to be benign, whereas others classify it as a subtype of squamous cell carcinoma. The keratoacanthoma is generally treated rather than observed for spontaneous resolution. This hampers evaluation of the true natural history of lesions diagnosed as keratoacanthoma. In addition, studies have not found a reliable marker to differentiate keratoacanthoma from squamous cell carcinoma. It currently remains unclear how the keratoacanthoma relates to squamous cell carcinoma, and continued investigation is necessary. PMID- 20541677 TI - White oral lesions, actinic cheilitis, and leukoplakia: confusions in terminology and definition: facts and controversies. AB - Many diseases affecting the cutaneous tissues may incur observable changes to the mucosal tissues of the oral cavity. As a consequence, the dermatologist should always assess the oral mucosal tissues of their patients as a matter of routine. Equivocal lesions should be referred to a dentist for further assessment. Although most encountered white oral lesions are innocuous, some potentially serious conditions may mimic an innocuous white lesion. As examples, oral lichen planus may cause significant patient discomfort and is associated with some degree of increased malignant risk, whereas actinic cheilitis and leukoplakia have a confirmed association with an increased malignant risk. This contribution reviews the characteristics and management strategies for some of the more common white oral lesions that the dermatologist may observe in clinical practice. PMID- 20541678 TI - Mohs micrographic surgery: Facts and controversies. AB - The field of Mohs micrographic surgery has expanded in the last 70 years, as have the indications for the procedure and the techniques that have been used. As a result, differences in the practice of Mohs micrographic surgery have emerged. This contribution explores current controversies within Mohs micrographic surgery and critically appraises the available evidence on both sides of the issues. PMID- 20541673 TI - Pheochromocytoma and paraganglioma. AB - Pheochromocytoma is a very special kind of tumor full of duplicity. On the one hand it represents its own microworld with unique clinical, biochemical and pathological features, while on the other it constitutes a tremendously significant part of whole body system, playing a vital role for practically every organ system. It has a very special character - sometimes like a child it can be sweet and predictable, while at times it can behave like a deadly wild beast, crashing and tearing everything on its path in a fierce rage. It also consists of the amazingly intelligent neuroendocrine cells that possess a magical ability to make miraculous substances of many kinds. But most of all, it is a system that is able to drive our curiosity and the itch of "Cogito, ergo sum" to limitless depths and year by year it still amazes us with new and unexpected discoveries that move our understanding of multiple pathways and metabolic events closer to the ultimate truth. Recent discoveries of succinate dehydrogenase (SHD) and prolyl hydroxylase (PHD) mutations, for example, propelled our understanding of neuroendocrine tumorigenesis as a whole, as well as physiology of mitochondrial respiratory chain and phenomenon of pseudohypoxia in particular. Good old discoveries make their way from dusty repositories to shine with new meaning, appropriate for the current level of knowledge. This acquired wisdom makes us better physicians - knowing the specific expression makeup of catecholamine transporters, GLUTs and SRIFs allows for better tailored imaging and therapeutic manipulations. There are still long ways to go, keeping in mind that pheochromocytoma is but so very special, and we are optimistic and expect many great things to come. PMID- 20541679 TI - Melanoma staging: facts and controversies. AB - The value of staging examinations remains controversial for the initial staging in melanoma patients at the time of the primary diagnosis and for surveillance. Issues concerning tumor recurrences and progression must be discussed separately for different risk groups. For low-risk patients (stage IA; tumor thickness less than 1 mm), staging examinations like sentinel lymph node biopsy (SLNB), blood tests, or imaging can generally be abandoned. Baseline staging with simple techniques is at the discretion of the physician. In intermediate-risk patients (stages IB and IIA), an initial staging examination involving SLNB and computed tomography (CT) scans is recommended. Further follow-up may be restricted to physical examinations, blood tests of tumor marker protein S100beta, and to lymph node ultrasonography. If findings are suspicious, further imaging procedures may be involved. In high-risk patients (stages IIB to III), an initial staging examination with CT is recommended, and regular follow-up every 6 months with whole body imaging by CT or magnetic resonance imaging seems useful. Physical examinations, blood tests of tumor marker protein S100beta, and lymph node ultrasound imaging should be routine. This intense follow-up may enable surgical treatments with complete removal of all recognizable metastases in about 15% to 25% of patients and improve their prognosis. The risk of recurrence or tumor progression is very high in stage IV patients, and their management is individualized. PMID- 20541680 TI - Melanoma epidemic: Facts and controversies. AB - The presence of a true melanoma epidemic has been a controversial topic for the past decade. A dramatic increase in the incidence of cutaneous malignant melanoma in developed countries is well documented, but mortality rates have not risen as rapidly. This has generated much discussion about whether there is a true increase in disease, or more of an apparent phenomenon that may be explained by multiple biases and other factors. The increase in incidence may be due to aggressive surveillance with increased detection of melanomas that are histologically worrisome but biologically benign. This argument, however, does not account for increased incidence of both thin and thicker melanomas. The controversy lies in the interpretation of these facts. This contribution reviews epidemiologic studies from the United States and worldwide to summarize the arguments for and against the debate about whether a melanoma epidemic exists. PMID- 20541681 TI - Do hormones influence melanoma? Facts and controversies. AB - The issue of whether hormones influence malignant melanoma (MM) has been controversial for many years. Although early case reports demonstrated a negative effect of hormones, recent evidence has not supported a potential role for hormones in MM. We address whether exogenous and endogenous hormones influence a woman's risk for MM or affect her prognosis if diagnosed with MM. Multiple epidemiologic studies show the use of oral contraceptives or hormone replacement therapy does not appear to increase a woman's risk for MM. Pregnancy does not appear to influence a woman's risk of MM, nor does pregnancy appear to affect prognosis in the woman diagnosed with MM. When counseling the woman who is diagnosed with MM during pregnancy or during the childbearing years, future use of oral contraceptives or hormone replacement therapy is not contraindicated; counseling concerning future pregnancies should be done on a case-by-case basis, with emphasis placed on established prognostic factors for MM. PMID- 20541682 TI - Congenital melanocytic nevi-when to worry and how to treat: Facts and controversies. AB - Congenital melanocytic nevi (CMN) are evident in 1% to 6% of neonates. In some studies, nevi with clinical, dermatoscopic, and histologic features identical to CMN have had a prevalence of more than 15% in older children and adults, possibly reflecting the "tardive" appearance of nevi programmed from birth. There is ongoing debate about the magnitude of the risk of melanoma and other complications associated with CMN of various sizes and the best approach to management of these lesions. We review the natural history of CMN, including proliferative nodules and erosions during infancy, neurotization, and spontaneous regression, and features of variants such as speckled lentiginous and congenital blue nevi. The risk of melanoma arising within small-sized (<1.5 cm) and medium sized CMN is low (likely <1% over a lifetime) and virtually nonexistent before puberty. Recent data suggest that melanoma (cutaneous or extracutaneous) develops in approximately 5% of patients with a large (>20 cm) CMN, with about half of this risk in the first few years of life. Melanoma and neurocutaneous melanocytosis (NCM) are most likely in patients with CMN that have a final size of >40 cm in diameter, numerous satellite nevi, and a truncal location. One-third of individuals with NCM have multiple medium-sized (but no large) CMN. In patients at risk for NCM, a screening gadolinium-enhanced magnetic resonance imaging, preferably before age 6 months, and longitudinal neurologic assessment are recommended. Management of CMN depends on such factors as the ease of monitoring (more difficult for large, dark, thick nevi) and cosmetic and psychologic benefits of excision or other procedures. CMN require lifelong follow up. Periodic total body skin examinations are necessary for all patients with large CMN, even when complete resection (often impossible) has been attempted. PMID- 20541683 TI - Dermatoscopy: Facts and controversies. AB - Especially notable in the past 10 years, dermatoscopy has gained attention for its proposed ability of increasing the agnostic accuracy of a variety of skin diseases, including melanoma. Despite the numerous publications applauding and promoting this relatively new diagnostic technique, the utility of dermatoscopy has yet to be fully validated. We present some of the leading arguments regarding dermatoscopy, with a particular focus on the applicability of dermatoscopy to the everyday practice of clinical dermatology. PMID- 20541684 TI - Excision guidelines and follow-up strategies in cutaneous melanoma: Facts and controversies. AB - The ongoing increase in melanoma incidence throughout Caucasian populations worldwide raises the question of an economic and efficient management of primary melanoma and follow-up. The primary treatment of a cutaneous melanoma is surgical excision. An excision biopsy is recommended, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for a higher tumor thickness should be applied at the primary excision or in a two-step procedure. When dealing with facial, acral, or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. Whereas the treatment for primary melanoma is accepted world wide, follow-up strategies for melanoma patients are discussed controversially, and so far, no international consensus has been reached. PMID- 20541686 TI - Sentinel lymph node biopsy in melanoma: Facts and controversies. AB - Three decades after its introduction in the 1990s, the sentinel lymph node biopsy for patients with localized cutaneous melanoma is still the subject of great debate in dermatology. Many questions remain unanswered, and studies currently in progress may or may not bring us any closer to determining the truth about sentinel lymph node biopsy and melanoma. We discuss the effect of sentinel lymph node biopsy on overall survival, the clinical and therapeutic implications of sentinel lymph node biopsy, and the melanoma patients who might be candidates for sentinel lymph node biopsy. PMID- 20541685 TI - Incisional biopsy and melanoma prognosis: Facts and controversies. AB - Facing the increasing number of melanoma patients is the controversial question of whether an incisional biopsy is associated with an unfavorable patient prognosis. Results of nine studies that occurred during the last four decades were reviewed. One of these studies was a large, prospective randomized controlled trial. Evidence from this trial and from most other studies is that incisional biopsies were not associated with an unfavorable prognosis for melanoma patients. Incisional biopsies are currently recommended for the histopathologic diagnosis of large tumors in facial, mucosal, and acral locations. Complete excisional biopsies are the generally recommended standard for melanoma surgery. Incisional biopsies of malignant melanoma do not negatively influence prognosis. Complete excision of primary melanoma is still the recommended standard of care and is a precondition for accurate histopathologic diagnosis. PMID- 20541687 TI - Muir-Torre syndrome: Facts and controversies. AB - The cutaneous presentation of a tumor sometimes has implications for a patient and his or her family, and Muir-Torre syndrome is an example of this. Because a single skin lesion can have broad consequences, it is important for clinicians to be aware of Muir-Torre syndrome. The definition, potential clues, the role of ancillary testing (microsatellite, immunohistochemical, and genetic), and screening recommendations are reviewed. PMID- 20541688 TI - The management of systemic lupus erythematosus: Facts and controversies. AB - Systemic lupus erythematosus is a multisystem disease of unknown etiology in which dysregulation of the innate and adaptive immune systems has a major effect in the pathogenesis of the disease. The treatment should be tailored for each patient according to how the disease manifests itself. Although there is no cure for systemic lupus erythematosus, the current treatment, using anti-inflammatory, antimalarial, and immunosuppressive agents, is fairly effective, but serious adverse events are possible. New biologic agents that target various components of the immune system recently have been developed for the treatment of patients with systemic lupus erythematosus. PMID- 20541689 TI - Adjuvant drugs in autoimmune bullous diseases, efficacy versus safety: Facts and controversies. AB - During the last decades, the conventional therapy for autoimmune blistering diseases has been high-dose, long-term systemic corticosteroid and immunosuppressive agents or adjuvant drugs. Long-term, high-dose steroid therapy can result in serious adverse effects. The rationale for using adjuvant drugs is that concerns reducing the need for corticosteroids, and hence, their side effects, or it may result in better control of the disease, or both. Immunosuppressive agents are not free of adverse effects, however. Prolonged immune suppression may account for high rates of morbidity, disability, and possible death. There is no consensus about the first-choice adjuvant drug for the management of blistering autoimmune diseases. This contribution evaluates six adjuvant drugs-cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin, and rituximab-and discusses the choice of a "winning drug" that is effective and safe. PMID- 20541690 TI - Severe cutaneous adverse drug reactions: who should treat, where and how?: Facts and controversies. AB - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are uncommon but extremely serious and often life-threatening mucocutaneous reactions characterized by extensive epithelial sloughing and systemic symptoms. There is no effective evidence-based treatment for severe cutaneous adverse reactions (SCAR) to drugs and no consensus on how to treat these patients. This contribution presents some of the controversies concerning the treatment of SCAR patients, including where and by whom, as well as the issue of the value of treatment with corticosteroids and intravenous immunoglobulin. Investigators agree that more studies are needed and that there are insufficient data to draw definite conclusions. The spectrum of disagreement is wide and the debate is ongoing. At the end, the important question is should we wait with our decisions until all these controversies are settled and we have more or full evidence. This question, as well as all others, is open for debate, evidently a "toxic" debate on toxic epidermal necrolysis. PMID- 20541691 TI - The challenge of drug-rechallenge: Facts and controversies. AB - The accurate identification of the culprit drug inducing a patient's cutaneous adverse drug reaction is important to avoid future adverse reactions and to provide safe alternative drugs. The assessment has to rely on the clinical signs, the time course, and response to treatment. Sometimes, additional diagnostic procedures are also needed. If diagnostic procedures such as in vivo skin testing and in vitro laboratory tests do not lead to conclusive results, confirmation of a presumptive diagnosis by a rechallenge test is often the only reliable way to establish a diagnosis. This procedure should be undertaken only with great caution and a compelling need, because a rechallenge test might cause severe or even fatal reactions. Contraindications and ethical considerations should be taken into account and an individual risk-benefit calculation must be performed in every case. PMID- 20541692 TI - On the practice of John Hall in the field of dermatology in the 17th century. PMID- 20541693 TI - Biomarkers in veterinary medicine: Towards targeted, individualised therapies for companion animals. PMID- 20541694 TI - Grappling with the androgen receptor: a new approach for treating advanced prostate cancer. AB - In this issue of Cancer Cell, Andersen et al. report on a small molecule that interacts with and blocks transactivation of the androgen receptor amino-terminal domain. This agent can overcome the shortcomings of clinically used antiandrogens, an important advance in the development of effective therapy for advanced prostate cancer. PMID- 20541695 TI - LKB1 and Src: antagonistic regulators of tumor growth and metastasis. AB - In this issue of Cancer Cell, Carretero and colleagues report that Src and FAK signaling pathways are activated in lung cancers when the tumor suppressor LKB1 is deleted. These findings suggest the use of unique combinatorial therapies for treatment of lung cancers. PMID- 20541696 TI - Glycogen synthase kinase-3 and leukemia: restoring the balance. AB - The role of GSK-3 in oncogenesis is paradoxical, acting as a tumor suppressor in some cancers and potentiating growth in others. In this issue of Cancer Cell, Wang et al. provide some mechanistic insight into GSK-3 activity's role in potentiating leukemias which are dependent on homeobox (HOX) gene misregulation. PMID- 20541697 TI - PAF is in the cabal of MLL1-interacting proteins that promote leukemia. AB - MLL1 fusions are among the most potent oncogenic drivers of leukemia development. In recent articles published in Molecular Cell and in Cancer Cell, researchers find that MLL1 fusions are reliant on a physical interaction with the PAF transcription elongation complex for their recruitment to chromatin and, consequently, leukemic transformation. PMID- 20541698 TI - Tumor vessels are Eph-ing complicated. AB - Two new studies have shown that there is considerable crosstalk and cross regulation of the Ephrin/VEGF pathways in endothelial cells. These findings illustrate how EphrinB2 signaling and VEGF, in a cooperative manner, induce VEGFR activation in endothelial cells and give new insight into how endothelial cell mediated construction of vessels is accomplished. PMID- 20541699 TI - Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. AB - Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity. PMID- 20541701 TI - NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-alpha (RXRalpha). We identified an N-terminally truncated RXRalpha (tRXRalpha) in several cancer cell lines and primary tumors, which interacted with the p85alpha subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-alpha (TNFalpha) promoted tRXRalpha interaction with the p85alpha, activating PI3K/AKT signaling. When combined with TNFalpha, Sulindac inhibited TNFalpha-induced tRXRalpha/p85alpha interaction, leading to activation of the death receptor-mediated apoptotic pathway. We designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXRalpha but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXRalpha dependent AKT activation and tRXRalpha tumor growth in animals. PMID- 20541700 TI - Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. AB - In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment. PMID- 20541702 TI - Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator. AB - Uptake of the anticancer drug cisplatin is mediated by the copper transporter CTR1 in cultured cells. Here we show in human ovarian tumors that low levels of Ctr1 mRNA are associated with poor clinical response to platinum-based therapy. Using a mouse model of human cervical cancer, we demonstrate that combined treatment with a copper chelator and cisplatin increases cisplatin-DNA adduct levels in cancerous but not in normal tissues, impairs angiogenesis, and improves therapeutic efficacy. The copper chelator also enhances the killing of cultured human cervical and ovarian cancer cells with cisplatin. Our results identify the copper transporter as a therapeutic target, which can be manipulated with copper chelating drugs to selectively enhance the benefits of platinum-containing chemotherapeutic agents. PMID- 20541703 TI - Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. AB - We report a Jak2V617F knockin mouse myeloproliferative neoplasm (MPN) model resembling human polycythemia vera (PV). The MPN is serially transplantable and we demonstrate that the hematopoietic stem cell (HSC) compartment has the unique capacity for disease initiation but does not have a significant selective competitive advantage over wild-type HSCs. In contrast, myeloid progenitor populations are expanded and skewed toward the erythroid lineage, but cannot transplant the disease. Treatment with a JAK2 kinase inhibitor ameliorated the MPN phenotype, but did not eliminate the disease-initiating population. These findings provide insights into the consequences of JAK2 activation on HSC differentiation and function and have the potential to inform therapeutic approaches to JAK2V617F-positive MPN. PMID- 20541705 TI - Renal stem cell biology starts to take spherical shape. Commentary on: Lusis et al., Isolation of clonogenic, long-term self renewing embryonic renal stem cells. AB - The nephron is the fundamental unit of renal function, yet the ability of the kidney to regenerate nephrons after birth is limited. Due to the medical and financial impact of chronic and end stage renal disease, an improved understanding of nephron formation is necessary if regenerative or cell therapy are to be a feasible alternative to dialysis or renal transplant. In the study presented by Lusis et al., the presence of metanephric mesenchymal stem cells is definitively demonstrated. However, these "Nephrospheres" have characteristics of mesenchymal stem cells and substantially lack the ability to undergo an epithelial-to-mesenchyme transition or to form epithelial elements otherwise necessary for building the constituent cells of the nephron. Nevertheless, this newly isolated cell population opens many opportunities to investigate the consequences of normal and aberrant nephrogenesis, including Wilm's tumor. PMID- 20541706 TI - Can we make peripheral CTA foolproof? PMID- 20541707 TI - Empirical cardiovascular CT training standards: did we get it right? PMID- 20541704 TI - GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis. AB - Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX associated transcription in a broad spectrum of leukemias. PMID- 20541708 TI - President's page: risk, benefit, and Las Vegas. PMID- 20541709 TI - Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy. AB - OBJECTIVES: The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. BACKGROUND: Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. METHODS: Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI < or =0.6 cm(2)/m(2). Patients were grouped into tertiles of peak transaortic velocity. RESULTS: Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = -0.049), male sex (beta = -0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R(2) = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. CONCLUSIONS: For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested. PMID- 20541710 TI - Determining that aortic valve stenosis is severe: back-to-the-future: physical examination and aortic valve area index/energy loss index < or =0.6 cm2/m2. PMID- 20541712 TI - RV electrical activation in heart failure during right, left, and biventricular pacing. PMID- 20541711 TI - RV electrical activation in heart failure during right, left, and biventricular pacing. AB - OBJECTIVES: To compare right ventricular (RV) activation during intrinsic conduction or pacing in heart failure (HF) patients. BACKGROUND: RV activation during intrinsic conduction or pacing in patients with left ventricular (LV) dysfunction is unclear but may affect the prognosis. In cardiac resynchronization therapy (CRT), timed LV pacing (CRT-LV) may be superior to biventricular pacing (CRT-BiV), and is hypothesized to be due to the merging of LV-paced and right bundle branch-mediated wavefronts, thus avoiding perturbation of RV electrical activation. METHODS: Epicardial RV activation duration (RVAD) (onset to end of free wall activation) was evaluated noninvasively by electrocardiographic imaging in healthy control subjects (n = 7) and compared with that of HF patients (LV ejection fraction 23 +/- 10%, n = 14). RVAD in HF was contrasted during RV pacing, CRT-BiV, and CRT-LV at optimized AV intervals. RESULTS: During intrinsic conduction in HF (n = 12), the durations of QRS and precordial lead rS complexes were 158 +/- 24 and 77 +/- 17 ms, respectively, indicating delayed total ventricular depolarization but rapid initial myocardial activation. Echocardiography demonstrated no significant RV disease. RV epicardial voltage, activation patterns, and RVAD in HF did not differ from normal (RVAD 32 +/- 15 vs. 28 +/- 3 ms, respectively, p = 0.42). In HF, RV pacing generated variable areas of slow conduction and prolonged RVAD (78 +/- 33 ms, p < 0.001). RVAD remained delayed during CRT-BiV at optimized atrioventricular intervals (76 +/- 32 ms, p = 0.87). In contrast, CRT-LV reduced RVAD to 40 +/- 26 ms (p < 0.016), comparable to intrinsic conduction (p = 0.39) but not when atrioventricular conduction was poor or absent. CONCLUSIONS: In HF patients without RV dysfunction treated with CRT, normal RV free wall activation in intrinsic rhythm indicated normal right bundle branch-mediated depolarization. However, the RV was vulnerable to the development of activation delays during RV pacing, whether alone or with CRT-BiV. These were avoided by CRT-LV in patients with normal atrioventricular conduction. PMID- 20541713 TI - A retrospective comparison of mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent. AB - OBJECTIVES: To compare acute mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (UCA). BACKGROUND: Because of serious cardiopulmonary reactions reported immediately after administration of perflutren-containing UCAs, the FDA required a black box safety warning for this class of agents, including perflutren protein-type A microspheres injectable suspension. METHODS: This study used the largest hospital service-level database in the U.S. All adult patients undergoing in-patient echocardiography between January 2003 and October 2005 were identified (n = 2,588,722, of which 22,499 received perflutren protein-type A microspheres injectable suspension). Of the 22,499 contrast echocardiography patients, 2,900 had diagnoses meeting criteria for critical illness (heart failure, acute myocardial infarction, arrhythmia, respiratory failure, pulmonary embolism, emphysema, and pulmonary hypertension). To control for the differences between the contrast and noncontrast patients, we used propensity score matching. Variables used in the construction of the propensity score included comorbidities, demographic factors, hospital-specific factors, level of care, and mechanical ventilation status. Patients receiving contrast echocardiography were matched to 4 control patients who received noncontrast echocardiography. Conditional logistic regression was used to estimate mortality effects. RESULTS: There were 167 deaths in the study among critically ill patients, 38 of 2,900 from the contrast group and 129 of 11,600 from the control group. The contrast agent was not associated with an increase in same-day mortality (odds ratio: 1.18; 95% confidence interval: 0.82 to 1.71; p = 0.37). Before matching, contrast patients showed greater morbidity than noncontrast patients (Deyo-Charlson comorbidity score 2.45 vs. 2.25, p < 0.0001). After propensity score matching, these differences were significantly reduced, showing that both groups were well balanced. CONCLUSIONS: There is no increase in mortality in critically ill patients undergoing echocardiography with the UCA compared with case-matched control patients. PMID- 20541714 TI - Detection of pulmonary congestion by chest ultrasound in dialysis patients. AB - OBJECTIVES: This study sought to investigate clinical and echocardiographic correlates of the lung comets score. BACKGROUND: Early detection of pulmonary congestion is a fundamental goal for the prevention of congestive heart failure in high-risk patients. METHODS: We undertook an inclusive survey by a validated ultrasound (US) technique in a hemodialysis center to estimate the prevalence of pulmonary congestion and its reversibility after dialysis in a population of 75 hemodialysis patients. RESULTS: Chest US examinations were successfully completed in all patients (N = 75). Before dialysis, 47 patients (63%) exhibited moderate to severe lung congestion. This alteration was commonly observed in patients with heart failure but also in the majority of asymptomatic (32 of 56, 57%) and normohydrated (19 of 38, 50%) patients. Lung water excess was unrelated with hydration status but it was strongly associated with New York Heart Association functional class (p < 0.0001), left ventricular ejection fraction (r = -0.55, p < 0.001), early filling to early diastolic mitral annular velocity (r = 0.48, p < 0.001), left atrial volume (r = 0.39, p = 0.001), and pulmonary pressure (r = 0.36, p = 0.002). Lung water reduced after dialysis, but 23 patients (31%) still had pulmonary congestion of moderate to severe degree. Lung water after dialysis maintained a strong association with left ventricular ejection fraction (r = 0.59, p < 0.001), left atrial volume (r = 0.30, p = 0.01), and pulmonary pressure (r = 0.32, p = 0.006) denoting the critical role of cardiac performance in the control of this water compartment in end-stage renal disease. In a multiple regression model including traditional and nontraditional risk factors only left ventricular ejection fraction maintained an independent link with lung water excess (beta = -0.61, p < 0.001). Repeatability studies of the chest US technique (Bland-Altman plots) showed good interobserver and inter-US probes reproducibility. CONCLUSIONS: Pulmonary congestion is highly prevalent in symptomatic (New York Heart Association functional class III to IV) and asymptomatic dialysis patients. Chest ultrasound is a reliable technique that detects pulmonary congestion at a pre-clinical stage in end-stage renal disease. PMID- 20541715 TI - Association between coronary artery calcification progression and microalbuminuria: the MESA study. AB - OBJECTIVES: This study sought to evaluate the relationship between microalbuminuria (MA) and the development and progression of atherosclerosis, as assessed by incident and progression of coronary artery calcification (CAC). BACKGROUND: MA is associated with an increased risk of cardiovascular disease, but the mechanism by which MA imparts this increased risk is not known. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) study is a prospective cohort study of 6,814 self-identified White, African-American, Hispanic, or Chinese participants free of clinical cardiovascular disease at entry. Of the 6,775 individuals with available urine albumin data, we excluded 97 subjects with macroalbuminuria and 1,023 with missing follow-up CAC data. The final study population consists of 5,666 subjects. RESULTS: At baseline, individuals with MA were more likely to have CAC >0 compared with those without MA (62% vs. 48%, p < 0.0001). During a mean follow-up of 2.4 +/- 0.8 years, those with MA and no CAC at baseline were more likely to develop CAC (relative risk [RR]: 2.05, 95% confidence interval [CI]: 1.41 to 3.02, p < 0.0001) as compared with those without MA in demographic-adjusted analyses. After multivariant adjustment, the relationship was attenuated but remained statistically significant (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005). Among those with CAC at baseline, those with versus those without MA had a 15 (95% CI: 8 to 22, p < 0.0001) volume units higher median increase in CAC in demographic-adjusted analyses. After multivariant adjustment, MA remained associated with incident CAC (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005) and with progression of CAC (median increase in CAC volume score of 9 [95% CI: 2 to 16, p = 0.009]), relative to those without MA. CONCLUSIONS: This large multiethnic, population-based study of asymptomatic individuals demonstrates an increased risk of incident CAC as well as greater CAC progression among those with MA. Further study is needed to determine the degree to which MA precedes and predicts progression of atherosclerosis and how this information can be used to reduce cardiovascular events. PMID- 20541716 TI - Left ventricular hypertrophy, aortic wall thickness, and lifetime predicted risk of cardiovascular disease:the Dallas Heart Study. AB - OBJECTIVES: To examine whether individuals with low short-term risk of coronary heart disease but high lifetime predicted risk of cardiovascular disease (CVD) have greater prevalence of left ventricular (LV) hypertrophy and increased aortic wall thickness (AWT) than those with low short-term and low lifetime risk. BACKGROUND: Lifetime risk prediction can be used for stratifying individuals younger than 50 years of age into 2 groups: low short-term/high lifetime and low short-term/low lifetime predicted risk of CVD. Individuals with low short term/high lifetime risk have a greater burden of subclinical atherosclerosis as measured by coronary artery calcium and carotid intima-media thickness. However, >75% of individuals with low short-term/high lifetime risk do not have detectable coronary artery calcium, suggesting the presence of alternative subclinical abnormalities. METHODS: We stratified 1,804 Dallas Heart Study subjects between the ages of 30 and 50 years who had cardiac magnetic resonance into 3 groups: low short-term (<10% 10-year risk of coronary heart disease)/low lifetime predicted risk (<39% lifetime risk of CVD), low short-term (<10%)/high lifetime risk (> or =39%), and high short-term risk (> or =10%, prevalent diabetes, or previous stroke, or myocardial infarction). In those with low short-term risk, we compared measures of LV hypertrophy and AWT between those with low versus high lifetime risk. RESULTS: Subjects with low short-term/high lifetime risk compared with those with low short-term/low lifetime risk had increased LV mass (men: 95 +/- 17 g/m(2) vs. 90 +/- 12 g/m(2) and women: 75 +/- 14 g/m(2) vs. 71 +/- 10 g/m(2), respectively; p < 0.001 for both). LV concentricity (mass/volume), wall thickness, and AWT were also significantly greater in those with high lifetime risk in this comparison (p < 0.001 for all), but LV end-diastolic volume was not (p > 0.3). These associations persisted among participants without detectable coronary artery calcium. CONCLUSIONS: Among individuals 30 to 50 years of age with low short-term risk, a high lifetime predicted risk of CVD is associated with concentric LV hypertrophy and increased AWT. PMID- 20541717 TI - Contractile reserve in segments with nontransmural infarction in chronic dysfunctional myocardium using low-dose dobutamine CMR. AB - OBJECTIVES: This study sought to quantify contractile reserve of chronic dysfunctional myocardium, in particular in segments with intermediate transmural extent of infarction (TEI), using low-dose dobutamine cardiac magnetic resonance (CMR) in patients with a chronic total coronary occlusion (CTO). BACKGROUND: Recovery of dysfunctional segments with intermediate TEI after percutaneous coronary intervention is variable and difficult to predict, and may be related to contractility of the unenhanced rim. METHODS: Fifty-one patients (mean age 60 +/- 9 years, 76% male) with a CTO underwent CMR at baseline and 35 patients underwent CMR at follow-up to quantify segmental wall thickening (SWT) at rest during 5 and 10 microg/kg/min dobutamine, and at follow-up. Delayed-enhancement CMR was performed to quantify TEI. Dysfunctional segments were stratified according to TEI, end-diastolic wall thickness (EDWT), or unenhanced rim thickness, and SWT was quantified. Segments with an intermediate TEI (25% to 75%) were further stratified according to baseline SWT of the unenhanced rim (SWT(UR)) (<45% and >45%), and SWT was quantified. For each parameter, odds ratio (OR) and diagnostic performance for the prediction of contractile reserve were calculated. RESULTS: Significant contractile reserve was present in dysfunctional segments with EDWT >6 mm, unenhanced rim thickness >3 mm, or TEI of <25%; only TEI had significant relation with contractile reserve (OR: 0.98; 95% confidence interval [CI]: 0.96 to 0.99; p = 0.02). In segments with intermediate TEI (n = 58), mean SWT did not improve significantly. However, segments with SWT(UR) <45% showed contractile reserve and improved at follow-up, whereas segments with SWT(UR) >45% were unchanged. SWT(UR) had a significant relation with contractile reserve (OR: 0.98; 95% CI: 0.97 to 0.99; p = 0.02). CONCLUSIONS: CMR quantification of transmurality of infarcted myocardium allows the assessment of the potential of dysfunctional segments to improve in function during dobutamine of most segments. However, in segments with intermediate TEI, measurement of baseline contractility of the epicardial rim better identifies which segments maintain contractile reserve. PMID- 20541718 TI - Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health. AB - Positron emission tomography (PET) myocardial perfusion imaging in concert with tracer-kinetic modeling affords the assessment of regional myocardial blood flow (MBF) of the left ventricle in absolute terms (milliliters per gram per minute). Assessment of MBF both at rest and during various forms of vasomotor stress provides insight into early and subclinical abnormalities in coronary arterial vascular function and/or structure, noninvasively. The noninvasive evaluation and quantification of MBF and myocardial flow reserve (MFR) extend the scope of conventional myocardial perfusion imaging from detection of end-stage, advanced, and flow-limiting, epicardial coronary artery disease (CAD) to early stages of atherosclerosis or microvascular dysfunction. Recent studies have shown that impaired hyperemic MBF or MFR with PET, with or without accompanying CAD, is predictive of increased relative risk of death or progression of heart failure. Quantitative approaches that measure MBF with PET identify multivessel CAD and offer the opportunity to monitor responses to lifestyle and/or risk factor modification and to therapeutic interventions. Whether improvement or normalization of hyperemic MBF and/or the MFR will translate to improvement in long-term cardiovascular outcome remains clinically untested. In the meantime, absolute measures of MBF with PET can be used as a surrogate marker for coronary vascular health, and to monitor therapeutic interventions. Although the assessment of myocardial perfusion with PET has become an indispensable tool in cardiac research, it remains underutilized in clinical practice. Individualized, image-guided cardiovascular therapy may likely change this paradigm in the near future. PMID- 20541719 TI - Takotsubo cardiomyopathy: a unique cardiomyopathy with variable ventricular morphology. AB - Takotsubo cardiomyopathy is an important differential diagnosis of acute coronary syndrome. It is characterized by normal (or near-normal) coronary arteries, regional wall motion abnormalities that extend beyond a single coronary vascular bed, and often, a precipitating stressor. Variants of the classical left ventricular apical ballooning, including mid- or basal left ventricular wall motion abnormalities, are increasingly recognized. Takotsubo cardiomyopathy is not rare, and heightened awareness of this unique cardiomyopathy likely will lead to a higher reported incidence. Diagnosis of takotsubo cardiomyopathy has important implications for clinical management at presentation and afterward. The long-term prognosis is generally favorable; however, a small subset has potentially life-threatening complications during the initial presentation. The pathophysiologic mechanism is unknown, but catecholamine excess likely has a central role. PMID- 20541720 TI - Multimodality imaging of pericardial diseases. AB - Pericardial disease is an important cause of morbidity and mortality in patients with cardiovascular disease. Inflammatory diseases of the pericardium constitute a spectrum ranging from acute pericarditis to chronic constrictive pericarditis. Other important entities that involve the pericardium include benign and malignant pericardial masses, pericardial cysts, and diverticula, as well as congenital absence of the pericardium. Recent advances in multimodality noninvasive cardiac imaging have solidified its role in the management of patients with suspected pericardial disease. The physiologic and structural information obtained from transthoracic echocardiography and the anatomic detail provided by cardiac computed tomography and magnetic resonance have led to growing interest in the complementary use of these techniques. Optimal management of the patient with suspected pericardial disease requires familiarity with the key imaging modalities and the ability to choose the appropriate imaging tests for each patient. This report reviews the imaging modalities most useful in the assessment of patients with pericardial disease, with an emphasis on the complementary value of multimodality cardiac imaging. PMID- 20541721 TI - Diagnostic value of CMR in patients with biomarker-positive acute chest pain and unobstructed coronary arteries. PMID- 20541722 TI - Hemorrhage in the myocardium following infarction. PMID- 20541723 TI - Accuracy of OCT in evaluating neointimal thickness after stent implantation. PMID- 20541726 TI - Cardiac ultrasound imaging in acute care settings. PMID- 20541727 TI - Factors associated with small head circumference at birth among infants born before the 28th week. AB - OBJECTIVE: We sought to identify risk factors for congenital microcephaly in extremely low gestational age newborns. STUDY DESIGN: Demographic, clinical, and placental characteristics of 1445 infants born before the 28th week were gathered and evaluated for their relationship with congenital microcephaly. RESULTS: Almost 10% of newborns (n = 138), rather than the expected 2.2%, had microcephaly defined as a head circumference >2 SD below the median. In multivariable models, microcephaly was associated with nonwhite race, severe intrauterine growth restriction, delivery for preeclampsia, placental infarction, and being female. The risk factors for a head circumference between <1 and >2 SD below the median were similar to those of microcephaly. CONCLUSION: Characteristics associated with fetal growth restriction and preeclampsia are among the strongest correlates of microcephaly among children born at extremely low gestational ages. The elevated risk of a small head among nonwhites and females might reflect the lack of appropriate head circumference standards. PMID- 20541728 TI - Does sildenafil citrate affect myometrial contractile response to nifedipine in vitro? AB - OBJECTIVE: We sought to test the hypothesis that sildenafil citrate (SC) at low concentrations potentiates the tocolytic effects of nifedipine in vitro. STUDY DESIGN: Myometrial biopsies were obtained from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10(-10) to 10(-5) mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P < .05). RESULTS: Nifedipine significantly inhibited spontaneous and oxytocin induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10(-8) mol/L, without affecting oxytocin-induced contractile response. CONCLUSION: At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine. PMID- 20541729 TI - Maternal lipopolysaccharide-induced inflammation during pregnancy programs impaired offspring innate immune responses. AB - OBJECTIVE: Because the fetal innate immune system is responsive, while still maturing during the preterm period, we hypothesized that the early activation of fetal inflammatory pathways may have an impact on the ultimate expression of immune competency. STUDY DESIGN: Pregnant Sprague Dawley rats (n = 7; Harlan Sprague Dawley Inc, Jerusalem, Israel) at 18 days gestation received intraperitoneal injections of saline solution or lipopolysaccharides (500 microg/kg). Pups were delivered spontaneously. At postnatal day 24, pups received intraperitoneal lipopolysaccharide (100 microg/kg), and plasma cytokine levels were measured before and 4 hours after lipopolysaccharide administration. RESULTS: In response to lipopolysaccharides, pups of the lipopolysaccharide injected dams had significantly (P < .05) reduced interleukin-6 (median [25th,75th percentile], 229 [84,6086] vs 4745 [2765,6643] pg/mL), interleukin 1beta (median [25th,75th percentile], 820 [125,1196] vs 1682 [1515,2127] pg/mL), tumor necrosis factor-alpha (median [25th,75th percentile], 4.8 [1.2,91] vs 163 [46,205] pg/mL), and interleukin-10 responses, when compared with saline solution injected dams. CONCLUSION: Maternal lipopolysaccharide exposure suppresses offspring innate immune response to inflammatory stimuli. These results suggest that maternal inflammatory exposures during pregnancy may impair newborn infant innate responses and increase susceptibility to infection. PMID- 20541731 TI - Hyperglycemia induces inducible nitric oxide synthase gene expression and consequent nitrosative stress via c-Jun N-terminal kinase activation. AB - OBJECTIVE: Maternal diabetes has an adverse impact on embryonic development. We tested the hypothesis that hyperglycemia-induced c-Jun N-terminal kinases (JNK) 1/2 activation mediates inducible nitric oxide synthase (iNOS) induction. STUDY DESIGN: Levels of iNOS messenger ribonucleic acid (mRNA) and nitrosylated protein were determined in cultured C57BL/6J conceptuses exposed to hyperglycemia (300 mg/dL glucose) and C57BL/6J embryos exposed to streptozotocin-induced diabetes. The iNOS-luciferase activity and endogenous reactive nitrogen species were determined in transfected PYS-2 (mouse teratocarcinoma) cells exposed to hyperglycemia (450 mg/dL glucose). RESULTS: Hyperglycemia increased iNOS mRNA, and SP600125, a potent JNK1/2 inhibitor, abolished this effect. Hyperglycemia increased iNOS-luciferase activities, and SP600125 blocked this effect. Diabetes increased iNOS mRNA and jnk2 gene deletion abrogated this effect. Correlated with iNOS gene induction, both hyperglycemia in vitro and diabetes in vivo enhanced the production of reactive nitrogen species and increased protein nitrosylation. The jnk2 gene deletion blocked diabetes-induced protein nitrosylation. CONCLUSION: JNK1/2 activation mediates hyperglycemia-induced iNOS gene expression and consequent nitrosative stress in diabetic embryopathy. PMID- 20541732 TI - Use of and attitudes toward complementary and alternative medicine among nurse midwives in Israel. AB - OBJECTIVE: The objective of the study was to evaluate the use and attitudes of nurse-midwives in Israel toward complementary and alternative medicine (CAM). STUDY DESIGN: In a cross-sectional study, nurse-midwives from 5 Israeli medical centers completed the CAM Health Belief Questionnaire, a validated tool examining data regarding personal health behavior, use of CAM therapies, and attitudes toward CAM. RESULTS: One hundred seventy-three of 238 potential respondents completed the questionnaires (72.7%). Most (87.3%) reported using CAM (67.1% massage, 48.6% herbal medicine, 42.2% meditation, 40.5% touch therapies, and 39.9% prayer) and agree with many fundamental tenets of CAM such as the existence of energy forces, self-healing, and integrating patients' health beliefs and values into their care. CONCLUSION: The majority of nurse-midwives studied reported using and recommending CAM to their patients and believe that CAM can complement conventional medical therapies. Health care providers could benefit from education with regard to the efficacy and safety of CAM modalities during pregnancy and childbirth. PMID- 20541733 TI - Association of midgestation paraoxonase 1 activity and pregnancies complicated by preterm birth. AB - OBJECTIVE: The objective of the study was to determine whether an association exists between low paraoxonase 1 activity and dyslipidemia at midgestation and preterm birth. STUDY DESIGN: We conducted a case-control study of 30 women with preterm birth and 90 women with uncomplicated term deliveries. Maternal serum collected at 15-20 weeks was used to measure lipid concentrations and paraoxonase 1 activity using 2 substrates: paraoxon and phenylacetate (arylesterase activity). RESULTS: The groups did not differ with respect to maternal demographics. Paraoxonase 1 activity (paraoxon) was significantly lower in women delivering preterm compared with controls (12.9 +/- 6.1 vs 16.6 +/- 7.7 dA/min; P = .02). Arylesterase activity and serum lipid concentrations were similar between women with preterm birth and controls. CONCLUSION: Midgestation paraoxonase 1 activity is lower in women who later experience spontaneous preterm birth compared with women who have term deliveries. Prospective studies are needed to determine the significance of paraoxonase 1 in the pathogenesis of preterm birth. PMID- 20541734 TI - Risk of preterm delivery in relation to maternal use of psychotropic medications during pregnancy: methodological issues. PMID- 20541735 TI - To the point: reviews in medical education-taking control of the hidden curriculum. AB - This article, the ninth in the "To the Point" series that is prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, discusses the role of the "hidden curriculum" in shaping the professional identity of doctors in training. The characteristics that distinguish the formal curriculum and hidden curriculum are defined. Specific examples of hidden curricula in clinical environments and the positive and negative impacts that may result are highlighted. Techniques to evaluate clinical training environments and to identify the hidden curriculum are provided and are followed by methods to promote its positive messages and lessen its negative ones. PMID- 20541736 TI - Impact of antenatal selective serotonin reuptake inhibitor exposure on pregnancy outcomes in mice. AB - OBJECTIVE: This study investigates fluoxetine (FLX) exposure as an etiology for altered gestational length and adverse pregnancy outcomes. STUDY DESIGN: Two experiments were performed exposing mice to drinking water (H(2)O) or H(2)O+FLX. Primary outcomes included gestational length, litter size, and live birth rate. In experiment 1, time-mated dams were monitored for spontaneous birth, and gestational length was calculated. In experiment 2, dams were dissected on day 14 to verify litter size and qualities of embryo implantation. RESULTS: There was no difference in gestational length between H(2)O dams (480.7 +/- 13.2 hours) and H(2)O+FLX dams (483.5 +/- 10.1 hours), P = .70. Mean litter size was decreased in H(2)O+FLX dams (4.1 +/- 1.3/litter) compared to H(2)O dams (5.5 +/- 1.9/litter), P = .04. H(2)O+FLX dams were less likely to have live births (25.4%) compared to H(2)O dams (49.3%), P = .01. CONCLUSION: Antenatal FLX exposure did not statistically alter gestational length, but did affect litter size and spontaneous loss in mice. This warrants further investigation. PMID- 20541737 TI - Periorbital contact sensitization. AB - PURPOSE: To identify frequency and pattern of contact sensitization among patients with periorbital dermatitis. DESIGN: Cross-sectional retrospective investigation of 1247 patients referred for patch testing over a 17-year period. METHODS: Data were collected for patients undergoing patch testing to the standard and customized trays between January 1990 and December 2006 at the Massachusetts General Hospital, Contact Dermatitis Clinic. Our study group consisted of 266 patients affected by periorbital dermatitis. Findings were compared to 981 referrals without periorbital dermatitis (controls). Patch test results were read after 48 and 72 hours and classified as allergic, questionable, irritant, or negative. Statistical analyses were carried out by using chi(2) test and Fisher exact test. RESULTS: General epidemiologic data among periorbital dermatitis patients showed significant predominance of female gender (87.6%) and of individuals aged 40 to 59 years (45.9%). Nickel (16.5%) and fragrance mix (13.2%) were the top-ranking sensitizers. Ingredients of topical ophthalmologic products did not result in significant sensitization. Comparison of the periorbital dermatitis group to the controls did not reveal significant differences in sensitization pattern. Patch testing confirmed the likelihood of allergic contact dermatitis in 50.8% of the periorbital dermatitis patients tested. CONCLUSIONS: Allergic contact dermatitis is a common cause of periorbital dermatitis. Patch testing should be considered in all patients with periorbital dermatitis when suspecting contact allergy in order to identify and avoid offending allergens. PMID- 20541738 TI - Fovea-sparing retinal detachments: time to surgery and visual outcomes. AB - PURPOSE: To study the effect of the duration from initial evaluation to repair on outcomes for fovea-sparing rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective, single-surgeon, consecutive case series. METHODS: Medical records were reviewed for preoperative and intraoperative factors possibly associated with visual and anatomic outcomes for all patients undergoing scleral buckling procedure (SBP) for fovea-sparing, primary RRD between 1989 and 2004. RESULTS: Fifty-five percent of 199 patients had symptoms for < or = 7 days, 83% had best corrected visual acuity (BCVA) > or = 20/40, and 33% had a RRD that had extended to within the macular arcade vessels. Eighty-five percent were operated within 3 days, including 56% within 24 hours. One case progressed to fovea-off status before surgery 4 days after initial evaluation (0.5%). The single-operation success rate was 88% and final anatomic success was 99.5% (1 patient refused reoperation). Eighty-six percent were examined postoperatively for at least 2 months; 73% had > or = 20/40 vision. The strongest predictor of postoperative BCVA was initial BCVA (r = 0.47; P < .001). There was no statistically significant difference in postoperative BCVA or single-operation success rate at any point within 3 days of initial examination. No statistically significant correlation was found between postoperative BCVA and duration of symptoms, RRD location, direction of the closest approach of the RRD to the fovea, or need for reoperation. CONCLUSIONS: Progression to fovea-off status was rare in this series when a selectively urgent, but not strictly emergent, surgical approach was employed for fovea-sparing RRD. PMID- 20541739 TI - Strabismus surgical skills assessment tool: development of a surgical assessment tool for strabismus surgery training. AB - PURPOSE: To develop a structured tool to assess strabismus surgical skills and to determine the face and content validity of this tool. DESIGN: Development of a surgical assessment tool and its validation by an expert panel. METHODS: A structured subjective evaluation form was developed to evaluate a trainee's technique and skill in strabismus surgery. The tool consists of strabismus surgery-specific components, such as conjunctival incision, muscle exposure, and suture placement, and global indices, such as hemostasis, tissue control, and knowledge of instruments. Each of these components was evaluated on a 5-point Likert scale. A survey of experienced strabismus surgeons was performed to establish the face and content validity of the tool. The results of the survey were used to amend the tool. RESULTS: The final tool comprises 10 strabismus surgery-specific competencies and 7 global indices. The final version of the tool was deemed to address the vital aspects of a strabismus surgical procedure (face validity), and the components of the assessment tool were deemed to assess appropriate competencies and skills associated with the procedure (content validity). CONCLUSIONS: The strabismus surgery skill assessment tool is a structured quantitative instrument designed to aid surgical evaluation and training of ophthalmic surgical trainees. The Strabismus Surgical Skill Assessment Tool is a paper-based tool that is easy to use, provides the trainee with detailed feedback and a measure of progression of their surgical skills, and stimulates discussion between trainee and trainer to direct further training. PMID- 20541740 TI - Posterior capsule opacification assessment and factors that influence visual quality after posterior capsulotomy. AB - PURPOSE: To study the correlation between posterior capsule opacification (PCO) and intraocular straylight and visual acuity. DESIGN: Prospective noninterventional study. METHODS: We measured visual acuity (VA), logarithm of minimal angle of resolution (logMAR) and intraocular straylight (C-Quant straylight parameter log[s]) under photopic conditions before and 2 weeks after YAG capsulotomy in 41 patients (53 eyes) from the Centro de Oftalmologia Barraquer in Barcelona and the University Eye Clinic, Paracelsus Medical University in Salzburg. Photopic pupil diameter was also measured. To document the level of opacification, pupils were dilated and photographs were taken with a slit lamp, using retroillumination and the reflected light of a wide slit beam at an angle of 45 degrees. PCO was subjectively graded on a scale of 0 to 10 and using the POCOman system. A multiple regression analysis was performed to evaluate factors that influence straylight after capsulotomy. RESULTS: Straylight correlated well with retroillumination and reflected-light PCO scores, whereas VA only correlated with retroillumination. Both VA and straylight improved after capsulotomy. Straylight values varied widely after capsulotomy. Multiple regression analysis showed that older age, large ocular axial length, hydrophobic acrylic intraocular lenses (IOLs), and small capsulotomies are factors that increased intraocular straylight. CONCLUSION: Intraocular straylight is a useful tool in the assessment of PCO. It correlates well with PCO severity scoring methods. When performing a posterior capsulotomy, factors such as age, IOL material, axial length, and capsulotomy size must be taken into consideration, as they influence intraocular straylight. PMID- 20541741 TI - A case study of ISO 11064 in control centre design in the Norwegian petroleum industry. AB - In 2006-2008 we performed a case study for the purpose of assessing the industrial application of the seven part Control Centre (CC) design standard ISO 11064 to identify positive and negative experiences among stakeholders in the Norwegian petroleum sector. We mainly focussed on ISO 11064 Part 1, because this was the most commonly used among the identified stakeholders. ISO 11064 is generally appreciated and applied in the industry, but we did observe a significant variance in use between the different parts of the standard. We also identified potential areas for improvements, like scope and application adaptation. Thus we suggest a more goal-based approach based on one normative part only. PMID- 20541743 TI - Behavioral treatment of obesity: Introduction. PMID- 20541742 TI - Estrogen deficiency increases variability of tissue mineral density of alveolar bone surrounding teeth. AB - OBJECTIVE: Estrogen deficiency increases bone remodeling leading to increased variability of tissue mineral density (TMD). Due to the functional demands of mastication, alveolar bone around teeth is inherently a highly remodeled region of bone tissue with a highly variable distribution of TMD. This study investigated the effect of estrogen deficiency on the TMD distribution of alveolar bone. DESIGN: Using three-dimensional micro-computed tomography images of sham surgery (Sham) and ovariectomized (OVX) rat mandible sections, alveolar bone region (AB) and control bone region (CB) of interest were isolated. Based on histograms of gray levels equivalent to TMD values, mean (Mean), standard deviation (SD) and coefficient of variation (COV=SD/Mean) were computed. Fifth and 95th percentile gray level values were also obtained (Low(5) and High(5), respectively). Absolute value of percentage (%) differences of the gray level parameters between AB and CB regions were computed. RESULTS: Both SD and COV were significantly higher in AB region than those in CB region for all specimens of both Sham and OVX groups (p<0.001). The mean values of % differences for SD were moderately higher (p<0.073) and those for COV and Low(5) were significantly higher for the OVX group than for the Sham group (p<0.04). CONCLUSIONS: Higher variability of mineralization observed in AB of OVX group indicates that estrogen deficiency amplifies the active bone remodeling of AB already present due to the mastication. These findings provide an insight that the increased variability of TMD induced by estrogen deficiency may compromise the mechanical stability of the tooth-bearing alveolar bone. PMID- 20541744 TI - Structural characterization of chondroitin sulfate from sturgeon bone. AB - Chondroitin sulfate (CS) was purified for the first time from the bones of sturgeon and analyzed to evaluate its structure and properties. A single polysaccharide was extracted from sturgeon bone in a concentration of 0.28-0.34% for dry tissue and characterized as CS. By means of specific chondroitinases and HPLC separation of generated unsaturated repeating disaccharides, this polymer was found to be composed of approximately 55% of disaccharide monosulfated in position 6 of the GalNAc, approximately 38% of disaccharide monosulfated in position 4 of the GalNAc, and approximately 7% of nonsulfated disaccharide. The charge density was 0.93 and the ratio of 4:6 sulfated residues was equal to 0.69, a value confirmed by (13)C NMR experiments. Chondroitinase B confirmed that the purified sturgeon CS contained mainly GlcA (>99.5%) as uronic acid. PAGE analysis showed a CS having a high molecular mass with an average value of 39,880 according to HPSEC values producing a weight average molecular weight (Mw) of 37,500. On the basis of the data collected, it is reasonable to assume that CS isolated from sturgeon bone might be potentially useful for scientific and pharmacological applications, making this bony fish, which is generally discarded after ovary collection, a useful source of this polymer. Finally, this newly identified source of CS would enable the production of this macromolecule having a particular repeating disaccharide composition, structure, and biological properties. PMID- 20541745 TI - Cryopreservation of prepubertal mouse testicular tissue by vitrification. AB - OBJECTIVE: To compare cryopreservation of prepubertal testicular tissue after vitrification (V) and slow-freezing (SF). DESIGN: Prospective experimental study. SETTING: Academic research unit. ANIMAL(S): Six-day-old mice. INTERVENTION(S): After cryopreservation, viability tests (n = 10) and short-term culture (1 and 3 days) (n = 5) were performed. A comparison was made with fresh (FR) and noncultured controls (FR Ctrl). MAIN OUTCOMES MEASURE(S): Tissue viability was assessed by lactate dehydrogenase release assay. Apoptosis (caspase-3) and proliferation (Ki67) were evaluated by immunohistochemistry, and tubular diameter, integrity, and cell density by light microscopy. RESULT(S): Lactate dehydrogenase release was greater after SF than V (54.6% vs. 26.7%), whereas the mean number of apoptotic cells/tubule was higher after V than SF (2.13 vs. 0.07). On day 1, a decrease in cell density was noted in both cryopreserved groups, but this difference was not subsequently observed. On day 3, an increase in proliferation was seen in the SF and V groups versus FR tissue, and similar tubular diameter, integrity, and cell density were found in all cultured groups. CONCLUSION(S): This study shows that both SF and V protocols preserve survival, development, and integrity of prepubertal mouse testicular tissue in short-term organotypic culture. Additional investigation should now be conducted to assess tissue functionality. PMID- 20541746 TI - Enteral nutrition access devices. AB - The ASGE Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, performing a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but, in many cases, data from randomized, controlled trials are lacking. In such situations, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the ASGE Governing Board. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through August 2009 for articles related to endoscopy in patients requiring enteral feeding access by using the keywords "endoscopy," "percutaneous," "gastrostomy," "jejunostomy," "nasogastric," "nasoenteric," "nasojejunal," "transnasal," "feeding tube," "enteric," and "button." Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment. PMID- 20541747 TI - Intestinal involvement by Micobacterium genavense in an immunodepressed patient. PMID- 20541748 TI - A pancreatic pseudocyst-portal vein fistula closed by endoscopic pancreatic stent insertion. PMID- 20541750 TI - Transgastric natural-orifice transluminal endoscopic surgery peritoneoscopy in humans: a pilot study in efficacy and gastrotomy site selection by using a hybrid technique. AB - BACKGROUND: Diagnostic natural-orifice transluminal endoscopic surgery (NOTES) peritoneoscopy can easily be performed with standard endoscopic equipment in animal studies. The efficacy and optimal transgastric site for NOTES access in humans, however, has not been determined. OBJECTIVE: To characterize the efficacy of various anterior gastric access locations for diagnostic transgastric NOTES peritoneoscopy in humans. DESIGN: Prospective clinical study. SETTING: Tertiary care center with experience in NOTES peritoneoscopy. PATIENTS: Patients undergoing planned laparoscopic gastrectomy or gastrotomy involving the anterior aspect of the stomach were eligible. INTERVENTIONS: An anterior gastric site for NOTES gastrotomy was chosen and transgastric NOTES access was independently established after laparoscopic abdominal exploration. Peritoneoscopy was then performed. The site of gastrotomy was closed as part of the intended laparoscopic procedure. MAIN OUTCOME MEASURES: The ability to visualize the abdominal and pelvic organs in all four quadrants was determined. Patients were evaluated postoperatively for complications. RESULTS: Eight patients requiring 9 procedures were studied. Gastrotomy sites were classified as body (n = 3), lesser curvature (n = 3), greater curvature (n = 1), fundus (n = 1), and antrum (n = 1). Satisfactory navigation could only be performed to the right upper and both lower quadrants. The left upper quadrant, specifically the spleen, was adequately visualized in only 1 case (11%), where the gastrotomy site was at the greater curvature. One patient developed a surgical site infection requiring oral antibiotic therapy. The median postoperative stay was 2 days (range, 0-3 days). LIMITATIONS: Small number of patients. CONCLUSION: NOTES peritoneoscopy with a gastrotomy on the anterior stomach permits adequate visualization of organs in the right upper and both lower quadrants. Visualization of the left upper quadrant and spleen is, however, limited unless access is gained on the greater curvature of the stomach. The accuracy of NOTES in identifying intra-abdominal pathology compared with laparoscopy remains to be determined. PMID- 20541751 TI - Menetrier disease manifested by polyposis in the gastric antrum and coexisting with gastritis cystica profunda. PMID- 20541752 TI - Extensive duodenal ulceration with massive GI bleeding after blunt trauma with subsequent duodenal stricture. PMID- 20541753 TI - An unusual case of acute pancreatitis secondary to an intraluminal duodenal diverticulum. PMID- 20541754 TI - An unusual case of diarrhea. PMID- 20541755 TI - Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). AB - BACKGROUND: Increased esophagogastric junction (EGJ) compliance is a key abnormality in GERD leading to increased volumes of reflux. To date, EGJ distensibility has been measured only with investigational barostat-based prototype devices. OBJECTIVES: The aim of the study was to test the endoscopic functional luminal imaging probe (EndoFLIP), a new commercially available technology designed to measure intraluminal distensibility, by assessing the EGJ of GERD patients and controls. DESIGN: Prospective case-control series. SETTING: Tertiary referral center. SUBJECTS: Twenty GERD patients and 20 controls studied during a routine esophagogastroduodenoscopy. METHODS: The EndoFLIP was passed through the endoscopic instrumentation channel and positioned across the EGJ. The EndoFLIP uses impedance planimetry to measure 16 cross-sectional areas (CSA) along with the corresponding intrabag pressure within a 4.6-cm cylindrical segment of a fluid-filled bag. MAIN OUTCOME MEASUREMENT: EGJ distensibility was assessed with 10- to 40-mL volume-controlled distentions. RESULTS: In both groups, the least distensible locus at the EGJ was usually at the hiatus. As a group, GERD patients exhibited two- to threefold increased EGJ distensibility compared with controls, particularly at 20- to 30-mL distention volumes, values quantitatively similar to previous measurements with barostat-based devices. The endoscopic estimation of EGJ distensibility, the flap valve grade, correlated poorly with EndoFLIP measurements. LIMITATIONS: Heterogeneity of GERD patients. CONCLUSIONS: Measurement of EGJ distensibility with EndoFLIP is feasible during clinical endoscopy. Stratifying GERD patients according to this physiological parameter may facilitate the identification of patient subgroups responsive or unresponsive to medical or surgical treatments. PMID- 20541756 TI - Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis. AB - Locally applied antibiotics support prophylaxis of highly feared implant associated infections. Implant coatings with poly(D,L-lactide) (PDLLA)/gentamicin seem to be a promising approach. Aims of this study were to analyse the release kinetics of gentamicin in vivo, in vitro, to analyse the antibacterial efficacy,the resistance development and its impact on osteoblasts. For the in vitro release experiments titanium implants were coated with PDLLA/gentamicin and the antibiotic release in aqueous solution was analysed at 20 time points (from 10 s to 110 days). For the in vivo experiments PDLLA/gentamicin-coated kirschner wires were implanted in the tibiae of 18 rats. Gentamicin concentration in the bone was analysed at several time points (n = 3 each, 1 h to 7 days). Bactericidal efficacy, bacterial adhesion on the implants and resistance development were tested. AP activity, cell count and CICP expression of osteoblasts were analysed. Gentamicin was released rapidly with an initial burst in aqueous solution and followed by a slow release. Similarly, in vivo gentamicin concentration reached a high peak initially followed by a decrease to a low level. No development of resistance was observed in the investigated setting, the antibacterial efficacy was not affected by the coating process and significantly fewer bacteria were attached to the implant. Osteoblasts were not negatively affected by the gentamicin released from the coating. PDLLA/gentamicin coating resulted in a desired antibiotic peak concentration within the bone. Bacterial adhesion was successfully prevented. No bacterial resistances were developed. This coating seems to be a suitable supplement for prophylaxis of implant associated infections. PMID- 20541757 TI - Association between aldehyde dehydrogenase 2 genetic polymorphism and serum lipids or lipoproteins: a meta-analysis of seven East Asian populations. PMID- 20541759 TI - Variability in kinematic coupling assessed by vector coding and continuous relative phase. AB - Variability in the spatio-temporal coordination of human movement kinematics is often assessed by vector coding and continuous relative phase (CRP). To facilitate appropriate comparisons between the findings of studies that have used different techniques to assess variability, the purposes of this study were: (1) to determine if both vector coding and CRP behave according to dynamical systems theories on variability and state space transitions; and (2) to determine if trends in coordination variability during movement are consistent when using either vector coding or CRP. We present both a theoretical case (the Lorenz Attractor) and two experimental cases (rearfoot-forefoot coupling during overground walking for 22 subjects; the effect of treadmill speed on thigh-leg coupling for five subjects). In the theoretical case, variability quantified by CRP agreed with dynamical systems theory on state space transitions more so than variability quantified by vector coding. In experimental cases, this distinction was less clear, although CRP appeared to be a more conservative metric for variability. The magnitudes (all p<0.001) and timings (all p<0.04) of peaks in variability during the stance phase of overground walking depended on whether vector coding or CRP was used for two couplings. Similar distinctions were observed for peaks during the stride cycle of treadmill locomotion (all effect sizes >2.8). However, changes in the average variability during the stride cycle as speed increased were consistent for both methods (all effect sizes <0.2). The results suggest that comparisons between the findings of studies that have quantified variability using CRP and those that have used vector coding should be made with caution. PMID- 20541758 TI - Three-month treatment with pioglitazone reduces circulating levels of thiobarbituric acid-reacting substances, a marker of reactive oxidative stress, without change in body mass index, in Japanese patients with type 2 diabetes. PMID- 20541760 TI - Upper limb joint kinetics during manual wheelchair propulsion in patients with different levels of spinal cord injury. AB - The purpose of this study was to compare the forces and moments of the whole upper limb, analyzing forces and moments at the shoulder, elbow and wrist joints simultaneously during manual wheelchair propulsion of persons with different levels of spinal cord injury (SCI) on a treadmill. Fifty-one people participated in this study and were grouped by their level of SCI: C6 tetraplegia (G1), C7 tetraplegia (G2), high paraplegia (G3), and low paraplegia (G4). An inverse dynamic model was defined to compute net joint forces and moments from segment kinematics, the forces acting on the pushrim, and subject anthropometrics. Right side, upper limb kinematic data were collected with four camcorders (Kinescan IBV). Kinetic data were recorded by replacing the wheels with SmartWheels (Three Rivers Holdings, LLC). All participants propelled the wheelchair at 3km/h for 1min. The most noteworthy findings in both our tetraplegic groups in relation to paraplegic groups were increased superior joint forces in the shoulder (G1 and G2 vs G3 p<0.001; G1 and G2 vs G4 p<0.01), elbow (G1 vs G3 p<0.001; G1 vs G4 p<0.05) and wrist (G1 vs G4 p<0.001), an increased adduction moment in the shoulder (G1 vs G3 p<0.001; G1 vs G4 p<0.01; G2 vs G3 and G4 p<0.05) and the constancy of the moments of force of the wrist the fact that they reached their lowest values in the tetraplegic groups. This pattern may increase the risk of developing upper limb overuse injuries in tetraplegic subjects. PMID- 20541761 TI - In vivo estimation of the short-range stiffness of cross-bridges from joint rotation. AB - Short-range stiffness (SRS) is a mechanical property of muscles that is characterized by a disproportionally high stiffness within a short length range during both lengthening and shortening movements. SRS is attributed to the cross bridges and is beneficial for stabilizing a joint during, e.g., postural conditions. Thus far, SRS has been estimated mainly on isolated mammalian muscles. In this study we presented a method to estimate SRS in vivo in the human wrist joint. SRS was estimated at joint level in the angular domain (Nm/rad) for both flexion and extension rotations of the human wrist in nine healthy subjects. Wrist rotations of 0.15rad at 3rad/s were imposed at eight levels of voluntary contraction ranging from 0 to 2.1Nm by means of a single axis manipulator. Flexion and extension SRS of the wrist joint was estimated consistently and accurately using a dynamic nonlinear model that was fitted onto the recorded wrist torque. SRS increased monotonically with torque in a way consistent with previous studies on isolated muscles. It is concluded that in vivo measurement of joint SRS represents the population of coupled cross-bridges in wrist flexor and extensor muscles. In its current form, the presented technique can be used for clinical applications in many neurological and muscular diseases where altered joint torque and (dissociated) joint stiffness are important clinical parameters. PMID- 20541762 TI - Direct measurement of power during one single sprint on treadmill. AB - We tested the validity of an instrumented treadmill dynamometer for measuring maximal propulsive power during sprint running, and sought to verify whether this could be done over one single sprint, as shown during sprint cycling. The treadmill dynamometer modified towards sprint use (constant motor torque) allows vertical and horizontal forces to be measured at the same location as velocity, i.e. at the foot, which is novel compared to existing methods in which power is computed as the product of belt velocity and horizontal force measured by transducers placed in the tethering system. Twelve males performed 6s sprints against default, high and low loads set from the motor torque necessary to overcome the friction due to subjects' weight on the belt (default load), and 20% higher and lower motor torque values. Horizontal ground reaction force, belt velocity, propulsive power and linear force-velocity relationships were compared between the default load condition and when taking all conditions together. Force and velocity traces and values were reproducible and consistent with the literature, and no significant difference was found between maximal power and force-velocity relationships obtained in the default load condition only vs. adding data from all conditions. The presented method allows one to measure maximal propulsive power and calculate linear force-velocity relationships from one single sprint data. The main novelties are that both force and velocity are measured at the same location, and that instantaneous values are averaged over one contact period, and not over a constant arbitrary time-window. PMID- 20541763 TI - Individual-specific muscle maximum force estimation using ultrasound for ankle joint torque prediction using an EMG-driven Hill-type model. AB - EMG-driven models can be used to estimate muscle force in biomechanical systems. Collected and processed EMG readings are used as the input of a dynamic system, which is integrated numerically. This approach requires the definition of a reasonably large set of parameters. Some of these vary widely among subjects, and slight inaccuracies in such parameters can lead to large model output errors. One of these parameters is the maximum voluntary contraction force (F(om)). This paper proposes an approach to find F(om) by estimating muscle physiological cross sectional area (PCSA) using ultrasound (US), which is multiplied by a realistic value of maximum muscle specific tension. Ultrasound is used to measure muscle thickness, which allows for the determination of muscle volume through regression equations. Soleus, gastrocnemius medialis and gastrocnemius lateralis PCSAs are estimated using published volume proportions among leg muscles, which also requires measurements of muscle fiber length and pennation angle by US. F(om) obtained by this approach and from data widely cited in the literature was used to comparatively test a Hill-type EMG-driven model of the ankle joint. The model uses 3 EMGs (Soleus, gastrocnemius medialis and gastrocnemius lateralis) as inputs with joint torque as the output. The EMG signals were obtained in a series of experiments carried out with 8 adult male subjects, who performed an isometric contraction protocol consisting of 10s step contractions at 20% and 60% of the maximum voluntary contraction level. Isometric torque was simultaneously collected using a dynamometer. A statistically significant reduction in the root mean square error was observed when US-obtained F(om) was used, as compared to F(om) from the literature. PMID- 20541764 TI - Two-dimensional liquid chromatography of diblock copolymers: simulation at various adsorption interaction conditions. AB - Diblock copolymers, which are heterogeneous in both molar mass and composition, can be fully characterized by using two-dimensional chromatography. Since the size-exclusion, the adsorption, and the critical interaction based modes of chromatography are possible for each of the polymers A and B, this leads to a variety of options for 2D-chromatography of copolymers AB. Using the theory of chromatography of block copolymers, 2D-chromatograms are simulated that correspond to the most interesting of these options. Orthogonal 2D-chromatograms are expected, if in the 1st dimension the critical condition is created for A, while in the 2nd dimension--for B. The situations, where A and B are both adsorbable, as well as those where the conditions of adsorption for A and SEC for B are created, are also considered. In particular, it is shown that the 2nd dimension combination of the critical condition for A and SEC--for B is preferable than that with SEC condition for both A and B. The simulated 2D chromatograms of low- and high molar mass diblock copolymers, as well as of copolymers with one short block are compared with the reported real ones; it is concluded that the corresponding virtual and real 2D-chromatograms are qualitatively very similar. PMID- 20541765 TI - Screening of degradation products, impurities and precursors of chemical warfare agents in water and wet or dry organic liquid samples by in-sorbent tube silylation followed by thermal desorption-gas chromatography-mass spectrometry. AB - A standard method used by inspection teams of the Organisation for the Prohibition of Chemical Weapons (OPCW) for preparation of aqueous samples requires several extraction and derivatization steps. This results in tedious and time consuming on-site analysis. A simple thermal desorption-gas chromatography mass spectrometry (TD-GC-MS) method was developed to analyse for a broad range of degradation products, impurities and precursors of chemical warfare agents (CWA) in water solutions and wet or dry organic liquid samples. The method is fast, sensitive, requires only microliter volumes of sample and enables the simultaneous determination of a wide range of compounds with widely differing polarity, volatility and reactivity. The applicability of the method was demonstrated by successful analysis of five OPCW Official Proficiency Test samples. PMID- 20541766 TI - Supercritical fluid extraction of microbial phospholipid fatty acids from activated sludge. AB - Supercritical carbon dioxide (scCO2) extraction was applied for the determination of microbial phospholipid fatty acids (PLFA) in activated sludge. Quantification was performed by using gas chromatography-mass spectrometry (GC-MS). The highest extraction yields of PLFA, at a concentration of 7.28 nmol/mg-dry activated sludge, was obtained at a temperature of 80 degrees C, pressure of 25 MPa and 10% (v/v) methanol for a 15-min extraction time. ScCO2 extraction results obtained in these conditions were comparable with those obtained by liquid organic solvent extraction (LSE) based on diversity and equalibility indices. The repeatability test showed that the relative standard deviation values were less than 13%. The experimental results show that the scCO2 extraction saves time and uses much less organic solvent. In addition, scCO2 extraction is a promising and alternative method for the analysis of microbial community structure in environmental assessment using the PLFA profile. PMID- 20541767 TI - Proteomic characterization of donkey milk "caseome". AB - At present, compared with bovine milk, the characterization of donkey milk caseins is at a relatively early stage progress, and only limited data are related to its genetic polymorphism. In this work, the heterogeneity of donkey caseome was investigated using a proteomic approach, based on one- (PAGE, UTLIEF) and two-dimensional (PAGE-->UTLIEF) electrophoresis, stained with either Coomassie Brilliant Blue or specific polyclonal antibodies, and structural MS analysis. These combined methodologies allowed the contemporary identification of donkey alpha(s1), alpha(s2), beta and kappa-CN with their related heterogeneity due to phosphorylation (alpha(s1), alpha(s2) and beta-CN), glycosylation (kappa CN) and incorrect splicing of RNA in mRNA (deleted forms of alpha(s1)-CN and beta CN). The results achieved showed 11 components for kappa-CN, six phosphorylated components for beta and alpha(s1)-CN and three main phosphorylated components for alpha(s2)-CN, each accounting for 10, 11 and 12 P/mole. At this regard, for the first time, the primary structure of the expressed protein corresponding to the only available donkey alpha(s2)-CN cDNA sequence was determined. Furthermore beta CN was found in homozygous and heterozygous state for the occurrence of a genetic beta-CN variant having a MW value 28 mass units higher than the common beta-CN phenotype. PMID- 20541768 TI - Sociolinguistic awareness and false belief in young Cantonese learners of English. AB - In this study, we examined whether sociolinguistic awareness and false belief were uniquely related in 3- and 4-year-old Cantonese-speaking children learning English as a second language. The English-use background of these children varied so that they possessed sociolinguistic awareness to different degrees. Results indicated that sociolinguistic awareness predicted false belief uniquely after controlling for age, nonverbal intelligence, English vocabulary, and family income for both the second language learners and the more balanced bilinguals. The group difference in false belief was adequately explained by the corresponding difference in sociolinguistic awareness over and above the other variables. Such findings provide evidence for the claim that false belief understanding is critically related to sociolinguistic awareness, which in turn is influenced by how a second language is learned. PMID- 20541769 TI - Age, sex and first treatment of schizophrenia in a population cohort. AB - OBJECTIVE: Schizophrenia affects men more than women, but this may not be true at all ages. This study examines the incidence of first hospitalization for treatment of schizophrenia in each sex over different ages. METHODS: We compared the incidence of first admission for treatment in a cohort of 46,388 males and 43,680 females followed from birth until ages 29-41, using life tables and proportional hazards methods. RESULTS: Life table estimates of cumulative incidence by age 40 were 1.44% in males and 0.86% in females. For over all ages the relative risk (RR) in males was 1.6 (95% confidence limits=1.4-1.8) compared with females. Before age 17 there was no significant difference between the sexes (RR=0.86, 0.56-1.3). Excess risk in males was observed only from age 17 (RR=1.7, 1.4-1.9). There was no evidence of the incidence in females catching up with that in males, during the 30s. CONCLUSION: In this population, there was a significant change, over age, in the relative incidence of first hospitalization for schizophrenia between the sexes; the excess incidence in males first developed at age 17. PMID- 20541770 TI - Peripheral biomarkers and illness activity in bipolar disorder. AB - Recent evidence suggests that peripheral markers related to oxidative stress, inflammation and neurotrophins may be altered during mood episodes in bipolar disorder. These can be seen as proxies of peripheral toxicity or markers of illness activity. Here we report an en bloc assessment of a set of previously described biomarkers in different mood states (n = 60) as well as in healthy subjects (n = 80). To make the point that these are ominous changes, we obtained the same measures from a group of septic patients (n = 15) as a "positive" control group. In this sample, we measured serum levels of brain derived neurotrophic factor, neurotrophin 3, tumor necrosis factor alpha, interleukin 6, interleukin 10, total reactive antioxidant potential, thiobarbituric acid reactive substances and protein carbonyl content. Several of the markers discriminated between the bipolar and control groups, especially when patients were in acute episodes. In some cases, toxicity was as high in bipolar disorder as that seen in patients with sepsis. We believe these findings highlight the potential of using biomarkers to assess illness activity in bipolar disorder. PMID- 20541771 TI - Jumping, lying, wandering: analysis of suicidal behaviour patterns in 1,004 suicidal acts on the German railway net. AB - Current knowledge on behavioural patterns and personal characteristics of subjects who choose the railway as means of suicide is sparse. The aim of this study was to determine the frequency of three distinct behaviour patterns (jumping, lying, wandering) in railway suicides and to explore associated variables. Cases were derived from the National Central Registry of person accidents on the German railway net covering the period from 2002 to 2006. A retrospective analysis of registry protocols of all 4127 suicidal acts allowed classification of behaviour patterns in 1004 cases. Types of suicidal behaviour occurred with nearly equal frequencies; jumping in 32.2%, lying in 32.6% and wandering in 34.2% of cases. Age and sex were not associated with type of suicidal behaviour. The proportion of jumping was highest during 9:01 am to 6:00 pm while at night, lying was used most frequently. Jumping predominated in the station area, while lying and wandering on the open track. Fatality was highest in liers and lowest in jumpers. The frequency of jumping decreased during the study period by 12.6% (p < .05). These findings may help to elucidate differential risk features of this highly lethal suicide method. PMID- 20541773 TI - Lower prevalence of sleep disturbances in familial versus sporadic Parkinson's disease: a questionnaire based study. AB - Parkinson's disease (PD) is a debilitating neurodegenerative disorder affecting 1.5% of all above 55 years of age. Sleep related complaints are commonly reported in patients with PD and may form an important determinant of their quality of life. Interactions among genetic and environmental factors may play an important role in the development of and also explain the difference in sleep disturbances in these groups. The aim of our study was to compare the prevalence and distribution of various sleep disorders in patients with familial PD versus those with sporadic PD. Consecutive patients with sporadic and familial PD were evaluated with detailed clinical history; examination and questionnaire on sleep related problems over a two year period. The study included a total of 134 patients, 104 had sporadic PD and 30 had familial PD. Insomnia and rapid eye movement (REM) sleep behavior disorders (RBD) were significantly common in sporadic group (26.9%and 25%) as compared to familial group (3.3%and 0%, P=0.006 and 0.002) despite comparable disease severity scores and duration of disease (P=0.116). Clinical RBD and other sleep disturbances are much less common in patients with familial PD as compared with those with sporadic PD. PMID- 20541772 TI - Progressive alterations of the auditory association areas in young non-psychotic offspring of schizophrenia patients. AB - BACKGROUND: Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis. AIMS: We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures. METHODS: Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within subject factors and gender and study group as between-subject factors. RESULTS: Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left-right/left + right * 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness. CONCLUSIONS: Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia. PMID- 20541774 TI - CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity. AB - BACKGROUND: Anti-aquaporin-4 (AQP4) antibody targets perivascular astrocyte foot processes, which contain abundant angiotensinogen, a precursor of angiotensin II, angiotensin-converting enzyme (ACE) and ACE2. OBJECTIVE: To disclose any abnormality in the intrathecal angiotensin II metabolic pathway in Japanese patients with neuromyelitis optica (NMO) or NMO spectrum disorders (NMOs) and positive for anti-AQP4 antibody. METHODS: We measured CSF angiotensin II, ACE and ACE2 levels in 15 anti-AQP4 antibody-positive patients with NMO or NMOs, 21 anti AQP4 antibody-negative multiple sclerosis (MS) patients, 32 patients with other neurological diseases (OND) and 24 non-neurologic controls, using established ELISAs. RESULTS: CSF angiotensin II levels were lower in patients with NMO/NMOs (2.01+/-1.82 pg/ml) and those with MS (3.15+/-1.67 pg/ml) than in the OND (5.41+/ 2.34 pg/ml) and control groups (6.71+/-2.65 pg/ml) (P(corr)<0.005). The difference in CSF angiotensin II levels between NMO/NMOs and MS patients was nearly significant (P(uncorr)=0.052). In NMO/NMOs and MS patients, angiotensin II levels were negatively correlated with CSF/serum albumin ratio (P<0.05). ACE levels in CSF were lower in patients with NMO/NMOs (34.3+/-5.61 ng/ml) than in MS patients (42.5+/-8.19 ng/ml, P(corr)=0.035) and controls (44.7+/-4.02 ng/ml, P(corr)<0.0003) while ACE2 levels were lower in NMO/NMOs (1.13+/-0.49 ng/ml) and MS (1.75+/-0.86 ng/ml) patients than in controls (2.76+/-0.23 ng/ml, P(corr)<0.001 for both). CONCLUSION: CSF angiotensin II, ACE, and ACE2 levels are decreased in NMO/NMOs patients with anti-AQP4 antibody, reflecting severe destruction of perivascular astrocytes. PMID- 20541775 TI - Dysregulated neurotrophin mRNA production by immune cells of patients with relapsing remitting multiple sclerosis. AB - Recent studies have suggested a neuroprotective activity of the lesion infiltrating immune cells in multiple sclerosis (MS) by secretion of neurotrophins. We had earlier reported that immune cells from relapsing remitting MS (RR-MS) patients secrete low levels of brain-derived neurotrophic factor (BDNF), and that its secretion is dysregulated after CD40 stimulation. Here, we measured mRNA levels for BDNF, NT3 and NGF-beta mRNA in unstimulated PBMCs and found levels lower in untreated RR-MS patients than in healthy controls (HC). T cell stimulation with anti-CD3/CD28 mAb up-regulated neurotrophin mRNA expression in untreated RR-MS patients and not in HC, whereas stimulation of PBMCs with anti CD40 mAb up-regulated neurotrophin mRNA expression in HC and not in RR-MS patients. Further cellular analyses of the production of the neurotrophin mRNA in individual cells revealed that T cells were the main producers of the neurotrophin mRNA in RR-MS patients, and that monocytes were the main producers of NT3 and NGF-beta mRNA in HC. BDNF mRNA was similarly produced in monocytes and T cells in the HC group. The cytokines TNF-alpha and IL-17 up-regulated the expression of neurotrophin mRNA in HC but not in RR-MS patients. The neuroprotective activity of PBMCs appeared to be dysregulated in untreated patients with RR-MS, while the differences between the IFN-beta-treated RR-MS patients and the HC were smaller. PMID- 20541776 TI - An empirical analysis of IOPCF oil spill cost data. AB - This paper reports on recent analysis of oil spill cost data assembled by the International Oil Pollution Compensation Fund (IOPCF). Regression analyses of clean-up costs and total costs have been carried out, after taking care to convert to current prices and remove outliers. In the first place, the results of this analysis have been useful in the context of the ongoing discussion within the International Maritime Organization (IMO) on environmental risk evaluation criteria. Furthermore, these results can be useful in estimating the benefit of regulations that deal with the protection of marine environment and oil pollution prevention. PMID- 20541777 TI - [Improving diagnosis? New sap for an old tree]. PMID- 20541778 TI - [Why radiofrequency for the treatment of primary lung tumors?]. PMID- 20541779 TI - [Severe infections in a cohort of patients with systemic lupus erythematosus]. AB - BACKGROUND AND OBJECTIVE: To study severe infectious complications in a cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHOD: Retrospective study of 705 patients followed from January 1980 to January 2008. Data are expressed in percentages. RESULTS: The frequency of severe infectious was 38.6%. The etiology was bacterial 54.4%, viric 30.4% and opportunist in 15.2% patients. Involved organs were: Lung 38.2%, kidney 48.9%, central nervous system 43%. 43.75% patients received pulsed ciclofosfamide therapy and 88.6% received glucocorticoids (39.7% pulsed). The mortality was 27.7%. CONCLUSIONS: At present, infection is an important cause of mortality in patients with SLE. Early diagnosis of infectious complications is very important in SLE. PMID- 20541780 TI - Cyclic fatty acyl glycosides in the glandular trichome exudate of Silene gallica. AB - Chemical investigation of the glandular trichome exudate from Silene gallica L. (Caryophyllaceae) resulted in isolation of 10 cyclic fatty acyl glycosides (gallicasides A-J). The cyclic structures were characterized by a glycosidic linkage of the glucose moiety to either the C-12 or the C-13 position of the octadecanoyl moiety, and by an ester linkage between the C-2 hydroxy group of the glucose moiety and the carboxyl group of the oxygenated octadecanoic acid. The structures of the cyclic fatty acyl glycosides were further distinguished from one another by acetylation and/or malonylation on the glucose moiety. Of these compounds, the 1,2'-cyclic ester of 12(R)-(6-O-acetyl-3-O-malonyl-beta-D glucopyranosyloxy)octadecanoic acid (gallicaside J) was the most abundant (30.7%). These secondary metabolites were found specifically in the glandular trichome exudate rather than in other aerial parts. PMID- 20541781 TI - Analysis of the cellulose synthase genes associated with primary cell wall synthesis in Bambusa oldhamii. AB - The synthesis of cell wall polysaccharides is highly active in rapidly growing bamboo shoots. We cloned a set of BoCesA cDNAs that encode cellulose synthase from bamboo (Bambusa oldhamii) and investigated the expression patterns of the BoCesA2, BoCesA5, BoCesA6 and BoCesA7 genes. The four BoCesA genes were differentially expressed in the different parts of growing bamboo shoots, in various organs, and in multiple shoots that were cultured in vitro. They were down-regulated by alpha-naphthaleneacetic acid and differentially affected by thidiazuron in the multiple shoots. In situ RT-PCR analyses demonstrated that BoCesA2, BoCesA5, BoCesA6, and BoCesA7 mRNAs were present throughout the base and the internode regions of the etiolated shoots that emerged from pseudorhizomes, and in the internode regions of the juvenile branch shoots that emerged from nodes of mature bamboo culms; however, the expression of the four genes in the lignified internode of the branch shoot was predominantly detected in the center of the vascular bundles. Our results for cDNA cloning, expression analyses, and phylogenetic analysis suggest that the 10 BoCesA genes cloned from the etiolated bamboo shoots participate in cellulose synthesis in the primary cell walls of the growing bamboo, and that at least three additional BoCesA genes involved in cellulose synthesis in the secondary walls may be present in the bamboo genome. The expressions of BoCesA genes may be under fine control in response to the various developmental stages and physiological conditions of bamboo. PMID- 20541782 TI - Effect of cold temperatures on mortality in Cantabria (Northern Spain): a case crossover study. AB - OBJECTIVES: To determine the impact of low temperatures on mortality in a Spanish region that includes both rural and urban areas. STUDY DESIGN: Case-crossover study. METHODS: A case-crossover study was conducted on the impact of cold temperatures on mortality in Cantabria, a Spanish region which includes both rural and urban areas, in 2004-2005. Odds ratios for several cold weather indicators were estimated using conditional logistic regression, adjusting for humidity and wind speed. Zero- to 6-day lags in the temperature effect were considered. RESULTS: Temperatures lower than the 5th percentile were strongly associated with mortality compared with temperatures above the 5th percentile (OR 3.40, 95% confidence interval 2.95-3.93 for 6-day lag). All temperature indices show a negative association with mortality; for instance, the maximum temperature had ORs of 0.71, 0.58, 0.32 and 0.16 for Quintiles 2-5 (reference: Quintile 1). This effect was common to all age groups. CONCLUSION: Cold weather is strongly associated with mortality in small cities and rural areas. PMID- 20541783 TI - [Unusual location of an inflammatory myofibroblastic tumor: a case report]. AB - Inflammatory myofibroblastic tumor is a rare lesion that is usually located in the lung. The most commonly reported extrapulmonary locations are the mesentery and the retroperitoneum. We report the case of an 8-year-old girl with an inflammatory myofibroblastic tumor in an unusual location. The patient was referred to our center for suspected complicated appendicitis. Abdominal ultrasonography detected ileoileal intussusception with a mass in the distal portion. Emergency laparotomy confirmed ileoileal intussusception secondary to an intraluminal tumor. Histologic study revealed the mass was an inflammatory myofibroblastic tumor. Inflammatory myofibroblastic tumors are rare mesenchymal masses usually found in children. When located in the abdomen, they can mimic malignant lesions like lymphomas, sarcomas, or metastases. The cause and prognosis of inflammatory myofibroblastic tumors are unknown. PMID- 20541784 TI - [Delayed diagnosis of a diaphragmatic hernia in a patient on mechanical ventilation]. AB - Traumatic rupture of the diaphragm is uncommon. Its early diagnosis is a challenge in diagnostic imaging. We present the case of a male multiple trauma patient in whom a left diaphragmatic hernia was discovered on weaning from mechanical ventilation 23 days after admission. We discuss the key imaging features of diaphragmatic rupture based on its physiopathology and thoracoabdominal pressure gradients. Very few cases of radiologically documented diaphragmatic hernias masked by mechanical ventilation have been reported. PMID- 20541785 TI - Pancreatic carcinoma cells are susceptible to noninvasive radio frequency fields after treatment with targeted gold nanoparticles. AB - BACKGROUND: Gold and carbon nanoparticles absorb nonionizing radio frequency (RF) energy and release heat. Solid gold nanoparticles are delivered to cancer cells via conjugation with targeting antibodies. Here, 20-nm gold particles were conjugated to cetuximab, which is an epidermal growth factor receptor-1 (EGFR-1) antibody. METHODS: A pancreatic carcinoma cell line that highly expresses EGFR-1, Panc-1, and Cama-1, which is a breast carcinoma cell line that minimally expresses EGFR-1, were treated with 100-nmol/L cetuximab-conjugated gold nanoparticles for 3 h (n = 4). Thirty-six hours later, the dishes were placed in an RF field with a generator power of 200 W for 5 min. After another 36 h, cell injury and death were evaluated with flow cytometry. RESULTS: The targeted cell line Panc-1 had a viability of 46% +/- 12%, whereas the Cama-1 cell had a viability of 92% +/- 2% after RF field exposure (P < .008). Transmission electron microscopy showed gold nanoparticle uptake in Panc-1 cells but negligible uptake by Cama-1 cells. Nontargeted cells do not internalize a sufficient amount of antibody-conjugated gold nanoparticles to induce injury in a noninvasive RF field. CONCLUSION: This technique could be useful in cancer treatment if a cancer specific antibody is used to localize gold nanoparticles to malignant cells. PMID- 20541786 TI - Plant-feeding insects harbor double-stranded RNA viruses encoding a novel proline alanine rich protein and a polymerase distantly related to that of fungal viruses. AB - Novel double-stranded RNAs (approximately 8 kbp) were isolated from threecornered alfalfa hopper (Spissistilus festinus) and beet leafhopper (Circulifer tenellus), two plant-feeding hemipteran insect pests. The two new viruses, designated Spissistilus festinus virus 1 (SpFV1) and Circulifer tenellus virus 1 (CiTV1), do not appear to be encapsidated in conventional virions and shared a genome organization similar to that of several unclassified fungal viruses. SpFV1 and CiTVl encode a proline-alanine rich protein (PArp) and an RNA-directed RNA polymerase (RdRp). Expression of the 3'-proximal RdRp ORF appears to result from 1 translational frameshifting of the PArp ORF. Phylogenetic analysis of the RdRp indicated that SpFV1 and CiTV1 were most closely related to each other and the unclassified plant virus Cucurbit yellows associated virus, and more distantly related to the unclassified fungal dsRNA viruses Phlebiopsis gigantea virus 2 and Fusarium graminearum virus 3. PMID- 20541787 TI - Microbial reduction of uranium under iron- and sulfate-reducing conditions: Effect of amended goethite on microbial community composition and dynamics. AB - There is a growing need for a better understanding of the biogeochemical dynamics involved in microbial U(VI) reduction due to an increasing interest in using biostimulation via electron donor addition as a means to remediate uranium contaminated sites. U(VI) reduction has been observed to be maximized during iron reducing conditions and to decrease upon commencement of sulfate-reducing conditions. There are many unknowns regarding the impact of iron/sulfate biogeochemistry on U(VI) reduction. This includes Fe(III) availability as well as the microbial community changes, including the activity of iron-reducers during the uranium biostimulation period even after sulfate reduction becomes dominant. Column experiments were conducted with Old Rifle site sediments containing Fe oxides, Fe-clays, and sulfate rich groundwater. Half of the columns had sediment that was augmented with small amounts of Fe(III) in the form of (57)Fe-goethite, allowing for a detailed tracking of minute changes of this added phase to study the effects of increased Fe(III) levels on the overall biostimulation dynamics. Mossbauer spectroscopy showed that the added (57)Fe-goethite was bioreduced only during the first thirty days of biostimultuion, after which it remained constant. Augmentation with Fe(III) had a significant effect on the total flux of electrons towards different electron acceptors; it suppressed the degree of sulfate reduction, had no significant impact on Geobacter-type bacterial numbers but decreased the bacterial numbers of sulfate reducers and affected the overall microbial community composition. The addition of Fe(III) had no noticeable effect on the total uranium reduction. PMID- 20541788 TI - Lentic Basommatophora molluscs and hygrophilous land snails as indicators of habitat and climate in the Early-Middle Pleistocene (0.78 Ma) at the site of Gesher Benot Ya'aqov (GBY), Israel. AB - The lentic Basommatophora molluscs and hygrophilous land snails of the Early Middle Pleistocene site of Gesher Benot Ya'aqov (GBY), 0.78 Ma, crossed by the Matuyama-Brunhes chron boundary [MBB] were studied in order to reconstruct their specific habitats and possible reactions to climate change along the site sequence. Samples of equal sizes from 27 of the 46 layers along the 100 k.yr. time-span of the site were examined. About 2000 specimens of 21 lentic and hygrophilous species belonging to five families: Planorbidae (11), Lymnaeidae (6), Acroloxidae (2), Carychiidae (1) and Succineidae (1) were identified. The family with the largest biodiversity is the Planorbidae and of these, the most abundant species include Gyraulus piscinarum (937), Planorbarius corneus (210) and Radix labiata (160). The recent known zoogeographic origin of 81% of the species is Palaearctic and Holarctic. The MBB coincides with remarkable environmental changes reflected in molluscs, other faunal and floral elements and stable isotopes. The Planorbidae and Lymnaeidae reach greater abundance (90% and 80% of their assemblages, respectively) pre-MBB, while Acroloxidae, Succineidae and Carychiidae are more abundant (74%, 64% and 90%) post-MBB. Our data indicate that GBY molluscs show a two-phase pattern (shallow and deep lake) in each of the five defined cycles. Their numbers increase during the shallow water phases, thus the site climate changes from cold and humid in the oldest layers, to dry and cold up to the MBB and few succeeding layers. Between cycles 2 and 3, post-MBB, we see a short period of warm and humid climate that enables the influx of African and Asian elements. At the same time, cold climate species of Euro Siberian and Palaearctic origin disappear. The succeeding layers indicate a cooler and humid climate. Finally, the sequence indicates deep water in the oldest layers and desiccation towards MBB and deeper water post-MBB. PMID- 20541789 TI - Possible paleohydrologic and paleoclimatic effects on hominin migration and occupation of the Levantine Middle Paleolithic. AB - This paper explores the impact of major glacial/interglacial paleohydrologic variations in the Middle-Paleolithic Levant on hominin migration and occupation. The climatic reconstruction is based primarily on the most straight-forward paleohydrologic records recently published. These terrestrial proxies convey direct paleoenvironmental signals of effective precipitation and aquifer recharge. The two main proxies are temporal changes of terminal lake levels in the Dead Sea basin and periods of deposition or non-deposition of speleothems. Other records, such as stable isotopes, if interpreted correctly, correspond well with these two direct proxies. All the records consistently indicate that the last two glacial periods in the central Levant were generally wet and cool, while the last two interglacials were dry and warm, so more water was available for the ecosystem and thus hominins during glacial periods than during interglacials. Some proxies indicate that the higher precipitation/evaporation ratio during glacial periods involved higher precipitation rather than only reduced evaporation. Beyond the general mean glacial/interglacial climate suggested here, variations occurred at all temporal scales throughout glacial or interglacial periods. In the Sahara-Negev arid barrier, moister conditions occurred during Marine Isotope Stage (MIS) 6a-5e, when Anatomically Modern Humans apparently migrated out of Africa. We suggest that this migration, as well as the later Neanderthal expansion from Southeast Europe or the Anatolian plateau into the Levant during early MIS 4, could be facilitated by the observed major climatic variations. PMID- 20541790 TI - Role of hormonal and environmental factors on early incidence of breast cancer in Iran. AB - Although the probability of having breast cancer increases with the age in general, this malignancy affects Iranian women at least one decade younger than their counterparts in other countries. However the underlying risk factors for the discrepancy have not been identified. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This study was aimed to compare the interactions between AhR and other fundamental genes (p53, K Ras, ER, PgR) in a clinical setting. To conduct the immunohistochemical studies using appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinoma, 29 postmenopausal invasive ductal carcinoma and 30 breast fibroadenoma were selected retrospectively from 2004 to 2007 in the pathology department of Imam Khomeini hospital complex of Tehran University of Medical Sciences . Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental induced tumors. AhR overexpression contributed to ER-/PgR-immunophenotype in young/premenopausal patients but the same pattern was not observed in benign and postmenopausal malignant tumors. It seems that early incidence of breast cancer in Iran is the result of interactions between hormonal and environmental factors. PMID- 20541791 TI - Comparison of symptoms, treatment, and outcomes of coronary artery disease among rheumatoid arthritis and matched subjects undergoing percutaneous coronary intervention. AB - OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased prevalence of coronary artery disease (CAD). We investigated the presenting symptoms of CAD, coronary anatomy (single versus multi-vessel CAD), and treatment among a group of subjects undergoing percutaneous coronary intervention (PCI) with angioplasty and/or stenting. METHODS: We evaluated a retrospective cohort of 43 RA subjects and 43 matched non-RA subjects undergoing PCI at 2 academic referral centers. RA subjects were matched to non-RA subjects on age, gender, history of coronary artery bypass grafting, date of PCI, and interventional cardiologist. We compared cardiac risk factors, presentation, treatment, and outcomes. RESULTS: The mean age of the study cohort was 71 +/- 10 years, and the distribution of traditional cardiac risk factors was similar in the subjects with RA compared with the matched non-RA subjects (all P values > 0.05). Seventy-four percent of subjects with RA compared with 67% of those without RA presented with an acute coronary syndrome before PCI (P = 0.48). All subjects in this cohort undergoing PCI had at least 1 stenosis in a major epicardial vessel and similar percentages of subjects with RA (44%) and without RA (40%) had multi-vessel CAD (P = 0.66). The administration of cardiac medications both at PCI and at hospital discharge was not different among subjects with RA compared with matched non-RA subjects. CONCLUSIONS: Among this cohort with significant CAD undergoing PCI, clinical characteristics, presentation, severity of CAD, treatment modalities, and outcomes were similar in subjects with RA and well-matched non-RA subjects. PMID- 20541792 TI - Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review. AB - OBJECTIVES: To review and summarize published information on the use, effectiveness, and adverse effects of danazol in patients with systemic lupus erythematosus (SLE). METHODS: A MEDLINE search from January 1950 to July 2009 was conducted using 2 search strategies retrieving 51 and 62 references, respectively. We also searched 2 standard reference textbooks and bibliographies of the 38 articles selected. RESULTS: Of the 38 articles selected, there were 19 case series/reports with a total of 153 patients, including 2 prospective trials of 7 and 16 patients, respectively, and 1 randomized controlled trial of 40 patients. Danazol has been used successfully in the treatment of hematologic manifestations of SLE such as thrombocytopenia, Evan's syndrome, autoimmune hemolytic anemia, and a case of red cell aplasia. Thirteen patients responded to danazol after failing splenectomy. There is limited information on the use of danazol in nonhematologic manifestations of SLE. Adverse effects were generally tolerable but high doses may produce undesirable side effects for female patients. CONCLUSIONS: Danazol is a useful drug in the treatment of SLE patients, especially in patients with refractory thrombocytopenia, autoimmune hemolytic anemia, and premenstrual flares, and in some mild nonhematologic manifestations of SLE. It appears to be relatively well tolerated, safe, and efficacious. PMID- 20541793 TI - Measurement of procoagulant platelet subpopulations in whole blood: development of an assay for population-based studies. PMID- 20541794 TI - Evaluation of a post-operative thrombin inhibitor replacement protocol to reduce haemorrhagic and thrombotic complications after paediatric liver transplantation. AB - INTRODUCTION: Bleeding and thrombotic complications contribute to morbidity and mortality following paediatric orthotopic liver transplantation (OLT). However, the pathophysiology of haemostasis during paediatric OLT is not well understood. This report consists of two complimentary studies examining the frequency of haemostatic complications before and after the introduction of a post-operative thrombin inhibitor replacement therapy protocol at a single institution. MATERIALS AND METHODS: A retrospective study of 40 patients who underwent 43 liver transplants between July 1992 and July 2002, identified bleeding to be the most frequent complication associated with OLT (30%), however thrombotic complications were also common (12.5%). In 2003, following a detailed analysis of haemostatic profiles of children undergoing OLT, a thrombin inhibitor replacement protocol was introduced. A prospective clinical outcome audit was undertaken from April 2003 to September 2008 to determine the effect of the new protocol on haemostasis. RESULTS: Commencement of the thrombin inhibitor replacement protocol significantly reduced the incidence of thrombosis (from 5 to 1, p<0.05), graft loss (from 4 to none, p<0.05), mortality due to thrombosis or bleeding (from 3 to none, p<0.05) and was associated with a 50% reduction in frequency of major bleeding. CONCLUSION: In conclusion, the introduction of a post-operative thrombin inhibitor replacement therapy protocol following paediatric OLT significantly improved haemostasis-related morbidity and mortality outcomes in children. PMID- 20541795 TI - The heart of Santa Rosa. PMID- 20541797 TI - Bioengineering endothelialized neo-corneas using donor-derived corneal endothelial cells and decellularized corneal stroma. AB - Corneal transplantation is a common transplant procedure performed to improve visual acuity by replacing the opaque or distorted host tissue by clear healthy donor tissue. However, its clinical utility is limited due to a lack of high quality donor corneas. Bioengineered neo-corneas, created using an expandable population of human donor-derived corneal endothelial cells (HCEC), could address this current shortage. The objectives of this study were to establish HCEC isolation and culture protocols and to investigate the feasibility of bioengineering corneal tissue constructs by seeding the cells on decellularized human corneal stroma. HCECs were removed from the discarded corneas of eye donors by enzymatic digestion. Cells were expanded and evaluated for their expression of Na(+)/K(+)-ATPase and zona occludens-1 (ZO-1). Donor corneal stromas were cut to 120-200 microm thickness slices using a microtome and then decellularized. Extracellular matrix components and mechanical properties of the scaffolds were measured after decellularization. To engineer neo-corneas, 130 HCEC/mm(2) were seeded on decellularized human corneal stromas. The resulting constructs were placed in growth medium for 14 days and then analyzed using scanning electron microscopy (SEM), histology, and immunocytochemistry. Seeded cells retain expression of the functional markers Na(+)/K(+)-ATPase and ZO-1 and constructs have biomechanical properties similar to those of normal corneas. These results indicate that construction of neo-corneas, using HCECs derived from discarded donor corneas and decellularized thin-layer corneal stromas, may create a new source of high quality corneal tissue for transplantation. PMID- 20541796 TI - Effect of media mixing on ECM assembly and mechanical properties of anatomically shaped tissue engineered meniscus. AB - This study investigated the hypothesis that controlled media mixing will enhance tissue formation and increase mechanical properties of anatomically-shaped tissue engineered menisci. Bovine meniscal fibrochondrocytes were seeded in 2% w/v alginate, cross-linked with 0.02 g/mL CaSO(4), and injected into molds of menisci. Engineered menisci were incubated for up to 6 weeks. A mixing media bioreactor was designed to ensure proper mixing of culture medium while protecting constructs from the spinning impeller. Impeller speeds were calibrated to produce Reynolds number (Re) of 0.5, 2.9, 5.8, 10.2, and 21.8. Constructs were divided a tested in confined compression and in tension to determine the equilibrium and tensile moduli, respectively. Media stimulation resulted in a 2-5 fold increase in mechanical properties and a 2-3 fold increase in matrix accumulation in constructs over 6 weeks in culture. Benefits from mixing stimulation for collagen accumulation and compressive modulus appeared to peak near Re 2.9, and decreased with increased mixing intensity. This study suggests that fluid mixing can be optimized to enhance mechanical properties of anatomically-shaped engineered constructs. PMID- 20541798 TI - Mechanical properties of DNA biofilms adsorbed on microcantilevers in label-free biodetections. AB - Biomolecule adsorption is a fundamental process in the design of biosensors. Mechanical/electrical/thermal properties of biofilms have great influences on biodetection signals. The double-stranded DNA (dsDNA) biofilm adhered on microcantilever is treated as a bending beam with a macroscopic elastic modulus in the viewpoint of continuum mechanics. Accounting for hydration force, electrostatic repulsion and conformational entropy, moment-angle diagrams of dsDNA biofilm in pure bending state are depicted with the help of the energy conservation law and a mesoscopic liquid crystal theory presented by Strey et al. An analytical model is provided to predict macroscopic elastic modulus of dsDNA biofilm as a function of nanoscopic properties of dsDNA, packing density, buffer salt concentration and etc. The parameters for microcantilever-DNA system are obtained by curve fitting with Stachowiak's experimental data based on a modified Stoney's formula. Elastic modulus grows exponentially with the enhancement of packaging density, but diminishes with the increase of buffer salt concentration, and its order is about 1 approximately 10 MPa. Conformational entropy is one of predominant factors considered in near-surface system whether in high or low salt consternation. PMID- 20541799 TI - The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation. AB - Delivery of nucleic acids with positively charged lipid nanoparticles ((+)NPs) is widely used as research reagents and potentially for therapeutics due to their ability to deliver nucleic acids into the cell cytoplasm. However, in most reports little attention has been made to their toxic effects. In the present study, we performed comprehensive analyses of the potential toxicity associated with (+)NPs. Mice treated with (+)NPs showed increased liver enzyme release and body weight loss compared to mice treated with neutral or negatively charged NPs ((-)NPs), suggesting hepatotoxicity. Intravenous administration of (+)NPs induced interferon type I response and elevated mRNA levels of interferon responsive genes 15-25-fold higher than neutral and (-)NPs in different subsets of leukocytes. Moreover, treatment with (+)NPs provoked a dramatic pro-inflammatory response by inducing Th1 cytokines expression (IL-2, IFN gamma and TNF alpha) 10 75-fold higher than treatment with control particles. Finally, we showed that activation of TLR4 might serve as the underlying mechanism for induction of an immune response when (+)NPs are used. These results suggest that a careful attention must be made when different types of (+)NPs are being developed as nanotherapeutics. PMID- 20541800 TI - Block-copolymer-stabilized iodinated emulsions for use as CT contrast agents. AB - The objective of this study was to develop radiopaque iodinated emulsions for use as CT blood pool contrast agents. Three hydrophobic iodinated oils were synthesized based on the 2,3,5-triiodobenzoate moiety and formulated into emulsions using either phospholipids or amphiphilic polymers, i.e. Pluronic F68 and poly(butadiene)-b-poly(ethylene glycol) (PBD-PEO), as emulsifiers. The size, stability and cell viability was investigated for all stabilized emulsions. Three emulsions stabilized with either lipids or PBD-PEO were subsequently tested in vivo as a CT blood pool contrast agent in mice. While the lipid-stabilized emulsions turned out unstable in vivo, polymer-stabilized emulsions performed well in vivo. In blood, a contrast enhancement of 220 Hounsfield Units (HU) was measured directly after intravenous administration of 520 mg I/kg. The blood circulation half-life of a PBD-PEO stabilized emulsion was approximately 3 h and no noticeable in vivo toxicity was observed. These results show the potential of above emulsions for use as blood pool agents in contrast enhanced CT imaging. PMID- 20541801 TI - Carbodiimide cross-linked amniotic membranes for cultivation of limbal epithelial cells. AB - In ophthalmic tissue engineering, amniotic membrane (AM) is one of the most prevalent natural matrices used for limbal epithelial cell (LEC) cultivation and transplantation. However, the application of AM as a scaffold is limited by its low biomechanical strength and rapid biodegradation. The present study reports the development of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) cross-linked AM as an LEC carrier. The collagenous tissue materials were modified with varying cross-linker concentrations (0-0.25 mmol EDC/mg AM) and were characterized by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), ninhydrin assays, electron microscopy, light transmission measurements, mechanical and in vitro degradation tests, as well as diffusion permeability and cell culture studies. Our results showed that chemical cross-linking approaches saturation at concentrations of 0.05 mmol EDC/mg AM. The formation of cross-links (i.e., amide bonds) in the samples treated with 0.05 mmol EDC/mg AM may cause significant aggregation of tropocollagen molecules and collagen microfibrils without affecting cell morphology of biological tissues. With the optimum concentration of 0.05 mmol EDC/mg AM, chemical cross-linker could significantly enhance the mechanical and thermal stability, optical transparency, and resistance to collagenase digestion. Continuous permeation of albumin through the cross-linked AM would be helpful to cell growth over the matrix surface. In addition, the EDC cross-linked samples were able to support LEC proliferation and preserve epithelial progenitor cells in vitro and in vivo. It is concluded that the AM cross-linked with 0.05 mmol EDC/mg AM may be a potential biomaterial for regenerative medicine. PMID- 20541802 TI - The biomechanical characteristics of the bone-periodontal ligament-cementum complex. AB - The relative motion between the tooth and alveolar bone is facilitated by the soft-hard tissue interfaces which include periodontal ligament-bone (PDL-bone) and periodontal ligament-cementum (PDL-cementum). The soft-hard tissue interfaces are responsible for attachment and are critical to the overall biomechanical efficiency of the bone-tooth complex. In this study, the PDL-bone and PDL cementum attachment sites in human molars were investigated to identify the structural orientation and integration of the PDL with bone and cementum. These attachment sites were characterized from a combined materials and mechanics perspective and were related to macro-scale function. High resolution complimentary imaging techniques including atomic force microscopy, scanning electron microscopy and micro-scale X-ray computed tomography (Micro XCT) illustrated two distinct orientations of PDL; circumferential-PDL (cir-PDL) and radial-PDL (rad-PDL). Within the PDL-space, the primary orientation of the ligament was radial (rad-PDL) as is well known. Interestingly, circumferential orientation of PDL continuous with rad-PDL was observed adjacent to alveolar bone and cementum. The integration of the cir-PDL was identified by 1-2 microm diameter PDL-inserts or Sharpey's fibers in alveolar bone and cementum. Chemically and biochemically the cir-PDL adjacent to bone and cementum was identified by relatively higher carbon and lower calcium including the localization of small leucine rich proteins responsible for maintaining soft-hard tissue cohesion, stiffness and hygroscopic nature of PDL-bone and PDL-cementum attachment sites. The combined structural and chemical properties provided graded stiffness characteristics of PDL-bone (E(r) range for PDL: 10-50 MPa; bone: 0.2 9.6 GPa) and PDL-cementum (E(r) range for cementum: 1.1-8.3 GPa), which was related to the macro-scale function of the bone-tooth complex. PMID- 20541803 TI - Mussel-inspired transformation of CaCO3 to bone minerals. AB - We report a mussel-inspired route to create carbonated bone hydroxyapatite from CaCO(3) vaterite microspheres. When catechol-containing dopamine, a biomimetic small molecule of mussel adhesive proteins, was incorporated during the mineralization of CaCO(3), the oxidative polymerization of dopamine stabilized the formation of spherical vaterite, the most unstable phase among CaCO(3) crystalline structures. Thus-formed vaterite microspheres were readily transformed to carbonated hydroxyapatite crystals when incubated in a simulated body fluid at human body temperature. We found that dopamine not only stabilized the vaterite phase but also influenced the level of conversion to carbonated hydroxyapatites. Considering that carbonated hydroxyapatites are highly bioresorbable, similar to natural bone and dentin, the synthesis of a mussel inspired hybrid material showing good in vitro bone bioactivity should present a new prospect for future applications in the treatment of bone defects and bone degenerative diseases. PMID- 20541804 TI - Trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta. AB - Congenital Chagas' disease, endemic in Latin America and also present with lower frequency in other countries, is associated with premature labor, miscarriage, and placentitis. The mechanism of tissue invasion and infection of human placenta by the parasite Trypanosoma cruzi (T. cruzi) remains unclear. In order to explore some morphological aspects of this infection in the placenta, we incubated chorionic villous explants from normal human placentae ex vivo with the parasite and studied the resulting effects by immunohistochemical and histochemical methods. Infection of the chorionic villi with the parasite was confirmed by immunofluoresence and PCR. T. cruzi induces syncytiotrophoblast destruction and detachment, selective disorganization of basal lamina and disorganization of collagen I in the connective tissue of villous stroma. These effects are a function of the number of parasites used for the infection. Our results suggest a participation of the proteolytic activity of the parasite on the placental basal lamina and connective tissue in the mechanism of infection of the fetus by T. cruzi. PMID- 20541805 TI - Translocation t(3;8;9)(p25;p21;q34) in a patient with features of 8p11 myeloproliferative syndrome: a unique case and review of the literature. PMID- 20541806 TI - Family violence and risk of substance use among Mexican adolescents. AB - OBJECTIVE: Determine the relationship between psychological and physical violence, exerted by fathers and/or mothers, and inter- or extra-familiar sexual violence with risk for consuming tobacco, alcohol and drugs among adolescents. METHOD: A cross-sectional study was carried out with students in two secondary schools in Mexico City. A total of 936 students participated: 54.3% males and 45.7% females, ranging between 12 and 16 years of age. A self-administered questionnaire was applied. This included Straus' Parent-Child Conflict Tactics Scales, as well as instruments to evaluate sexual violence and substance use, among other components. RESULTS: Over half of the adolescents reported psychological or physical violence exerted by their parents, and 1 in 10, sexual violence. The proportion of use of the 3 substances was similar in both sexes. Logistic regression analysis for males showed that psychological violence, exerted by either parent, implied twice the risk for the victims to use tobacco. For males, having suffered sexual violence increased the risk of consuming drugs various times. For females, being a victim of multiple forms of violence within the family increased the risk of consuming tobacco, alcohol and drugs notably, in comparison to non-victims. CONCLUSIONS: Treatment programs for young people who have suffered family violence should consider adolescence not only as a stage of vulnerability for substance use but also as a critical time to implement preventive measures. For these measures, a joint strategy for both parents and adolescents should be considered, not only to stop the violence but also warn the parents about the serious consequences of the same. PMID- 20541807 TI - Characterization of IgE-binding epitopes of peanut (Arachis hypogaea) PNA lectin allergen cross-reacting with other structurally related legume lectins. AB - Sera from peanut allergic patients contain IgE that specifically interact with the peanut lectin PNA and other closely related legume lectins like LcA from lentil, PsA from pea and PHA from kidney bean. The IgE-binding activity of PNA and legume lectins was assessed by immunoblotting, surface plasmon resonance (SPR) and ELISA measurements, using sera from peanut allergic patients as a IgE source. This IgE-binding cross-reactivity most probably depends on the occurrence of structurally related epitopes that have been identified on the molecular surface of PNA and other legume lectins. These epitopes definitely differ from those responsible for the allergenicity of the major allergens Ara h 1, Ara h 2 and Ara h 3, also recognized by the IgE-containing sera of peanut allergic patients. Peanut lectin PNA and other legume lectins have been characterized as potential allergens for patients allergic to edible legume seeds. However, the clinical significance of the lectin-IgE interaction has to be addressed. PMID- 20541808 TI - Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate. AB - NK cells express toll-like receptors (TLR) that recognize conserved pathogen or damage associated molecular patterns and play a fundamental role in innate immunity. Low molecular weight dextran sulfate (DXS), known to inhibit the complement system, has recently been reported by us to inhibit TLR4-induced maturation of human monocyte-derived dendritic cells (MoDC). In this study, we investigated the capability of DXS to interfere with human NK cell activation triggered directly by TLR2 agonists or indirectly by supernatants of TLR4 activated MoDC. Both TLR2 agonists and supernatants of TLR4-activated MoDC activated NK cells phenotypically, as demonstrated by the analysis of NK cell activation markers (CD56, CD25, CD69, NKp30, NKp44, NKp46, DNAM-1 and NKG2D), and functionally as shown by increased NK cell degranulation (CD107a surface expression) and IFN-gamma secretion. DXS prevented the up-regulation of NK cell activation markers triggered by TLR2 ligands or supernatants of TLR4-activated MoDC and dose-dependently abrogated NK cell degranulation and IFN-gamma secretion. In summary our results suggest that DXS may be a useful reagent to inhibit the direct and indirect TLR-mediated activation of NK cells. PMID- 20541809 TI - Novel association of smaller anterior chamber width with angle closure in Singaporeans. AB - PURPOSE: To describe variations in anterior chamber width (ACW) and investigate its association with the presence of narrow angles. DESIGN: Cross-sectional study. PARTICIPANTS: We recruited 2047 subjects aged 50 years or more from a community polyclinic and 111 subjects with primary angle closure (PAC) or primary angle closure glaucoma (PACG) from an eye hospital in Singapore. METHODS: All participants underwent gonioscopy, anterior chamber depth (ACD) and axial length (AL) measurement (IOLMaster; Carl Zeiss, Jena, Germany), and anterior-segment optical coherence tomography (AS-OCT, Visante, Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure the ACW, defined as the distance between the scleral spurs in the horizontal (nasal-temporal) axis of AS-OCT scans. An eye was deemed to have narrow angles if the posterior trabecular meshwork was not visible for at least 180 degrees on non-indentation gonioscopy with the eye in the primary position. MAIN OUTCOME MEASURES: Anterior chamber width and narrow angles. RESULTS: Data on 1465 community-based subjects were available for analysis. Anterior chamber width was significantly smaller in women compared with men (11.70 mm vs. 11.81 mm, respectively, P<0.001) and decreased significantly with age (P for trend <0.001). Significant predictors of smaller ACW were lower educational level, lower body mass index, shorter AL, shallower ACD, and Chinese race. Of the 1465 subjects, 315 (21.5%) had narrow angles on gonioscopy. Mean ACW was smaller in eyes with narrow angles compared with those without narrow angles (11.60 mm vs. 11.80 mm, P<0.001). The age- and gender-adjusted odds ratio for the highest quartile compared with the lower 3 quartiles of ACW with the presence of narrow angles was 3.4 (95% confidence interval, 2.3-5.0; P for trend <0.001). Hospital-based subjects with PAC/PACG had even smaller ACW than community subjects with narrow angles (11.33 mm vs. 11.60 mm, P<0.001). CONCLUSIONS: In this cross-sectional study, ACW was smaller in women, Chinese persons, and older persons, and was associated with narrow angles in 2 different study populations. These data suggest that a smaller ACW may represent a novel risk indicator for angle closure. PMID- 20541810 TI - Bipolar disorder and metabolic syndrome: an international perspective. AB - INTRODUCTION: The ubiquity and hazards posed by abnormal body composition and metabolic parameters in the bipolar population are a priority research and clinical issue. Herein, we summarize and synthesize international studies describing the rate of US National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III])- and International Diabetes Federation (IDF)-defined metabolic syndrome and its criterion components in individuals with bipolar disorder. METHODS: We conducted a PubMed search of all English-language articles published between January 2005 and July 2009 with the following search terms: metabolic syndrome and bipolar disorder, mania and manic-depression. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. RESULTS: The rate of metabolic syndrome in individuals with bipolar disorder is increased relative to the general population. Disparate estimates are reported ranging from comparability to approximately twofold greater than the general population. The increased hazard for metabolic syndrome amongst bipolar individuals is now documented in twelve countries from Europe, Australia, Asia, North and South America. The co-occurrence of metabolic syndrome in the bipolar population is associated with a more complex illness presentation, less favourable response to treatment, and adverse course and outcome. The association between metabolic syndrome and bipolar disorder is mediated/moderated by both iatrogenic and non-iatrogenic factors. DISCUSSION: The increased hazard for metabolic syndrome in bipolar populations is due to the clustering of traditional (and emerging) risk factors as well as iatrogenic and health systems factors. Extant data support recommendations for prioritizing, surveillance, prevention, diagnosis and management of metabolic syndrome as routine care of the bipolar patient. PMID- 20541811 TI - Generalized anxiety disorder, with or without co-morbid major depressive disorder, in primary care: prevalence of painful somatic symptoms, functioning and health status. AB - BACKGROUND: Painful physical symptoms (PPS) have received little attention in patients with generalized anxiety disorder (GAD). The objective of the present study was to assess the prevalence of PPS in patients with GAD vs patients with GAD and co-morbid major depressive disorder (MDD) and a control group (patients neither with GAD nor MDD). METHODS: This is a cross-sectional, multi-center, epidemiological study, in primary care. Patients were screened for GAD (HADS-A), followed by a diagnosis confirmation (MINI). Patients were considered to have PPS when VAS overall pain score >30. Functioning and health status was assessed (SDS, EUROQoL-5D). Relationships between the presence of PPS and functioning and health status was analyzed (ANCOVA models). Results were adjusted for confounding factors. RESULTS: Of 7152 patients, 1546 (22%) screened positive for GAD, 981 (14%) had confirmed GAD diagnosis, of whom 559 (8%) had GAD with co-morbid MDD and 422 (6%) had GAD alone. Of the 5292 (74%) patients screened negative for GAD, 336 (5%) were confirmed as controls. PPS in patients with GAD were twice as prevalent as in the control group: 59.0% vs. 28.3%; p<0.001. The presence of co morbid MDD was associated with a significantly higher prevalence of PPS: 78.0% vs. 59.0%; p<0.001. PPS were significantly associated with functioning and health status impairment (p<0.001) both in GAD alone and in GAD and co-morbid MDD compared with controls. LIMITATIONS: Results do not prove causal relationships. CONCLUSIONS: Our results support the clinical relevance of PPS in patients suffering from GAD; therefore they need to be considered when evaluating the patient. PMID- 20541812 TI - Prevalence of signs and symptoms of temporomandibular dysfunction in male adolescent athletes and non-athletes. AB - PURPOSE: The aim of the study was to compare the prevalence of signs and symptoms of temporomandibular dysfunction (TMD) in male adolescent athletes-basketball players and non-athletes and to examine the association between signs and symptoms of TMD in male adolescents in different Tanner stages. METHODS: The subjects were 46 male basketball players ages 10-13 years and 41 male adolescent non-athletes ages 10-18 years selected from the Department of Pediatrics (School of Medicine, Federal University of Sao Paulo) as a control group. A questionnaire was used to assess the signs and symptoms of TMD. According to the answers on the questionnaire the adolescents were classified in two categories: no signs or symptoms present (score A-absent), at least one sign or symptom present (score P present). The ones who got score "P" were submitted to a standardized functional examination of the masticatory system by the same examiner. Pubertal status was assessed based on physical examination by physicians from our Division. The adolescents were classified according to Tanner stages into three subgroups: subgroup 1 (before the growth spurt), subgroup 2 (growth spurt period), subgroup 3 (end of growth spurt). Significant differences between athletes and non athletes were assessed using non-parametric Wilcoxon test for continuous variables and the Fisher's exact test for categorical variables. The level of significance used was 5%. RESULTS: There was no significant difference between the athletes and non-athletes in exhibiting at least one sign or symptom of TMD (p=0.1148). When comparing the adolescents who presented at least one symptom of TMD to the different subgroups of Tanner Stages no statistically significant differences were found (p=0.8357). CONCLUSION: The lack of significant differences among male adolescents athletes and non-athletes may be caused by the size of the sample, the age of the athletes or by a probable protective action of testosterone levels in male athletes. The lack of statistical difference comparing the adolescents who presented at least one sign or symptom of TMD to subgroups of Tanner is probably because estrogen is the risk factor hormone and the levels of estrogen in male adolescents are very low. PMID- 20541813 TI - Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton. AB - In the past decades, a range of post-translational modifications has been discovered on tubulins, the major constituents of microtubules. Pioneering studies have described the occurrence and dynamics of these modifications and provided first insights into their potential functions in regulating the microtubule cytoskeleton. By contrast, several tubulin-modifying enzymes were only discovered in the last few years, and studies on molecular mechanisms and cellular functions of tubulin modifications are just beginning to emerge. This review highlights the roles of tubulin modifications in neurons. Recent studies are also discussed in relation to how the combinatorial use of tubulin modifications could generate a dynamic microtubule code, and how such a code might regulate basic as well as higher-order neuronal functions. PMID- 20541815 TI - Temporal patterns in the transcriptomic response of rainbow trout, Oncorhynchus mykiss, to crude oil. AB - Time is often not characterized as a variable in ecotoxicogenomic studies. In this study, temporal changes in gene expression were determined during exposure to crude oil and a subsequent recovery period. Juvenile rainbow trout, Oncorhynchus mykiss, were exposed for 96 h to the water accommodated fractions of 0.4, 2 or 10 mgl(-1) crude oil loadings. Following 96 h of exposure, fish were transferred to recovery tanks. Gill and liver samples were collected after 24 and 96 h of exposure, and after 96 h of recovery for RNA extraction and microarray analysis. Fluorescently labeled cDNA was hybridized against matched controls, using salmonid cDNA arrays. Each exposure scenario generated unique patterns of altered gene expression. More genes responded to crude oil in the gill than in the liver. In the gill, 1137 genes had altered expression at 24 h, 2003 genes had altered expression levels at 96 h of exposure, yet by 96 h of recovery, no genes were significantly altered in expression. In the liver at 10 mgl(-1), only five genes were changed at 24 h, yet 192 genes had altered expression after 96 h recovery. At 2 mgl(-1) in the liver, many genes had altered regulation at all three time points. The 0.4 mgl(-1) loading also showed 289 genes upregulated at 24 h after exposure. The Gene Ontology terms associated with altered expression in the liver suggested that the processes of protein synthesis, xenobiotic metabolism, and oxidoreductase activity were altered. The concentration responsive expression profile of cytochrome P450 1A, a biomarker for oil exposure, did not predict the majority of gene expression profiles in any tissue or dose, since direct relationships with dose were not observed for most genes. While the genes and their associated functions agree with known modes of toxic action for crude oil, the gene lists obtained do not match our previously published work, presumably due to array analysis procedures. These results demonstrate that changes in gene expression with time and dose may be complicated, and should be characterized in controlled laboratory settings before attempts are made to interpret responses in field-collected organisms. Further, processes for analyzing microarray data need to be developed such that standardized gene lists are developed, or that analysis does not rely on lists of significantly altered genes before arrays can be further evaluated as a monitoring tool. PMID- 20541814 TI - Building a bridal chamber: development of the thalamus. AB - The thalamus is a central brain region that plays a crucial role in distributing incoming sensory information to appropriate regions of the cortex. The thalamus develops in the posterior part of the embryonic forebrain, where early cell fate decisions are controlled by a local signaling center - the mid-diencephalic organizer - which forms at the boundary between prospective prethalamus and thalamus. In this review we discuss recent observations of early thalamic development in zebrafish, chick, and mouse embryos, that reveal a conserved set of interactions between homeodomain transcription factors. These interactions position the organizer along the neuraxis. The most prominent of the organizer's signals, Sonic hedgehog, is necessary for conferring regional identity on the prethalamus and thalamus and for patterning their differentiation. PMID- 20541816 TI - Molecular evidence and physiological characterization of iron absorption in isolated enterocytes of rainbow trout (Oncorhynchus mykiss): implications for dietary cadmium and lead absorption. AB - Recent studies suggested the probable involvement of an apical iron (Fe(2+)) transporter, the divalent metal transporter-1 (DMT1), in the uptake of several divalent metals in fish. The present study examined the gastrointestinal expression of the DMT1 gene, and investigated the kinetics of Fe(2+) uptake and its interactions with cadmium and lead in isolated enterocytes of freshwater rainbow trout (Oncorhynchus mykiss). The expressions of two DMT1 isoforms (Nramp beta and -gamma) were recorded along the entire gastrointestinal tract of fish as well as in the enterocytes. Fe(2+) uptake in isolated enterocytes was saturable and sensitive to the proton gradient and membrane potential, suggesting DMT1 mediated transport. Both cadmium and lead inhibited Fe(2+) uptake in isolated enterocytes in a concentration-dependent manner, and lead appeared to be a stronger inhibitor than cadmium. The kinetic characterization of Fe(2+) uptake revealed that the apparent affinity of uptake was significantly decreased (increased K(m)) in the presence of either cadmium or lead, whereas the maximum uptake rate (J(max)) remained unchanged-indicating that the interaction between Fe(2+) and cadmium or lead is competitive in nature. Overall, our study suggests that the uptake of dietary cadmium and lead may occur via the iron-transporting pathway in fish. PMID- 20541817 TI - Enhanced bioaccumulation of dietary contaminants in catfish with exposure to the waterborne surfactant linear alkylbenzene sulfonate. AB - Fish bioaccumulate a variety of contaminants and act as an exposure portal to the human consumer. Surfactants, known pharmaceutically to alter membrane permeability, change drug bioavailability and attenuate transporter function are also found in contaminant mixtures in the aquatic environment. The overall objective of this study was to determine if the surfactant C-12 linear alkylbenzene sulfonate (LAS) at environmentally relevant concentrations, alters the disposition and enhances bioaccumulation of co-exposed dietary xenobiotics in the catfish. Included for study were the carcinogen benzo(a)pyrene (BaP), pharmaceutical, ivermectin (IVM), and P-glycoprotein (P-gp) substrate rhodamine 123 (Rho-123), each exhibiting different dispositional footprints. Rho-123 transport into bile and membrane fluidity was examined in isolated perfused livers from control and LAS exposed catfish. Mass balance residue assessments were performed on catfish following in vivo exposure for 12 days to LAS in water at 0, 100 or 300 microg/L with 6 days of (3)H-IVM or (3)H-BaP gavage treatments. LAS at 1, 5 and 20 microM in the perfused liver, significantly decreased the transport of Rho-123 (1 microM) into bile by 18.6, 38.1 and 66.7%, respectively. Fluorescence anisotropy measurements demonstrated a 29.7% increase in fluidity at the (1 microM, 348 microg/L) LAS concentration. In vivo mass balance studies indicated that waterborne LAS (100 and 300 microg/L) increased the dietary dose remaining in fish by 39% and 78% for (3)H-IVM and 50 and 157% for (3)H-BaP. LAS at environmentally relevant concentrations altered the bioavailability and disposition of dietary xenobiotics in the catfish. Co-exposure with LAS increases xenobiotic bioaccumulation, potential toxicity of mixture components to the fish and the potential for residue transfer from fish to the consumer. PMID- 20541818 TI - Receptors and aging: structural selectivity of the rhamnose-receptor on fibroblasts as shown by Ca(2+)-mobilization and gene-expression profiles. AB - Qualitative and quantitative modifications of receptors were shown to play a key role in cell and tissue aging. We recently described the properties of a rhamnose recognizing receptor on fibroblasts involved in the mediation of age-dependent functions of these cells. Using Ca(2+)-mobilization and DNA-microarrays we could show in the presence of rhamnose-rich oligo- and polysaccharides (RROPs) Ca(2+) mobilization and changes in gene regulation. Here, we compared the effects of several RROPs, differing in their carbohydrate sequence and molecular weights, in normal human dermal fibroblasts (NHDFs). It appeared that different structural features were required for maximal effects on Ca(2+)-mobilization and gene expression profiles. Maximal effect on Ca(2+) influx and intracellular free calcium regulation was exhibited by RROP-1, a 50 kDa average molecular weight polysaccharide, and RROP-3, a 5 kDa average molecular weight oligosaccharide with a different carbohydrate sequence. Maximal effect on gene-expression profiles was obtained with RROP-3. These results suggest the possibility of several different transmission pathways from the rhamnose-receptor to intracellular targets, differentially affecting these two intracellular functions, with potential consequences on aging. Although of only relative specificity, this receptor site exhibits a high affinity for rhamnose, absent from vertebrate glycoconjugates. The rhamnose-receptor might well represent an evolutionary conserved conformation of a prokaryote lectin. PMID- 20541819 TI - All cause mortality of cardiac resynchronization therapy with implantable cardioverter defibrillator: a meta-analysis of randomized controlled trials. AB - PURPOSE: Cardiac resynchronization therapy with implantable cardioverter defibrillator (CRT-D) has been shown to improve symptoms in patients with chronic heart failure (CHF). However, reduction of all cause mortality is being debated. To evaluate whether CRT-D reduces all cause mortality compared with no-CRT-D in patients with CHF, a meta-analysis of randomized controlled trials was performed. DATA SOURCES: Data sources are MEDLINE (1994-2008), EMBASE (1994-2008), the Cochrane Controlled Trials Register (Second Quarter, 2008), the National Institutes of Health Clinical Trials.gov database of clinical trials and the US Food and Drug Administration Website (1994-2008). Search terms included cardiac resynchronization therapy with implantable cardioverter defibrillator, biventricular implantable cardioverter defibrillator, cardiac resynchronization therapy, and CRT-D. REVIEW METHODS: Two reviewers independently assessed trial eligibility and quality. Eligible studies were randomized controlled trials of CRT-D for the treatment of CHF. Eligible studies reported all cause deaths as outcomes. Seven randomized trials were included in the meta-analysis, comparing CRT-D with no-CRT-D. The outcome was all cause mortality. RESULTS: A total of 747 events occurred in 4531 patients from seven randomized trials. Follow-up in the included trials ranged from 6 to 69 months. Most trials were high-quality. Pooled analysis demonstrated CRT-D significantly reduced all cause mortality (odds ratios (OR) 0.55, 95% confidence interval 0.40 to 0.76, P=0.0002). Subgroup analysis CRT-D vs CRT alone and CRT-D vs medical therapy alone, significantly reduced all cause mortality (OR 0.48, 95% confidence interval 0.31 to 0.75, P=0.001; OR 0.64, 95% confidence interval 0.46 to 0.90, P=0.009; respectively). CONCLUSIONS: CRT-D significantly reduces all cause mortality in patients with advanced CHF. PMID- 20541820 TI - Acute inferior myocardial infarction with low atrial rhythm due to propyphenazone: Kounis syndrome. PMID- 20541821 TI - Limited value of brain natriuretic peptide as a prognostic marker in acute heart failure--a meta-analysis. PMID- 20541822 TI - Variation in herd level mastitis indicators between primi- and multiparae in Dutch dairy herds. AB - Composite somatic cell count data from the national test day recording and reported cases of farmer diagnosed clinical mastitis were used to estimate the occurrence of mastitis from July 2004 to June 2005 in primi- and multiparae in the Netherlands. Herds had to participate in the test day recording and had to have at least 50 cows. A random selection of 396 of these dairy herds provided composite somatic cell count data, while 205 dairy herds additionally reported on clinical mastitis cases. Prevalence of subclinical mastitis was calculated per herd as the proportion of cows with somatic cell count>200,000cells/ml. The incidence rate to clinical mastitis was calculated as the number of clinical mastitis cases divided by the number of cow days at risk per herd. Negative binomial models were used to correct for overdispersion. Mean herd level subclinical mastitis prevalence was 12.8% (95% CI: 12.2-13.5%) in primi- and 27.1% (95% CI: 26.2-28.1%) in multiparae. Mean herd level clinical mastitis cases were observed 20.2 (95% CI: 18.3-22.4) and 39.6 (95% CI: 37.1-42.3) times per 100 cow-years at risk, respectively. Some herds had a high mastitis occurrence in one parity group, while it was low in the other. Parity-specific monitoring is needed to identify such herds. PMID- 20541823 TI - Post-operative radiotherapy in N2 non-small cell lung cancer: a retrospective analysis of 175 patients. AB - BACKGROUND AND PURPOSE: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated. MATERIAL AND METHODS: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT). RESULTS: At a median follow up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24 0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild. CONCLUSION: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity. PMID- 20541824 TI - Silencing inducible nitric oxide synthase protects rat pancreatic islet. AB - OBJECTIVE: To investigate the effect of inducible nitric oxide synthase (iNOS) RNA interference on cytokine-induced injury of pancreatic islet in rats. MATERIALS AND METHODS: Islets from Wistar rats were cultured in vitro and then randomly divided into five groups: group A, islets were cultured exclusively; group B, islets were transfected with negative control siRNA; group C, islets were transfected with iNOS siRNA; group D, islets were transfected with iNOS siRNA and then treated with TNF-alpha+IL-1beta; group E, islets were treated with TNF-alpha+IL-1beta. The expression of iNOS, Bax and Fas was determined by RT-PCR and Western blot. The viability of islet was examined by AO/EB staining and function was examined by glucose-stimulated insulin secretion (GSIS) assay. RESULTS: The expression of iNOS and the promoting apoptosis gene Bax and Fas were significantly up-regulated by the induction of IL-1beta and TNF-alpha. Thus they led to apoptosis increase and the insulin secretion index decrease (1.87+/-0.31 vs 3.83+/-1.40, P<0.01). Silencing iNOS by RNAi prevented the up-regulation of Bax and Fas induced by cytokine, thus reduced apoptosis of islets and recovered the insulin secretion index (3.43+/-0.24 vs 1.87+/-0.31, P<0.01). CONCLUSION: The apoptosis from cytokines to islets mediated by iNOS could be suppressed by RNA interference, which favors the survival and function of islets. PMID- 20541825 TI - The efficacy of lowering glycated haemoglobin with a gliclazide modified release based intensive glucose lowering regimen in the ADVANCE trial. AB - The aim of these analyses was to examine the efficacy of the intensive gliclazide MR-based glucose lowering regimen used in the ADVANCE trial in lowering the level of glycated haemoglobin (HbA1c). All 11,140 randomised patients were included in analyses of treatment efficacy. Treatment efficacy was also examined in subgroups defined by baseline characteristics and treatments. At the end of 5 years follow up, the mean HbA1c was reduced from 7.5% at baseline to 6.5% in those on intensive glucose control and to 7.3% in those on standard glucose control. With intensive glucose lowering greater proportions achieved HbA1c levels of < or =7.0%, < or =6.5% and < or =6.0%. With intensive glucose lowering substantial reductions in HbA1c were observed across subgroups defined by baseline age, sex, duration of diabetes, BMI, HbA1c or treatment regimen (p<0.0001). The main independent predictors of reduction in HbA1c during follow-up were baseline HbA1c, duration of diabetes and BMI. There was no weight gain in the intensive glucose control group and severe hypoglycaemia was uncommon, though more frequent than in the standard control group. Intensive glucose control with a gliclazide MR-based regimen was well tolerated and consistently effective in lowering HbA1c across a broad range of patient with type 2 diabetes. PMID- 20541826 TI - Hypoglycemic symptoms in patients with type 2 diabetes in Asia-Pacific-Real-life effectiveness and care patterns of diabetes management: the RECAP-DM study. AB - Symptoms of hypoglycemia were reported by 35.8% of patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region. Symptoms were severe in 11.6% and very severe in 8.2% of patients experiencing hypoglycemia. PMID- 20541828 TI - Effects of a selective vasopressin V2 receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis. AB - BACKGROUND & AIMS: Cirrhotic patients with recurrent ascites frequently require paracentesis despite diuretic therapy. Vasopressin receptor antagonists, by increasing free water clearance, may reduce the recurrence of ascites. To investigate the effects of the addition of a vasopressin V(2) receptor antagonist, satavaptan, to 100mg spironolactone on ascites recurrence after a large volume paracentesis in patients with liver cirrhosis irrespective of the presence of hyponatraemia. METHODS: One hundred and fifty one cirrhotic patients with recurrent ascites with or without hyponatraemia, and normal to mildly abnormal renal function were randomised in a double-blind study to receive either 5mg (n=39), 12.5mg (n=36), 25mg (n=40) of satavaptan or placebo (n=36) for 12 weeks. Their Child-Pugh scores were 9.2+/-1.3, 8.7+/-1.7, 8.8+/-1.3, and 9.0+/ 1.5, respectively. RESULTS: Median time to first paracentesis was 23, 26, and 17 days with satavaptan 5, 12.5, and 25mg, respectively, versus 14 days with placebo (ns for all doses). The frequency of paracenteses was decreased significantly (p<0.05) in all satavaptan groups versus placebo. Mean increase in ascites was 2.82+/-0.48 L/week for placebo versus 2.12+/-0.40, 2.14+/-0.33, and 2.06+/-0.40 L/week for the 5, 12.5, and 25mg of satavaptan, respectively (ns for all doses). Similar numbers of patients experienced major adverse events in all groups. Increases in serum creatinine, orthostatic changes in systolic pressure and thirst were more common with satavaptan. CONCLUSIONS: Satavaptan has the potential to reduce recurrence of ascites after a large volume paracentesis at doses from 5 to 25mg in cirrhotic patients with ascites. PMID- 20541829 TI - Modeling the glucose regulatory system in extreme preterm infants. AB - BACKGROUND: Premature infants represent a significant proportion of the neonatal intensive care population. Blood glucose homeostasis in this group is often disturbed by immaturity of endogenous regulatory systems and the stress of their condition. Hypo- and hyperglycemia are frequently reported in very low birth weight infants, and more mature infants often experience low levels of glycemia. A model capturing the unique fundamental dynamics of the neonatal glucose regulatory system could be used to develop better blood glucose control methods. METHODS: A metabolic system model is adapted from adult critical care to the unique physiological case of the neonate. Integral-based fitting methods were used to identify time-varying insulin sensitivity and non-insulin mediated glucose uptake profiles. The clinically important predictive ability of the model was assessed by assuming insulin sensitivity was constant over prediction intervals of 1, 2 and 4h forward and comparing model-simulated versus actual clinical glucose values for all recorded interventions. The clinical data included 1091 glucose measurements over 3567 total patient hours, along with all associated insulin and nutritional infusion data, for N=25 total cases. Ethics approval was obtained from the Upper South A Regional Ethics Committee for this study. RESULTS: The identified model had a median absolute percentage error of 2.4% [IQR: 0.9-4.8%] between model-fitted and clinical glucose values. Median absolute prediction errors at 1-, 2- and 4-h intervals were 5.2% [IQR: 2.5 10.3%], 9.4% [IQR: 4.5-18.4%] and 13.6% [IQR: 6.3-27.6%] respectively. CONCLUSIONS: The model accurately captures and predicts the fundamental dynamic behaviors of the neonatal metabolism well enough for effective clinical decision support in glycemic control. The adaptation from adult to a neonatal case is based on the data from the literature. Low prediction errors and very low fitting errors indicate that the fundamental dynamics of glucose metabolism in both premature neonates and critical care adults can be described by similar mathematical models. PMID- 20541830 TI - ODmixed: a tool to obtain optimal designs for heterogeneous longitudinal studies with dropout. AB - ODMixed is a computer program to obtain optimal designs for linear mixed models of longitudinal studies. These designs account for heterogeneous correlated errors and for data with dropout. Designs are compared by using relative efficiencies, e.g., between a D-optimal design for homogeneous data and another for heterogeneous data or between a D-optimal design for complete data against another that optimizes designs when data is missing at random. Two examples are worked out to illustrate how researchers could use this computer program to profit of optimal design theory at the planning stage of longitudinal studies. PMID- 20541831 TI - Narrow band imaging with high-resolution bronchovideoscopy: a new approach for visualizing angiogenesis in squamous cell carcinoma of the lung. AB - OBJECTIVES: We investigated the ability of a high-resolution bronchovideoscopy system with narrow band imaging (NBI) to detect blood vessel structures in squamous cell carcinoma (SCC) of bronchi, as well as squamous dysplasia. METHODS: Seventy-nine patients with either abnormal sputum cytology or lung cancer were entered into the study. First, high-resolution bronchovideoscopy with white light was performed. Observations were repeated using NBI light to examine microvascular structures in the bronchial mucosa. Spectral features of the RGB (red/green/blue) sequential videoscope system were changed from a conventional RGB filter to the new NBI filter. The wavelength ranges of the NBI filter were: 400-430 nm (blue), 400-430 nm (green) and 520-560 nm (red). RESULTS: The following were clearly observed with NBI with high-resolution bronchovideoscopy: increased vessel growth and complex networks of tortuous vessels of various sizes, in squamous dysplasia; some dotted vessels, in addition to increased vessel growth and complex networks of tortuous vessels, in ASD; several dotted vessels and spiral or screw type tumor vessels of various sizes and grades, in SCC. Capillary blood vessel and/or tumor vessel mean diameters of ASD, CIS, microinvasive and invasive carcinoma were 41.4+/-9.8 microm, 63.7+/-8.2 microm, 136.5+/-29.9 microm and 259.4+/-29.6 microm, respectively. These results indicated a statistically significant increase of mean vessel diameters in the four groups (P<0.0001). CONCLUSION: NBI with high-resolution bronchovideoscopy was useful for detecting the increased vessel growth and complex networks of tortuous vessels, dotted vessels and spiral or screw type tumor vessels of bronchial mucosa. This may enable detecting the onset of angiogenesis during multi-step carcinogenesis of the lung. PMID- 20541832 TI - Evaluation of an early exercise intervention after thoracotomy for non-small cell lung cancer (NSCLC), effects on quality of life, muscle strength and exercise tolerance: randomised controlled trial. AB - Deterioration in exercise tolerance and impairment in quality of life (QoL) are common consequences of lobectomy. This study evaluates additional exercise and strength training after lung resection on QoL, exercise tolerance and muscle strength. Fifty-three (28 male) patients attending thoracotomy for lung cancer, mean age, range 64 (32-82) years; mean pack years (SD) 31.9 (26.8); BMI 25.6 (4.2); FEV1 2.0 (0.7) l were randomised to control (usual care) or intervention (twice daily training plus usual care). After discharge the intervention group received monthly home visits and weekly telephone calls, the control group received monthly telephone calls up to 12 weeks. Assessment pre-operatively, 5 day and 12 weeks post-operatively consisted of quadriceps strength using magnetic stimulation, 6 Minute Walking Distance (6MWD) and QoL-EORTC-QLQ-LC13. QoL was unchanged over 12 weeks; 6MWD showed significant deterioration at 5 days post operatively compared with pre-operatively, mean difference (SD)-131.6 (101.8) m and -128.0 (90.7) m in active and control groups respectively (p=0.89 between groups) which returned to pre-operative levels by 12 weeks in both groups. Quadriceps strength over the 5 day in-patient period showed a decrease of -8.3 (11.3) kg in the control group compared to increase of 4.0 (21.2) kg in the intervention group (p=0.04 between groups). Strength training after thoracotomy successfully prevented the fall in quadriceps strength seen in controls, however, there was no effect on 6MWD or QoL. 6MWD returned to pre-operative levels by 12 weeks regardless of additional support offered. PMID- 20541833 TI - Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: satellite--a phase II study from the Swedish Lung Cancer Study Group. AB - BACKGROUND: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. METHODS: Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1>1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m2 and cisplatin 75 mg/m2 with 3 weeks interval. An initial dose of cetuximab 400 mg/m2 was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m2. TOXICITY was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. RESULTS: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. HISTOLOGY: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss>5%. TOXICITY: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. CONCLUSION: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. TOXICITY, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option. PMID- 20541834 TI - Imaging in pleural mesothelioma: a review of imaging research presented at the 9th International Meeting of the International Mesothelioma Interest Group. AB - Imaging of malignant pleural mesothelioma (MPM) poses many challenges for imaging specialists and clinicians due to the anatomic location and unique growth pattern of this tumor. Nevertheless, imaging in MPM plays a critical role in diagnosis, prognostication, prediction or measurement of response to therapy, and monitoring of disease recurrence after aggressive surgical management. Imaging-based studies presented at the 9th International Conference of the International Mesothelioma Interest Group (IMIG) in October 2008 sought to further define the current practice and future potential of imaging for the mesothelioma patient. The Imaging Session was dominated by presentations that addressed the use of fluorodeoxyglucose positron emission tomography (FDG-PET), a clear indication of the expanding role of this modality. These uses included FDG-PET imaging at the point of diagnosis, in prognostication, and in the assessment of response to chemotherapy. Often FDG-PET studies were combined with computed tomography (CT) scans in an attempt to overcome limitations associated with either imaging modality alone. At diagnosis, FDG-PET parameters had a high sensitivity and specificity for differentiation of benign from malignant pleural disease. The use of FDG-PET to extract quantitative features from metabolically active tumor volume was shown to be a significant factor in the prediction of patient survival. The prognostic value of FDG-PET was not confounded by prior talc pleurodesis, despite the inflammatory response associated with the procedure. Metabolic response based on FDG-PET was found to be significantly correlated with progression-free survival. CT-based assessment of mesothelioma was determined to be inconsistent with spherical-model-based criteria so that changes in tumor area, a presumably more complete assessment of tumor burden, exhibited a 46% concordance rate with changes in linear measurements. PMID- 20541835 TI - On the link between contaminant source release conditions and plume prediction uncertainty. AB - The initial width of contaminant plumes is known to have a key influence on expected plume development, dispersion and travel time statistics. In past studies, initial plume width has been perceived identical to the geometric width of a contaminant source or injection volume. A recent study on optimal sampling layouts (Nowak et al., 2009) showed that a significant portion of uncertainty in predicting plume migration stems from the uncertain total hydraulic flux through the source area. This result points towards a missing link between source geometry and plume statistics, which we denote as the effective source width. We define the effective source width by the ratio between the actual and expected hydraulic fluxes times the geometric source width. The actual hydraulic flux through the source area is given by individual realizations while the expected one represents the mean over the ensemble. It is a stochastic quantity that may strongly differ from the actual geometric source width for geometrically small sources, and becomes identical only at the limit of wide sources (approaching ergodicity). We derive its stochastic ensemble moments in order to explore the dependency on source scale. We show that, if the effective source width is known rather than the geometric width, predictions of plume development can greatly increase in predictive power. This is illustrated on plume statistics such as the distribution of plume length, average width, transverse dispersion, total mass flux and overall concentration variance. The analysis is limited to 2D depth averaged systems, but implications hold for 3D cases. PMID- 20541836 TI - Cannabis-based medicines in multiple sclerosis--a review of clinical studies. AB - For some years a mixture of anecdotal report and data from animal models have implied a potential role for cannabis-based medicines in ameliorating a variety of symptoms of multiple sclerosis. Only recently however have large randomised controlled trials (RCTs) examined these potential effects rigorously. At present the results of RCTs have lacked a coherent message to the prescribing clinician and reasons for such heterogeneity in cannabinoid trials are discussed. PMID- 20541837 TI - Diagnostic power of default mode network resting state fMRI in the detection of Alzheimer's disease. AB - Functional magnetic resonance imaging (fMRI) of default mode network (DMN) brain activity during resting is recently gaining attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. The aim of this study was to determine which method of data processing provides highest diagnostic power and to define metrics to further optimize the diagnostic value. fMRI was acquired in 21 healthy subjects, 17 subjects with mild cognitive impairment and 15 patients with Alzheimer's disease (AD) and data evaluated both with volumes of interest (VOI)-based signal time course evaluations and independent component analyses (ICA). The first approach determines the amount of DMN region interconnectivity (as expressed with correlation coefficients); the second method determines the magnitude of DMN coactivation. Apolipoprotein E (ApoE) genotyping was available in 41 of the subjects examined. Diagnostic power (expressed as accuracy) of data of a single DMN region in independent component analyses was 64%, that of a single correlation of time courses between 2 DMN regions was 71%, respectively. With multivariate analyses combining both methods of analysis and data from various regions, accuracy could be increased to 97% (sensitivity 100%, specificity 95%). In nondemented subjects, no significant differences in activity within DMN could be detected comparing ApoE epsilon4 allele carriers and ApoE epsilon4 allele noncarriers. However, there were some indications that fMRI might yield useful information given a larger sample. Time course correlation analyses seem to outperform independent component analyses in the identification of patients with Alzheimer's disease. However, multivariate analyses combining both methods of analysis by considering the activity of various parts of the DMN as well as the interconnectivity between these regions are required to achieve optimal and clinically acceptable diagnostic power. PMID- 20541838 TI - Cell cycle regulation distinguishes lymphocytes from sporadic and familial Alzheimer's disease patients. AB - Cell cycle (CC) reactivation in neurons seems to underlie the development of Alzheimer's disease (AD). We analyzed whether CC alterations can be detected in immortalized lymphocytes from patients with the sporadic and the familial form of AD (SAD and FAD). Real-time polymerase chain reaction (PCR)-arrays, immunoblotting, and flow cytometry demonstrated differences in the regulation of G1/S phases between SAD lymphocytes and cells from nondemented subjects, as well as between SAD and FAD cells. SAD compared to FAD lymphocytes showed differences in expression profiles of the 90 CC genes, and a marked increase in the level of the p21 protein, which promotes G1-arrest. Accordingly, SAD but not FAD cells had a prolonged G1-phase. gamma-secretase inhibition did not change the CC profiles of the cell lines. These data show that SAD involves a prolongation of the G1 phase driven by p21 pathway, which is not activated in FAD cells. Thus, the mechanism in SAD differs from FAD. Moreover, disturbances of the CC in lymphocytes have a potential diagnostic value. PMID- 20541840 TI - Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP) dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell. At a critical threshold where denervation outpaces reinnervation, a vicious cycle is established where the remaining innervated muscle fibers are required to work harder to compensate for normal function, and in so doing produce toxic lactate concentrations which induces further denervation and neuronal death. This mechanism explains the exponential progression of ALS leading to paralysis. The molecular events leading to the dysregulation of the MNLS and the dismantling of NMJ are explained in the context of known ALS familial mutations and age-related endocrine dyscrasia. Combination drug therapies that inhibit lactate accumulation at the NMJ, enhance respiratory chain function, and/or promote reinnervation are predicted to be effective therapeutic strategies for ALS. PMID- 20541839 TI - Effects of aging and calorie restriction on white matter in rhesus macaques. AB - Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging. PMID- 20541841 TI - An MRI substudy of a donepezil clinical trial in mild cognitive impairment. AB - A magnetic resonance imaging (MRI) study was conducted as part of an intervention study in subjects with amnestic mild cognitive impairment (aMCI) to assess donepezil's treatment effect on brain atrophy. Adults with aMCI were randomly assigned to double-blind treatment with 10 mg/day donepezil hydrochloride or placebo for 48 weeks. Brain MRI scans were acquired at baseline and endpoint. The primary outcome measure was annualized percentage change (APC) in hippocampal volume; the main secondary outcome measure was APC in whole brain volumes. An analysis of variance (ANOVA) model including terms for treatment, site, and age was used to compare the treatment groups. APCs for hippocampal volumes were not significantly different between treatment groups. There were significant differences favoring the donepezil group for total (p = 0.001), ventricular region (p = 0.0002), and cortical region (p = 0.003) whole brain volumes. Although the primary MRI outcome measure was negative, the main secondary MRI outcome measure showed a positive result. These findings suggest a treatment effect of donepezil on brain atrophy in aMCI. PMID- 20541842 TI - Age-related effects of vagotonic atropine on cardiovagal baroreflex gain. AB - Impaired neural transduction of barosensory vessel stretch into vagal outflow is a primary determinant of reduced cardiovagal baroreflex gain with human aging. We set out to determine whether age-related reductions in this neural component of the baroreflex might be offset by enhancing the central integration/efferent responsiveness of the neural arc. Low vagotonic doses of atropine were employed to enhance central neural outflow and peripheral sinus node effects. Baroreflex gain and its neural and mechanical components were pharmacologically assessed before and after intravenous vagotonic atropine in 16 older and 14 young healthy subjects. Vagotonic atropine increased cardiovagal baroreflex gain (~30%) and its neural component (~20%) in older but not young individuals. Moreover, the atropine-induced increases in integrated gain and in its neural component were inversely related to baseline levels. Thus, age-related neural deficits in the baroreflex arc appear to play a determining role in reduced cardiovagal baroreflex gain with age and the compromised neural baroreflex function can be acutely improved by a single pharmacologic intervention. PMID- 20541843 TI - [Seasonal influence in the characteristics of patients admitted to an intensive care unit]. PMID- 20541844 TI - [Osteoporosis treatment with biphosphonates: Approaches to care reality]. AB - OBJECTIVE: Osteoporosis predominantly affects menopausal women and has a significant morbidity expressed as fractures. The study aimed to describe the types of bisphosphonates used to treat osteoporosis in post-menopausal women and to establish how treatment non-compliance affects the fracture rate. DESIGN: Retrospective cohort study of women on active treatment with bisphosphonates for the past five years. LOCATION: Utebo Health Centre (Zaragoza) (16,000 inhabitants) with a general medical quota of 1,890 patients). PARTICIPANTS: A total of 129 women who were on active treatment with bisphosphonates for five years were included. MAIN MEASURES: The distribution by drug was analysed, as well as the percentage of women who did not comply with the treatment correctly and any identified fractures. RESULTS: A total of 129 women on treatment were identified (13.0% of all women patients): alendronic acid (45.7%), ibandronic acid (21.7%), risedronic acid (19.4%) and alendronic acid plus cholecalciferol (13,2%). 19.4% of women stopped their treatment after at least 3 months. Thirteen hip fractures were identified. CONCLUSIONS: The overall treatment compliance was 80.6%, Depending on the type of bisphosphonate: alendronic acid plus cholecalciferol (88.2%), risedronic acid (88.0%), alendronic acid (78.0%), ibandronic acid (75.0%). The incidence of hip fractures was similar incidence to that observed with respect to non-compliance to treatment. Lack of therapeutic compliance is common in menopausal women, and measures should be promoted to increase effectiveness as well as to make patients aware of the importance of continuing treatment. PMID- 20541845 TI - [Delayed diagnosis of HIV infection in Spain]. AB - OBJECTIVES: To analyse the prevalence of delayed diagnosis (DD) of human immunodeficiency virus (HIV) infection, the trends over time and its determining factors from the Newly Diagnosed HIV-infected individuals Information System (SINIVIH) data, in process of being implemented in Spain. METHODS: Cross sectional study of newly diagnosed HIV-infected individuals between 2003 and 2007 in the 8 currently participating Spanish autonomous regions (AR). DD was defined as a CD4 count <200cells/MUL at diagnosis. Adjusted odds ratios with 95% confidence interval were calculated using logistic regression (OR; 95%CI). RESULTS: Among the 5785 newly diagnosed HIV cases reported, 4798 had a CD4 cell count at diagnosis. Of these, 37.3% met the DD definition. An additional 19% had between 200 and 350cells/MUL. The proportion of DD was lower for women than for men (32.9% versus 38.6%). According to exposure category, it was higher in heterosexuals (42.4%) and injecting drug users (IDUs) (40.1%) than in men who have sex with men (MSM) (26.7%). In the Spanish patient group, in multivariate logistic regression analyses, adjusting for AR and year of diagnosis, men were more likely to have a DD (OR=1.49; 95%CI:1.21-1.85). Compared to younger patients (20-29 years), LD was more frequent in older: 30-39 years (OR=2.08; 95% CI:1.63 2.67), 40-49 years (OR=3.98; 95% CI:3.07-5.16) and >49 years (OR=6.77; 95% CI:5.10-9.00); and compared to MSM, was more frequent in heterosexuals (OR=1.75; 95% CI:1.43-2.15) and IDUs (OR=1.75; 95% CI:1.38-2.22). DD decreased from 2003 to 2007 (OR=1.38; 95% CI:1.08-1.76). The same associated factors were found in immigrants, but with different magnitude: stronger association with men, heterosexuals and IDUs, and weaker association with older age. CONCLUSIONS: DD affects almost four in every ten newly diagnosed HIV-infected individuals, and is significantly more common among men, age group over 30 years, IDUs and heterosexuals. These are associated factors both in Spanish and immigrants, but in the last group the association is stronger. Strategies to increase the perception of risk among these groups are needed, as well as the implementation of the SINIVIH in the whole country to improve and to extend the information on DD. PMID- 20541846 TI - [Reproducibility of a method to quantify vaginal human immunodeficiency virus viral load]. AB - OBJECTIVE: To assess the reproducibility of a method to collect and quantify HIV nucleic acids in vaginal secretions. METHODS: We analysed two consecutive vaginal samples collected by direct aspiration from 52 HIV infected women. Nucleic acids were extracted by QIAamp RNA-viral and quantified with a modified Cobas Amplicor HIV-1 Monitor. RESULTS: Intra-class correlation coefficient between matched samples: 0.99. Differences of pooled HIV DNA+RNa and RNA were <0.40 uLog for 95% of all samples (Bland-Altman plots). CONCLUSIONS: This method is a standard and reproducible assay to detect and measure HIV vaginal viral load. PMID- 20541847 TI - [Organochlorine pesticides in the general adult population of Biscay (Spain)]. AB - OBJECTIVE: To identify and analyze levels of seven organochlorine pesticides [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), gamma hexachlorocyclohexane (gamma-HCH), heptachlor epoxide, beta-endosulfan, dichlorodiphenyldichloroethylene (p,p'-DDE) and dichlorodiphenyltrichloroethane (p,p'-DDT)] in the serum of adults of four areas of Biscay (Spain) not exposed to known sources of pesticides. METHOD: We analyzed 283 individual samples from volunteers recruited from the census. The volunteers were interviewed using a questionnaire with items on demographic variables and consumption. Data were analyzed using the chi-square test for discrete variables and analysis of variance and multiple linear regression models for continuous variables. RESULTS: We detected p,p'-DDE in 100% of the volunteers (mean: 191.43ng/g lipid), while 31% had detectable levels of p,p'-DDT (mean: 18.9ng/g lipid). Detectable levels of HCB were found in 96.5% of the volunteers (mean: 78.56ng/g lipid), beta-HCH in 90.4% (mean: 42.78ng/g lipid) and gamma-HCH in 3.5%. Heptachlor epoxide and beta endosulfan were not detected. In the regression model higher levels of all pesticides were found with increasing age (p<0.05). There were no significant differences by area of residence, except for HCB and p,p'-DDE. Women had significantly higher levels of HCB and beta-HCH (p<0.001). Body mass index showed a significant positive gradient in HCB and beta-HCH (p<0.05). There was no association between pesticides and other variables, breast feeding, occupation or social class. CONCLUSIONS: These results indicate that the general adult population of Biscay has been and is exposed to organochlorine pesticides. However, their levels are within the range observed by other authors. PMID- 20541848 TI - Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors. AB - Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 microM against the enzyme. PMID- 20541849 TI - Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure activity study. AB - The first structure-activity relationship study of vinyl sulfones as caspase-3 inhibitors is reported. A series of 12 vinyl sulfones was synthesized and evaluated for two downstream caspases (caspases-3 and -7). Dipeptidyl derivatives were significantly superior to their counterparts containing only Asp at P(1), as caspase-3 inhibitors. Fmoc-Val-Asp-trans-CH=CH-SO(2)Me was the most potent inhibitor of caspase-3 in the series, with a IC(50) of 29 microM and a second order rate constant of inactivation, k(inact)/K(i), of 1.5 M(-1) s(-1). Computational studies suggest that the second amino acid occupies position S(3) of the enzyme. In addition, Fmoc-Val-Asp-trans-CH=CH-SO(2)Ph was inactive for caspase-7 for the tested concentrations. PMID- 20541850 TI - [Inflammasome and interleukin 1]. AB - The innate immune system, which corresponds to the first line of defense against microorganisms, brings into play cell surface and intracellular sensors that detect pathogen ligands and danger signals. Among them, NOD-like receptors (NLRs) are intracellular proteins involved in inflammatory signaling pathways. NLRs are part of multiprotein complexes, called inflammasomes, which usually bring into play a NLR, an adaptor protein called ASC, and the pro-inflammatory caspase 1 protein. The activation of inflammasome by different stimuli triggers the proteolytic cleavage of pro-caspase 1 into active caspase 1, which, in turn, converts pro-interleukin 1beta (pro-IL1beta) into the mature IL1beta. IL1beta plays a crucial role in systemic inflammation due to its ability to induce the expression of a large panel of pro-inflammatory genes and to act on various target organs. Mutations in NLR genes are responsible for several autoinflammatory and/or autoimmune disorders. For example, mutations in NLRP3, which are responsible for three Mendelian autoinflammatory disorders called cryopyrinopathies, lead to inflammasome autoactivation. Peripheral blood mononuclear cells from patients carrying NLRP3 mutations secrete high levels of IL1beta; in many patients presenting with autoinflammatory disorders, blocking IL1 activity by anti-IL1 therapy significantly improves their manifestations. The mechanisms leading to IL1beta hypersecretion in other autoinflammatory disorders remain to be identified, as is the case for the role of each inflammasome in vivo. Better knowledge in this field should also contribute to the development of new anti-inflammatory treatments. PMID- 20541851 TI - [Circulating endothelial cells, microparticles and progenitors: towards the definition of vascular competence]. AB - Exposure to deleterious processes of metabolic, infectious, autoimmune or mechanical origin, alters the endothelium which progresses towards a proinflammatory and procoagulant activation, senescence and apoptosis. This "response to injury" of the endothelium plays a key role in the initiation and progression of cardiovascular disorders. In the last 10 years, identification in peripheral blood of circulating endothelial cells (CEC) and endothelial-derived microparticles (EMP) reflecting endothelium damage has led to the development of new noninvasive methods for endothelium exploration. Indeed, these biomarkers were associated with most of the cardiovascular risk factors, were correlated with established parameters of endothelial dysfunction, and were indicative of a poor clinical outcome. Moreover, they behave as biological vectors able to disseminate deleterious signals in the vascular compartment. More recently, this concept has been enlarged by the discovery of a potent repair mechanism based on the recruitment of the circulating endothelial progenitors cells (EPC) from the bone marrow, able to regenerate injured endothelial cells. Cardiovascular risk factors alter EPC number and function. Because the damage/repair balance plays a critical role in the endothelium homeostasis, CEC, EMP and EPC could be combined in an endothelium phenotype that defines the "vascular competence" of each individual. In the future, progress in standardization of available methodologies to measure these emerging biomarkers is a crucial step to establish their clinical interest for assessment of vascular risk and monitoring of vascular directed therapeutics. PMID- 20541852 TI - [A coloured cerebrospinal fluid]. PMID- 20541853 TI - [Key points of the follow-up plan in the care of Alzheimer's disease patients]. AB - The following article presents the main points of the follow-up plan of Alzheimer's disease (AD) and related syndromes patients. The general objective of this follow-up plan is to improve the quality of live of these subjects and their family. The key points are assessments of cognitive decline, functional decline and complications such as behavioural and psychological symptoms of dementia (BPSD), malnutrition and gait and balance disorders. In clinical practice, different tools are available, but frequency of evaluation is not consensual. However, the aim of this follow-up is to detect, prevent and treat complications and to improve the use of residual functional abilities in basic activities of daily living. The physician also needs to detect and prevent caregiver's exhaustion and to consider the ethical issues raised by the disease. The care plan is based on non pharmacological and pharmacological measures. The non pharmacological approach must be implemented first. The place of anti-dementia drugs is considered. Lastly, this follow-up plan aims to limit iterative admissions to emergency room and to increase the access to geriatric units. Communication and collaboration between specialist, family practitioner and caregivers are needed in order to reach the objective of quality of life improvement in AD patients. PMID- 20541854 TI - [A big purple leg]. PMID- 20541855 TI - [Atypical recurrent aseptic cutaneous abscesses as the presenting manifestation of Crohn's disease]. AB - INTRODUCTION: We report here a case of chronic inflammatory bowel disease revealed by multiple large cutaneous aseptic distal necrotic ulcers. CASE REPORT: A 44-year-old male presented with high fever at 40 degrees C associated with multiple necrotic abcesses located on the distal part of his limbs. They were treated successfully by debridment and dressings associated with antibiotics allowing complete healing after 1 month. Six months later, the patient relapsed on his left hand with a short episode of diarrhoea. A total coloscopy revealed a Crohn's disease. Systemic corticotherapy and azathioprine were administered and complete remission was obtained with a 1-year follow-up. CONCLUSION: Skin manifestations that this patient presented were atypical because of their number, size, and location, exclusively distally on the limbs. This report illustrates an unusual presentation of Crohn's disease with multiple necrotic ulcers only located on the patient extremities. PMID- 20541856 TI - Reproducibility of hand-held ankle dynamometry to measure altered ankle moment angle characteristics in children with spastic cerebral palsy. AB - BACKGROUND: In children with spastic cerebral palsy, the range of motion of the ankle joint is often limited. Measurement of range of motion may be hampered by a non-rigid foot deformity. We constructed a hand-held instrument which allows measurements of static ankle angle and moment in children with cerebral palsy while correcting for foot deformity. This study aimed to test the reproducibility of the instrument and to use it for measuring ankle moment-angle characteristics in individual children who are typically developing and children with cerebral palsy. METHODS: Ankle angles and moments were measured at five standardized positions in ten children who are typically developing and ten children with cerebral palsy. The intraclass correlation coefficient was calculated for test retest reliability. For precision, the standard error of measurement and smallest detectable difference were determined. The ankle range of motion and the slope of the moment-angle curve were determined, both towards plantar flexion and dorsiflexion. FINDINGS: The reproducibility study revealed a high reliability of the dynamometer at 5 repetitions (>0.97). Precision lies within 5 degrees for angle measurements and within 0.2 Nm for moment measurements. In the children with cerebral palsy, the range of motion towards dorsiflexion was 18 degrees lower and the slope of the moment-angle curve towards dorsiflexion was substantially higher. INTERPRETATION: We developed a hand-held dynamometer which allows reliable and precise measurements of static ankle angle and moment in children with cerebral palsy. The hand-held dynamometer allows corrections of foot deformities and is qualified to reproducibly evaluate moment-angle characteristics in a clinical context. PMID- 20541857 TI - Role of extracellular compounds in Cd-sequestration relative to Cd uptake by bacterium Sinorhizobium meliloti. AB - The role of bacterially derived compounds in Cd(II) complexation and uptake by bacterium Sinorhizobium meliloti wild type (WT) and genetically modified ExoY mutant, deficient in exopolysaccharide production, was explored combining chemical speciation measurements and assays with living bacteria. Obtained results demonstrated that WT- and ExoY-strains excreted siderophores in comparable amounts, while WT-strain produced much higher amount of exopolysaccharides and less exoproteins. An evaluation of Cd(II) distribution in bacterial suspensions under short term exposure conditions, showed that most of the Cd is bound to bacterial surface envelope, including Cd bound to the cell wall and to the attached extracellular polymeric substances. However, the amount of Cd bound to the dissolved extracellular compounds increases at high Cd(II) concentrations. The implications of these findings to more general understanding of the Cd(II) fate and cycling in the environment is discussed. PMID- 20541858 TI - Relationships between lichen community composition and concentrations of NO2 and NH3. AB - The relationship between different features of lichen communities in Quercus robur canopies and environmental variables, including concentrations of NO(2) and NH(3) was investigated. NO(2) concentration was the most significant variable, it was positively correlated with the proportion of lichen cover comprising nitrophytes and negatively correlated with total lichen cover. None of the lichen community features were correlated with NH(3) concentrations, which were relatively low across the site. Since nitrophytes and nitrophobes are likely to react in opposite directions to nitrogenous compounds, total lichen cover is not a suitable indicator for these pollutants. It is, therefore, suggested that the proportion of lichen cover comprising nitrophytes may be a suitable simple indicator of air quality, particularly in locations where the pollution climate is dominated by oxides of nitrogen. PMID- 20541859 TI - Peer norms and consistent condom use with female sex workers among male clients in Sichuan province, China. AB - Despite their crucial role in HIV infection and transmission, commercial sex male clients (CSMCs) are rarely studied. The purpose of this study was to examine the relationship between peer norms and consistent condom use with female sex workers (FSWs) among CSMCs in Sichuan province, China. Male clients with peers who had paid for sex (n = 562) were recruited by local health workers through snowball sampling. Measures of peer norms included 1) descriptive norms which were evaluated by perceptions of peer's condom attitudes and behaviors with FSWs; 2) injunctive norms which were assessed by the perceived peer approval of using condoms with FSWs; and 3) communication of HIV-related topics with peers. The outcome was consistent condom use with FSWs. Results of multivariate logistic regression models revealed that consistent condom use with FSWs was significantly more likely among male clients who perceived more pro-condom descriptive and injunctive norms among their peer groups. In addition, the pattern of commercial sex visits moderated the relations between peer norms and consistent condom use with FSWs. More peer approval of condom use and more HIV-related communication were significantly associated with consistent condom use among clients who visited FSWs with friends but not among those who visited FSWs alone. The findings suggest that social activities surrounding commercial sex visits may provide an entry point for HIV prevention intervention with men who patronize FSWs and that such efforts should tap into existing dynamics of social interaction to promote pro-condom norms. PMID- 20541861 TI - Implementation of an MgO-based metal removal step in the passive treatment system of Shilbottle, UK: column experiments. AB - Three laboratory column experiments were performed to test the suitability of two different MgO-rich reagents for removal of Mn and Al from the out-flowing waters of Shilbottle passive treatment system (Northumberland, UK). The input water was doped with 100 mg/L Zn in order to extrapolate results to waters in sulphide mining districts. One column was filled with a Dispersed Alkaline Substrate (DAS) containing 12.5% (v/v) caustic magnesia precipitator dust (CMPD) from Spain mixed with wood shavings, two columns were filled with DAS containing wood shavings and 12.5% or 25% (v/v), respectively, of dolomitic lime precipitator dust (DLPD) from Thrislington, UK. The two columns containing 12.5% of CMPD or DLPD completely removed the contaminants from the inflow water during the first 6 weeks of the experiment (mean removal of 88 mg/L Al, 96 mg/L Zn and 37 mg/L Mn), operating at an acidity load of 140 g acidity/m(2)day. At this moment, a substantial increase of the Al and Mn water concentration in the out-flowing waters of Shilbottle occurred (430 g acidity/m(2)day), leading to passivation of the reactive material and to the development of preferential flow paths within less than another 6 weeks, probably mainly due to Al precipitates. Al should be removed prior to MgO treatment. PMID- 20541860 TI - Smooth muscle differentiation and patterning in the urinary bladder. AB - Smooth muscle differentiation and patterning is a fundamental process in urinary bladder development that involves a complex array of local environmental factors, epithelial-mesenchymal interaction, and signaling pathways. An epithelial signal is necessary to induce smooth muscle differentiation in the adjacent bladder mesenchyme. The bladder epithelium (urothelium) also influences the spatial organization of the bladder wall. Sonic hedgehog (Shh), which is expressed by the urothelium, promotes mesenchymal proliferation and induces differentiation of smooth muscle from embryonic bladder mesenchyme. Shh, whose signal is mediated through various transcription factors including Gli2 and BMP4, is likely also important in the patterning of bladder smooth muscle. However, it is not known to what extent early mediators of mesenchymal migration, other Shh-associated transcription factors, and crosstalk between the Shh signaling cascade and other pathways are involved in the patterning of bladder smooth muscle. Here we review the role of epithelial-mesenchymal interaction and Shh signaling in smooth muscle differentiation and patterning in the bladder. We also discuss emerging signaling molecules, transcription factors, and mesenchyme properties that might be fruitful areas of future research in the process of smooth muscle formation in the bladder. PMID- 20541862 TI - Numerical simulations of large-scale detonation tests in the RUT facility by the LES model. AB - The LES model based on the progress variable equation and the gradient method to simulate propagation of the reaction front within the detonation wave, which was recently verified by the ZND theory, is tested in this study against two large scale experiments in the RUT facility. The facility was 27.6 m x 6.3 m x 6.55 m compartment with complex three-dimensional geometry. Experiments with 20% and 25.5% hydrogen-air mixture and different location of direct detonation initiation were simulated. Sensitivity of 3D simulations to control volume size and type were tested and found to be stringent compared to the planar detonation case. The maximum simulated pressure peak was found to be lower than the theoretical von Neumann spike value for the planar detonation and larger than the Chapman-Jouguet pressure thus indicating that it is more challenging to keep numerical reaction zone behind a leading front of numerical shock for curved fronts with large control volumes. The simulations demonstrated agreement with the experimental data. PMID- 20541863 TI - Ligand-assisted preparation of highly active and stable nanometric Pd confined catalysts for deep catalytic oxidation of toluene. AB - In this study, mesoporous SBA-15 supported Pd catalysts were synthesized through impregnation and grafting approaches. Moreover, the influences of different solvents (ethanol, H(2)O, tetrahydrofuran, dimethyl sulphoxide and N,N dimethylformamide) on the dispersion of supported Pd nanoparticles were also systematically investigated. The prepared materials were comprehensively explored by various techniques, including XRD, EDS, ICP-OES, H(2) chemisorption, N(2) adsorption/desorption, TG-DSC, FT-IR, TEM and STEM. It is found that the traditional impregnation method has some disadvantages in obtaining highly dispersed Pd active phase. Whereas, the grafting method could highly disperse Pd nanoparticles within the mesoporous channels of support material, and the grafting procedure should be promising in designing highly dispersed Pd particles on the silica-based mesoporous materials. The catalyst prepared via the grafting procedure possesses much higher activity and selectivity than that prepared by impregnation method for deep catalytic oxidation of toluene. PMID- 20541864 TI - Mass balance for POPs in a real scale fluidized bed combustor co-incinerating automotive shredder residue. AB - The European directive 2000/53/EC implies a "reuse and recovery" rate for end-of life vehicles (ELVs) of 95% to be reached by the year 2015. One of the options to increase the actual average European "reuse and recovery" rate of approximately 78% (EU 15, 2008) is incineration of automotive shredder residue (ASR) with energy-recovery. The mass balance and the congener fingerprints for PCDD/Fs, dioxin-like PCBs, PCBs and PAHs in a real scale fluidized bed combustor (FBC) incinerating 25% ASR with 25% refuse derived fuel (RDF) and 50% waste water treatment sludge (WWT sludge) were investigated. The PCDD/F, dioxin-like PCB, PCB and PAH concentrations in this input waste mix were more than hundred times higher than in the usual waste feed of the incinerator (30% RFD and 70% WWT sludge). In the outputs of the FBC, however, the concentrations of these POP groups were comparable or only slightly higher than in the outputs generated during the incineration of the usual waste feed. The considered POPs in the waste were destroyed efficiently and the formation of new POPs during cooling of the flue gas appeared to a large extent independent of the POP concentrations in the incinerated waste. PMID- 20541865 TI - Heavy metals in northern Chilean rivers: spatial variation and temporal trends. AB - Rivers of central-northern Chile are exposed to pollution from different sources, including mining activities, natural orogenic process, volcanic activity, and geology. In order to determine the contribution of mining to river pollution, the spatio-temporal dynamics of chemical species dissolved in 12 rivers of central northern Chile was assessed. Of all the rivers studied, the Elqui showed the highest historical mean concentrations of As, Cu and Pb. The Aconcagua had the highest concentration of Hg and a large Cr concentration, while the Rapel showed elevated concentrations of Cu and Mo. The Elqui and the Aconcagua were clustered as distinct groups by a cluster analysis based on two independent principal components. Hierarchical Bayesian models showed annual trends but no seasonal effects in heavy metal concentrations. As and Cu in the Elqui had positive annual slopes. Sulphate concentration exceeded 100 mg L(-1) in nine rivers, and in seven of them it had positive annual slopes. Our findings suggest that mining pollution is the main process contributing to this increasing annual trend in As, Cu and SO(4)(2-). Therefore, in order to improve the water quality of these rivers it is necessary to identify the main sources of heavy metals associated with mining activities. PMID- 20541866 TI - Yet another questionnaire is born! PMID- 20541867 TI - Exteroceptive aspects of nociception: insights from graphesthesia and two-point discrimination. AB - The exteroceptive capabilities of the nociceptive system have long been thought to be considerably more limited than those of the tactile system. However, most investigations of spatio-temporal aspects of the nociceptive system have largely focused on intensity coding as consequence of spatial or temporal summation. Graphesthesia, the identification of numbers "written" on the skin, and assessment of the two-point discrimination thresholds were used to compare the exteroceptive capabilities of the tactile and nociceptive systems. Numbers were "written" on the forearm and the abdomen by tactile stimulation and by painful non-contact infrared laser heat stimulation. Subjects performed both graphesthesia tasks better than chance. The tactile graphesthesia tasks were performed with 89% (82-97%) correct responses on the forearm and 86% (79-94%) correct responses on the abdomen. Tactile graphesthesia tasks were significantly better than painful heat graphesthesia tasks that were performed with 31% (23 40%) and 44% (37-51%) correct responses on the forearm and abdomen, respectively. These findings demonstrate that the central nervous system is capable of assembling complex spatio-temporal patterns of nociceptive information from the body surface into unified mental objects with sufficient accuracy to enable behavioral discrimination. PMID- 20541868 TI - Metarhizium anisopliae (Ascomycota: Hypocreales): an effective alternative to chemical acaricides against different developmental stages of fowl tick Argas persicus (Acari: Argasidae). AB - The fowl bloodsucking tick Argas persicus is of great medical and veterinary importance in tropical and subtropical regions because of its role as vector of certain parasitic, bacterial and viral pathogens. A variety of acaricides are used for the control of tick infestation in poultry, resulting in environmental contamination and the development of resistance. In order to develop an alternative control method, the efficacy of three strains (V245, 685 and 715C) of entomopathogenic fungus Metarhizium anisopliae against different life stages of A. persicus including eggs, larvae, unfed and engorged adult females was evaluated under laboratory conditions. Five concentrations of different strains of M. anisopliae ranging from 10(3) to 10(7)conidia/ml were utilized. The effects of fungal strains on egg hatchability and larva and adult female mortality were significant and dose-dependent compared to the control groups (P<0.05). The mortality rates of larvae ranged from 92% to 100% for two different concentrations (10(3) and 10(4)conidia/ml) of M. anisopliae strains. Treated engorged females were more susceptible than the unfed females reaching mortality rate of 100% at the highest concentration (10(7)conidia/ml) at 18 days post inoculation. Among strains used in this study, V245 was the most virulent strain regarding the LC(50) values for adult females exposed to fungal conidia. The results demonstrate that the application of M. anisopliae as a biocontrol agent is a promising option in reducing the use of chemical acaricides, resulting in benefits to poultry and the environment. PMID- 20541869 TI - Induction of immune responses in mice by a DNA vaccine encoding Cryptosporidium parvum Cp12 and Cp21 and its effect against homologous oocyst challenge. AB - Cp12 and Cp21 surface proteins on the sporozoite of Cryptosporidium parvum have been identified as the immunodominant antigens involved in the immune response to C. parvum infection. In the present study, the efficacy of Cp12 and Cp21 antigens as vaccine candidates was investigated in BALB/c mice that were susceptible to C. parvum infection. DNA sequences of Cp12, Cp21, Cp12-Cp21, and C (CpG oligodeoxynucleotide (ODN))-Cp12-Cp21 were amplified and then cloned into pVAX1 vector to form the four recombinant plasmids pVAX1-Cp12, pVAX1-Cp21, pVAX1-Cp12 Cp21, and pVAX1-C-Cp12-Cp21. Recombinant protein expression from these four plasmids in HeLa cells were confirmed by indirect immunofluorescence staining and Western blot analysis. The in vivo efficacies of the four DNA vaccines were tested in BALB/c mice. The results indicated that the four DNA vaccines elicited significant antibody responses and specific cellular responses when compared to control mice that received vector only or PBS. Among those four plasmids, pVAX1-C Cp12-Cp21 elicited significantly higher levels of IgG. Also, the percentages of CD4(+) and CD8(+) T cells were significantly higher in the group with pVAX1-C Cp12-Cp21 nasal sprays. Their efficacy in immunoprotection against homologous challenge was also detected after administration of the four DNA vaccines. The results showed that mice in the pVAX1-C-Cp12-Cp21 nasal group had a 77.5% reduction in the level of oocyst shedding and a significant difference was detected when this group was compared with the pVAX1, PBS, pVAX1-Cp12, and pVAX1 Cp21 groups. The reduction in the level of oocysts shedding from the group of pVAX1-C-Cp12-Cp21 nasal spray was also higher than that of pVAX1-Cp12-Cp21 group. These results suggested that C-Cp12-Cp21-DNA may provide an effective means of eliciting humoral and cellular responses and generating protective immunity against C. parvum infections in BALB/c mice. PMID- 20541870 TI - Immunoenhancing effects of Montanide ISA oil-based adjuvants on recombinant coccidia antigen vaccination against Eimeria acervulina infection. AB - The current study was conducted to investigate the immunoenhancing effects of Montanide adjuvants on protein subunit vaccination against avian coccidiosis. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with one of four adjuvants (ISA 70 VG, ISA 71 VG, ISA 201 VG or ISA 206 VG), and body weight gains, fecal oocyst shedding, and humoral and innate immune responses were evaluated following oral challenge infection with live E. acervulina oocysts. Immunization with profilin plus ISA 70 VG or ISA 71 VG increased body weight gains compared with vaccination with profilin alone. Profilin plus ISA 71 VG also reduced fecal oocyst shedding compared with vaccination in the absence of adjuvant. All adjuvants enhanced profilin serum antibody titers. Increased levels of gene transcripts encoding IL-2, IL-10, IL-17A, and IFN-gamma, but decreased levels of IL-15 mRNAs, were seen in intestinal intraepithelial lymphocytes of chickens immunized with profilin plus adjuvants compared with immunization with profilin alone. Finally, increased infiltration of lymphocytes, especially CD8(+) lymphocytes at the site of immunization was observed in birds given profilin plus ISA 71 VG compared with profilin alone. These results demonstrate that vaccination with the E. acervulina profilin subunit vaccine in combination with Montanide adjuvants enhances protective immunity against avian coccidiosis. PMID- 20541871 TI - Age and puberty differences in stress responses during a public speaking task: do adolescents grow more sensitive to social evaluation? AB - During adolescence pubertal development is said to lead to an increase in general stress sensitivity which might create a vulnerability for the emergence of psychopathology during this period. However, the empirical evidence for increasing stress sensitivity is scarce and mixed. Biological responses (salivary cortisol and alpha-amylase) were investigated during a social-evaluative stressor, the Leiden Public Speaking Task, in 295 nine to 17-year olds. Specific attention was paid to different elements of the task, that is anticipation to and delivery of the speech. Biological reactivity to the speech task increased with age and puberty, particularly during anticipation. Current findings support the idea that biological stress sensitivity increases during adolescence, at least in response to a social-evaluative situation. The increasing stress sensitivity appears related to both age and pubertal maturation, but unique contribution could not be distinguished. The importance of measuring anticipation is discussed. PMID- 20541872 TI - Physicochemical changes in dry-cured hams salted with potassium, calcium and magnesium chloride as a partial replacement for sodium chloride. AB - The reduction of added sodium chloride in dry-cured ham has been proposed to reduce dietary sodium intake in Mediterranean countries. The effect of substituting sodium chloride with potassium chloride, calcium chloride and magnesium chloride on some physicochemical characteristics of dry-cured ham during processing was evaluated. The results showed that hams salted with a mixture of sodium and potassium chloride registered higher salt concentrations and lower water contents and thus, needed less time to reach the required weight loss at the end of the process. The opposite effect was observed when calcium and magnesium chloride were added to the salt mixture. The observed differences in the texture and colour parameters were mainly due to differences in water and salt content. PMID- 20541873 TI - Fatty acid composition of minced meat, longissimus muscle and omental fat from Small East African goats finished on different levels of concentrate supplementation. AB - Effects of supplementing Small East African (SEA) goats with concentrate diets on fatty acids composition of minced meat, M. longissimus dorsi (LD) and omental fat were assessed using 23 animals (14.5 months old and 20.1 kg body weight). Goats were subjected to four levels of concentrate supplementation: ad libitum concentrate allowance (T100), 66% (T66), 33% (T33) and 0% (T0) of ad libitum concentrate allowance. All goats were slaughtered after 90 days of experimental period. Minced meat from concentrate-supplemented goats had higher (P<0.05) proportions of unsaturated fatty acids (UFA), monounsaturated fatty acids (MUFA) and desirable fatty acid (DFA) than that of non-supplemented ones (T0). Minced meat from T00 and T66 goats had similar proportions of polyunsaturated fatty acids (PUFA) and n-6 PUFA that were higher (P<0.05) than that of other dietary groups. There was limited variation in fatty acids composition of LD attributable to concentrate supplementation. Trans-vaccenic and linoleic acids were in higher (P<0.05) proportion in omental fat from concentrate-supplemented goats whereas margaric and arachidonic acids were in higher (P<0.05) proportion in omental fat from non-supplemented goats. Overall, LD was associated with PUFA, omental fat with saturated fatty acids (SFA), minced meat with MUFA. It is concluded that finishing SEA goats on concentrate diets will increase the proportion of DFA in meat from them. In addition, the proportion of PUFA in meat from such goats will peak at concentrate supplementation equivalent to 66% of their ad libitum intake. Consumers should avoid high intake of internal fat due to their richness in SFA. PMID- 20541874 TI - [First trimester screening for Down syndrome: five years prospective experience]. AB - First trimester screening for Down syndrome is yet to become the first intention strategy in France. This screening program at 11-14 weeks of gestation using maternal age, fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A has already been validated for a long time by many international studies. It seems to improve detection rate and decrease false positive rates. We report here five years prospective experience. PMID- 20541875 TI - Neighborhood education inequality and drinking behavior. AB - BACKGROUND: The neighborhood distribution of education (education inequality) may influence substance use among neighborhood residents. METHODS: Using data from the New York Social Environment Study (conducted in 2005; n=4000), we examined the associations of neighborhood education inequality (measured using Gini coefficients of education) with alcohol use prevalence and levels of alcohol consumption among alcohol users. Analyses were adjusted for neighborhood education level, income level and income inequality, as well as for individual demographic and socioeconomic characteristics and history of drinking prior to residence in the current neighborhood. Neighborhood social norms about drinking were examined as a possible mediator. RESULTS: In adjusted generalized estimating equation regression models, one-standard-deviation-higher education inequality was associated with 1.18 times higher odds of alcohol use (logistic regression odds ratio=1.18, 95% confidence interval 1.08-1.30) but 0.79 times lower average daily alcohol consumption among alcohol users (Poisson regression relative rate=0.79, 95% confidence interval 0.68-0.92). The results tended to differ in magnitude depending on respondents' individual educational levels. There was no evidence that these associations were mediated by social drinking norms, although norms did vary with education inequality. CONCLUSIONS: Our results provide further evidence of a relation between education inequality and drinking behavior while illustrating the importance of considering different drinking outcomes and heterogeneity between neighborhood subgroups. Future research could fruitfully consider other potential mechanisms, such as alcohol availability or the role of stress; research that considers multiple mechanisms and their combined effects may be most informative. PMID- 20541876 TI - Classical swine fever virus in South-Eastern Europe--retrospective analysis of the disease situation and molecular epidemiology. AB - Classical swine fever (CSF) is among the most important diseases of domestic pigs and causes great socio-economic losses. Therefore, control of CSF is given high priority within the European Union, including financial support of concerted control actions in candidate and in potential candidate countries. Unfortunately, from some of these countries information on the CSF situation and related data is very limited. This study was undertaken to gather all available information on the domestic pig population and husbandry, and of the CSF situation in domestic pigs and wild boar in South-Eastern European countries that have recently joined or are applying to join the European Union. A characteristic feature of pig production in Eastern Europe is that most of them are in backyard holdings. Although mandatory vaccination is carried out in most of these countries, sporadic CSF outbreaks still occur. Little is still known about the CSF situation in wild boar. In addition, molecular epidemiology of 97 CSF virus isolates available from these countries, from outbreaks that occurred between 1994 and 2007, was performed. Most of the isolates were from Romania and Bulgaria. Genetic typing showed that almost all isolates (with exception of Croatian and of the Macedonian isolates) belonged to genotype 2.3. On the basis of these sequences, and additional sequences from outbreaks in Eastern and Western European countries taken from the database held at the European Union Reference Laboratory (EURL), two clusters could be distinguished within subtype 2.3. They were tentatively named 2.3.1 and 2.3.2. PMID- 20541877 TI - Magnetic resonance imaging in hypoxic-ischaemic encephalopathy. AB - Magnetic resonance imaging of the brain is invaluable in assessing the neonate who presents with encephalopathy. Successful imaging requires adaptations to both the hardware and sequences used for adults. Knowledge of the perinatal and postnatal details are essential for the correct interpretation of the imaging findings. Perinatal lesions are at their most obvious on conventional imaging between 1 and 2weeks from delivery. Very early imaging is useful to guide management in ventilated neonates but abnormalities may be subtle on conventional sequences. Diffusion-weighted imaging (DWI) is clinically useful for the early identification of ischaemic tissue in the neonatal brain, the pattern of which can predict outcome. DWI may underestimate the final extent of injury, particularly basal ganglia and thalamic lesions. Serial imaging with quantification of both tissue damage and structure size provides invaluable insights into the effects of perinatal injury on the developing brain. PMID- 20541878 TI - Estrous cycle-dependent activity of neutrophils in the porcine endometrium: possible involvement of heat shock protein 27 and lactoferrin. AB - Neutrophil infiltration into the porcine endometrium is thought to be a specific feature during the follicular phase of the estrous cycle. To specify the localization and distribution of neutrophil granulocytes at different stages of the estrous cycle, porcine uterine samples were evaluated by immunohistochemical methods using anti-bovine lactoferrin (LF) antibody. Additionally, blood samples were collected from 30 pigs at different stages of the estrous cycle with a special focus on peri-estrous phase. Manual 100-cell differential counts were performed on routinely stained blood smears and evaluated statistically. Finally, the expression of granulocyte-colony-stimulating factor (G-CSF) and heat shock protein 27 (HSP 27), which are known to influence activation of the neutrophilic granulocytic lineage, was analyzed in porcine uteri using immunohistochemistry. Results show that LF is expressed regularly in the cytoplasm of neutrophil granulocytes. An increasing infiltration of subepithelial neutrophils was detected in the follicular phase. The highest number of intra- and subepithelial LF-positive cells was found on d 2 of the estrous cycle. Maximum level was followed by a strong decrease on d 3. Blood analysis revealed that the percentage of neutrophil granulocytes was significantly lower at d 2 (26.2+/-11.1%) than d 1 (42.1+/-11%) of the estrous cycle. HSP 27 staining was predominantly localized to luminal epithelium (LE) and glandular epithelium (GE) depending on stage of the estrous cycle. Strong immunostaining of HSP 27 is only found in LE during estrus. At d 2 of the estrous cycle, HSP 27 immunoreactivity in LE and superficial GE is reduced but moderate staining is found in deep GE. G-CSF immunostaining is uniformly not detected in endometrial cells of cyclic pigs. In conclusion, there is a clinically relevant relationship between neutrophil count in the blood and neutrophil infiltrate in the endometrium of the pig during the estrous cycle. This association may reflect the possibility of translocation of neutrophils from the blood to the endometrium up to d 2 of the estrous cycle. Additionally, HSP 27 could be a good candidate involved in migration and/or function of neutrophils within the porcine endometrium. PMID- 20541879 TI - Mammography screening for breast cancer. PMID- 20541880 TI - Sexually transmitted infections and the aging female: placing risks in perspective. AB - Gynecological literature is replete with multiple papers on sexually transmitted infections (STIs) in young women. Although those past the reproductive prime may well be at lower risk for STIs than women in the peak reproductive years, STIs are regularly seen in the older cohort and are a cause for significant morbidity and distress. Care givers reluctantly approach or are outright amiss in assessing sexual health of their aging patients, nor is this population adequately counseled regarding practices of safe sex. Sexuality among the aging population, safe behaviors, and diagnostic challenges of STIs in an older cohort are herein discussed. PMID- 20541881 TI - An uncommon case of a suicide with inhalation of hydrogen cyanide. AB - An uncommon suicide by oral ingestion of potassium cyanide salts and contemporaneous inhalation of hydrogen cyanide is presented. A 48-year-old tradesman was found dead sitting in his car. A penetrating odor of bitter almonds was noticed when opening the doors. A camping stove and a cooking pot containing large amounts of dark blue crystals were found in the footwell of the car. White powder adhered to his fingers and to the area around the mouth. Furthermore bottles containing potassium ferrocyanide and different kinds of acid and leach were found in the car together with internet information about, e.g. potassium ferrocyanide and potassium cyanide. At autopsy hemorrhages and erosions of the mucosa of the respiratory tract, esophagus and stomach were found. Concentrations of cyanide were 0.2mg/l in stomach contents, 0.96mg/kg in brain tissue, 2.79mg/kg in lungs, and 5.3mg/l in blood. The white and toxic powder potassium cyanide was formed by heating of the yellow crystals of potassium ferrocyanide on the camping stove. This powder was probably ingested orally. Addition of acid converted the salt into the highly toxic gas hydrogen cyanide. Oxidation with atmospheric oxygen built the dark blue ferrous compound Prussian blue. This case report of a person who was not familiar with chemicals demonstrates the acquisition of professional information via the internet, enabling a suicide with a complex procedure. PMID- 20541882 TI - LC-determination of five paraben preservatives in saliva and toothpaste samples using UV detection and a short monolithic column. AB - The present study reports the development and application of an HPLC-UV method for the simultaneous separation and determination of five paraben preservatives (methyl-, ethyl-, propyl-, n-butyl- and iso-butyl-paraben) in real samples. All analytes were separated efficiently in less than 20 min using a simple H(2)O:ACN linear gradient and a short monolithic column (50 mm x 4.6mm i.d.) at a flow rate of 3.0mL min(-1). Phenoxyethanol was used as chromatographic internal standard. The method was validated for linearity, limits of detection and quantification, accuracy and precision. Human saliva and toothpaste samples were analyzed after SPE pretreatment on Licrolut RP-18 cartridges. The detection limits varied between 0.1 and 0.3 mg L(-1) in all cases and the percent recoveries between 86 and 113%. PMID- 20541883 TI - Evaluation of the antioxidants activities of four Slovene medicinal plant species by traditional and novel biosensory assays. AB - We investigated the antioxidant activity of methanolic and water extracts of Slovene accessions of four medicinal plant species (Salvia officinalis, Achillea millefolium, Origanum vulgare subsp. vulgare and Gentiana lutea). Their free radical-scavenging activity against the DPPH. free radical was studied with a spectrophotometric assay, while their biological activity with the help of a laboratory-made biosensor based on immobilized fibroblast cells (assay duration: 3 min). The observed antioxidant activity of the extracts from the four investigated medicinal plant species was dependent on both the solvent used for extraction and the assay method (conventional or biosensor-based). Independently from the assay method and the solvent used for extraction, the lowest scavenging activity was observed in root extracts of G. lutea. Treatment of the immobilized cells with the plant extracts resulted in an increase of the cell membrane potential (membrane hyperpolarization), possibly due to the reduction of membrane damage due to oxidation. The novel cell biosensor could be utilized as a rapid, high throughput tool for screening the antioxidant properties of plant-derived compounds. PMID- 20541884 TI - Non-adherence to medication and doctor-patient relationship: Evidence from a European survey. AB - OBJECTIVE: Studies on the determinants of non-adherence to medication have put emphasis in understanding the role of the doctor-patient relationship in individuals' decision to follow recommendations. Yet, evidence on general perceptions that individuals hold about doctors and their impact on their decision to non-adhere is lacking. This paper aims to explore the issue using data from the European Social Survey (ESS). METHODS: The ESS was conducted in 2004/2005 and included 45,700 participants from 24 countries in Europe. A Heckman probit model with sample selection was used for the analysis. RESULTS: The results show that perceptions about doctors constitute the model that better explains non-adherence to prescribed medication. CONCLUSION AND PRACTICE IMPLICATIONS: Our findings confirm that general beliefs individuals have about the doctor-patient relationship impact significantly on their decision to non adhere to prescribed medication. Key points were shown to be involvement in the decision making process, treating patients as equals and avoiding leaving unresolved issues when prescribing. PMID- 20541885 TI - Early- and late-term dislocation risk after primary hip arthroplasty in the Medicare population. AB - From 1998 to 2007 Medicare 5% national sample dataset, 39 271 primary total hip arthroplasty (THA) patients were identified. Dislocations within 2 years (early) and after 2 years (late) of primary THA were identified. Cox regression was used to evaluate patient, hospital, and procedure characteristics for risk of dislocation, and 1540 (3.92%) and 451 (1.15%) patients were diagnosed with early and late dislocations, respectively. Dislocation rate at 6 months' follow-up decreased steadily between 1998 and 2007 from 4.21% to 2.14%. Early and late dislocation risks were lower by 35% (P < .001) and 43% (P = .01), respectively, for patients operated during 2004 and 2007 compared with 1998 and 2003. Higher Charlson index scores (i.e., more comorbid conditions) and surgeon volume were significant risk factors (P < or = .04). Decrease in dislocation risks after primary THA seems to coincide with increasing use of larger diameter femoral heads. An awareness of risk factors for dislocation can help surgeons identify high-risk patients so as to prescribe appropriate intervention strategies. PMID- 20541886 TI - Temporal relationship between knee arthroscopy and arthroplasty: a quality measure for joint care? AB - This study examined the incidence and rates of knee arthroscopy in patients older than 65 years and the risk of subsequent knee arthroplasty. Medicare claims data (1997-2006, 5% sample) were used to identify 78,137 knee arthroscopy patients. Performance of arthroscopy increased 56.1%. Prevalence increased 44.6% from 362.2 to 523.7 per 100,000 Medicare patients. The prevalence was greater for women and white patients. Prevalence of knee arthroscopy was greater in the South. Within 1 year after arthroscopy, 10.2% of arthropathy patients and 8.5% of injury patients underwent knee arthroplasty. A progressive increase was seen in the rates of use of knee arthroscopy in elderly Medicare patients for a 10-year period. A 10.2% failure rate 1 year after knee arthroscopy may be a reasonable benchmark against which performance of knee arthroscopy in patients older than 65 years can be measured. PMID- 20541887 TI - Flexion contracture persists if the contracture is more than 15 degrees at 3 months after total knee arthroplasty. AB - After total knee arthroplasty, it is common for flexion contracture to exist during the early stages of postoperative course. We retrospectively investigated whether the early postoperative contracture would finally disappear, in 104 osteoarthritic knees after surgery with posterior-stabilized prostheses. The knees were divided into 5 groups based on their contracture 3 months after surgery (group I: no contracture, group II: 5 degrees , group III: 10 degrees , group IV: 15 degrees , group V: >=20 degrees ). The proportion of patients with residual contracture (>=5 degrees ) 2 years after surgery was 1/34 in group I, 4/30 in group II, 6/23 in group III, 6/6 in group IV, and 11/11 in group V. The results show that flexion contracture eventually existed if the contracture was more than 15 degrees 3 months after surgery. PMID- 20541888 TI - Recurrent hematomas within the iliopsoas muscle caused by impingement after total hip arthroplasty. AB - Impingement of the iliopsoas muscle after total hip arthroplasty is a potential cause of postoperative groin pain. In addition, hematoma within the iliopsoas sheath has been documented as a cause of groin pain in patients on long-term anticoagulation. We present the case of a patient on long-term anticoagulation presenting after total hip arthroplasty with recurrent, symptomatic iliopsoas sheath hematomas. We believe this was due to iliopsoas impingement caused by a malpositioned acetabular component. His pain was relieved after revision of the acetabular component and debridement of the inflamed psoas tendon. PMID- 20541889 TI - Mini-midvastus vs standard medial parapatellar approach: a prospective, randomized, double-blinded study in patients undergoing bilateral total knee arthroplasty. AB - The purpose of this study was to determine whether the mini-midvastus approach to total knee arthroplasty (TKA) results in differences in quadriceps muscle strength as well as previously cited advantages in a double blind prospective randomized trial. Twenty-seven patients (54 TKAs) scheduled for bilateral TKA were randomized to undergo mini-midvastus approach on one knee and standard approach on the other. Incision lengths were the same. Postoperative strength was determined by isokinetic and isometric peak torque testing. Range of motion, pain Visual analog scale, side-preference, and gait analysis were assessed preoperatively and postoperatively. The only significant difference in strength testing was increased isokinetic and isometric extension torque at 3 weeks postoperatively for the mini-midvastus approach. No differences between the mini midvastus and standard approach were observed for stride length, stance time, pain Visual analog scale, or knee range of motion. The mini-midvastus approach has limited benefit compared to the standard approach for TKA. PMID- 20541890 TI - Oblique posterior trochanteric osteotomy in revision total hip arthroplasty. AB - Modular polyethylene failure and attendant revision play an increasing role in hip arthroplasty. In spite of well-fixed, well-aligned components, bearing exchange has a high risk of chronic instability, which may be attributed to the resection of stabilizing soft tissue structures to gain exposure. This creates a difficult situation for the surgeon and an inexplicable one for the patient with a previously well-functioning implant. The senior author modified a technique previously described by Shaw that included an osteotomy of the posterior one third of the greater trochanter and preservation of posterior soft tissues. Thirty-five patients underwent 47 revision procedures utilizing this approach, including 16 modular component and 31 more extensive procedures. There were no dislocations or significant complications and no loss of reduction or nonunion. The approach offers excellent exposure while preserving stabilizing soft tissues. PMID- 20541891 TI - Primary hip arthroplasty with 28-mm Metasul articulation. AB - This follow-up study reports on 69 patients at mean 13 years with total hip arthroplasty using 28-mm Metasul (Zimmer, Winterthur, Switzerland) metal-on-metal articulation. These results are not transferable to large-diameter head metal-on metal articulations. Four new revisions, 3 for disassociation of the liner and 1 for mechanical loosening of the acetabulum, occurred since the previous report of mean 7.3 years. The prevalent cause of late revision is disassociation, which suggests a high frictional torque or impingement in these articulation surfaces. No revision was done for osteolysis. Overall, of the original 127 hips, 116 (91%) were known to have maintained their original components. PMID- 20541892 TI - High preoperative range of motion is a significant risk factor for dislocation in primary total hip arthroplasty. AB - Dislocation after total hip arthroplasty (THA) is multifactorial and is dependent on surgical, implant, and patient factors. We hypothesized that high preoperative hip range of motion is an important variable contributing to instability after THA. We retrospectively reviewed 3379 THAs performed during a 21-year period. Average follow-up was 6.6 years. We examined the effect of surgical approach, femoral head size, and preoperative range of motion on dislocation rates. Patients with a posterior approach and 115 degrees or greater of combined preoperative flexion, adduction, and internal rotation dislocated at a significantly higher frequency than those with less than 115 degrees of combined motion (odds ratio, 1.9; P = .007). High preoperative motion in conjunction with a posterior approach and femoral head size less than 32 mm had the highest dislocation rate in our sample (5.9%). Preoperative range of motion is an important variable that should be taken into consideration during operative planning to help reduce the risk of dislocation. PMID- 20541893 TI - Reinfection after prior staged reimplantation for septic total knee arthroplasty: is salvage still possible? AB - Although results of staged reimplantation for septic total knee arthroplasty (TKA) are well-known, the outcomes of a subsequent repeat infection are not well studied. We studied 34 patients (35 TKA), who were treated for reinfection after prior staged reimplantation for septic TKA. Successful outcome was defined an infection-free prosthetic joint at the time of the last follow-up or death. At a mean follow-up of 59.2 (24-168) months, success was achieved in 24 (68.6%) of 35 knees. Among the failures were 5 amputations, 2 arthrodeses, 1 resection arthroplasty, and 3 continued antibiotic cement spacers. Failure was significantly (P = .02) related to growth of resistant microorganisms. Success was achieved significantly more often (P = .002) with complete prosthetic removal and reimplantation rather than debridement and retention of component(s). Reinfection after prior reimplantation for septic TKA is challenging but success is possible, although less frequent as compared to first time infection after a primary TKA. PMID- 20541894 TI - Periprosthetic stress fractures at the sleeve/stem junction of the Sivash-Range of Motion modular femoral stem. AB - We report on 13 cases of periprosthetic stress fracture at the sleeve/stem junction using the Sivash-Range of Motion femoral prosthesis. Radioisotope bone scans confirmed the incidence of fracture, and review of the lateral radiographs revealed anteromedial notching of the distal sleeve on the metaphyseal throat of the femur. Treatment in all cases was expectant with full resolution of symptoms. However, there were 3 cases of recurrence, 1 of which needed revision to a more distally loading stem. This is a rare complication when using this prosthesis, but we recommend a slight alteration of the entry point for the femoral reamer when using this stem and advise nonsurgical management if it occurs, as the natural history is for the condition to settle. PMID- 20541896 TI - Determinants of patient-family caregiver congruence on preferred place of death in taiwan. AB - CONTEXT: Patient-family caregiver congruence on preferred place of death not only increases the likelihood of dying at home but also contributes significantly to terminally ill cancer patients' quality of life. OBJECTIVES: To examine the determinants of patient-family caregiver congruence on the preferred place of death in Taiwan. METHODS: Patient-family caregiver dyads (n=1,108) were surveyed on preferences and needs for end-of-life (EOL) care. Determinants of congruence on preferences were identified by multivariate logistic regression. RESULTS: Patient-caregiver dyads achieved 78.1% agreement on the preferred place of death. The kappa coefficient of congruence was 0.55 (95% confidence interval [CI]=0.50, 0.60). The extent of patient-family caregiver congruence on preferred place of death increased with the patient's higher functional dependence (adjusted odds ratio [AOR] and 95% CI=1.04 [1.02, 1.05]), higher patient-rated importance for dying at preferred place of death (AOR [95% CI]=1.60 [1.43, 1.79]), and having a spousal caregiver (AOR [95% CI]=1.62 [1.14, 2.31]). Other determinants of patient family caregiver congruence included patient age (AOR [95% CI]=1.01 [1.00, 1.03]), patient-family concordance on preferred EOL care options (AOR=1.68-1.73), patient knowledge of prognosis (AOR [95% CI]=0.68 [0.48, 0.97]), and impact of caregiving on the family caregiver's life (AOR [95% CI]=0.98 [0.96, 0.99]). CONCLUSION: Increasing patient-family congruence on preferred place of death not only requires knowledge of the patient's prognosis and advance planning by both parties but also depends on family caregivers endorsing patient preferences for EOL care options and ensuring that supporting patients dying at home does not create an intolerable burden for family caregivers. PMID- 20541895 TI - Reasons for revision of first-generation highly cross-linked polyethylenes. AB - Over a 10-year period, we prospectively evaluated the reasons for revision of contemporary and highly cross-linked polyethylene formulations in amulticenter retrieval program. Two hundred twelve consecutive retrievals were classified as conventional gamma inert sterilized (n = 37), annealed (Cross fire,[Stryker Orthopedics, Mahwah, NJ] n = 72), or remelted (Longevity [Zimmer ,Warsaw, Ind], XLPE[Smith and Nephew, Memphis, Tenn], Durasul [Zimmer,Warsaw, Ind] n = 103) liners. The most frequent reasons for revision were loosening (35%), instability(28%), and infection (21%) and were not related to polyethylene formulation (P = .17). Annealed and remelted liners had comparable linear penetration rates(0.03 and 0.04 mm/y, respectively, on average), and these were significantly lower than the rate in conventional retrievals (0.11 mm/y, P <= .0005). This retrieval study including first-generation highly cross linked liners demonstrated lower wear than conventional polyethylene. Although loosening remained as the most prevalent reason for revision, we could not demonstrate a relationship between wear and loosening.The long-term clinical performance of first-generation highly cross-linked liners remains promising based on the midterm outcomes of the components documented in this study [corrected]. PMID- 20541897 TI - Exploring the meaning of chronic rejection after lung transplantation and its impact on clinical management and caregiving. AB - Although the literature continues to portray chronic rejection after lung transplantation as ominous with no known treatment, no studies have examined family and clinician caregivers' perceptions of the diagnosis of chronic rejection and its impact on the course of clinical care. We explored the meaning and impact of chronic rejection from the perspective of family (n=10) and clinician (n=3) caregivers. We found that family caregivers considered the onset of chronic rejection to be inevitable, irreversible, unpredictable, and going back to pretransplant. Clinicians considered chronic rejection as a harbinger of deterioration and peril and expressed trepidation about informing recipients and their family caregivers about the diagnosis. Despite the heightened caregiving duties and challenges of treating chronic rejection, its unpredictable course and the prospect of retransplant instilled hope for stabilization or cure among most clinicians and caregivers, leading them to support recipients' wishes to pursue potentially futile treatments. Until recipients were no longer competent, caregivers believed all treatment options (including retransplant) had been exhausted, or suffering was prolonged, caregivers were reluctant to halt extraordinary treatment measures. Caregivers perceived that certainty regarding poor prognosis was required for palliative care and that palliative care was end of-life care. Consequently, trials of aggressive treatment typically precluded palliative care. PMID- 20541898 TI - Content and spiritual items of quality-of-life instruments appropriate for use in palliative care: a review. AB - Despite the importance of palliative care and quality of life (QoL) as an outcome measure, little research evaluated the QoL instruments that are used in end-of life situations. We evaluated the content of and domains measured by QoL instruments that are suitable for use in palliative care and how the domain of spirituality was operationalized in these instruments. We conducted two literature reviews. One identified the domains that are most important for the QoL of incurably ill patients and resulted in a framework of QoL domains. The other review identified 29 instruments measuring (at least one domain of) QoL that are appropriate for use in palliative care. Most of the instruments covered only one or two QoL domains, and none of the instruments covered all QoL domains included in the framework. Among the 29 instruments, 15 included items on spirituality. We also categorized the spirituality items contained in the instruments into the spirituality aspects in the framework. Most spirituality items concerned the meaning or purpose of life. This study provides information about the domains included in QoL instruments that are suitable for use in palliative care and provides insights into the differences in content, which can be helpful when choosing an instrument for use in palliative care. PMID- 20541899 TI - Clinical trials focusing on cancer pain educational interventions: core components to include during planning and reporting. AB - CONTEXT: Robust recommendations on the reporting of methods and results of clinical trials such as therapeutic intervention trials are widely used, such as the Consolidated Standards of Reporting Trials (CONSORT) recommendation. There has not been agreement on analogous publication standards for educational intervention trials, making interpretation of educational intervention studies difficult. OBJECTIVES: The purpose of this report is to describe common deficiencies in reporting of educational intervention trials for cancer pain control, and to offer suggestions for authors to consider as they plan their studies, and report and publish research findings for educational interventions that use randomized controlled trials and other educational trial methodologies. METHODS: A systematic review of published knowledge translation intervention trials intended to improve cancer pain was undertaken, of which most were educational interventions. RESULTS: Many educational intervention clinical trials designed to improve management of cancer pain appeared methodologically weak, and their results were more difficult to interpret because of reporting deficiencies. In the course of the review, patterns of deficiencies in reporting of methods and trial results were documented. Deficiencies in reporting were compared with the CONSORT recommendations for reporting clinical trials, and parallel recommendations were drafted for educational intervention trials. Patterns of deficiency in reporting cancer pain educational intervention trials were synthesized into seven domains, generically applicable to a range of study designs. Draft recommendations intended to address these deficiencies were constructed to improve communication of educational research results. CONCLUSION: Development of a standardized reporting template for clinical trials in cancer pain educational interventions could advance knowledge transfer research and thereby increase effectiveness of national and international cancer control policy designed to support cancer pain control. PMID- 20541900 TI - A randomized, double-blind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain. AB - CONTEXT: Osteoarthritis (OA) is a common cause of chronic pain, particularly in the older population. Modern approaches to the management of OA pain recommend tailoring treatment to the individual. This study examines treatment options for OA pain in the form of low-dose transdermal and sublingual opioid analgesia. OBJECTIVES: The aims of this trial were to compare the efficacy and tolerability of seven-day, low-dose transdermal buprenorphine patches (BuTrans, Napp Pharmaceuticals Limited UK) with sublingual buprenorphine (Temgesic, Schering Plough Limited UK) in patients with moderate to severe pain caused by OA of the hip(s) and/or knee(s), and to establish analgesic equivalence of the two products. METHODS: Two hundred forty-six patients with OA pain in the hip(s) and/or knee(s) were enrolled in this randomized, double-blind, parallel-group study; 110 completed the study. Patients were randomized to receive transdermal buprenorphine patches (5, 10, and 20 microg/hour) or sublingual buprenorphine (200 and 400 microg tablets). Their medication was titrated to pain control and they were treated for up to seven weeks. The main outcome measures were pain intensity (primary outcome), sleep disturbance, quality of life, and safety assessments. RESULTS: Patients' Box Scale-11 pain scores decreased between entry and assessment in both treatment groups. During the 28-day assessment period, the estimated mean treatment differences (95% confidence intervals) were 0.00 ( 0.68,0.69), -0.11 (-0.85,0.63), and -0.13 (-0.95,0.68), for the morning, midday, and evening scores, respectively. All the confidence intervals were within the prespecified limits for equivalence (-1.5, 1.5). Use of escape medication was low. In both treatment groups, sleep disturbance caused by pain decreased between entry and assessment. Patients' quality of life improved during the study. Significantly fewer patients receiving the transdermal buprenorphine patches reported nausea (P=0.035), dizziness (P=0.026), and vomiting (P=0.039). CONCLUSION: In conclusion, seven-day, low-dose transdermal buprenorphine patches are as effective as sublingual buprenorphine, with a better tolerability profile. PMID- 20541902 TI - Sublingual atropine drops for the treatment of pediatric sialorrhea. AB - Excess oral secretions or sialorrhea is a common problem affecting children and adults with neurological disorders, as well as those approaching the end of life because of a variety of underlying illnesses. Systemic anticholinergic medications are often prescribed in an attempt to improve quality of life and reduce complications; yet, response rates are variable, and a sizable proportion of patients discontinue these drugs as a result of intolerable side effects. This report describes the successful use of a local treatment, sublingually delivered ophthalmic atropine drops, to reduce sialorrhea in a child receiving palliative care. In addition, medical evidence for the safety and efficacy of traditionally prescribed systemic medications for the treatment of pediatric sialorrhea is reviewed. PMID- 20541901 TI - Age-associated differences in fatigue among patients with cancer. AB - CONTEXT: There has been some suggestion that the fatigue experienced by older cancer patients is more severe than that of younger cohorts; however, there is little empirical evidence to support this claim. OBJECTIVES: The goal of the present study was to determine the differential impact of age and cancer diagnosis on ratings of fatigue using a validated self-report instrument. METHODS: The Functional Assessment of Chronic Illness Therapy-Fatigue subscale consists of 13 items measuring fatigue experience and its impact on daily life, with scores ranging from 0 (severe fatigue) to 52 (no fatigue). Fatigue data were available from the U.S. general population (n=1075; 51.3% female, 45.9+/-16.5 years) and a sample of mixed-diagnosis cancer patients (n=738; 64.3% female, 58.7+/-13.6 years). General population participants were recruited using an Internet-based survey panel; patients with cancer were recruited from Chicago area oncology clinics. RESULTS: On average, the cancer patient group reported more severe fatigue than the general population group (36.9 vs. 46.6; F[1,1797]=271.95, P<0.001). There was evidence for increased fatigue with age (F[6,719]=2.56, P<0.02) among patients with cancer, but not in the general population (P=0.06). Furthermore, the group x age interaction was not significant (P=0.44). Hemoglobin (Hgb) was treated as a covariate for 430 patients with available data; there was no main effect for age in this analysis. CONCLUSION: Older adults, whether they had a cancer diagnosis, reported more fatigue than younger adults. These differences may be explained, in part, by Hgb level. Future research would be helpful to explore longitudinal changes in fatigue in the general population and guide fatigue management for the older cancer patient. PMID- 20541903 TI - Self-perceived burden in terminally ill cancer patients: a categorization of care strategies based on bereaved family members' perspectives. AB - CONTEXT: Terminally ill cancer patients often experience a self-perceived burden that affects their quality of life; however, no standard care strategy for coping with this form of suffering has ever been established. OBJECTIVES: The objectives of this present study were 1) to investigate the prevalence of self-perceived burden among terminally ill cancer patients based on a survey of family members, 2) to assess the level of family perceived usefulness of expert-recommended care strategies, and 3) to categorize the care strategies. METHODS: The subjects were bereaved family members of patients who had died in certified palliative care units throughout Japan. The Good Death Inventory was used to evaluate patients' self-perceived burden based on the proxy ratings of family members. The perceived usefulness of care was assessed using a 27-item questionnaire developed by a focus group of palliative experts and a systematic review. RESULTS: A total of 429 responses (64%) received from a member of each of 666 bereaved families was analyzed. In their responses, 25% of the bereaved family members reported that the patient had experienced a mild self-perceived burden, whereas 25% reported that the patient had experienced a moderate to severe self-perceived burden. The family members recommended the following as particularly effective care strategies: "Eliminate pain and other symptoms that restrict patient activity (53%);" "Quickly dispose of urine and stools so that they are out of sight (52%);" and "Support patients' efforts to care for themselves (45%)." A factor analysis showed that the expert-recommended care strategies could be categorized into seven different components. CONCLUSION: Many terminally ill cancer patients suffer from a self-perceived burden. Family members recommended a variety of care strategies to alleviate patient-perceived burden. Palliative care specialists should have adequate knowledge of promising care strategies for alleviating patient-perceived burden. PMID- 20541904 TI - Three patients with cancer who developed rapid-eye-movement sleep behavior disorder. AB - This article discusses the clinical significance of differentiating parasomnia, such as rapid-eye-movement (REM) sleep behavior disorder (RBD), from delirium in patients with advanced cancer. We describe three patients with advanced cancer who presented with aberrant behavior at night. All three patients developed violent behaviors when they were administered opioids and/or chemotherapy. Polysomnography (PSG) showed REM sleep with tonic electromyography. Previous treatment with neuroleptics had failed to improve their problematic behaviors. Diagnosis was made using criteria for REM behavior disorder of the International Classification of Sleep Disorders, 2nd edition, and PSG. Clonazepam (0.5 mg/day) was administered orally once at night. After treatment with clonazepam, aberrant and violent behaviors were improved. It should be noted that it is not rare for patients with advanced cancer to present with parasomnia, such as RBD, although organic brain syndrome, such as delirium, is more prevalent. Therefore, it is necessary to provide adequate assessment and treatment of aberrant behaviors in cancer patients. PMID- 20541905 TI - Psychological and marital distress in spouses of Vietnam veterans: importance of spouses' perceptions. AB - Spouses of combat veterans with PTSD have greater psychological and marital distress than spouses of veterans without PTSD; however, few studies have examined how variables related to the spouses (e.g., cognitions) may play a role in their own distress. The current study examined spouses' perceptions of combat veterans' PTSD symptom severity in 465 spouses of veterans from the National Vietnam Veterans Readjustment Study. Spouses' perceptions of veterans' symptom severity were positively associated with spouses' psychological and marital distress; furthermore, spouses' perceptions fully mediated the effects of veterans' self-reported PTSD severity on spouses' distress. Additionally, for spouses who provided complete data with regard to their perceptions of veterans' PTSD, distress was highest when they perceived high levels of symptoms but veterans reported low levels. These results highlight the importance of interpersonal perceptions in intimate relationships and provide preliminary groundwork for future research on cognitions in spouses of combat veterans with PTSD. PMID- 20541906 TI - Which method of posttraumatic stress disorder classification best predicts psychosocial function in children with traumatic brain injury? AB - Controversy surrounds the classification of posttraumatic stress disorder (PTSD), particularly in children and adolescents with traumatic brain injury (TBI). In these populations, it is difficult to differentiate TBI-related organic memory loss from dissociative amnesia. Several alternative PTSD classification algorithms have been proposed for use with children. This paper investigates DSM IV-TR and alternative PTSD classification algorithms, including and excluding the dissociative amnesia item, in terms of their ability to predict psychosocial function following pediatric TBI. A sample of 184 children aged 6-14 years were recruited following emergency department presentation and/or hospital admission for TBI. PTSD was assessed via semi-structured clinical interview (CAPS-CA) with the child at 3 months post-injury. Psychosocial function was assessed using the parent report CHQ-PF50. Two alternative classification algorithms, the PTSD-AA and 2 of 3 algorithms, reached statistical significance. While the inclusion of the dissociative amnesia item increased prevalence rates across algorithms, it generally resulted in weaker associations with psychosocial function. The PTSD-AA algorithm appears to have the strongest association with psychosocial function following TBI in children and adolescents. Removing the dissociative amnesia item from the diagnostic algorithm generally results in improved validity. PMID- 20541907 TI - Factor structure and measurement invariance of the Yale-Brown Obsessive Compulsive Scale across four racial/ethnic groups. AB - The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most commonly used instrument for assessing OCD in clinical trials, but little information is available regarding its appropriateness with patients of diverse racial and ethnic backgrounds. We examined the factor structure and measurement invariance of this widely used measure, across individuals from four racial and ethnic groups utilizing both university and outpatient samples. Results indicated that a two-factor (Obsessions and Compulsions) model fit the undergraduate and outpatient samples and was structurally invariant across racial/ethnic groups. Minimal evidence of non-invariance was observed across racial/ethnic groups, with the exception that items on the Obsessions subscale may, at lower levels, under estimate obsessive concerns among Black individuals. Overall, the Y-BOCS appears to show invariance across people of different racial and ethnic backgrounds, although caution should be taken in comparing scores obtained from Black patients to current norms given evidence of substantial non-invariance on the Obsessions scale. PMID- 20541908 TI - Bone mineral density and respiratory muscle strength in male individuals with mental retardation (with and without Down Syndrome). AB - The purpose of this study was to assess the respiratory muscle strength (RMS) in individuals with mental retardation (MR), with or without Down Syndrome (DS), and its association with bone mineral density (BMD). Forty-five male individuals (15 with DS, 15 with mental retardation (MR) and 15 apparently healthy controls), aged 20-35, participated in this study. Subject assessment included pulmonary function tests, RMS (maximal inspiratory pressure, MIP, and maximal expiratory pressure, MEP) and BMD of the second and fourth lumbar vertebrae. ANOVA was used to test differences amongst groups. Tukey post hoc test was utilized when significant differences were detected with ANOVA. Bivariate correlation for BMD and respiratory muscle strength was calculated with Pearson's coefficient of correlation. Individuals with MR, both with and without DS, have lower FEV1, FVC, MIP and MEP (p<0.001) compared to controls. Individuals with DS also had lower BMD, which was associated with lower MIP and MEP. Hypotonia, sedentary lifestyle and obesity are factors that may explain lower MIP and MEP in DS. Strategies to increase RMS could decrease the risk of osteoporosis in the DS population. PMID- 20541909 TI - Complications of pediatric cardiac catheterization and system of catheterization laboratories minimizing complications--a Japanese multicenter survey. AB - BACKGROUND: Pediatric cardiac catheterization is sometimes associated with serious complications. However, there are no data regarding the organization of pediatric cardiac catheterization laboratories to minimize complications. OBJECTIVES: The aim of this study was to determine the current organization of pediatric cardiac catheterization laboratories with regard to patient safety in Japan. METHODS AND RESULTS: We sent questionnaires to 105 institutions and obtained data from 82. Major complications requiring surgical therapy or death occurred in 22 institutes (27%). The incidence of major complications did not relate to the number of procedures performed. The procedures were performed without written informed consent in 21% of all institutions. The time to inform about the procedures was within 30 min in 43 institutes (52%). A pre-procedure meeting was held in 56 institutions (68%). The anesthetist attended the diagnostic procedures in 23% and the therapeutic procedures in 53%. The drugs and defibrillator for resuscitation were available in almost all institutions, but a pacemaker was not in 23 institutions (28%). The procedures were performed under the "back-up" of cardiovascular surgeons in 38 institutions (46%). CONCLUSION: There are still large numbers of institutions in Japan, which need much improvement in the organization of pediatric cardiac catheterization laboratories as an aspect of patient safety. PMID- 20541910 TI - High dose D-serine in the treatment of schizophrenia. AB - BACKGROUND: D-serine is an allosteric modulator of the brain N-methyl-d-aspartate (NMDA) receptor and a potential novel treatment of schizophrenia. Double-blind studies have been performed at 30 mg/kg/day (approximately 2 g/day) with encouraging results, but no formal dose escalation studies have been performed. We describe the first evaluation of the efficacy and safety of d-serine at doses >30 mg/kg/day; a 4-week, open-label trial of adjunctive D-serine (30, 60 or 120 mg/kg/day). METHODS: 42 antipsychotic-stabilized patients with schizophrenia or schizoaffective disorder participated. PANSS was obtained bi-weekly and neuropsychological (MATRICS) was obtained pre- and post medication phase. The pharmacokinetics/pharmacodynamics (PK/PD), and safety of doses> or =30 mg/kg was also evaluated. RESULTS: Significant improvement in symptoms and neuropsychological measures was noted across doses. On the PANSS, improvement was observed for positive (p=0.006;d=0.46), negative (p<0.001;d=0.68), general (p=0.001;d=0.53), and total (p<0.0001;d=0.74) symptoms. On MATRICS, while only non-significant improvement was noted at 30 mg/kg, highly significant, large effect size improvement was noted on the composite score (p<0.01;d=1.0) for doses> or =60 mg/kg, leading to a significant dose-by-time interaction (p<0.01). In PK analyses, significant dose-dependent increases in plasma D-serine levels were seen during the study, predictive of significantly increased brain levels. Furthermore, increases in plasma levels correlated with improved symptomatic and neuropsychological function. DISCUSSION: These findings support double-blind investigation of D-serine at doses> or =60 mg/kg/d, and suggest effectiveness in treatment of both persistent symptoms and neurocognitive dysfunction. PMID- 20541911 TI - Deficient visual sensitivity in schizotypal personality disorder. AB - Schizotypal personality disorder is a personality disorder in the schizophrenia spectrum, sharing genetic and neurobiologic characteristics with schizophrenia. Visual contrast detection, found to be abnormal in chronic schizophrenia, was investigated in schizotypal personality disorder (SPD). Since dopamine in the retina enhances visual contrast detection and SPD patients have relatively reduced dopaminergic activity in the brain compared to schizophrenia patients, it was hypothesized that SPD patients would have decreased to normal contrast sensitivity. Twenty-one subjects with DSM-IV diagnosed SPD, 18 healthy controls, and 12 subjects with a personality disorder unrelated to schizophrenia (OPD) were evaluated for contrast detection using a sinusoidal grating presented at varying temporal frequencies. Subjects also were evaluated neuropsychologically using several standardized neurocognitive tests. A significant effect of subject group was found on the contrast detection threshold (p<0.01) with a significant difference between the SPD group and the healthy control group but not between the OPD group and the healthy control group. The SPD group had higher contrast detection thresholds at all temporal frequencies tested. Correlations were found between contrast detection and performance on the Trail-Making, N-Back, and CPT tasks in SPD patients. These results, based upon a paradigm reflecting dopamine activity in the early visual system, highlight the differences as well as similarities between SPD and schizophrenia with regard to the dopamine system in schizophrenia spectrum (Siever and Davis, 2004). PMID- 20541912 TI - The development of the S-QoL 18: a shortened quality of life questionnaire for patients with schizophrenia. AB - OBJECTIVE: The S-QoL 41 is a French self-administered questionnaire that assesses quality of life (QoL) among people with schizophrenia. This study aims to validate a shortened version of the S-QoL for more widespread use in clinical practice. METHODS: We used data from four studies conducted in four psychiatric hospitals in France (n=507). The item reduction and validation processes were based on both item response theory and classical test theory. The final version of the S-QoL was tested for construct validity, reliability, external validity, reproducibility and sensitivity to change. In addition, differential item functioning (DIF) analyses were performed to see whether all items behave in the same way in subgroups divided by age, gender, educational level and clinical form. RESULTS: The S-QoL 18 evaluates eight dimensions: psychological well-being, self-esteem, family relationships, relationships with friends, resilience, physical well-being, autonomy and sentimental life. The factor structure accounted for 78% of the total variance. Internal consistency was satisfactory (item-internal consistency greater than 0.40; Cronbach's alpha coefficients ranged from 0.72 to 0.84). The scalability was satisfactory, with INFIT statistics within an acceptable range. In addition, the results confirmed the absence of DIF and supported the invariance of the item calibrations. CONCLUSIONS: The S-QoL 18 is a short self-administered QoL instrument that has a high degree of comparability with S-QoL 41 and presents satisfactory psychometric properties. Future studies should confirm its sensitivity to change. PMID- 20541913 TI - Synergistic activities between carbapenems and other antimicrobial agents against Acinetobacter baumannii including multidrug-resistant and extensively drug resistant isolates. AB - Treatment options for multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii have been seriously limited and may require combination antimicrobial therapy. In this study, we searched for synergistic activity between carbapenems (doripenem, imipenem and meropenem) and various non traditional agents (cefoperazone/sulbactam, doxycycline, rifampicin, netilmicin and moxifloxacin) against 40 A. baumannii clinical isolates, including MDR and XDR isolates. The results showed that combination of each carbapenem with cefoperazone/sulbactam, based on the Etest method, demonstrated synergy more frequently (17.5-32.5%) than the other tested agents, which may suggest a role in combination therapy against highly resistant A. baumannii. PMID- 20541914 TI - Prevalence of decreased susceptibility to triclosan in Salmonella enterica isolates from animals and humans and association with multiple drug resistance. AB - Previous laboratory studies have implicated triclosan as a possible selective force driving resistance to multiple antibiotics and have identified a number of triclosan resistance mechanisms in Salmonella enterica. The aim of this work was to determine the prevalence of decreased susceptibility to triclosan in a panel of human and animal isolates of S. enterica and to identify the mechanisms of triclosan resistance in these strains. Over 400 animal and human isolates of non typhoidal Salmonella were screened for decreased susceptibility to triclosan and a panel of antibiotics. The prevalence of decreased susceptibility to triclosan was ca. 4%. Of the isolates with decreased triclosan susceptibility, 56% were multidrug-resistant (MDR) compared with 12% of triclosan-sensitive isolates. MDR and triclosan-resistant strains showed increased efflux activity compared with strains with reduced susceptibility to triclosan alone. No high-level triclosan resistance was seen in this panel of isolates. A reservoir of strains with low level decreased triclosan susceptibility is present in animals and humans. These isolates are MDR as a result of generic mechanisms of antimicrobial resistance and do not carry specific mutations within fabI. PMID- 20541915 TI - Hypermutability in clinical isolates of Klebsiella pneumoniae is uncommon and is unrelated to ciprofloxacin resistance. AB - We investigated hypermutability in Klebsiella pneumoniae and its association with ciprofloxacin resistance and mutations in the quinolone resistance-determining region (QRDR). Sixty-four strains of K. pneumoniae isolated in London, UK, between 1995 and 2002 with widely differing ciprofloxacin minimum inhibitory concentrations (MICs) and known gyrA and parC sequences were tested for mutation frequencies by selection with rifampicin. Only three hypermutable (frequency >or=10(-6)) strains were identified, with ciprofloxacin MICs of 0.25 microg/mL, 8 microg/mL and 64 microg/mL. There was no relationship between hypermutation and the ciprofloxacin MIC or QRDR mutations. Screening selected strains with streptomycin did not reveal any hypermutators, and screening with ciprofloxacin identified only two of the three hypermutators identified by rifampicin. Hypermutation in K. pneumoniae is uncommon and does not contribute to accumulation of QRDR mutations or directly to ciprofloxacin resistance. PMID- 20541916 TI - Enemy within: strategies to kill 'superbugs' in hospitals. PMID- 20541917 TI - Early retirement from work among employees with a diagnosis of personality disorder compared to anxiety and depressive disorders. AB - OBJECTIVE: Risk of retirement from work before statutory retirement age among employees with personality disorders is unknown. METHOD: We used diagnoses of awarded medical rehabilitations and hospitalisations to select two clinical cohorts from a population of 151,618 employees: participants in rehabilitation (total N=1942, 233 personality disorder, 419 anxiety disorder and 1290 depression cases) and hospitalised patients (N=1333, 354, 126 and 853, respectively). Early retirement from work was tracked through national registers during a period of 5 years. Cox proportional hazard models were used to examine the association of diagnostic groups with risk of early retirement. RESULTS: In models adjusted for age, sex and socioeconomic position, the relative risk of early retirement for patients with personality disorders was 3.5-fold (95% CI 2.1 to 5.8) in the rehabilitation cohort and 2.3-fold (95% CI 1.6 to 3.5) in the hospital cohort compared with anxiety disorders. The corresponding hazard ratios of early retirement for personality disorders compared with depressive disorders were 1.1 (95% CI 0.8-1.5) and 1.7 (95% CI 1.4-2.1), respectively. CONCLUSIONS: Personality disorders increase the risk of early retirement at least to an equal extent as depression and more than twice that of anxiety disorders. PMID- 20541918 TI - Electrically controlling cell adhesion, growth and migration. AB - We have developed a neurochip to control the adhesion and outgrowth of individual neurons by electrochemical removal of protein repellent molecules from transparent electrodes. The neurochip architecture is based on three parallel indium-tin-oxide (ITO) electrodes on a SiO(2) substrate and a photoresist structure forming a landing spot for the neuron soma and two lateral outgrowth pathways for the neurites. The whole surface was turned protein and cell repellent with poly(ethylene glycol) grafted-poly(L-lysine) (PLL-g-PEG) before enabling neuron soma adhesion by selective PLL-g-PEG removal. After the neuron has settled down a potential was applied to the pathway electrodes to permit the neurite outgrowth along pathways formed by the SU8 structure. We also show the possibility to control cell migration by small pulsed currents. Myoblasts were therefore seeded on a chemical pattern of cell adhesive PLL and cell resistant PLL-g-PEG. The PLL-g-PEG was then removed electrochemically from the electrodes to permit migration onto the cell free electrodes. Electrodes without applied current were confluently overgrown within 24 h but a small pulsed current was able to inhibit cell growth on the bare ITO electrode for more than 72 h. With both techniques, cell adhesion, growth and migration can be controlled dynamically after the cells started to grow on the substrate. This opens new possibilities: we believe the key to control the development of topologically controlled neuron networks or more complex co-cultures is the combination of passive surface modifications and active control over the surface properties at any time of the experiment. PMID- 20541919 TI - Potential of self-organizing nanogel with acetylated chondroitin sulfate as an anti-cancer drug carrier. AB - In order to obtain feasibility data regarding the possibility of using chondroitin sulfate (CS) in an anti-cancer drug delivery system, CS was chemically modified by a one-step process with acetic anhydride. Although 3 samples with different degrees of acetylation were synthesized, only the sample with the highest degree of acetylation (AC-CS3) was tested as a nanogel because the others (AC-CS1 and 2) dissolved in distilled water (DW) in the test range (1 10 mg/ml). The AC-CS3 nanogel was characterized by fluorescence probe and dynamic light scattering (DLS) techniques. Its critical aggregation concentration (CAC) was <2.0 x 10(-2) mg/ml at 25 degrees C. The partition equilibrium constant, K(v), of the nanogel (7.88 x 10(5)) was similar to that of polymeric micelles, which means that the acetyl group may act as a hydrophobic core controlling pharmacokinetic behavior. The higher surface charge value in the nanogel, above - 40 due to carboxyl and sulfate groups in CS, explains its good stability. The anticancer drug doxorubicin (DOX) loading efficiency of the AC-CS3 nanogel was also superior, at above 90%. Changes in the size of the polydispersion index (PDI) of nanogels loaded with DOX over a 3-week period were negligible. The nanogels interacted with HeLa cells and were internalized together with the entrapped drug within the cytoplasm, probably via an endocytic mechanism exploited by sugar receptors. Based on these results, the AC-CS3 nanogel is expected to prove useful as an anti-cancer drug carrier for chemotherapy. PMID- 20541920 TI - Amlodipine treatment decreases plasma and carotid artery tissue levels of endothelin-1 in atherosclerotic rabbits. AB - Alteration in transferring of calcium ions are seen in atherosclerotic cells and amlodipine can positively influence risk factors associated with atherosclerosis, but all mechanisms are not known. Recent studies indicate that endothelin-1 (ET 1) contributes to the atheroma formation and progression of atherosclerosis. In this study, we have evaluated the effects of amlodipine treatment and/or high cholesterol diet on blood and carotid artery tissue concentration of ET-1 in the atherosclerotic rabbits. Thirty six male New Zealand white rabbits were randomly divided into four groups: normal-diet control (NC), normal-diet receiving amlodipine (NA), high-cholesterol diet (HC) and high-cholesterol diet receiving amlodipine (HA) groups. After 8 weeks all animals were anesthetized and blood or carotid tissue samples were colleted. Eight weeks of amlodipine treatment reduced significantly total cholesterol, LDL and TG in hypercholesterolemic (HA) group. Significant increase in plasma HDL-C and decrease in TG were the main effects of amlodipine treatment on serum lipid profiles in the control group. The plasma and carotid tissue levels of ET-1 in HC group were significantly increased as compared with the NC group (p<0.01). Amlodipine treatment significantly reduced ET-1 level in NA and HA rabbits (p<0.01). Furthermore, high-cholesterol diet induced atherosclerotic lesions as shown by the enhancement of endothelial cell diameter and accumulation of lipid droplets under endothelial cells. Amlodipine treatment reduced atherotic lesions in these rabbits. Amlodipine treatment reduced levels of total cholesterol, LDL and TG as well as plasma and carotid tissue levels of ET-1 in high lipid situation. We suggest that amlodipine treatment by reducing the ET-1 may contribute to reducing the progression of atherosclerotic disease. PMID- 20541921 TI - Quantitative prediction of MHC-II binding affinity using particle swarm optimization. AB - OBJECTIVE: Helper T-cell epitopes (Th epitopes) are the basic units which activate helper T-cell's immune response, and they are helpful for understanding the immune mechanism and developing vaccines. Peptide and major histocompatibility complex class II (MHC-II) binding is an important prerequisite event for helper T-cell immune response, and the binding peptides are usually recognized as Th epitopes, therefore we can identify Th epitopes by predicting MHC-II binding peptides. Recently, instead of differentiating the peptides as binder or non-binder, researchers are more interested in predicting binding affinities between MHC-II molecules and peptides. METHODOLOGY: Motivated by the collective search strategy of the particle swarm optimization algorithm (PSO), a method was developed to make the direct prediction of peptide binding affinity. In our paper, PSO was utilized to search for the optimal position-specific scoring matrices (PSSM) from the experimentally derived allele-related peptides, and then the prediction models were constructed based on the matrices. Moreover, we evaluated several factors influencing the binding affinity, including peptide length and flanking residue length, and incorporated them into our models. RESULTS: The performance of our models was evaluated on three MHC-II alleles from AntiJen database and 14 MHC-II alleles from IEDB database. When compared to the existing popular quantitative methods such as MHCPred, SVRMHC, ARB and SMM-align, our method can give out better performance in terms of correlation coefficient (r) and area under ROC curve (AUC). In addition, the results demonstrated that the performance of models was further improved by incorporating the global length information, achieving average AUC value of 0.7534 and average r value of 0.4707. CONCLUSIONS: Quantitative prediction of MHC-II binding affinity can be modeled as an optimization problem. Our PSO based method can find the optimal PSSM, which will then be used for identifying the binding cores and scoring the binding affinities of the peptides. The experiment results show that our method is promising for the prediction of MHC-II binding affinity. PMID- 20541922 TI - Quantitative analysis of AgNOR proteins in buccal epithelial cells of Indian street boys addicted to gasp 'golden glue'. AB - The effect of glue snuffle on the expression of argyrophilic nucleolar organizer regions (AgNORs), an indicator of ribosome biosynthesis, in epithelial cells of oral mucosa has been investigated. AgNOR was evaluated by cytochemical staining in 148 Indian street boys (median age 12 year) who had different bad addictions like tobacco smoking, chewing and most importantly inhaling glue and 20 age- and body mass index-matched school boys who had no such type of bad habit. Compared with school boys, glue addicted street boys showed remarkably increased number of AgNOR dots per nucleus (9.38+/-1.84 vs. 3.12+/-0.87, p<0.001), AgNOR size (1.34+/ 0.52 vs. 0.43+/-0.02 MUm(2), p<0.001) and percentage of AgNOR occupied nuclear area (9.38+/-2.12 vs. 0.99+/-0.03%, p<0.001). Increase in number and size of the dots is also higher in tobacco smokers and chewers when compared with school boys but a remarkable difference was recorded in glue addicted boys. The changes in AgNOR expression were positively associated with years of addiction after controlling potential confounders. Thus, glue snuffle appeared to be a risk factor for abnormal cell growth via up-regulation of ribosome biogenesis. PMID- 20541923 TI - Potential antidepressant properties of Radix Polygalae (Yuan Zhi). AB - Radix Polygalae ("Yuan Zhi", the roots of Polygala tenuifolia Willd., YZ) is an important herb used in traditional Chinese medicine to mediate depression. The present study was designed to verify the antidepressant effects of the standardized YZ ethanol extract (YZE) and its four fractions YZ-30, YZ-50, YZ-70 and YZ-90 on the tail suspension (TST) and forced swimming test (FST). Furthermore, the standardization of the fractions obtained from the separation procedures was carried out by high-performance liquid chromatography (HPLC) fingerprint. The YZ-50 fraction (Oligosaccharide esters--enriched, oral (200 mg/kg) showed a significant anti-immobility like effects. The data of YZ-50 on the corticosterone-induced injure of SH-SY5Y human neuroblastoma cell indicated that YZ-50 may have biological effects on neuroprotection. Proliferation of cell lines was assessed by dimethylthiazoldiphenyltetrazoliumbromide (MTT) and 5-bromo 2'-deoxyuridine (BrdU) incorporation assays. It was found that YZ-50 and its two bioactive compounds, 3,6'-di-o-sinapoyl-sucrose (DISS) and tenuifoliside A(TEA) showed protection activities in SY5Y cells from the lesion. By using bioassay screening methods, our results indicate that the presence of oligosaccharide esters such as DISS and TEA in this herb may be responsible for the cytoprotective activity effects. PMID- 20541926 TI - Availability of body art facilities and body art piercing do not predict hepatitis C acquisition among injection drug users in Montreal, Canada: Results from a cohort study. AB - BACKGROUND: Cross-sectional associations suggest that body art piercing (BAP) is a risk factor for hepatitis C (HCV) infection among injection drug users. The temporal basis of the relationship has not been established. METHODS: Associations between HCV seropositivity, HCV incidence, recent BAP and BAP facility availability were evaluated among IDUs followed biannually between 2004 and 2008 in Montreal, Canada. A geographic information system was used to determine the availability of BAP facilities for each participant. Statistical models included individual and neighbourhood covariates. Logistic regression was used for analysis of HCV seropositivity. Cox proportional hazards regression was used for analysis of HCV incidence. RESULTS: Of 784 IDUs, 73% were seropositive for HCV. In multivariable logistic regression, HCV seropositivity was associated with BAP availability (OR: 1.32 95% confidence interval (CI): 1.1, 1.6) but not recent BAP. Of 145 initially HCV-negative participants, 52 seroconverted to HCV for an incidence of 27.7/100 person-years (95%CI: 20.9, 36.0). Crude hazard ratios (HR) for the association between HCV infection and BAP variables were: recent BAP, HR 0.98 (95%CI: 0.4, 2.7) and BAP facilities availability, HR 1.43 (95%CI: 1.1, 1.9). After accounting for individual and neighbourhood factors, crude associations between HCV infection and recent BAP and BAP facilities availability were: HR recent BAP, 0.96, 95%CI: 0.3, 2.7; and HR BAP facility availability, 1.21, 95%CI: 0.9, 1.7. CONCLUSION: BAP facility availability is a marker of neighbourhood disadvantage associated with HCV seropositivity. Longitudinal analyses accounting for behaviour risk factors and neighbourhood characteristics do not support a temporal association between BAP acquisition, BAP facility availability, and HCV infection among IDUs. PMID- 20541927 TI - The effect of using a geotextile in a monolithic (evapotranspiration) alternative landfill cover on the resulting water balance. AB - This paper examines the potential effects of a geotextile layer used in a lysimeter pan experiment conducted in a monolithic (evapotranspiration) soil cover trial on its resulting water balance performance. The geotextile was added to the base of the lysimeter to serve as a plant root barrier in order to delineate the root zone depth. Both laboratory data and numerical modelling results indicated that the geotextile creates a capillary barrier under certain conditions and retains more water in the soil above the soil/geotextile interface than occurs without a geotextile. The numerical modelling results also suggested that the water balance of the soil cover could be affected by an increase in plant transpiration taking up this extra water retained above the soil/geotextile interface. This finding has a practical implication on the full-scale monolithic cover design, as the absence of the geotextile in the full-scale cover may affect the associated water balance and hence cover performance. Proper consideration is therefore required to assess the final monolithic cover water balance performance if its design is based on the lysimeter results. PMID- 20541925 TI - Transport at the recycling endosome. AB - The recycling endosome (RE) has long been considered as a sub-compartment of the early endosome that recycles internalized cargoes to the plasma membrane. The RE is now appreciated to participate in a more complex set of intracellular itineraries. Key cargo molecules and transport factors that act in these pathways are being identified. These advancements are beginning to reveal complexities in pathways involving the RE, and also suggest ways of further delineating functional domains of this compartment. PMID- 20541928 TI - Bacteriophage tailspike proteins as molecular probes for sensitive and selective bacterial detection. AB - We report the use of genetically engineered tailspike proteins (TSPs) from the P22 bacteriophage for the sensitive and selective detection of Salmonella enterica serovar Typhimurium. High yields of two mutant TSPs, one with an N terminal cysteine (N-Cys) and another with a C-terminal cysteine (C-Cys), have been obtained using recombinant protein expression and purification in Escherichia coli. The mutant TSPs did not have the native endorhamnosidase enzymatic activity of intact P22 phage as well as wild type TSPs (wtTSPs). We have used the Cys-tag to immobilize these TSPs onto gold coated surfaces using thiol-chemistry. Our results demonstrate that the N-Cys configuration of TSPs gives a bacterial capture density of 25.87 +/- 0.61 bacteria/100 MUm(2) while the C-Cys configuration shows a density of 8.57 +/- 0.19 bacteria/100 MUm(2). This confirms that the appropriate orientation of the TSPs on the surface is important for efficient capture of the host bacteria. The bacterial capture density of the mutant N-Cys TSP was also 6-fold better than that obtained for intact P22 phage as well as wtTSPs. Bovine-serum albumin was used as a protective layer to prevent any non-specific binding of the bacteria onto the gold substrate. The recognition specificity was confirmed using 3 strains of E. coli which showed negligible binding. In addition, the host bacteria did not show any binding in the absence of the TSPs on the surface. We further show a selective real-time analytical detection of Salmonella by N-Cys mTSP-immobilized on gold coated SF-10 glass plates using surface plasmon resonance. The sensitivity of detection was found to be 10(3)cfu/ml of bacteria. PMID- 20541929 TI - Liquid crystals decorated with linear oligopeptide FLAG for applications in immunobiosensors. AB - Immunobiosensors are emerging as powerful tools for diagnostic applications. In this paper, we exploit optical properties of liquid crystal (LC) and the specific epitope-antibody interaction to develop an optical immunobiosensor which can be used to detect monoclonal anti-FLAG M2, a model antibody. The sensitive layer of this immunobiosensor is a monolayer of immobilized oligopeptide CDYKDDDDK (FLAG) at an LC/aqueous interface. The linear oligopeptide can function as an epitope which can be recognized by anti-FLAG M2. When the LC is modified with 50 MUM of FLAG and then exposed to an aqueous solution containing anti-FLAG, anti-FLAG binds to the immobilized FLAG epitope and triggers orientational transition of LC. Because of the optical birefringence of the LC, the orientational transition is accompanied by changes in the optical images of LC from dark to bright under crossed polarizers. The detection limit for the system is 27 ng/mL of anti-FLAG, and the response time is < 1 h. The binding of anti-FLAG to its motif FLAG oligopeptide is also very specific. When a variant epitope CDAKDDDDK is used, no apparent optical response can be observed after the addition of anti-FLAG. PMID- 20541930 TI - Electrochemical detection of transketolase activity using a tyrosinase biosensor. AB - This paper proposes a new concept of transketolase (TK) activity profiling. A tyrosinase (PPO) biosensor, based on the immobilization of this enzyme in a Mg(2)Al-Cl layered double hydroxide, was developed for the amperometric detection of N-acetyl-l-tyrosine ethyl ester monohydrate (N-Ac-Tyr-OEt) at -0.2V. This compound was released during an enzymatic reaction catalyzed by TK with N-acetyl O-(2R, 3S, 5-trihydroxy-4-oxopentyl)-l-tyrosine ethyl ester used as donor substrate. This tyrosinase biosensor was optimized for the detection of TK activity, including PPO optimum substrate concentration, electrolyte nature, pH, and influence of bovine serum albumin (BSA). It was found that N-Ac-Tyr-OEt release is dependent on TK concentration (U/mL) in the electrolyte medium. These results demonstrate the sensitivity and specificity of the tyrosinase biosensor designed for in vitro detection of TK activity, which is known to be involved in several diseases. PMID- 20541931 TI - Cohesin: a global player in chromosome biology with local ties to gene regulation. AB - Cohesin complexes hold sister chromatids together, which is essential for proper chromosome segregation during cell division and for post-replicative DNA repair. Recent studies suggest that, in addition to this global role in chromosome biology, cohesin is recruited to specific chromosomal locations by CTCF, and perhaps by other sequence-specific DNA binding factors. Once in position, cohesin controls chromosome conformation at the local level. Could this be key to understanding cohesin's role in gene expression? PMID- 20541932 TI - Biosynthesis and mobilization of a novel polyhydroxyalkanoate containing 3 hydroxy-4-methylvalerate monomer produced by Burkholderia sp. USM (JCM15050). AB - We attempted to synthesize a polyhydroxyalkanoate (PHA) containing newly reported 3-hydroxy-4-methylvalerate (3H4MV) monomer by using wild type Burkholderia sp. USM (JCM15050) and its transformed strain harboring the PHA synthase gene of Aeromonas caviae (phaCAc). The introduction of 3H4MV as a second monomer will improve the material properties of 3HB-based polymers. To promote the accumulation of PHA containing 3H4MV monomer, isocaproic acid was provided as co carbon source. Approximately 1mol% of 3H4MV was detected in wild type Burkholderia sp. cultures when they were fed glucose or fructose together with isocaproic acid. Thus, the wild type strain can synthesize the 3H4MV monomer. High 3H4MV fractions, of about 40mol%, were obtained when the transformed strain was cultivated on glucose or fructose together with isocaproic acid. In addition, the ability of the transformed strain to mobilize accumulated PHA containing 3H4MV monomer was demonstrated in this study. This is the first report on mobilization of the 3H4MV monomer. PMID- 20541933 TI - Kinetics and mechanism of autohydrolysis of hardwoods. AB - Autohydrolysis using water is a promising method to extract hemicelluloses from wood prior to pulping in order to make co-products such as ethanol and acetic acid besides pulp. Many studies have been carried out on the kinetics and mechanism of autohydrolysis using batch reactors. The present study was performed in a continuous mixed flow reactor where the wood chips are retained in a basket inside the reactor. This reactor is well suited to determine intrinsic kinetics of hemicellulose dissolution because the dissolved products are rapidly removed from the reactor, thus minimizing further hydrolysis and degradation of the hemicelluloses in solution. The xylan removal rate follows an S-shaped behavior. GPC analysis of the continuously removed extract shows that the dissolved xylan oligomers have a DP smaller than about 25. Lignin-free xylan oligomers and cellulose oligomers are the major components dissolved in the initial stage of autohydrolysis, while xylan covalently bound to lignin (i.e. an LCC) is the major component removed during the later stage of autohydrolysis. The molecular weight of the dissolved components decreases with time in the second stage. The kinetics of xylan removal are explained in terms of a mechanism based on recent knowledge of the ultrastructure of the cell fibre wall. PMID- 20541934 TI - Broad spectrum alkynyl inhibitors of T315I Bcr-Abl. AB - A series of alkyne-containing type II inhibitors with potent inhibitory activity of T315I Bcr-Abl has been identified. The most active compound 4 exhibits an EC(50) of less than 1 nM against wild-type Bcr-Abl and an EC(50) of 10 nM against T315I mutant but is broadly active against a number of other kinases. PMID- 20541935 TI - 4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: drug-like and non xanthine based A2B adenosine receptor antagonists. AB - 7-N-Acetamide-4-methoxy-2-aminobenzothiazole 4-fluorobenzamide (compound 1) was chosen as a drug-like and non-xanthine based starting point for the discovery of A(2B) receptor antagonists because of its slight selectivity against A(1) and A(2A) receptors and modest A(2B) potency. SAR exploration of compound 1 described herein included modifications to the 7-N-acetamide group, substitution of the 4 methoxy group by halogens as well as replacement of the p-flouro-benzamide side chain. This work culminated in the identification of compound 37 with excellent A(2B) potency, modest selectivity versus A(2A) and A(1) receptors, and good rodent PK properties. PMID- 20541936 TI - Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. AB - Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrollment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70-0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71-1.41). Compared to non drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation. PMID- 20541938 TI - cAMP and cGMP signaling: sensory systems with prokaryotic roots adopted by eukaryotic cilia. AB - An exciting discovery of the new millennium is that primary cilia, organelles found on most eukaryotic cells, play crucial roles in vertebrate development by modulating Hedgehog, Wnt and PDGF signaling. Analysis of the literature and sequence databases reveals that the ancient signal transduction pathway, which uses cGMP in eukaryotes or related cyclic di-GMP in bacteria, exists in virtually all eukaryotes. However, many eukaryotes that secondarily lost cilia during evolution, including flowering plants, slime molds and most fungi, lack otherwise evolutionarily conserved cGMP signaling components. Based on this intriguing phylogenetic distribution, the presence of cGMP signaling proteins within cilia, and the indispensable roles that cGMP plays in transducing environmental signals in divergent ciliated cells (e.g. vertebrate photoreceptors and Caenorhabditis elegans sensory neurons), we propose that cGMP signaling has a strong ciliary basis. cAMP signaling, also inherent to bacteria and crucial for cilium-dependent olfaction, similarly appears to have widespread usage in diverse cilia. Thus, we argue here that both cyclic nucleotides play essential and potentially ubiquitous roles in modulating ciliary functions. PMID- 20541939 TI - The effects of shoe fit on gait in community-dwelling older adults. AB - Shoes have a beneficial function in physical performance, particularly for gait. The purpose of this study was to investigate the association of shoe fit with gait parameters in community-dwelling older people. The fit of habitual shoes (HS) was evaluated in healthy older subjects and subjects were classified into well-fit (n=48) and poorly-fit (n=37) groups. The sizes of their feet were measured using an optical laser scanning system to provide newly-fitted shoes (NFS). Gait experiments were performed while wearing HS and NFS, separately. Trunk linear accelerations were measured along the vertical, anteroposterior and mediolateral axes using a tri-axial accelerometer attached to the L3 spinous process. Measurements were sampled at 200-Hz during a 20-m gait task at a self selected speed. After signal processing, the gait velocity, stride duration, stride length and gait regularity (Reg) were obtained. Among the poorly-fit group, 86% wore shoes that were too loose. Subjects wearing ill-fitting shoes had a tendency to walk slower, had shorter stride lengths and lower Reg in the vertical direction than those wearing well-fitting shoes. Whereas NFS increased the gait velocity, the stride length and the Reg in the vertical direction, the increases in subjects that previously wore ill-fitting HS was significantly greater than in subjects that originally wore well-fitting HS. In conclusion, our study indicates that a significant proportion of older adults wear ill-fitting shoes and that well-fitting shoes are important to improve gait performance. PMID- 20541937 TI - Building RNA-protein granules: insight from the germline. AB - The germline originates from primordial embryonic germ cells which give rise to sperm and egg cells and consequently, to the next generation. Germ cells of many organisms contain electron-dense granules that comprise RNA and proteins indispensable for germline development. Here we review recent reports that provide important insights into the structure and function of crucial RNA and protein components of the granules, including DEAD-box helicases, Tudor domain proteins, Piwi/Argonaute proteins and piRNA. Collectively, these components function in translational control, remodeling of ribonucleoprotein complexes and transposon silencing. Furthermore, they interact with each other by means of conserved structural modules and post-translationally modified amino acids. These data suggest a widespread use of several protein motifs in germline development and further our understanding of other ribonucleoprotein structures, for example, processing bodies and neuronal granules. PMID- 20541940 TI - Lower limb biomechanics during gait do not return to normal following total hip arthroplasty. AB - Although total hip arthroplasty (THA) is known to be a successful surgical procedure to alleviate hip pain and to improve health-related quality of life, these outcome measures in THA patients do not reach those of the general population. As a result, several investigators have assessed THA patients' gait mechanics, but most of them have ignored adjacent joints, as well as the effect that THA may have on the non-operated limb. The purpose of this investigation was to determine the effect of THA on the pelvis, hip, knee and ankle joint kinematics, as well as the hip, knee and ankle kinetics of both the operated and non-operated limbs during walking. These data were recorded for 20 patients having undergone unilateral THA and 20 healthy, matched control participants. Results revealed that the gait mechanics of THA patients did not return to normal 10.6 months, on average (+/-2.6 mo), following surgery. THA patients walked with lower operated-hip abduction moments, sagittal-plane range of motion, as well as lower generated and absorbed power, that may be consequential to pain-avoidance strategies adopted pre-operatively or to apprehensions associated with their new prosthesis. They also displayed various kinematic adaptations at the ankle joint of the operated limb and at the non-operated hip joint that may be leaving them at risk of developing other joint diseases. Further investigation is needed to confirm the reasons why THA patients' gait mechanics do not return to normal following surgery to develop better surgical techniques and/or rehabilitation programs. PMID- 20541941 TI - Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic. AB - Vasospasm after subarachnoid hemorrhage (SAH) is attributable to inflammation and oxidative stress associated with extracellular hemoglobin (Hb). Haptoglobin (Hp) binds free Hb and the Hp-Hb complex is cleared by macrophages, and the Hp-2 isoform of Hp is associated with more oxidative stress and more severe vasospasm. We hypothesized that treatment with an anti-oxidant, the glutathione peroxidase mimetic SYI-2074, would reduce vasospasm after SAH in Hp-2 mice. We found that SAH induced significant vasospasm in Hp-2 mice (lumen patency reduced to 65.9%), but no vasospasm was seen in mice that received SYI-2074 after SAH (lumen patency of 98.7%). We conclude that vasospasm after SAH in Hp-2 mice can be prevented with SYI-2074, suggesting that oxidative stress contributes significantly to vasospasm. PMID- 20541942 TI - Proteolytic cascades and their involvement in invertebrate immunity. AB - Bacteria and other potential pathogens are cleared rapidly from the body fluids of invertebrates by the immediate response of the innate immune system. Proteolytic cascades, following their initiation by pattern recognition proteins, control several such reactions, notably coagulation, melanisation, activation of the Toll receptor and complement-like reactions. However, there is considerable variation among invertebrates and these cascades, although widespread, are not present in all phyla. In recent years, significant progress has been made in identifying and characterizing these cascades in insects. Notably, recent work has identified several connections and shared principles among the different pathways, suggesting that cross-talk between them may be common. PMID- 20541944 TI - New 2-arylnaphthalenediols and triol inhibitors of HIV-1 integrase--discovery of a new polyhydroxylated antiviral agent. AB - A series of 13 hydroxylated 2-arylnaphthalenes have been synthesized and evaluated as HIV-1 integrase inhibitors. 7-(3,4,5-trihydroxyphenyl)naphthalene 1,2,3-triol 1c revealed chemical instability upon storage, leading to the isolation of a dimer 5c which was also tested. In the 2-arylnaphthalene series, all compounds were active against HIV-1 IN with IC50's within the 1-10 microM range, except for 1c and 5c which displayed submicromolar activity. Antiviral activity against HIV-1 replication was measured on 1b-c and 5c. Amongst the tested molecules, only 5c was found to present antiviral properties with a low cytotoxicity on two different cell lines. PMID- 20541943 TI - Induced fit, conformational selection and independent dynamic segments: an extended view of binding events. AB - Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here, we describe an extended conformational selection model that embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes and, as such, might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment. PMID- 20541945 TI - MyoD expression profile and developmental differences of leg and breast muscle in Peking duck (Anas platyrhynchos Domestica) during embryonic to neonatal stages. AB - In order to investigate the developmental differences between the duck breast muscle and leg muscle tissues during the embryonic stage to neonatal stages, as well as the expression profile of MyoD between the two muscle tissues, the morphologic characteristics in the two muscle tissues during duck embryo stages at E14, E18, E22, E27 and D7 were compared through the muscle paraffin sections. The coding domain sequence of duck MyoD gene was cloned, and then the expression of MyoD in duck leg muscle and breast muscle during embryo stage on E10, E14, E18, E22, E27 and D7 was detected using qRT-PCR method. Results showed that the developmental status of the duck breast muscle in embryonic phrases lag behind that of leg muscle. The CDS of duck MyoD gene consists of 894 nucleotides, and showed relatively high similarity with the gene of other species. The MyoD mRNA expressed in both kinds of muscle tissues and the expression profile had a similar trend, although the expression level of MyoD in the breast muscle was significantly higher than that in the leg muscle at each developmental stages (p<0.05). Results suggested that MyoD might have potential functions in controlling muscle fiber phenotype during the secondary myogenesis of muscle development. These fundamental works may provide some valuable clues for knowing the roles of MyoD in the myogenesis and the muscle fiber type differentiation in birds. PMID- 20541946 TI - Species dependent studies of no-carrier-added (93m)Mo: A green method. AB - The present paper reports a combination of radioanalytical and green methodology for the ultra-trace scale speciation of molybdenum. The differential attitude of iron-doped calcium alginate (Fe-CA) and chitosan biopolymers towards no-carrier added (93m)Mo radionuclide was studied to develop environmentally sustainable speciation methodology in ultra-trace scale. The affinity of (93m)Mo towards the Fe-CA beads is greater than that of chitosan. Species information was obtained by comparing the adsorption profile of (93m)Mo on Fe-CA and chitosan biopolymer with the software code CHEAQS PRO program. From the experimental results it is concluded that no-carrier-added (93m)Mo radionuclide form mononuclear species instead of polynuclear species in aqueous solution. Use of biodegradable, non toxic biopolymer makes this method a step forward towards green chemistry. PMID- 20541947 TI - Determination of radiostrontium isotopes: a review of analytical methodology. AB - A great number of analytical methods have been developed and applied for the determination of (90)Sr and (89)Sr in environmental and nuclear samples using various measuring techniques, i.e. beta counting, liquid scintillation spectrometry and mass spectrometry. This paper is intended to give an overview about the development of the radiochemical procedures for the separation of strontium and/or yttrium including the classical procedure based on a series of semi-selective precipitations, the ion exchange and solvent extraction procedures and the recently developed extraction chromatographic ones offering high selectivity. An outlook to the procedures under development aiming the technological separation of strontium from radioactive wastes and process solutions is also given. Nuclear measuring techniques and mass spectrometric techniques will be comparatively evaluated. PMID- 20541948 TI - A new surgical technique for transcatheter Fontan completion. AB - OBJECTIVES: Patients with complex congenital heart defects and univentricular heart usually required multiple palliative surgery aiming to separate pulmonary and systemic circulations. Various groups work on trying to perform the Fontan completion by a transcatheter technique. We developed and report here a modified technique to prepare the patient for this type of procedure. METHODS: Sixteen sheep were included and prepared through a midline sternotomy. Preparation for transcatheter completion was performed using specially designed devices. The superior vena cava (SVC) was connected to the pulmonary artery (PA) using a Goretex conduit. The connection between the SVC and the right atrium (RA) was interrupted using a vascular stent occluded in the middle by a polytetrafluoroethylene (PTFE) membrane. Two nitinol rings were placed around the inferior vena cava (IVC). Immediately after preparation, the transcatheter completion was performed by first perforating the membrane of the occluded stent and by placing covered stents from IVC rings to the SVC stent. RESULTS: Creation of the SVC to PA connection was uneventful. The insertion of the rings was done successfully in all animals very easily. All stents but one were completely occluding the SVC. Once, a tiny leak was noticed and successfully treated by additional stitches around the stent. Perforation of the membrane was done successfully in all animals re-establishing the pathway between the SVC and the RA. After dilatation of the stent, one animal required surgical control of a haemorrhage related to disruption of the SVC anastomosis. Three to four Cheatham platinum (CP)-covered stents were necessary to complete the Fontan-like circulation. In the first animal, one stent moved downward missing its target. The placement between the two rings was easily performed using fluoroscopic guidance. No stents were positioned above the SVC stent keeping this part free of material. CONCLUSIONS: We describe new improvements for surgical preparation for transcatheter completion of partial cavopulmonary connection. For superior connection, we developed an occluding stent that helps to re-establish RA to PA connection, alloys precise placement and enhances the stability of the completion stents. Inferiorly, anchorage of the covered stents is also improved by the use of nitinol rings. PMID- 20541949 TI - Efficacy and safety of TachoSil(r) versus standard treatment of air leakage after pulmonary lobectomy. AB - OBJECTIVES: Alveolar air leakage remains a serious problem in lung surgery, being associated with increased postoperative morbidity, prolonged hospital stay and greater health-care costs. The aim of this study was to evaluate the sealing efficacy and safety of the surgical patch, TachoSil(r), in lung surgery. METHODS: Patients undergoing elective pulmonary lobectomy who had grade 1 or 2 air leakage (evaluated by the water submersion test) after primary stapling and limited suturing were randomised at 12 European centres to open-label treatment with TachoSil(r) or standard surgical treatment (resuturing, stapling or no further treatment at the surgeons' discretion). Randomisation was performed during surgery using a centralised interactive voice response system. Duration of postoperative air leakage (primary end point), reduction of intra-operative air leakage intensity (secondary end point) and adverse events (AEs), including postoperative complications, were assessed. RESULTS: A total of 486 patients were screened and 299 received trial treatment (intent-to-treat (ITT) population: TachoSil(r), n=148; standard treatment, n=151). TachoSil(r) resulted in a reduction in the duration of postoperative air leakage (p=0.030). Patients in the TachoSil(r) group also experienced a greater reduction in intra-operative air leakage intensity (p=0.042). Median time until chest drain removal was 4 days with TachoSil(r) and 5 days in the standard group (p=0.054). There was no difference between groups in hospital length of stay. AEs were generally similar in both groups, including postoperative complications. CONCLUSIONS: TachoSil(r) was superior to standard surgical treatment in reducing both postoperative air leakage duration and intra-operative air leakage intensity in patients undergoing elective pulmonary lobectomy. PMID- 20541950 TI - Beta-carboline alkaloids bind DNA. AB - Beta-carboline alkaloids present in Peganum harmala (harmal) have recently drawn attention due to their antitumor activities. The mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. They interact with DNA via both groove binding and intercalative modes and cause major DNA structural changes. The aim of this study was to examine the interactions of five beta-carboline alkaloids (harmine, harmane, harmaline, harmalol and tryptoline) with calf-thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various alkaloids/polynucleotide (phosphate) ratios of 1/240, 1/160, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of alkaloids-DNA complexes in aqueous solution. Spectroscopic evidence showed major binding of alkaloids to DNA with overall binding constants of K(harmine)-DNA=3.44x10(7) M(-1), K(harmane) DNA=1.63x10(5) M(-1), K(harmaline)-DNA=3.82x10(5) M(-1), K(harmalol) DNA=6.43x10(5) M(-1) and K(tryptoline)-DNA=1.11x10(5) M(-1). The affinity of alkaloids-DNA binding is in the order of harmine>harmalol>harmaline>harmane>tryptoline. No biopolymer secondary structural changes were observed upon alkaloid interaction and DNA remains in the B-family structure in these complexes. PMID- 20541952 TI - Alzheimer's disease: brain expression of a metabolic disorder? AB - Alzheimer's disease (AD) is the most common form of dementia and is of rapidly increasing health, social and economic impact. Recent evidence suggests a strict link between metabolic disorders and AD. In the last decade much attention has focused specifically on the connection between dysfunction of lipid metabolism and AD. Here we discuss aspects of lipid regulation, including changes in cholesterol levels, function of apolipoproteins and leptin, and how these relate to AD pathogenesis. Despite the vast literature available, many aspects still need clarification. Nevertheless, the route is already delineated to directly connect aspects of lipid regulation to AD. This could represent a starting point to identify novel potential targets for a preventive and/or treatment strategy of the disease. PMID- 20541951 TI - Lymphatic lipid transport: sewer or subway? AB - The lymphatics began receiving attention in the scientific community as early as 1622, when Gasparo Aselli noted the appearance of milky-white vessels in the mesentery of a well-fed dog. Since this time, the lymphatic system has been historically regarded as the sewer of the vasculature, passively draining fluid and proteins from the interstitial spaces (along with lipid from the gut) into the blood. Recent reports, however, suggest that the lymphatic role in lipid transport is an active and intricate process, and that when lymphatic function is compromised, there are systemic consequences to lipid metabolism and transport. This review highlights these recent findings, and suggests future directions for understanding the interplay between lymphatic and lipid biology in health and disease. PMID- 20541953 TI - Effect of the His residue on the cyclization of b ions. AB - The MS(n) spectra of the [M + H](+) and b(5) peaks derived from the peptides HAAAAA, AHAAAA, AAHAAA, AAAHAA, and AAAAHA have been measured, as have the spectra of the b(4) ions derived from the first four peptides. The MS(2) spectra of the [M + H](+) ions show a substantial series of b(n) ions with enhanced cleavage at the amide bond C-terminal to His and substantial cleavage at the amide bond N-terminal to His (when there are at least two residues N-terminal to the His residue). There is compelling experimental and theoretical evidence for formation of nondirect sequence ions via cyclization/reopening chemistry in the CID spectra of the b ions when the His residue is near the C-terminus. The experimental evidence is less clear for ions when the His residue is near the N terminus, although this may be due to the use of multiple alanine residues in the peptide making identifying scrambled peaks more difficult. The product ion mass spectra of the b(4) and b(5) ions from these isomeric peptides with cyclically permuted amino acid sequences are similar, but also show clear differences. This indicates less active cyclization/reopening followed by fragmentation of common structures for b(n) ions containing His than for sequences of solely aliphatic residues. Despite more energetically favorable cyclization barriers for the b(5) structures, the b(4) ions experimental data show more clear evidence of cyclization and sequence scrambling before fragmentation. For both b(4) and b(5) the energetically most favored structure is a macrocyclic isomer protonated at the His side chain. PMID- 20541954 TI - Learning of predictive relations between events depends on attention, not on awareness. AB - It is generally assumed that storing predictive relations between two events (E(1) consistently precedes E(2)) in memory as bi-directional associations does not require conscious awareness of this relation, whereas the formation of unidirectional associations that capture the direction of the relation (priming e(1) activates e(2), but e(2) not e(1)) does. This study reports a set of experiments demonstrating that unidirectional associations can be formed even when awareness of the relation is actively prevented, if attention is "tuned" to process predictive relations. When participants engaged in predicting targets based on cues in an unrelated task before the actual acquisition phase, unidirectional associations were formed during this acquisition phase even though E(1) was presented subliminally. This suggests that although processing the relation between events may often be accompanied by awareness of this relation, awareness is not a prerequisite for the formation of unidirectional associations. PMID- 20541955 TI - Constitutively active Lck kinase in T cells drives antigen receptor signal transduction. AB - T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was readily detectable in these cells in lymphoid organs. In naive T cells up to approximately 40% of total Lck was constitutively activated, part of which was also phosphorylated on the C-terminal inhibitory site. Formation of activated Lck was independent of TCR and coreceptors but required Lck catalytic activity and its maintenance relied on monitoring by the HSP90-CDC37 chaperone complex to avoid degradation. The amount of activated Lck did not change after TCR and coreceptor engagement; however it determined the extent of TCR-zeta phosphorylation. Our findings suggest a dynamic regulation of Lck activity that can be promptly utilized to initiate T cell activation and have implications for signaling by other immune receptors. PMID- 20541956 TI - Comparison of subjective scoring systems used to evaluate equine laminitis. AB - This study compared three subjective scoring systems used to assess lameness associated with equine laminitis: (1) visual analogue scale, (2) Obel score and (3) clinical grading system (CGS). Two groups of 12 observers, consisting of equine veterinarians and final-year veterinary students, scored lameness severity after watching video footage of 14 horses on two occasions. Generalizability theory was used to investigate the reliability of the three systems and the effects of observer experience. Overall reliability across all times and observers was high. Intra-observer reliability was higher than inter-observer reliability for all scoring systems, with student reliability being consistently lower than veterinarians, especially for Obel and CGS. All three methods were reasonably reliable tools for assessing lameness, but they were more limited in the hands of inexperienced observers. PMID- 20541957 TI - An overview of glomerular filtration rate testing in dogs and cats. AB - Determination of glomerular filtration rate (GFR) is a valuable, yet underused, diagnostic tool for evaluating renal function in dogs and cats. This article first reviews the hormonal and hemodynamic factors which contribute to GFR, followed by a description of considerations when selecting a pharmacokinetic model and methods of animal-to-animal standardization. The best-characterized existing GFR markers, including creatinine, radiolabeled markers, and iohexol, are reviewed in depth, as well as alternative but lesser used techniques. A weighted means analysis of reported GFR measurements in healthy dogs and cats and a review of selected studies that have examined GFR alterations in animals with naturally occurring and experimental diseases provide the reader with preliminary guidelines on expected GFR results in these species and disease conditions. PMID- 20541958 TI - [Analysis of the induced prescription in a primary care region]. AB - OBJECTIVES: To find out the prevalence, origin and cost associated with Induced Prescription (IP) in Primary Health Care (PHC) in the West of Gipuzkoa (WG). To find out the extent to which PHC doctors agree with IP. To analyse the adaptation of IP to PHC clinical management contract indicators. MATERIALS AND METHODS: Design descriptive multi-centre cross-study. LOCATION: Primary Health Care, 38 doctors from 17 WG PHC units. PARTICIPANTS: Pharmaceutical prescriptions eligible for finance over a period of two days in outpatients and chronic diseases generated by the Osabide computer application. Variables analysed: type of prescription, origin, prescriber, diagnosis, price and level of agreement. RESULTS: A total of 6.919 prescriptions were made out, with 44% (95% CI: 42.8 45.1) being IP. Of the total cost, 62.2% was put down to IP, with an average price per prescription of ?22.3,and in non-induced prescription (NIP) it was ?10.62. The therapeutic subgroups with the highest cost were lipid lowering and bronchodilator drugs. The level of disagreement of the doctors taking part in IP was 28.8%. The adaptation to the quality indicators of the prescription was higher in NIP than in IP. CONCLUSIONS: There is a high percentage of IP associated with high costs attributed to PHC. The percentage of disagreement in PHC with regard to IP is significant. There is a high influence of IP on the evaluation of the quality indicators established in PHC. PMID- 20541959 TI - Mycobacterium marinum infection following kayaking injury. PMID- 20541960 TI - Peruvian community health promoters: expanding the spaces of health voluntarism. AB - This paper emphasises the importance of recognising the global South as a key site for understanding the patterning of geographies of health voluntarism. Feeding into a broader critique of neoliberal health and development policies, the paper explores what a case study of health promoters in a popular settlement in Lima, Peru, can add to our understanding of practices of health voluntarism rooted in distinct places, emphasising the uneven and gendered nature of such voluntary activity. In particular, the paper considers the ways in which urban community spaces are negotiated, inhabited and shaped by volunteer women health workers, arguing that an exploration of these everyday practices provides a more nuanced picture of the role of voluntarism in healthcare provisioning under neoliberal regimes. PMID- 20541961 TI - A triptych of the evolution of plant transposable elements. AB - Transposable elements (TEs) constitute the majority of angiosperm DNA, but the processes that govern their accumulation remain mysterious. Here we discuss the three major forces that govern the accumulation of TEs, corresponding to the three panels of a triptych. The first force, transposition, creates new copies of TEs, but is regulated by both host- and TE-specific mechanisms. The second force, deletion of TE DNA, is capable of removing vast swaths of genomic regions via recombinational processes, but we still have very little insight into how deletion varies across species and even among TE types. Finally, we focus on the often-ignored third panel of our triptych - the population processes that determine the ultimate evolutionary fate of TE insertions. PMID- 20541962 TI - Flagellum assembly and function during the Leishmania life cycle. AB - During a complex digenetic life cycle flagellated Leishmania parasites alternate between promastigote and amastigote forms which differ significantly in cellular morphology and flagellum length. Recent studies have provided important new insights into mechanisms by which Leishmania regulate expression of genes required for flagellum assembly, and mechanisms used to modify flagellum length. While the critical role of the promastigote flagellum in parasite biology has long been appreciated, the importance of the amastigote flagellum has often been disregarded. However, recent work suggests that the 'rudimentary' amastigote flagellum may serve indispensable roles in cellular organisation, and/or sensory perception, which are critical for intracellular survival of Leishmania within host macrophages. PMID- 20541963 TI - Simultaneous spectrophotometric determination of cyproterone acetate and ethinyl estradiol in tablets using continuous wavelet and derivative transform. AB - In this study a zero crossing technique based on continuous wavelet transform (CWT) as well as classical derivative spectrophotometry (CDS) is presented for simultaneous determination of cyproterone acetate and ethinyl estradiol in binary mixtures and commercial dosage of drug, without using prior chemical pre treatment. Absorption spectra were recorded in the wavelength range 200-400 nm. Absorbance data were subjected to various mother wavelets from continuous wavelet transform family to find the optimum point of the wavelet signal processing (Matlab 7.5) gaus 15 and morl wavelet functions with scaling factor, a=70 and 3rd derivative with Deltalambda=10 nm, were selected. Optimum value of scaling factor was chosen to obtain an appropriate calibration for each method. The validation of proposed methods was investigated by several synthetic mixtures and obtained results were successfully compared among each other. Mean recovery values were found between 96.93% and 101.7% for CWT and 95.55% and 104.22% for DS, respectively for the determination of cyproterone acetate and ethinyl estradiol in synthetic mixtures. The developed methods are rapid, precise and easy to apply for the analysis of overlapping signals of the components in the mixtures. Obtained results from the CWT were compared to those yielded by CDS which were in good agreement and therefore led to a successful determination. PMID- 20541964 TI - Competitive adsorption study of CO2 and SO2 on CoII3[CoIII(CN)6]2 using DRIFTS. AB - Diffuse reflectance infrared Fourier transform spectroscopy was used to study the competitive adsorption of CO(2) and SO(2) on the cobalt Prussian blue analogue Co(II)(3)[Co(III)(CN)(6)](2) at 298 K. Characteristic peaks for adsorbed CO(2) and SO(2) species were identified and their relative areas, measured simultaneously as a function of pressure at 298 K, varied in accordance with a Langmuir-Freundlich isotherm fitted to both gases in the low-coverage Henry's Law limit. Evidence for co-adsorption of trace water was also obtained, as well as the apparent formation of an analogous cobalt nitroprusside compound as a reaction product under certain conditions. The several aspects of the adsorption of CO(2) and SO(2) determined in this work point to an important role for real time diffuse reflectance infrared measurements in adsorption studies, particularly in the case of competitive adsorption where the occurrence and fate of molecular-level markers arising from more than one adsorbed species can be monitored simultaneously. Depending on the application, this may more than offset certain quantitative limitations of the technique that confine measurements to a relatively narrow set of experimental conditions and demand careful consideration of the effects of sample preparation and treatment. PMID- 20541965 TI - Synchrotron radiation linear dichroism (SRLD) investigation of the electronic transitions of quinizarin, chrysazin, and anthrarufin. AB - The electronic transitions of the three alpha,alpha'-dihydroxy derivatives of anthraquinone, 1,4-dihydroxy-, 1,8-dihydroxy-, and 1,5-dihydroxy-9,10 anthraquinone (quinizarin, chrysazin, and anthrarufin), were investigated by synchrotron radiation linear dichroism (SRLD) spectroscopy on samples aligned in stretched polyethylene. With synchrotron radiation, polarization data could be determined in the UV region up to ca. 58,000 cm(-1) (7.2 eV), which amounts to an extension by ca. 11,000 cm(-1) (1.4 eV) relative to the range accessible with a conventional light source. Throughout the investigated region (15,000-58,000 cm( 1)), essentially similar wavenumbers, intensities, and transition moment directions were determined for chrysazin and anthrarufin, while the spectrum of quinizarin deviated significantly. The results of time-dependent density functional theory (TD-DFT) calculations were in good agreement with the experimental spectra, leading to the assignment of 10 electronic states for quinizarin, and 8 electronic states for chrysazin and anthrarufin. No evidence was found for contributions from different tautomeric or rotameric forms to the observed spectra. PMID- 20541966 TI - Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection. AB - BACKGROUND: Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. OBJECTIVES: To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). STUDY DESIGN: The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. RESULTS: HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in 0.05 for all comparisons). In conclusion, resection or deafferentation of an amygdala with a volume within the normal range was associated with increased postoperative anxiety. PMID- 20541982 TI - Characterization of combat-related spinal injuries sustained by a US Army Brigade Combat Team during Operation Iraqi Freedom. AB - BACKGROUND CONTEXT: The United States is presently engaged in the largest scale armed conflict since Vietnam. Despite recent investigations into the scope of injuries sustained by soldiers in Iraq and Afghanistan, little information is available regarding the incidence and epidemiology of spine trauma in this population. PURPOSE: Characterize the incidence and epidemiology of spinal injuries sustained during combat by soldiers of a US Army Brigade Combat Team (BCT) that participated in Operation Iraqi Freedom. STUDY DESIGN: Descriptive epidemiologic study. PATIENT SAMPLE: A total of 4,122 soldiers who served in Iraq with an Army BCT during "The Surge" operation. OUTCOME MEASURES: Spine injury epidemiology was calculated for the BCT, including the spine combat casualty rate, and percent medically evacuated (MEDEVAC). METHODS: Unit rosters were obtained, and a comprehensive database identifying all combat-related spine injuries was created by querying each soldiers' electronic medical record and the unit's casualty rosters. Demographic information was recorded including age, sex, rank, injury mechanism, presence of polytrauma, and injury outcome. Injury outcomes were classified as killed in action, died of wounds, MEDEVAC, or returned to duty. The incidence of spine injuries was determined, and epidemiology was characterized using calculations of the spine combat casualty rate and percent MEDEVAC. Comparisons were made to published reports from previous conflicts. RESULTS: A total of 29 soldiers sustained 31 combat-related spine injuries. These accounted for 7.4% (29 out of 390) of all casualties sustained during combat. Blunt trauma to the spine, often resulting from an explosive mechanism, was encountered in 65% of cases. Closed fractures of the spine occurred in 21% of casualties and open injuries occurred in 7%. The spine combat casualty rate was 5.6 out of 1,000 soldier combat-years, and the percent MEDEVAC was 19%. CONCLUSIONS: This investigation is the first of its kind, documenting the nature of spine trauma in a major American conflict. The incidence of spine injuries in this study is the highest ever documented and is indicative of the tactics used by the enemy in the current war. Given this fact, it is likely that the prevalence of combat-related spine trauma will increase in the future. Larger, more extensive, studies of this kind must be conducted in the future. PMID- 20541983 TI - DNA ligase 4 stabilizes the ribosomal DNA array upon fork collapse at the replication fork barrier. AB - DNA double-strand breaks (DSB) were shown to occur at the replication fork barrier in the ribosomal DNA of Saccharomyces cerevisiae using 2D-gel electrophoresis. Their origin, nature and magnitude, however, have remained elusive. We quantified these DSBs and show that a surprising 14% of replicating ribosomal DNA molecules are broken at the replication fork barrier in replicating wild-type cells. This translates into an estimated steady-state level of 7-10 DSBs per cell during S-phase. Importantly, breaks detectable in wild-type and sgs1 mutant cells differ from each other in terms of origin and repair. Breaks in wild-type, which were previously reported as DSBs, are likely an artefactual consequence of nicks nearby the rRFB. Sgs1 deficient cells, in which replication fork stability is compromised, reveal a class of DSBs that are detectable only in the presence of functional Dnl4. Under these conditions, Dnl4 also limits the formation of extrachromosomal ribosomal DNA circles. Consistently, dnl4 cells displayed altered fork structures at the replication fork barrier, leading us to propose an as yet unrecognized role for Dnl4 in the maintenance of ribosomal DNA stability. PMID- 20541984 TI - Simultaneous determination of active xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration of Zi-Shen Pill extract for the pharmacokinetic study by liquid chromatography-tandem mass spectrometry. AB - A sensitive and reliable liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for simultaneous determination of active components, i.e., xanthone glycosides (neomangiferin and mangiferin), timosaponins (timosaponin E1, timosaponin B-II and timosaponin B) and alkaloids (palmatine and berberine) in rat plasma after oral administration of Zi-Shen Pill extract. Plasma samples were pretreated by protein precipitation with acetonitrile containing the internal standards ginsenoside Re (for xanthone glycosides and timosaponins) and tetrahydroberberine (for alkaloids). LC separation was achieved on a Zorbax SB-C(18) column (150 mm x 2.1 mm I.D., 3.5 microm) with gradient elution using a mobile phase consisting of acetonitrile-0.1% formic acid in water at a flow rate of 0.25 mL/min. The detection was carried out by a triple-quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via polarity switching between negative (for xanthone glycosides and timosaponins) and positive (for alkaloids) ionization mode. Linear calibration curves were obtained over the concentration range of 5-1000 ng/mL for mangiferin, 0.5-100 ng/mL for neomangiferin, timosaponin E1, timosaponin B-II and timosaponin B, and 0.05-10 ng/mL for palmatine and berberine. The mean recovery of all the analytes ranged from 64.7 to 93.8%. The intra- and inter-day precision (% R.S.D.) was within 11.7% and accuracy (% bias) ranged from -9.0 to 10.9%. This fully validated method was successfully applied to pharmacokinetic study of the above seven compounds in rats. PMID- 20541985 TI - Role of polymer-protein interaction on partitioning pattern of bovine pancreatic trypsinogen and alpha-chymotrypsinogen in polyethyleneglycol/sodium tartrate aqueous two-phase systems. AB - The partitioning pattern of bovine trypsinogen (TRPz) and alpha-chymotrypsinogen (ChTRPz) was investigated in a low impact aqueous two-phase system formed by polyethyleneglycol (PEG) and sodium tartrate (NaTart) pH 5.00. ChTRPz exhibited higher partition coefficients than TRPz did in all the assayed systems. The decrease in PEG molecular weight and the increase in tie line length were observed to displace the partitioning equilibrium of both proteins to the top phase, while phase volume ratios in the range 0.5-1.5 showed not to affect protein partitioning behaviour. Systems formed by PEG of molecular weight 600 with composition corresponding to a high tie line length (PEG 12.93%, w/w and NaTart 21.20%, w/w) are able to recover most of both zymogens in the polymer enriched phase. A crucial role of PEG-protein interaction in the partitioning mechanism was evidenced by isothermal calorimetric titrations. The major content of highly exposed tryptophan rests, present in ChTRPz molecule, could be considered to be determinant of its higher partition coefficient due to a selective charge transfer interaction with PEG molecule. A satisfactory correlation between partition coefficient and protein surface hydrophobicity was observed in systems formed with PEGs of molecular weight above 4000, this finding being relevant in the design of an extraction process employing aqueous two-phase systems. PMID- 20541986 TI - Relations of changes in self-regulatory efficacy and physical self-concept with improvements in body satisfaction in obese women initiating exercise with cognitive-behavioral support. AB - Effects of exercise on body image are not well understood. Obese women seeking weight loss were randomly assigned to groups of exercise supported by a cognitive behavioral protocol (n=68) or typical introductory methods (n=66), and assessed on body satisfaction (Body Areas Satisfaction Scale; BASS), self-regulatory efficacy (Exercise Self-Efficacy Scale; ESE), physical self-concept (Physical Self-Concept; PSC), weight, and body composition, over 6 months. Improvements on all measures were greatest in the cognitive-behavioral support condition. Improvement in BASS scores was better predicted by changes in the two psychological measures (PSC, ESE; R2(adj)=.30 and .32, respectively) than changes in the two physiological measures (weight and body composition; R2(adj)=.07 and .00, respectively). When all four predictors were entered into a multiple regression equation, only changes in ESE and PSE demonstrated significant unique contributions to the overall explained variance in BASS change. Theory and treatment implications were discussed. PMID- 20541987 TI - Spermatogonial transplantation in fish: A novel method for the preservation of genetic resources. AB - Recent progress in genome-based breeding has created various fish strains carrying desirable genetic traits; however, methods for the long-term preservation of their genetic resources have not yet been developed, mainly due to the lack of cryopreservation techniques for fish eggs and embryos. Recently, we established an alternative cryopreservation technique for fish spermatogonia using a slow-freezing method. Furthermore, we developed a transplantation system to produce functional eggs and sperm derived from spermatogonia. Spermatogonia isolated from the testes of vasa-green fluorescent protein (Gfp) transgenic rainbow trout (Oncorhynchus mykiss) were transplanted into the peritoneal cavity of triploid masu salmon (Oncorhynchus masou) hatchlings of both genders. The transplanted trout spermatogonia migrated towards the gonadal anlagen of the recipient salmon, into which they were subsequently incorporated. We confirmed that the donor-derived spermatogonia resumed gametogenesis, and produced sperm and eggs in male and female recipient salmon, respectively. Fertilization of the resultant eggs and sperm produced only rainbow trout in the first filial (F1) generation, suggesting that the sterile triploid recipient salmon produced functional eggs and sperm derived from the trout donors. A combination of spermatogonial transplantation and cryopreservation could be a powerful tool for preserving valuable fish strains with desirable genetic traits and endangered species. PMID- 20541988 TI - Reconstruction of large defects of the neck using an extended vertical lower trapezius island myocutaneous flap following salvage surgery for neck recurrence of oral carcinoma. AB - This article describes the extended vertical lower trapezius island myocutaneous flap for reconstructing large defects of the neck. A total of 11 patients with neck recurrence of oral carcinoma were treated using salvage surgery and an extended vertical lower trapezius island myocutaneous flap based on the transverse cervical artery was used to repair the large defect in the neck. No major flap failure occurred. No disabilities were observed in terms of shoulder motion. The patients were followed up for 6-22 months. Four patients developed local recurrence: two of them are still alive with the disease and two have died. The extended vertical lower trapezius island myocutaneous flap is a large, simple and reliable flap, which is a salvage flap preferred for reconstructing large defects of the neck following the ablation of neck recurrence of oral carcinoma. PMID- 20541989 TI - Atypical diffuse lipomatosis with multifocal abdominal involvement: a case report. AB - We present the case of an 8-year-old child with diffuse lipomatosis simultaneously involving the intra-peritoneum, retro-peritoneum and abdominal wall. To the best of our knowledge, this is the first case of diffuse lipomatosis with simultaneous multi-focal involvement of the entire abdomen. PMID- 20541990 TI - Elastofibroma dorsi: the need to operate? PMID- 20541991 TI - Evaluation of nucleosome forming potentials (NFPs) of forensically important STRs. AB - Degraded forensic samples have proved difficult to analyze and interpret. New analysis techniques are constantly being discovered and improved but researchers have overlooked the structural properties that could prevent or slow the process of degradation. In theory, DNA that are bound to histones as nucleosomes are less prone to degradation, because nucleosomes prevent DNA from being exposed to degradative enzymes. In this study we determined the probability of 60 forensic DNA markers to be bound to histones based on their base sequence composition. Two web-based tools - NXSensor and nuScore - were used to analyze four hundred base pairs surrounding each DNA marker for properties that inhibit or promote the binding of DNA to histones. Our results showed that the majority of markers analyzed were likely to be bound as nucleosomes. Selection of the markers that are more protected to form a multiplex could increase the chance of obtaining a better balanced, easier to interpret DNA profile from degraded samples. PMID- 20541992 TI - Tibial intercondylar eminence fractures in children: The long-term perspective. AB - PURPOSE OF THE STUDY: To analyze objective and subjective results on medium-term follow-up of intercondylar fractures of the tibia in children. MATERIAL AND METHODS: A retrospective, single-center study of 32 fractures (17 boys, 14 girls) was performed. Fractures were itemized on the Meyers and McKeever classification as modified by Zaricznyj: there were eight type-I, 17 type-II, five type-III and two type-IV fractures. Treatment was conservative for type-I and II fractures (with mild displacement) and for the others surgical. Seven patients were lost to follow-up and one had insufficient follow-up for inclusion. Thirteen patients were assessed on a KT 1000 arthrometer and a dynamometer, and on the IKDC and ARPEGE scoring systems. Ten patients chose to answer only the subjective IKDC questionnaire, by mail. RESULTS: The mean IKDC score of subjects answering by mail was 91 and of those with clinical examination was 80. Mean ARPEGE score was 8.3. Subjective IKDC score classified four patients as A, four as B, four as C and one as D. Mean difference in tibial anterior translation between affected and unaffected knees was 0.88mm for type I fractures, 0.82mm for type II and 0.30mm for types III and IV together. DISCUSSION: The mean difference in tibial anterior translation between affected and unaffected knees was greater in patients with conservative treatment (0.96mm for conservative vs. 0.29mm for surgical treatment). Seventy per cent of patients reported pain at follow-up. Only two had pathological knee laxity. Twelve out of thirteen had returned to sport activity, half of them at the same level as before injury. CONCLUSION: The cases treated surgically had a better objective result than those treated conservatively. Nevertheless there was no correlation between subjective evaluation and degree of knee laxity. Overall, intercondylar fractures of the tibial eminence in children have good long-term prognosis, at least subjectively. This study shows that, in spite of a very satisfactory subjective result for most patients, results were not so good on objective measures. LEVEL OF EVIDENCE: Level IV: retrospective study. PMID- 20541993 TI - Ubiquitin recognition by the Cockayne syndrome group B protein: binding will set you free. AB - Transcription-coupled nucleotide excision repair (TC-NER) requires the coordinated efforts of many proteins. In this issue of Molecular Cell, Anindya et al. (2010) show that the proteins assemble at the site of DNA damage but cannot begin repair until the Cockayne syndrome group B protein (CSB) binds ubiquitin. PMID- 20541994 TI - Regulating the regulator: Rsp5 ubiquitinates the proteasome. AB - In this issue of Molecular Cell, Isasa et al. (2010) show that the Rsp5 ubiquitin ligase regulates substrate recruitment to the 26S proteasome by ubiquitinating Rpn10, the proteasome's polyubiquitin degradation signal receptor. PMID- 20541995 TI - Waste and yet want not. AB - In this issue of Molecular Cell, Shachrai et al. (2010) demonstrate that the cost of wasteful protein expression in E. coli is specific to the transition from stationary phase to balanced exponential growth, probably because of a shortage of ribosomes during this growth phase. PMID- 20541996 TI - The diversity of ubiquitin recognition: hot spots and varied specificity. AB - Ubiquitin is attached to a large number of proteins and gives rise to signaling events that modulate many cellular functions. These signals are often based on the recognition of polyubiquitin chains, which are produced in a variety of lengths and linkage patterns. In addition, proteins that are similar to ubiquitin in structure and function are often recognized by an overlapping set of partners. Research over the past several years has expanded our understanding of how ubiquitin and ubiquitin-like proteins are recognized. Most interactions occur at a few distinct surface areas; however, individual binding partners have specific, unique contacts that impart specificity. In this review, we summarize available information to facilitate comparisons across the ubiquitin-like family. PMID- 20541997 TI - A ubiquitin-binding domain in Cockayne syndrome B required for transcription coupled nucleotide excision repair. AB - Transcription-coupled nucleotide excision repair (TC-NER) allows RNA polymerase II (RNAPII)-blocking lesions to be rapidly removed from the transcribed strand of active genes. Defective TCR in humans is associated with Cockayne syndrome (CS), typically caused by defects in either CSA or CSB. Here, we show that CSB contains a ubiquitin-binding domain (UBD). Cells expressing UBD-less CSB (CSB(del)) have phenotypes similar to those of cells lacking CSB, but these can be suppressed by appending a heterologous UBD, so ubiquitin binding is essential for CSB function. Surprisingly, CSB(del) remains capable of assembling nucleotide excision repair factors and repair synthesis proteins around damage-stalled RNAPII, but such repair complexes fail to excise the lesion. Together, our results indicate an essential role for protein ubiquitylation and CSB's UBD in triggering damage incision during TC-NER and allow us to integrate the function of CSA and CSB in a model for the process. PMID- 20541998 TI - Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks. AB - DNA damage that blocks replication is bypassed in order to complete chromosome duplication and preserve cell viability and genome stability. Rad5, a PCNA polyubiquitin ligase and DNA-dependent ATPase in yeast, is orthologous to putative tumor suppressors and controls error-free damage bypass by an unknown mechanism. To identify the mechanism in vivo, we investigated the roles of Rad5 and analyzed the DNA structures that form during damage bypass at site-specific stalled forks present at replication origins. Rad5 mediated the formation of recombination-dependent, X-shaped DNA structures containing Holliday junctions between sister chromatids. Mutants lacking these damage-induced chromatid junctions were defective in resolving stalled forks, restarting replication, and completing chromosome duplication. Rad5 polyubiquitin ligase and ATPase domains both contributed to replication fork recombination. Our results indicate that multiple activities of Rad5 function coordinately with homologous recombination factors to enable replication template switch events that join sister chromatids at stalled forks and bypass DNA damage. PMID- 20541999 TI - Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. AB - Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression. PMID- 20542000 TI - Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. AB - Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, approximately 50-200 nucleotides in length, transcribed from the 5' end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes. PMID- 20542001 TI - Negative regulation of tumor suppressor p53 by microRNA miR-504. AB - Tumor suppressor p53 plays a central role in tumor prevention. p53 protein levels and activity are under a tight and complex regulation in cells to maintain the proper function of p53. MicroRNAs play a key role in the regulation of gene expression. Here we report the regulation of p53 through miR-504. miR-504 acts as a negative regulator of human p53 through its direct binding to two sites in the p53 3' untranslated region. Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53 mediated apoptosis, and cell-cycle arrest in response to stress, and furthermore promotes tumorigenecity of cells in vivo. These results demonstrate the direct negative regulation of p53 by miR-504 as a mechanism for p53 regulation in cells, which highlights the importance of microRNAs in tumorigenesis. PMID- 20542002 TI - Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. AB - The TIP60 tumor suppressor is a histone acetyltransferase involved in transcriptional regulation, checkpoint activation, and p53-directed proapoptotic pathways. We report that human papillomavirus (HPV) E6 destabilizes TIP60 both in vivo and in vitro. TIP60 binds to the HPV major early promoter and acetylates histone H4 to recruit Brd4, a cellular repressor of HPV E6 expression. Both low- and high-risk HPV E6 destabilize TIP60, thereby derepressing their own promoter. Destabilization of TIP60 by HPV E6 also relieves cellular promoters from TIP60 initiated repression and abrogates p53-dependent activation of apoptotic pathway. Degradation of TIP60, therefore, allows low- and high-risk HPV to promote cell proliferation and cell survival. PMID- 20542003 TI - The AAA-ATPase Rea1 drives removal of biogenesis factors during multiple stages of 60S ribosome assembly. AB - The AAA(+)-ATPase Rea1 removes the ribosome biogenesis factor Rsa4 from pre-60S ribosomal subunits in the nucleoplasm to drive nuclear export of the subunit. To do this, Rea1 utilizes a MIDAS domain to bind a conserved motif in Rsa4. Here, we show that the Rea1 MIDAS domain binds another pre-60S factor, Ytm1, via a related motif. In vivo Rea1 contacts Ytm1 before it contacts Rsa4, and its interaction with Ytm1 coincides with the exit of early pre-60S particles from the nucleolus to the nucleoplasm. In vitro, Rea1's ATPase activity triggers removal of the conserved nucleolar Ytm1-Erb1-Nop7 subcomplex from isolated early pre-60S particle. We suggest that the Rea1 AAA(+)-ATPase functions at successive maturation steps to remove ribosomal factors at critical transition points, first driving the exit of early pre-60S particles from the nucleolus and then driving late pre-60S particles from the nucleus. PMID- 20542004 TI - The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. AB - ISG15 is an interferon-induced and antiviral ubiquitin-like protein (Ubl). Herc5, the major E3 enzyme for ISG15, mediates the ISGylation of more than 300 proteins in interferon-stimulated cells. In addressing this broad substrate selectivity of Herc5, we found that: (1) the range of substrates extends even further and includes many exogenously expressed foreign proteins, (2) ISG15 conjugation is restricted to newly synthesized pools of proteins, and (3) Herc5 is physically associated with polyribosomes. These results lead to a model for ISGylation in which Herc5 broadly modifies newly synthesized proteins in a cotranslational manner. This further suggests that, in the context of an interferon-stimulated cell, newly translated viral proteins may be primary targets of ISG15. Consistent with this, we demonstrate that ISGylation of human papillomavirus (HPV) L1 capsid protein has a dominant-inhibitory effect on the infectivity of HPV16 pseudoviruses. PMID- 20542005 TI - Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome. AB - The proteasome recognizes its substrates via a diverse set of ubiquitin receptors, including subunits Rpn10/S5a and Rpn13. In addition, shuttling factors, such as Rad23, recruit substrates to the proteasome by delivering ubiquitinated proteins. Despite the increasing understanding of the factors involved in this process, the regulation of substrate delivery remains largely unexplored. Here we report that Rpn10 is monoubiquitinated in vivo and that this modification has profound effects on proteasome function. Monoubiquitination regulates the capacity of Rpn10 to interact with substrates by inhibiting Rpn10's ubiquitin-interacting motif (UIM). We show that Rsp5, a member of NEDD4 ubiquitin protein ligase family, and Ubp2, a deubiquitinating enzyme, control the levels of Rpn10 monoubiquitination in vivo. Notably, monoubiquitination of Rpn10 is decreased under stress conditions, suggesting a mechanism of control of receptor availability mediated by the Rsp5-Ubp2 system. Our results reveal an unanticipated link between monoubiquitination signal and regulation of proteasome function. PMID- 20542006 TI - Systematic analysis of essential genes reveals important regulators of G protein signaling. AB - The yeast pheromone pathway consists of a canonical heterotrimeric G protein and MAP kinase cascade. To identify additional signaling components, we systematically evaluated 870 essential genes using a library of repressible promoter strains. Quantitative transcription-reporter and MAPK activity assays were used to identify strains that exhibit altered pheromone sensitivity. Of the 92 newly identified essential genes required for proper G protein signaling, those involved with protein degradation were most highly represented. Included in this group are members of the Skp, Cullin, F box (SCF) ubiquitin ligase complex. Further genetic and biochemical analysis reveals that SCF(Cdc4) acts together with the Cdc34 ubiquitin-conjugating enzyme at the level of the G protein; promotes degradation of the G protein alpha subunit, Gpa1, in vivo; and catalyzes Gpa1 ubiquitination in vitro. These insights to the G protein signaling network reveal the essential genome as an untapped resource for identifying new components and regulators of signal transduction pathways. PMID- 20542008 TI - Morphological tegument alterations of adult Schistosoma mansoni, harbored in non anti-helminthic treated, high-immune-tolerogenic and low-inflammatory mice. AB - The present study exhibits original results of S. mansoni tegumental alterations due to contact with the immune system of non anti-helminthic treated mice. We compared, by SEM, the tegument of adult worms recovered from strains of mice genetically selected to extreme phenotypes of resistance (TR strain) and susceptibility (TS strain) to egg-albumin oral tolerance (OT). The parasites recovered from TR mice displayed no morphologic alteration, while specimens collected from TS mice presented tubercle swelling with blunted and shortened spines in lower density, increased sensory organelle numbers, fusion and tegumental ridge peeling. These tegument alterations were similar to those described for Artemether or Praziquantel treatment, supporting observations that the host immune system influences the development and function of the tegument of worms harbored in both anti-helminthic treated and non-treated mice. Our results are indicative that the development and function of the worm tegument depend on the immune regulatory capacity of each individual host. PMID- 20542007 TI - Structure of the human mTOR complex I and its implications for rapamycin inhibition. AB - The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth in response to the nutrient and energy status of the cell, and its deregulation is common in human cancers. Little is known about the overall architecture and subunit organization of this essential signaling complex. We have determined the three-dimensional (3D) structure of the fully assembled human mTORC1 by cryo electron microscopy (cryo-EM). Our analyses reveal that mTORC1 is an obligate dimer with an overall rhomboid shape and a central cavity. The dimeric interfaces are formed by interlocking interactions between the mTOR and raptor subunits. Extended incubation with FKBP12-rapamycin compromises the structural integrity of mTORC1 in a stepwise manner, leading us to propose a model in which rapamycin inhibits mTORC1-mediated phosphorylation of 4E-BP1 and S6K1 through different mechanisms. PMID- 20542009 TI - Molecular phylogenetic study of Culex quinquefasciatus mosquito from different geographical regions of India using 16S rRNA gene sequences. AB - Culex quinquefasciatus is a major vector of filariasis and various encephalitis in India and worldwide. Vector control remains the most successful strategy for the suppression of mosquito borne diseases. The genetic structure of vector populations in terms of insecticide resistance and susceptibility or refractoriness to infection may possibly vary. To exploit the genetic variability in vector population could pave the path for the alternative strategies in vector management. The sequences of ribosomal RNA molecules have been widely used for such studies. Here, we examined the molecular phylogenetic relationship among the Cx. quinquefasciatus collected from different geographical regions of India, using 16S ribosomal RNA (16S rRNA) gene nucleotide sequences. The distances among the species were measured using Pearson correlation; the Neighbor-Joining (NJ) method was used for the clustering with appropriate bootstrap values using Data Analysis in Molecular Biology and Evolution (DAMBE) software. The results revealed that the populations are genetically diverse. Based on the distance values and the tree topology on the basis of 16S rRNA sequences reflected the clear biogeographical and geoclimatic pattern among the different geographical populations from India. PMID- 20542010 TI - Adrenal gland and bone. AB - The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing's disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study. PMID- 20542011 TI - Cardiovascular disease and bone. AB - Osteoporosis-related fractures and coronary artery disease, stroke and peripheral artery disease are common conditions, particularly in the elderly. However, there is now strong evidence indicating that these conditions are associated with one another. Furthermore, there are common pathways in the pathophysiology of these two conditions. PMID- 20542012 TI - Electronic structure of the primary electron donor of Blastochloris viridis heterodimer mutants: high-field EPR study. AB - High-field electron paramagnetic resonance (HF EPR) has been employed to investigate the primary electron donor electronic structure of Blastochloris viridis heterodimer mutant reaction centers (RCs). In these mutants the amino acid substitution His(M200)Leu or His(L173)Leu eliminates a ligand to the primary electron donor, resulting in the loss of a magnesium in one of the constituent bacteriochlorophylls (BChl). Thus, the native BChl/BChl homodimer primary donor is converted into a BChl/bacteriopheophytin (BPhe) heterodimer. The heterodimer primary donor radical in chemically oxidized RCs exhibits a broadened EPR line indicating a highly asymmetric distribution of the unpaired electron over both dimer constituents. Observed triplet state EPR signals confirm localization of the excitation on the BChl half of the heterodimer primary donor. Theoretical simulation of the triplet EPR lineshapes clearly shows that, in the case of mutants, triplet states are formed by an intersystem crossing mechanism in contrast to the radical pair mechanism in wild type RCs. Photooxidation of the mutant RCs results in formation of a BPhe anion radical within the heterodimer pair. The accumulation of an intradimer BPhe anion is caused by the substantial loss of interaction between constituents of the heterodimer primary donor along with an increase in the reduction potential of the heterodimer primary donor D/D+ couple. This allows oxidation of the cytochrome even at cryogenic temperatures and reduction of each constituent of the heterodimer primary donor individually. Despite a low yield of primary donor radicals, the enhancement of the semiquinone iron pair EPR signals in these mutants indicates the presence of kinetically viable electron donors. PMID- 20542013 TI - Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems. AB - The modified ISCOMs, so-called Posintro nanoparticles, provide an opportunity for altering the surface charge of the particles, which influences their affinity for the negatively charged antigen sites, cell membranes and lipids in the skin. Hypothetically, this increases the passage of the ISCOMs (or their components) and their load through the stratum corneum. The subsequent increase in the uptake by the antigen-presenting cells results in enhanced transcutaneous immunization. To understand the nature of penetration of Posintro nanoparticles into the intercorneocyte space of the stratum corneum, the interaction between the nanoparticles and lipid model systems in form of liposomes and/or supported lipid bilayer was studied. As a lipid model we used Stratum Corneum Lipid (SCL), a mixture similar in composition to the lipids of the intercorneocyte space. By Forster Resonance Energy Transfer (FRET), Atomic Force Microscopy (AFM), Electrochemical Impedance Spectroscopy (EIS) and cryo-Transmission Electron Microscopy (cryo-TEM) it was shown that application of nanoparticles to the SCL bilayers results in lipid disturbance. Investigation of this interaction by means of Isothermal Titration Calorimetry (ITC) confirmed existence of an enthalpically unfavorable reaction. All these methods demonstrated that the strength of electrostatic repulsion between the negatively charged SCL and the nanoparticles affected their interaction, as decreasing the negative charge of the Posintro nanoparticles leads to enhanced disruption of lipid organization. PMID- 20542015 TI - Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat. AB - Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn. PMID- 20542014 TI - Rapamycin promotes beta-amyloid production via ADAM-10 inhibition. AB - Rapamycin is a well known immunosuppressant drug for rejection prevention in organ transplantation. Numerous clinical trials using rapamycin analogs, involving both children and adults with various disorders are currently ongoing worldwide. Most recently, rapamycin gained much attention for what appears to be life-span extending properties when administered to mice. The risk for Alzheimer disease (AD) is strongly and positively correlated with advancing age and is characterized by deposition of beta-amyloid peptides (Abeta) as senile plaques in the brain. We report that rapamycin (2.5muM), significantly increases Abeta generation in murine neuron-like cells (N2a) transfected with the human "Swedish" mutant amyloid precursor protein (APP). In concert with these observations, we found rapamycin significantly decreases the neuroprotective amino-terminal APP (amyloid precursor protein) cleavage product, soluble APP-alpha (sAPP-alpha) while increasing production of the beta-carboxyl-terminal fragment of APP (beta CTF). These cleavage events are associated with decreased activation of a disintegrin and metallopeptidase domain-10 (ADAM-10), an important candidate alpha-secretase which opposes Abeta generation. To validate these findings in vivo, we intraperitoneal (i.p.) injected Tg2576 Abeta-overproducing transgenic mice with rapamycin (3mg/kg/day) for 2weeks. We found increased Abeta levels associated with decreased sAPP-alpha at an average rapamycin plasma concentration of 169.7+/-23.5ng/mL by high performance liquid chromatography (HPLC). These data suggest that although rapamycin may increase the lifespan in some mouse models, it may not decrease the risk for age-associated neurodegenerative disorders such as AD. PMID- 20542016 TI - Desipramine attenuates forced swim test-induced behavioral and neurochemical alterations in mice: an in vivo(1)H-MRS study at 9.4T. AB - The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development. PMID- 20542018 TI - HPLC determination of plasma dimethylarginines: method validation and preliminary clinical application. AB - BACKGROUND: Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. RESULTS: The intra- and inter-assay CVs (<5.2%), the absolute and relative recoveries (96 106%) were highly satisfactory. ADMA levels were significantly elevated in all groups of patients compared with controls (p<0.001) with the exception of samples from patients with type II diabetes. SDMA levels were significantly elevated both in the patients with chronic kidney disease and in the patients with type II diabetes complicated by renal insufficiency, the values being closely correlated with both eGFR (R=0.740) and plasmatic creatinine (R=0.700). CONCLUSIONS: The findings made in the present study shows that ADMA levels are significantly increased in patients with diseases associated with endothelial dysfunction This molecule might, therefore, be used as a biochemical marker for the evaluation of endothelial function. Furthermore, the preliminary results reported suggest that SDMA might be a reliable marker of renal function, especially in peadiatric populations, for which the use of eGFR is not recommended. PMID- 20542019 TI - Breath biomarkers for lung cancer detection and assessment of smoking related effects--confounding variables, influence of normalization and statistical algorithms. AB - BACKGROUND: Up to now, none of the breath biomarkers or marker sets proposed for cancer recognition has reached clinical relevance. Possible reasons are the lack of standardized methods of sampling, analysis and data processing and effects of environmental contaminants. METHODS: Concentration profiles of endogenous and exogenous breath markers were determined in exhaled breath of 31 lung cancer patients, 31 smokers and 31 healthy controls by means of SPME-GC-MS. Different correcting and normalization algorithms and a principal component analysis were applied to the data. RESULTS: Differences of exhalation profiles in cancer and non-cancer patients did not persist if physiology and confounding variables were taken into account. Smoking history, inspired substance concentrations, age and gender were recognized as the most important confounding variables. Normalization onto PCO2 or BSA or correction for inspired concentrations only partially solved the problem. In contrast, previous smoking behaviour could be recognized unequivocally. CONCLUSION: Exhaled substance concentrations may depend on a variety of parameters other than the disease under investigation. Normalization and correcting parameters have to be chosen with care as compensating effects may be different from one substance to the other. Only well-founded biomarker identification, normalization and data processing will provide clinically relevant information from breath analysis. PMID- 20542020 TI - Confirmation of top polymorphisms in hypertension genome wide association study among Han Chinese. AB - BACKGROUND: Confirmation of genome wide association (GWA) results in independent samples has recently become new research tendency. METHODS: We focused on 8 positive top polymorphisms identified in the to-date largest hypertension GWA study and determined whether these polymorphisms were associated with hypertension among Han Chinese. Genotyping was performed among 548 patients diagnosed with essential hypertension and 560 age- and gender-matched controls using ligase detection reactions method. Statistical analyses were conducted using Logistic regression and genotype risk score. RESULTS: Except for a rare polymorphism (rs653178), no deviation from Hardy-Weinberg equilibrium was observed for genotype distributions of others. There was significant differences in the genotype/allele distribution (P=0.006/P=0.002) of rs16998073 in FGF5 (fibroblast growth factor 5) upstream and the allele distribution (P=0.037) of rs16948048 in ZNF652 (zinc finger protein 652) upstream between hypertensive patients and controls. Strong significance was also noted under assumption of different genetic models for the two coalescent polymorphisms, even after controlling covariates of interest. For example, rs16998073 had a 72% increased risk for hypertension under the co-dominant model (95% confidence interval: 1.20 2.45; P=0.003). However, construction of genetic risk scores on common polymorphisms did not reveal any significance with both hypertension and blood pressure, suggesting that contribution of these polymorphisms to hypertension moderate or small in magnitude. CONCLUSIONS: Our results implicate variation in FGF5 and ZNF652 gene upstream regions with altered susceptibility to hypertension in Han Chinese. PMID- 20542021 TI - Inverse relationship between fasting direct bilirubin and metabolic syndrome in Korean adults. AB - BACKGROUND: Studies on the effects of bilirubin on cardiovascular disease have typically focused only on total serum bilirubin composed with direct bilirubin plus indirect bilirubin. In this study, we examined which type of fasting bilirubin is more associated with the metabolic syndrome (MS). METHODS: Five thousand six hundred and fifty-four individuals who visited the Center for Health Promotion for a periodic medical health check-up were screened for inclusion in the study. We excluded subjects who had a chronic viral liver disease, an alcoholic liver disease, or an abnormal liver function defined as a serum aspartate aminotransferase or alanine aminotransferase >100IU/l, a gamma glutamyltransferase >100IU/l, or a fasting total bilirubin level >3mg/dl. RESULTS: In men, only fasting direct bilirubin levels decreased with an increase in the number of MS components (p=0.001). However, all three types of fasting bilirubin decreased when the subjects had more components of MS (p<0.001) in women. Both in men and women fasting direct bilirubin levels were related with the MS (p for trend=0.003 in men and <0.001 in women) after the adjustments for age, body mass index, smoking, alcohol drinking, exercise habits, and presence of fatty liver. The odds ratio (95% confidence interval) of MS for each fasting direct bilirubin quartile was 0.88 (0.59-1.29), 0.63 (0.42-0.95), 0.61 (0.38 0.97) in men, and 0.66 (0.50-0.87), 0.52 (0.35-0.78), 0.27 (0.12-0.59) in women, respectively. However, fasting total and indirect bilirubin levels were related with the MS in women, but not in men. CONCLUSION: Our findings suggest that MS is more related to the fasting direct bilirubin in Korean adults than the other types of fasting bilirubin. PMID- 20542017 TI - Molecular mechanisms of pesticide-induced neurotoxicity: Relevance to Parkinson's disease. AB - Pesticides are widely used in agricultural and other settings, resulting in continued human exposure. Pesticide toxicity has been clearly demonstrated to alter a variety of neurological functions. Particularly, there is strong evidence suggesting that pesticide exposure predisposes to neurodegenerative diseases. Epidemiological data have suggested a relationship between pesticide exposure and brain neurodegeneration. However, an increasing debate has aroused regarding this issue. Paraquat is a highly toxic quaternary nitrogen herbicide which has been largely studied as a model for Parkinson's disease providing valuable insight into the molecular mechanisms involved in the toxic effects of pesticides and their role in the progression of neurodegenerative diseases. In this work, we review the molecular mechanisms involved in the neurotoxic action of pesticides, with emphasis on the mechanisms associated with the induction of neuronal cell death by paraquat as a model for Parkinsonian neurodegeneration. PMID- 20542022 TI - Absence of nerve growth factor and comparison of tyrosine kinase receptor A levels in mature spermatozoa from oligoasthenozoospermic, asthenozoospermic and fertile men. AB - BACKGROUND: Nerve growth factor (NGF) and the Tyrosine kinase receptor (TrkA) are expressed in mammalian ovaries and testes, where they are involved in oocyte maturation and spermatogenesis. We assessed the possibility that NGF and TrkA gene products are present in human spermatozoa, and explored differences in levels of NGF and TrkA in spermatozoa from oligoasthenozoospermic, asthenozoospermic and fertile men. METHODS: The presence of NGF and TrkA in human spermatozoa was investigated using RT-PCR, immunofluorescence and Western blotting. Real-time PCR and ELISA were used to determine expression levels of NGF and TrkA. RESULTS: No NGF transcripts were detected in human spermatozoa. The levels of TrkA mRNA in spermatozoa from oligoasthenozoospermic samples were significantly lower than those in spermatozoa from fertile and asthenozoospermic samples (P<0.05). NGF concentrations in seminal plasma samples from oligoasthenozoospermic men were lower than those in seminal plasma from fertile and asthenozoospermic men, but these differences were not statistically significant (P>0.05). CONCLUSIONS: The levels of both NGF protein in seminal plasma and TrkA mRNA in spermatozoa are low in samples from oligoasthenozoospermic men. PMID- 20542023 TI - Extra blood tubes - An affordable excess? PMID- 20542024 TI - Mutations of DMYPT cause over constriction of contractile rings and ring canals during Drosophila germline cyst formation. AB - Ring canals, also known as stable intercellular bridges, are derived from the contractile rings of incomplete cytokinesis (IC) in most organisms. Formation of ring canals is necessary to generate functional eggs and sperm in multiple organisms including insects, birds, mammals and various plants. How the constriction of a contractile ring is arrested and how an arrested contractile ring is transformed into a ring canal is unknown. We describe here the function of the Drosophila melanogaster myosin binding subunit of myosin phosphatase (DMYPT) in both processes. We have found that DMYPT is highly enriched in the cytoplasm of cells undergoing IC during oogenesis. DMYPT mutations in germ cells, but not in somatic follicle cells, resulted in over-constriction of contractile rings and ring canals. This leads to formation of small ring canals and mis regulation of centriole migration during female germline cyst formation. Our results suggest that there may be two parallel mechanisms to prevent the contractile rings from being completely closed, physical resistance and inhibition of myosin II activity via DMYPT. PMID- 20542025 TI - Novel insight into the function and regulation of alphaN-catenin by Snail2 during chick neural crest cell migration. AB - The neural crest is a transient population of migratory cells that differentiates to form a variety of cell types in the vertebrate embryo, including melanocytes, the craniofacial skeleton, and portions of the peripheral nervous system. These cells initially exist as adherent epithelial cells in the dorsal aspect of the neural tube and only later become migratory after an epithelial-to-mesenchymal transition (EMT). Snail2 plays a critical role in mediating chick neural crest cell EMT and migration due to its expression by both premigratory and migratory cranial neural crest cells and its ability to down-regulate intercellular junctions components. In an attempt to delineate the role of cellular junction components in the neural crest, we have identified the adherens junction molecule neural alpha-catenin (alphaN-catenin) as a Snail2 target gene whose repression is critical for chick neural crest cell migration. Knock-down and overexpression of alphaN-catenin enhances and inhibits neural crest cell migration, respectively. Furthermore, our results reveal that alphaN-catenin regulates the appropriate movement of neural crest cells away from the neural tube into the embryo. Collectively, our data point to a novel function of an adherens junction protein in facilitating the proper migration of neural crest cells during the development of the vertebrate embryo. PMID- 20542026 TI - Effects of a synthetic protease inhibitor (gabexate mesilate) and a neutrophil elastase inhibitor (sivelestat sodium) on acid-induced lung injury in rats. AB - The present study was designed to examine the combined effects of a synthetic protease inhibitor, gabexate mesilate, with a specific neutrophil elastase inhibitor, sivelestat sodium, on acid-induced lung injury. Adult male Sprague Dawley rats weighing 300-350 g were anaesthetised intraperitoneally with pentobarbitone sodium and the right jugular vein was cannulated. Following tracheostomy, rats were ventilated mechanically and underwent intratracheal instillation of hydrochloric acid (HCl, 0.1N 1.5 ml/kg) or normal saline. Gabexate mesilate (10mg/kg, i.p.) and/or sivelestat sodium (10mg/kg/h, i.v.) were administered 30 min before HCl instillation. Bronchoalveolar lavage fluid samples were obtained 5h after HCl instillation. In bronchoalveolar lavage fluid, the HCl induced increases in total nucleated cell counts, neutrophil counts, optical density at 412 nm as an index of pulmonary haemorrhage, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) were significantly attenuated by either gabexate mesilate or sivelestat sodium treatment. Gabexate mesilate or sivelestat sodium treatment also significantly attenuated the wet to dry weight ratio induced by HCl. However, combined treatment with both gabexate mesilate and sivelestat sodium did not show additive effects on HCl-induced lung injury, compared with single treatments. These findings suggested that gabexate mesilate and sivelestat sodium each exhibited protective effects on acid-induced lung injury, but that synergistic effects of both agents are limited in this acid induced lung injury model. PMID- 20542027 TI - Genetic recombination pathways and their application for genome modification of human embryonic stem cells. AB - Human embryonic stem cells are pluripotent cells derived from early human embryo and retain a potential to differentiate into all adult cell types. They provide vast opportunities in cell replacement therapies and are expected to become significant tools in drug discovery as well as in the studies of cellular and developmental functions of human genes. The progress in applying different types of DNA recombination reactions for genome modification in a variety of eukaryotic cell types has provided means to utilize recombination-based strategies also in human embryonic stem cells. Homologous recombination-based methods, particularly those utilizing extended homologous regions and those employing zinc finger nucleases to boost genomic integration, have shown their usefulness in efficient genome modification. Site-specific recombination systems are potent genome modifiers, and they can be used to integrate DNA into loci that contain an appropriate recombination signal sequence, either naturally occurring or suitably pre-engineered. Non-homologous recombination can be used to generate random integrations in genomes relatively effortlessly, albeit with a moderate efficiency and precision. DNA transposition-based strategies offer substantially more efficient random strategies and provide means to generate single-copy insertions, thus potentiating the generation of genome-wide insertion libraries applicable in genetic screens. PMID- 20542028 TI - Hsp105 reduces the protein aggregation and cytotoxicity by expanded-polyglutamine proteins through the induction of Hsp70. AB - Hsp105alpha and Hsp105beta are major heat shock proteins in mammalian cells and belong to the HSP105/110 family. Hsp105alpha is expressed constitutively in the cytoplasm of cells, while Hsp105beta, an alternatively spliced form of Hsp105alpha, is expressed specifically in the nucleus of cells during mild heat shock. Here, we show that not only Hsp105beta but also Hsp105alpha accumulated in the nucleus of cells following the expression of enhanced green fluorescent protein with a pathological length polyQ tract (EGFP-polyQ97) and suppressed the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. Mutants of Hsp105alpha and Hsp105beta with changes in the nuclear localization signal sequences, which localized exclusively in the cytoplasm with or without the expression of EGFP-polyQ97, did not suppress the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. Furthermore, Hsp70 was induced by the co-expression of Hsp105alpha and EGFP-polyQ97, and the knockdown of Hsp70 reduced the inhibitory effect of Hsp105alpha and Hsp105beta on the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. These observations suggested that Hsp105alpha and Hsp105beta suppressed the expanded polyQ tract-induced protein aggregation and apoptosis through the induction of Hsp70. PMID- 20542029 TI - NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance. AB - Altered pH-regulatory ion transport is characteristic of many cancers; however, the mechanisms and consequences are poorly understood. Here, we investigate how a truncated, constitutively active ErbB2 receptor (DeltaNErbB2) common in breast cancer impacts on the Na(+)/H(+)-exchanger NHE1 and the Na(+),HCO(3)(-) cotransporter NBCn1 in MCF-7 human breast cancer cells and address the roles of these transporters in chemotherapy resistance. Upon DeltaNErbB2 expression, mRNA and protein levels of NBCn1, yet not of NHE1, increased several-fold, and the localization of both transporters was altered paralleling extensive morphological changes. The rate of pH(i) recovery after acid loading increased by 50% upon DeltaNErbB2 expression. Knockdown and pharmacological inhibition confirmed the involvement of both NHE1 and NBCn1 in acid extrusion. NHE1 inhibition or knockdown sensitized DeltaNErbB2-expressing cells to cisplatin-induced programmed cell death (PCD) in a caspase-, cathepsin-, and reactive oxygen species-dependent manner. NHE1 inhibition augmented cisplatin-induced caspase activity and lysosomal membrane permeability followed by cysteine cathepsin release. In contrast, NBCn1 inhibition attenuated cathepsin release and had no net effect on viability. These findings warrant studies of NHE1 as a potential target in breast cancer and demonstrate that in spite of their similar transport functions, NHE1 and NBCn1 serve different functions in MCF-7 cells. PMID- 20542030 TI - Regulation of p53 in embryonic stem cells. AB - Despite an increasing interest in the role of the p53 tumour suppressor protein in embryonic stem cells, not much is known about its regulation in this cell type. We show that the relatively high amount of p53 protein correlates with a higher amount of p53 RNA in ES cells compared to differentiated cells. Moreover, p53 RNA is more stable in embryonic stem cells and the p53 protein is more often transcribed. This is at least partly due to decreased expression of miRNA-125a and 125b in embryonic stem cells. Despite its cytoplasmic localisation, p53 is degraded in 26S proteasomes in embryonic stem cells. This process is controlled by Mdm2, the deubiquitinating enzyme Hausp and Ubc13. In contrast, the E3 ligase PirH2 appears to be less important for the control of p53 in embryonic stem cells. During differentiation, p53 protein and RNA levels are decreased which corresponds to increased expression of miRNA-125a and miRNA-125b. PMID- 20542031 TI - Mouse lens stiffness measurements. AB - Presbyopia is a gradual loss of accommodation with age. Various studies have shown that an age-related increase in lens stiffness may be one factor involved. Lens stiffness has previously been measured using lens spinning experiments, resistance to conical probe penetration and dynamic mechanical analysis. In the current study, two different techniques have been used to evaluate the stiffness of isolated mouse lenses. In the first method, compressive forces were applied to mouse lenses using microscope cover-slips to exert incremental forces on the lens. Lens images were captured for analysis of change in diameter. In the second method, a fully automated squeezer system with an actuator, electronic scale and a CCD camera was used to apply incremental compressive forces to the lenses. The actuator exerted forces comparable to those exerted by cover-slips. Force and actuator displacement data together with images of the lenses as they were compressed were captured. Images were analyzed for change in lens diameter on application of force and also with actuator displacement. Lenses from 19 young male mice (4-weeks old) and 28 male retired breeders (7-9 months old) were tested. Lenses were used immediately after sacrificing the mice and extracting the lenses. The lenses from the older male mice were stiffer compared to the lenses from the younger male mice. This was determined by comparing the average change in lens diameter at various force values used. The two methods provide a good indication of the stiffness properties of mouse lenses. PMID- 20542032 TI - Taenia saginata: production and characterization of monoclonal antibodies against Taenia saginata metacestode antigens. AB - Cysticercosis is a major cause of economic loss in bovine production due to meat condemnation. Chemotherapy is being used in Brazilian cattle and a diagnostic test to improve the treatment program is desired. We produced monoclonal antibodies against crude (TAEB) and cyst fluid (TAEF) Taenia saginata metacestode antigens using immunized BALB/c mice. After cell fusion, 10 TAEB and nine TAEF hybrids were selected and cloned resulting in 18 IgG(1) and 32 IgM TAEB clones, and 9 IgG(1) and 9 IgM TAEF clones. Ascites was produced and Western blot testing was performed resulting in reactivity to protein fractions of low molecular weight (<18kDa), 43, 55, 66 and 100kDa. The indirect immunofluorescence test, with one monoclonal antibody against crude and one against cyst fluid antigens, recognized antigenic fractions of both the scolex and the bladder wall of metacestodes from naturally infected bovine. PMID- 20542034 TI - Assaying and investigating Alternative Lengthening of Telomeres activity in human cells and cancers. AB - Alternative Lengthening of Telomeres (ALT) activity can be deduced from the presence of telomere length maintenance in the absence of telomerase activity. More convenient assays for ALT utilize phenotypic markers of ALT activity, but only a few of these assays are potentially definitive. Here we assess each of the current ALT assays and their implications for understanding the ALT mechanism. We also review the clinical situations where availability of an ALT activity assay would be advantageous. The prevalence of ALT ranges from 25% to 60% in sarcomas and 5% to 15% in carcinomas. Patients with many of these types of ALT[+] tumors have a poor prognosis. PMID- 20542033 TI - Leishmania infantum chagasi: a genome-based approach to identification of excreted/secreted proteins. AB - The parasitic protozoan, Leishmania, survives in harsh environments within its mammalian and sand fly hosts. Secreted proteins likely play critical roles in the parasite's interactions with its environment. As a preliminary identification of the spectrum of potential excreted/secreted (ES) proteins of Leishmania infantum chagasi (Lic), a causative agent of visceral leishmaniasis, we used standard algorithms to screen the annotated L. infantum genome for genes whose predicted protein products have an N-terminal signal peptide and lack transmembrane domains and membrane anchors. A suite of 181 candidate ES proteins were identified. These included several that were documented in the literature to be released by other Leishmania spp. Six candidate ES proteins were selected for further validation of their expression and release by different parasite stages. We found both amastigote-specific and promastigote-specific released proteins. The ES proteins of Lic are candidates for future studies of parasite virulence determinants and host protective immunity. PMID- 20542035 TI - Evolution of MHC class I genes in two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis). AB - Here we present the first isolation of major histocompatibility complex (MHC) class I genes from two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis). Seventeen sequences obtained showed high polymorphism and positive natural selection with dN/dS>1. Evolutionary relationships revealed that sequences from paddlefish and Chinese sturgeon distinguished from other vertebrate class I and had an intermingling of alleles, which indicates that Acipenseriformes have a common ancestral gene of class I and a trans-species polymorphism across Acipenseriformes. We also found clear evidence of recombination among class I genes of paddlefish and Chinese sturgeon. PMID- 20542036 TI - PPARgamma in adipocyte differentiation and metabolism--novel insights from genome wide studies. AB - Adipocyte differentiation is controlled by a tightly regulated transcriptional cascade in which PPARgamma and members of the C/EBP family are key players. Here we review the roles of PPARgamma and C/EBPs in adipocyte differentiation with emphasis on the recently published genome-wide binding profiles for PPARgamma and C/EBPalpha. Interestingly, these analyses show that PPARgamma and C/EBPalpha binding sites are associated with most genes that are induced during adipogenesis suggesting direct activation of many more adipocyte genes than previously anticipated. Furthermore, an extensive overlap between the C/EBPalpha and PPARgamma cistromes indicate a hitherto unrecognized direct crosstalk between these transcription factors. As more genome-wide data emerge in the future, this crosstalk will likely be found to include several other adipogenic transcription factors. PMID- 20542038 TI - Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. AB - In the late 1800s, hemochromatosis was considered an odd autoptic finding. More than a century later, it was finally recognized as a hereditary, multi-organ disorder associated with a polymorphism that is common among white people: a 845G ->A change in HFE that results in C282Y in the gene product. Hemochromatosis is now a well-defined syndrome characterized by normal iron-driven erythropoiesis and the toxic accumulation of iron in parenchymal cells of liver, heart, and endocrine glands. It can be caused by mutations that affect any of the proteins that limit the entry of iron into the blood. In mice, deletion of the iron hormone hepcidin and any of 8 genes that regulate its biology, including Hfe, transferrin receptor 2 (Tfr2), and hemojuvelin (Hjv) (which all sense the accumulation of iron that hepcidin corrects) or ferroportin (Fpn) (the cellular iron exporter down-regulated by hepcidin), cause iron overload but not organ disease. In humans, loss of TfR2, HJV, and hepcidin itself or FPN mutations result in full-blown hemochromatosis. Unlike these rare instances, in white people, homozygotes for C282Y polymorphism in HFE are numerous, but they are only predisposed to hemochromatosis; complete organ disease develops in a minority, when these individuals abuse alcohol or from other unidentified modifying factors. HFE gene testing can be used to diagnose hemochromatosis, but analyses of liver histology and clinical features are still required to identify patients with rare, non-HFE forms of the disease. The role of hepcidin in the pathogenesis of hemochromatosis reveals its similarities to endocrine diseases such as diabetes and indicates new approaches to diagnosis and management of this common disorder in iron metabolism. PMID- 20542037 TI - Indian hedgehog regulates intestinal stem cell fate through epithelial mesenchymal interactions during development. AB - BACKGROUND & AIMS: Intestinal stem cells (ISCs) are regulated by the mesenchymal environment via physical interaction and diffusible factors. We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by which perturbations in epithelial-mesenchymal interactions affect ISC fate. METHODS: We generated mice with intestinal epithelial-specific disruption of Ihh. Gross and microscopic anatomical changes were determined using histologic, immunohistochemical, and in situ hybridization analyses. Molecular mechanisms were elucidated by expression profiling and in vitro analyses. RESULTS: Deletion of intestinal epithelial Ihh disrupted the intestinal mesenchymal architecture, demonstrated by loss of the muscularis mucosae, deterioration of the extracellular matrix, and reductions in numbers of crypt myofibroblasts. Concurrently, the epithelial compartment had increased Wnt signaling, disturbed crypt polarity and architecture, defective enterocyte differentiation, and increased and ectopic proliferation that was accompanied by increased numbers of ISCs. Mechanistic studies revealed that Hh inhibition deregulates bone morphogenetic protein signaling, increases matrix metalloproteinase levels, and disrupts extracellular matrix proteins, fostering a proliferative environment for ISCs and progenitor cells. CONCLUSIONS: Ihh regulates ISC self-renewal and differentiation. Intestinal epithelial Ihh signals to the mesenchymal compartment to regulate formation and proliferation of mesenchymal cells, which in turn affect epithelial proliferation and differentiation. These findings provide a basis for analyses of the role of the muscularis mucosae in ISC regulation. PMID- 20542039 TI - A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses. AB - The objective of this study was to produce and evaluate the immunogenic potential of a recombinant HLA-class I antigen linked to dextran. The HLA-A*0201 heavy chain and beta2 microglobulin were cloned by PCR amplification of overlapping oligonucleotides and produced in E. coli. These were assembled with a CMV binding peptide motif, the HLA complex was biotinylated and bound by streptavidin coated dextran at a ratio of 24 HLA to 1 dextran molecule (termed Dextramer). Allostimulation of human PBMC in vitro and in vivo immunization of Balb c mice with the HLA-A*0201 construct elicited CD4+ and CD8+ T cell proliferative responses, IgG specific antibodies in mice and in human T cell proliferation and APOBEC3G mRNA. These adaptive and innate immune responses induced by a novel recombinant HLA construct in human cells and mice suggest their application as a potential vaccine candidate against HIV infection. PMID- 20542040 TI - Evolved Lactococcus lactis strains for enhanced expression of recombinant membrane proteins. AB - The production of complex multidomain (membrane) proteins is a major hurdle in structural genomics and a generic approach for optimizing membrane protein expression is still lacking. We have devised a selection method to isolate mutant strains with improved functional expression of recombinant membrane proteins. By fusing green fluorescent protein and an erythromycin resistance marker (ErmC) to the C-terminus of a target protein, one simultaneously selects for variants with enhanced expression (increased erythromycin resistance) and correct folding (green fluorescent protein fluorescence). Three evolved hosts, displaying 2- to 8 fold increased expression of a plethora of proteins, were fully sequenced and shown to carry single-site mutations in the nisK gene. NisK is the sensor protein of a two-component regulatory system that directs nisin-A-mediated expression. The levels of recombinant membrane proteins were increased in the evolved strains, and in some cases their folding states were improved. The generality and simplicity of our approach allow rapid improvements of protein production yields by directed evolution in a high-throughput way. PMID- 20542041 TI - The structure of the FnIII Tandem A77-A78 points to a periodically conserved architecture in the myosin-binding region of titin. AB - Titin is a large intrasarcomeric protein that, among its many roles in muscle, is thought to modulate the in vivo assembly of the myosin motor filament. This is achieved through the molecular template properties of its A-band region, which is composed of fibronectin type III (FnIII) and immunoglobulin (Ig) domains organized into characteristic 7-domain (D-zone) and 11-domain (C-zone) superrepeats. Currently, there is little knowledge on the structural details of this region of titin. Here we report the conformational characterization of three FnIII tandems, A77-A78, A80-A82, and A84-A86, which are components of the representative fourth C-zone superrepeat. The structure of A77-A78 has been elucidated by X-ray crystallography to 1.65 A resolution, while low-resolution models of A80-A82 and A84-A86 have been calculated using small-angle X-ray scattering. A77-A78 adopts an extended "up-down" domain arrangement, where domains are connected by a hydrophilic three-residue linker sequence. The linker is embedded in a rich network of polar contacts at the domain interface that results in a stiff molecular conformation. The models of A80-A82 and A84-A86, which contain hydrophobic six-residue-long interdomain linkers, equally showed elongated molecular shapes, but with slightly coiled or zigzagged conformations. Small-angle X-ray scattering data further suggested that the long linkers do not result in a noticeable increase in molecular flexibility but lead to semibent domain arrangements. Our findings indicate that the structural characteristics of FnIII tandems from A-band titin contrast markedly with those of poly-Ig tandems from the elastic I-band, which exhibit domain interfaces depleted of interactions and compliant conformations. Furthermore, the analysis of sequence conservation in FnIII domains from A-band titin points to the existence of conformationally defined interfaces at specific superrepeat positions, possibly leading to a periodic and locally ordered architecture supporting the molecular scaffold properties of this region of titin. PMID- 20542042 TI - A two-sex demographic model with single-dependent divorce rate. AB - Divorce appears to be one of the least studied demographic processes, both empirically and in two-sex demographic models. In this paper, we study mathematical as well as biological implications of the assumption that the divorce rate is positively affected by the amount of single (i.e., unmarried/unpaired) individuals in the population. We do that by modifying the classical exponential two-sex model accounting for pair formation and separation. We model the divorce rate as an increasing function of the single population size and show that the single population pressure on the established couples alters the exponential behavior of the classical model in which the divorce rate is assumed constant. In particular, the total population size becomes bounded and a unique positive equilibrium exists. In addition, a Hopf bifurcation analysis around the positive equilibrium shows that the modified model may exhibit sustained oscillations. PMID- 20542043 TI - Comparing strategies to preserve evolutionary diversity. AB - The likely future extinction of various species will result in a decline of two quantities: species richness and phylogenetic diversity (PD, or 'evolutionary history'). Under a simple stochastic model of extinction, we can estimate the expected loss of these quantities under two conservation strategies: An 'egalitarian' approach, which reduces the extinction risk of all species, and a 'targeted' approach that concentrates conservation effort on the most endangered taxa. For two such strategies that are constrained to experience the same expected loss of species richness, we ask which strategy results in a greater expected loss of PD. Using mathematical analysis and simulation, we describe how the strategy (egalitarian versus targeted) that minimizes the expected loss of PD depends on the distribution of endangered status across the tips of the tree, and the interaction of this status with the branch lengths. For a particular data set consisting of a phylogenetic tree of 62 lemur species, with extinction risks estimated from the IUCN 'Red List', we show that both strategies are virtually equivalent, though randomizing these extinction risks across the tip taxa can cause either strategy to outperform the other. In the second part of the paper, we describe an algorithm to determine how extreme the loss of PD for a given decline in species richness can be. We illustrate the use of this algorithm on the lemur tree. PMID- 20542044 TI - Study of proteome maps using partial ordering. AB - This paper describes numerical characterization of proteome maps based on partial ordering of protein spots with respect to the mass and the charge. The partial ordering diagram is embedded directly over the 2D map and the corresponding adjacency matrix is constructed. The adjacency matrix is augmented by including the information on the abundance of proteins in a gel as suitably scaled diagonal entries of the matrix. The approach is illustrated on proteome maps of Anderson et al. (1996) based on experimental results from liver cells of rats exposed to four peroxisome proliferators. We used the leading eigenvectors of the adjacency matrices as maps descriptors in order to determine the degree of similarity between proteome maps. PMID- 20542045 TI - Contribution of the superior colliculi to post-stroke unilateral spatial neglect and recovery. AB - Unilateral spatial neglect (USN) is a highly prevalent and disabling consequence of stroke that often responds poorly to existing interventions. Its underlying neural mechanisms are still unclear. Recent work suggests that post-stroke USN may be partly related to a disruption of top-down and bottom-up control of visual attention mediated in part through the midbrain superior colliculi (SC). With mounting evidence from animal and human research, our objectives were: (1) to synthesize the literature implicating the SC in USN; (2) to review the rationale and potential for using eye patching and prism adaptation as USN treatment approaches that recruit SC involvement; and (3) to provide recommendations for research on the potential of therapeutic interventions that involve and/or target the retino-collicular pathway. Given the paucity of human studies, the contribution of the SC in USN, while plausible, remains to be confirmed. Further exploration of the mechanisms involved and their impact on USN in human subjects will help develop theoretically based intervention strategies tailored to USN type. PMID- 20542046 TI - Neural activity before and after conscious perception in dichotic listening. AB - The neural basis of conscious perception can be studied using stimuli that elicit different percepts on different occasions (multistable perception). Multistable perception allows direct comparisons between brain activity and conscious perception that control for sensory input, and also serves as a model for attentional competition, with the winning perceptual outcome varying across trials. Dichotic listening tasks present multistable stimuli consisting of two different consonant-vowels (CVs, one/ear). For each trial one ear usually conveys the dominant percept. We used EEG to measure neural activity before and after dichotic stimulus presentation to compare activity among left vs. right ear percepts and a control task. Consonant-vowels were perceived more often to the right vs. left ear. Pre-stimulus EEG power in the beta band (16-20 Hz) increased for left compared to right ear percepts and control trials. Event-related potentials after stimulus onset showed smaller P50 amplitudes ( approximately 50 ms latency) for left ear compared to right ear and control trials. Results indicate that neural activity for right ear percepts is comparable to control conditions, while activity for the atypical left ear percept differs before and after stimulus onset. Pre-stimulus EEG changes for left ear percepts may indicate a mechanism of spontaneous fluctuations in cortical networks that bias attentional competition during subsequent sensory processing. The P50 amplitude differences among perceived ears suggests that rapid sensory and/or arousal related activities contribute to the content of conscious perception, possibly by biasing attentional competition away from the dominant right ear channel. PMID- 20542047 TI - Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology--a review of current data and future implications. AB - Transcranial direct current stimulation (tDCS) is a noninvasive, low-cost and easy-to-use technique that can be applied to modify cerebral excitability. This is achieved by weak direct currents to shift the resting potential of cortical neurons. These currents are applied by attaching two electrodes (usually one anode and one cathode) to distinct areas of the skull. Galvanic Vestibular Stimulation (GVS) is a variant of tDCS where the electrodes are attached to the mastoids behind the ears in order to stimulate the vestibular system. tDCS and GVS are safe when standard procedures are used. We describe the basic physiological mechanisms and application of these procedures. We also review current data on the effects of tDCS and GVS in healthy subjects as well as clinical populations. Significant effects of such stimulation have been reported for motor, visual, somatosensory, attentional, vestibular and cognitive/emotional function as well as for a range of neurological and psychiatric disorders. Moreover, both techniques may induce neuroplastic changes which make them promising techniques in the field of neurorehabilitation. A number of open research questions that could be addressed with tDCS or GVS are formulated in the domains of sensory and motor processing, spatial and nonspatial attention including neglect, spatial cognition and body cognition disorders, as well as novel treatments for various neuropsychological disorders. We conclude that the literature suggests that tDCS and GVS are exciting and easily applicable research tools for neuropsychological as well as clinical-therapeutic investigations. PMID- 20542048 TI - Exceptions and anomalies: an ERP study on context sensitivity in autism. AB - Several studies have demonstrated that people with ASD and intact language skills still have problems processing linguistic information in context. Given this evidence for reduced sensitivity to linguistic context, the question arises how contextual information is actually processed by people with ASD. In this study, we used event-related brain potentials (ERPs) to examine context sensitivity in high-functioning adults with autistic disorder (HFA) and Asperger syndrome at two levels: at the level of sentence processing and at the level of solving reasoning problems. We found that sentence context as well as reasoning context had an immediate ERP effect in adults with Asperger syndrome, as in matched controls. Both groups showed a typical N400 effect and a late positive component for the sentence conditions, and a sustained negativity for the reasoning conditions. In contrast, the HFA group demonstrated neither an N400 effect nor a sustained negativity. However, the HFA group showed a late positive component which was larger for semantically anomalous sentences than congruent sentences. Because sentence context had a modulating effect in a later phase, semantic integration is perhaps less automatic in HFA, and presumably more elaborate processes are needed to arrive at a sentence interpretation. PMID- 20542049 TI - Withanolides from Withania aristata and their cytotoxic activity. AB - Seven new withanolides (1-7), along with three known ones (8-10), were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 2D NMR experiments and spectrometric techniques, and the absolute configuration of 1 and 2 was established by CD analysis. In the search for new cytotoxic compounds from Withania species, the isolated compounds 1-9, along with two derivatives, were assayed for their cytotoxicity against HeLa, MCF-7 and A-549 human tumor cell lines. Derivative (4S,20R,22R)-27-acetoxy-4-p-bromobenzoyloxy-1-oxo-witha-2,5,16,24-tetraenolide (13) showed cytotoxicity against all the cell lines assayed with IC(50) values ranging from 2.8 to 3.6microM, and (4S,20R,22R)-4,27-diacetoxy-4-hydroxy-1-oxo witha-2,5,16,24-tetraenolide (12) exhibited an IC(50) value of 5.4microM on the MCF-7 cell line. PMID- 20542050 TI - Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity. AB - 20S-hydroxyvitamin D3 (20S-(OH)D3), an in vitro product of vitamin D3 metabolism by the cytochrome P450scc, was recently isolated, identified and shown to possess antiproliferative activity without inducing hypercalcemia. The enzymatic production of 20S-(OH)D3 is tedious, expensive, and cannot meet the requirements for extensive chemical and biological studies. Here we report for the first time the chemical synthesis of 20S-(OH)D3 which exhibited biological properties characteristic of the P450scc-generated compound. Specifically, it was hydroxylated to 20,23-dihydroxyvitamin D3 and 17,20-dihydroxyvitamin D3 by P450scc and was converted to 1alpha,20-dihydroxyvitamin D3 by CYP27B1. It inhibited proliferation of human epidermal keratinocytes with lower potency than 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in normal epidermal human keratinocytes, but with equal potency in immortalized HaCaT keratinocytes. It also stimulated VDR gene expression with similar potency to 1,25(OH)2D3, and stimulated involucrin (a marker of differentiation) and CYP24 gene expression, showing a lower potency for the latter gene than 1,25(OH)2D3. Testing performed with hamster melanoma cells demonstrated a dose-dependent inhibition of cell proliferation and colony forming capabilities similar or more pronounced than those of 1,25(OH)2D3. Thus, we have developed a chemical method for the synthesis of 20S-(OH)D3, which will allow the preparation of a series of 20S-(OH)D3 analogs to study structure-activity relationships to further optimize this class of compound for therapeutic use. PMID- 20542051 TI - Dual protective role for glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary. AB - The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/kg/day; 15days, i.p.). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium+/-VCD (30muM) for 2-8days. VCD increased ovarian GSTp mRNA (P <0.05) relative to control on d4-d8; whereas GSTp protein was increased (P<0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P=0.09), while unbound JNK was decreased (P<0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis. PMID- 20542053 TI - Rapid visual grouping and figure-ground processing using temporally structured displays. AB - We examine the time course of visual grouping and figure-ground processing. Figure (contour) and ground (random-texture) elements were flickered with different phases (i.e., contour and background are alternated), requiring the observer to group information within a pre-specified time window. It was found this grouping has a high temporal resolution: less than 20ms for smooth contours, and less than 50ms for line conjunctions with sharp angles. Furthermore, the grouping process takes place without an explicit knowledge of the phase of the elements, and it requires a cumulative build-up of information. The results are discussed in relation to the neural mechanism for visual grouping and figure ground segregation. PMID- 20542052 TI - Impact of developmental lead exposure on splenic factors. AB - Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb's inhibition of hemoglobin synthesis and Pb's induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effects are, as yet, not completely understood. Therefore, we performed gene expression analysis, via microarray, on RNA from the spleens of developmentally Pb-exposed mice, in order to gain further insight into these Pb effects. Splenic RNA microarray analysis indicated strong up-regulation of genes coding for proteolytic enzymes, lipases, amylase, and RNaseA. The data also showed that Pb affected the expression of many genes associated with innate immunity. Analysis of the microarray results via GeneSifter software indicated that Pb increased apoptosis, B-cell differentiation, and Th2 development. Direct up-regulation by Pb of expression of the gene encoding the heme-regulated inhibitor (HRI) suggested that Pb can decrease erythropoiesis by blocking globin mRNA translation. Pb's high elevation of digestive/catabolizing enzymes could generate immunogenic self peptides. With Pb's potential to induce new self-peptides and to enhance the expression of caspases, cytokines, and other immunomodulators, further evaluation of Pb's involvement in autoimmune phenomena, especially Th2-mediated autoantibody production, and alteration of organ system activities is warranted. PMID- 20542054 TI - The contribution of the upper and lower face in happy and sad facial expression classification. AB - We used a happy/sad classification task and a psychophysical model to study the tuning properties of facial expression processors across viewing conditions. Using morphed faces, in this study we measured the extent to which classification of facial expressions depends on the intensity of a particular expression on either the upper or lower face. In the fovea, the upper and lower parts of the test image were either aligned or had a lateral shift of 44' visual angle. In the periphery, the aligned test image was placed at a 6 degrees visual angle to the left of the fixation. Observers were asked to classify a test image of a facial expression as happy or sad. We discovered that the alignment of the upper and lower halves of the face had no effect on happy/sad classification in the fovea, suggesting that the classification of facial expressions is an analytic process. The model also showed no interaction between the two halves of the face in foveal facial expression classification. In addition, the poor performance of observers in recognizing happiness in the periphery manifests a computational complexity, suggesting a model in which the happy-face processor relies on both facial features and the interaction between them to recognize happiness in the periphery. PMID- 20542055 TI - Dichoptic reduction of the direction illusion is not due to binocular rivalry. AB - Simultaneous direction repulsion (the direction illusion) occurs in bidirectional motion displays, typically transparent motion random dot kinematograms. Several laboratories have reported a greatly reduced illusion with dichoptic presentation of the two coherently translating stimuli as compared to monocular or binocular presentation. Some researchers have argued that those results might be due to a confounding factor, namely binocular rivalry occurring between test and inducing stimuli in the dichoptic condition, and so have attributed decisive weight to the results reported by Kim and Wilson (1997, Vision Research, 37, 991-1005) who used centre-surround grating stimuli and found large monocular as well as large dichoptic effects. Here we use centre-surround dot stimuli - with which no binocular rivalry occurs - to confirm a strong monocular contribution to the direction illusion. In addition, we fail to find evidence of a direction illusion with centre-surround grating stimuli, even when seeking to replicate the methods of Kim and Wilson (1997). In light of other evidence that a global motion sensitive mechanism can determine the magnitude of the direction illusion, we propose that simultaneous direction repulsion can result from activity at multiple stages of the motion processing hierarchy. PMID- 20542056 TI - Effects of attention on a relative mislocalization with successively presented stimuli. AB - Previous studies yielded evidence that the precision, with which stimuli are localized in the visual periphery, is improved under conditions of focused attention. The present study examined whether focused attention is able to correct a mislocalization recently observed with successively presented stimuli: when observers are asked to localize the peripheral position of a briefly presented target with respect to a previously presented comparison stimulus, they tended to judge the target as being more towards the fovea than was its actual position. In three experiments the mislocalization was tested under conditions with focused and distributed attention. Results revealed that the mislocalization increased with distributed attention and disappeared when stimuli appeared consistently at predictable positions and thus under conditions of focused attention. However, when a procedure with a trial-by-trial cueing was applied the mislocalization was only reduced, but not wiped out completely. In a recently developed dynamic field model consisting of interacting excitatory and inhibitory neuronal cell populations the results were explained as an attentional modulation of spontaneous (baseline) levels of neural activity. PMID- 20542057 TI - Cholinesterase inhibitors and stress: effects on brain muscarinic receptor density in mice. AB - Exposure to the reversible cholinesterase inhibitor, pyridostigmine bromide (PB), in conjunction with stress, has been suggested as a possible cause of Gulf War Syndrome. This work explores the hypothesis that PB exposure coupled with stress will alter cholinergic receptor density based on the rationale that prolonged exposure to PB and stress will lead to increased stimulation of cholinergic receptors due to the reduced capacity to degrade acetylcholine, leading to changes in receptor levels. Male C57Bl6 mice were exposed to PB (3 or 10 mg/kg/day) or physostigmine (2.88 mg/kg/day) for 7 days via ALZET mini-osmotic pumps implanted subcutaneously. The mice were stressed by shaking at random intervals (avg of 2 min/30 min) for 1 week, which was sufficient to increase blood cortisol levels. Brain tissue for autoradiographic analysis was collected on day 7 of treatment. While we examined many brain regions, analysis revealed that most of the significant changes (p<0.05) were seen in cholinergic nuclei. Stress typically increased muscarinic receptor density, while PB and PHY generally decreased muscarinic receptor density. PMID- 20542058 TI - Drug interactions among the epidermal growth factor receptor inhibitors, other biologics and cytotoxic agents. AB - The epidermal growth factor receptor (EGFR) signalling pathway is a key element in the growth of several epithelial malignancies. Small molecules tyrosine kinase inhibitors (TKIs) and anti-EGFR monoclonal antibodies (mAbs) prevent the phosphorylation of the receptor, leading to cell cycle arrest at G(1) phase, apoptosis, inhibition of angiogenesis and metastasis. To increase the antitumoral effects of EGFR inhibitors (EGFRIs), a number of combinatory regimens have been evaluated and planned with standard cytotoxic drugs and/or inhibitors of EGFR complementary pathways such as mTOR, VEGF and Ras/Raf/ERK. Compared to EGFRI monotherapy, the combination approach is a promising strategy to improve tumor response and survival. However, pharmacokinetic (absorption, distribution, metabolism and excretion) and pharmacodynamic drug interactions can occur, affecting the outcome. Pharmacokinetics of TKIs can be affected by drugs used in combination: conversely, pharmacokinetic interactions have not been reported for EGFR mAbs. Potential pharmacokinetic interactions occur between EGFRIs and other factors such as food and hydrocarbons in tobacco smoke were also considered. EGFRIs are characterized by a number of pharmacodynamic interactions that must be taken into consideration to avoid adverse events, to increase antitumoral activity, and define potential new strategies for developing efficient combination regimens. In this context, treatment schedule and drug sequence appear to be particularly relevant for combination regimens with EGFRIs. Improved molecular characterisation of the EGFR pathway and its complementary pathways in tumor cells is required to better define predictive pharmacokinetic and pharmacodynamic biomarkers for optimum treatment outcome. PMID- 20542059 TI - Generalized framework for stimulus artifact removal. AB - Stimulation is extensively used in neuroscience research in diverse fields ranging from cognitive to clinical. Studying the effect of electrical and magnetic stimulation on neuronal activity is complicated by large stimulation derived artifacts on the recording electrodes, which mask the spiking activity. Multiple studies have suggested a variety of solutions for the removal of artifacts and were typically directed at specific stimulation setups. In this study we introduce a generalized framework for stimulus artifacts removal, the Stimulus Artifact Removal Graphical Environment (SARGE). The framework provides an encapsulated environment for a multi-stage removal process, starting from the stimulus pulse detection, through estimation of the artifacts and their removal, and finally to signal reconstruction and the assessment of removal quality. The framework provides the user with subjective graphical and objective quantitative tools for assessing the resulting signal, and the ability to adjust the process to optimize the results. This extendable publicly available framework supports different types of stimulation, stimulation patterns and shapes, and a variety of artifact estimation methods. We exemplify the removal of artifacts generated by electrical micro- and macro-stimulation and magnetic stimulation and different stimulation protocols. The use of different estimation methods, such as averaging and function fitting is demonstrated, and the differences between them are discussed. Finally, the quality of removal is assessed and validated using quantitative measures and combined experimental-simulation studies. The framework marks a shift from "algorithm" and "data" centric approach to a "workflow" centric approach, thus introducing an innovative concept to the artifact removal process. PMID- 20542060 TI - Data-driven approach to the estimation of connectivity and time delays in the coupling of interacting neuronal subsystems. AB - One of the challenges in neuroscience is the detection of directionality between signals reflecting neural activity. To reveal the directionality of coupling and time delays between interacting multi-scale signals, we use a combination of a data-driven technique called empirical mode decomposition (EMD) and partial directed coherence (PDC) together with the instantaneous causality test (ICT). EMD is used to separate multiple processes associated with different frequency bands, while PDC and ICT allow to explore directionality and characteristic time delays, respectively. We computationally validate our approach for the cases of both stochastic and chaotic oscillatory systems with different types of coupling. Moreover, we apply our approach to the analysis of the connectivity in different frequency bands between local field potentials (LFPs) bilaterally recorded from the left and right of subthalamic nucleus (STN) in patients with Parkinson's disease (PD). We reveal a bidirectional coupling between the left and right STN in the beta-band (10-30 Hz) for an akinetic PD patient and in the tremor band (3 5 Hz) for a tremor-dominant PD patient. We detect a short time delay, most probably reflecting the inter-hemispheric transmission time. Additionally, in both patients we observe a long time delay of approximately a mean period of the beta-band activity in the akinetic PD patient or the tremor band activity in the tremor-dominant PD patient. These long delays may emerge in subcortico-thalamic loops or longer pathways, comprising reflex loops, respectively. We show that the replacement of EMD by conventional bandpass filtering complicates the detection of directionality and leads to a spurious detection of time delays. PMID- 20542061 TI - Estrogen receptor profiles in human peripheral blood lymphocytes. AB - Estrogens are well-known regulators of the immune responses. Most of their effects are mediated by two receptors: estrogen receptor (ER)alpha and ERbeta. Up to date the presence of intracellular ER in human immune cells represents a controversial issue, while their surface membrane expression has scarcely been explored. In this study we investigated the intracellular and cell surface expression of ERalpha and ERbeta in human peripheral blood lymphocytes (PBL) by flow and static cytometry as well as by Western Blot. To this aim we used five different commercial antibodies recognizing distinct ER epitopes. We observed that CD4(+) and CD8(+) T lymphocytes, B lymphocytes and NK cells contain intracellular ERalpha and ERbeta, being the ERalpha46 isoform the most represented ER. However, significant differences could be observed among the antibodies studied in terms of immunoreactivity and specificity. Importantly, we also found a cell surface expression of ERalpha46 isoform. We also observed that a membrane-impermeant form of E2 induced a rapid phosphorylation of extracellular signal-regulated kinase (ERK), a significant proliferation of T lymphocytes, and IFN-gamma production by NK cells, thus suggesting the expression of a functional mERalpha. In conclusion our data could provide new insights as concerns the estrogen-related mechanisms of immune system modulation. They also suggest the need for a reappraisal of the experimental conditions for the characterization of the ER expression. PMID- 20542062 TI - The importance of the basolateral/basomedial amygdala for goal-directed maternal responses in postpartum rats. AB - A model of the neural regulation of maternal behavior in rats proposes that the basolateral amygdala (BLA) provides pup-related sensory inputs to the nucleus accumbens-ventral pallidum (NA-VP) circuit and that medial preoptic area activation of the mesolimbic dopamine system potentiates the ability of BLA neurons to stimulate goal-directed maternal responses, such as pup retrieval behavior. Previous research using electrical lesions has provided some direct support for the importance of BLA. In the current study, we examined the effects of temporary inactivation of neurons within BLA and the adjoining basomedial nucleus of the amygdala (BMA) on maternal behavior in postpartum rats. For an anatomical control, muscimol was injected into the medial amygdala (MeA). Since research has shown that MeA plays an inhibitory role in maternal behavior, it was predicted that muscimol injections restricted to that site would not disrupt maternal behavior. The results showed that muscimol injections into BLA/BMA, at dosage levels between 100 and 200 ng/side, produced major deficits in retrieval behavior and minor deficits in nursing behavior. In contrast, muscimol injections into MeA left maternal behavior relatively unaffected. These results show that neuron-specific inactivation of BLA/BMA causes severe deficits in what can be considered a goal-directed and appetitive maternal response, pup retrieval, while leaving the consummatory aspect of maternal behavior, nursing, relatively unaffected. Since oxytocin is important for maternal behavior, and since both BMA and MeA neurons contain OT-binding sites, perhaps OT stimulates BMA output and suppresses MeA output to influence aspects of maternal behavior. PMID- 20542063 TI - The effect of exercise intensity on plasma and tissue acyl ghrelin concentrations in fasted rats. AB - OBJECTIVE: This study was conducted to investigate the effect of exercise training and feeding status on plasma and tissue acyl ghrelin concentrations. MATERIALS AND METHODS: Thirty-two, eight-week-old male Wistar rats (185+/-5g) were randomly assigned to one of four groups: high intensity (HI: 34 m/min ~80 85% VO(2)max), moderate intensity (MI: 28 m/min ~70-75% VO(2)max), low intensity (LI: 20 m/min ~50-55% VO(2)max), and sedentary control (SED) groups. All experimental groups performed a 12-week exercise program consisting of treadmill running on a 0 degrees slope for 1 h/day, 5 days/week at their respective training intensity. Twenty four hours following the last training session the animals completed a 12h fast. Rats were then killed, blood was collected and plasma separated; the fundus and soleus muscle were excised and frozen in liquid nitrogen for later analysis. Fasting levels of circulating acyl ghrelin and acyl ghrelin content in the soleus muscle and fundus, as well as glycogen in the soleus muscle were measured. Data were analyzed using one-way ANOVA. RESULTS: Results demonstrated that 12 weeks of exercise training combined with a 12h fast significantly increased plasma as well as soleus muscle concentrations of acyl ghrelin in the HI and MI groups (p<0.05) and reduced acyl ghrelin concentrations in the fundus (p<0.05). CONCLUSION: The results of the study indicate that chronic treadmill exercise training enhances fasting plasma acyl ghrelin in an intensity-dependent manner which is accompanied by a significant increase in soleus muscle and reduction in fundus acyl ghrelin levels. PMID- 20542064 TI - Locomotor response to L-DOPA in reserpine-treated rats following central inhibition of aromatic L-amino acid decarboxylase: further evidence for non dopaminergic actions of L-DOPA and its metabolites. AB - L-DOPA is the most widely used treatment for Parkinson's disease. The anti parkinsonian and pro-dyskinetic actions of L-DOPA are widely attributed to its conversion, by the enzyme aromatic L-amino acid decarboxylase (AADC), to dopamine. We investigated the hypothesis that exogenous L-DOPA can induce behavioural effects without being converted to dopamine in the reserpine-treated rat-model of Parkinson's disease. A parkinsonian state was induced with reserpine (3 mg/kg s.c.). Eighteen hours later, the rats were administered L-DOPA plus the peripherally acting AADC inhibitor benserazide (25 mg/kg), with or without the centrally acting AADC inhibitor NSD1015 (100 mg/kg). L-DOPA/benserazide alone reversed reserpine-induced akinesia (4158+/-1125 activity counts/6 h, cf vehicle 1327+/-227). Addition of NSD1015 elicited hyperactive behaviour that was approximately 7-fold higher than L-DOPA/benserazide (35755+/-5226, P<0.001). The hyperactivity induced by L-DOPA and NSD1015 was reduced by the alpha(2C) antagonist rauwolscine (1 mg/kg) and the 5-HT(2C) agonist MK212 (5 mg/kg), but not by the D2 dopamine receptor antagonist remoxipride (3 mg/kg) or the D1 dopamine receptor antagonist SCH23390 (1 mg/kg). These data suggest that L-DOPA, or metabolites produced via routes not involving AADC, might be responsible for the generation of at least some L-DOPA actions in reserpine-treated rats. PMID- 20542065 TI - Distribution of lysine-specific demethylase 1 in the brain of rat and its response in transient global cerebral ischemia. AB - The lysine-specific histone demethylase 1 (LSD1) is a chromatin modifying enzyme that specifically removes methyl groups from lysine 4 of histone 3 (H3-K4) and induces transcriptional repression. However, limited knowledge exists, regarding the existence and significance of LSD1 in the brain. We identified the distribution of LSD1 and H3-K4 mono-, di-, and tri-methylation in the brain of rats, respectively. The temporal and spatial distribution of LSD1 during ischemic brain injury was also explored. LSD1 immunoreactive cells were nucleus positive and were concentrated in the neurons of the hippocampus, cerebral cortex, striatum and amagdala. The distributions of H3-K4 mono-, di-, and tri-methylation exhibited exactly the same pattern as LSD1. LSD1 expression was induced both region and cell specifically after ischemic/perfusion, and complied with the two peak mode of expression. These studies revealed a tightly regulated distribution for LSD1 in the brain of rats under ischemic insult, suggesting a critical role in neuron function. PMID- 20542066 TI - Studies of porcine circovirus type 2, porcine boca-like virus and torque teno virus indicate the presence of multiple viral infections in postweaning multisystemic wasting syndrome pigs. AB - In a previous study, using random amplification and large-scale sequencing technology, we identified a novel porcine parvovirus belonging to the genus Bocavirus in the background of porcine circovirus type 2 (PCV-2) in Swedish pigs with postweaning multisystemic wasting syndrome (PMWS). In addition to bocavirus we demonstrated the presence of torque teno virus (TTV) genogroups 1 and 2 in these cases of PMWS, indicating the simultaneous presence of several viruses in this disease complex. In the present study, 34 PMWS-affected animals and 24 pigs without PMWS were screened by PCR for the presence of PCV-2, TTV-1, TTV-2 and porcine boca-like virus (Pbo-likeV). The studies revealed the following infection rates in the PMWS-affected pigs: PCV-2 100%, TTV-1 77%, TTV-2 94% and Pbo-likeV 88%. In comparison, the pigs without PMWS had the following rates: PCV-2 80%, TTV 1 79%, TTV-2 83% and Pbo-likeV 46%. The sequence identity between the different Swedish Pbo-likeV sequences ranged between 98% and 100%. By checking co infection, it was found that 71% of the PMWS-affected pigs harbor simultaneously all these viruses. As a contrast, in the group without PMWS only 33% of the animals were positive simultaneously for these viruses. These observations indicate a multiple viral infection in PMWS-affected pigs. It has to be studied further if the clinical manifestation of PMWS might be due to synergistic effects of different viruses acting together. PMID- 20542068 TI - Liking of health-functional foods containing lupin kernel fibre following repeated consumption in a dietary intervention setting. AB - Liking of a particular food after repeated consumption may be reduced, limiting the effectiveness of health-functional foods requiring on-going consumption to deliver their benefits. This study examined the effect of repeated consumption of foods containing the novel ingredient, Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKFibre) on sensory acceptability in the dietary intervention setting. In a single-blind randomised crossover 4-week intervention, participants consumed both control and equivalent LKFibre-containing products daily on separate interventions separated by a 4-week period on habitual diet. Seven products: muesli, bread, muffin, chocolate brownie, chocolate milk drink, pasta and instant mashed potato were assessed twice (days 4 and 18 of intervention), by 38 participants for appearance, texture, flavour and general acceptability using a structured graphic hedonic scale. Overall the results showed there was no reduction (P=0.594) in general acceptability of LKFibre foods after repeated consumption, suggesting potential for long-term consumption. The control food products were however generally preferred (P<0.001) over the LKFibre foods; the mean difference for general acceptability between being <6% (0.82cm) of the 15cm hedonic scale used, suggesting LKF addition did not severely affect product palatability. PMID- 20542069 TI - The broad-spectrum antitumor action of cyclosporin A is due to its tachykinin receptor antagonist pharmacological profile. AB - Cyclosporin A (CsA) is an immunosuppressive drug. In human cancer cells substance P (SP) and neurokinin-1 (NK-1) receptor antagonists, respectively, induce cell proliferation and inhibition. CsA is a tachykinin receptor antagonist that showed selectivity for both NK-1 and NK-2 receptors. CsA exerts antitumor action against gastric (AGS) and colon (HT29) carcinoma cell lines. However, the mechanisms involved in this action remain unknown, and it is unknown whether CsA exerts an antitumor action on other human cancer cell lines or not. To demonstrate that CsA exerts a broad-spectrum antitumor action, we carried out an in vitro study of the growth-inhibitory capacity of CsA against seven human cancer cell lines, namely GAMG glioma, SKN-BE(2) neuroblastoma, WERI-Rb-1 retinoblastoma, HEp-2 larynx carcinoma, CAPAN pancreas carcinoma, 23132/87 gastric carcinoma, and SW-403 colon carcinoma. A Coulter counter was used to determine viable cell numbers followed by application of the MTS colorimetric method. Micromolar concentrations of CsA inhibited the growth of these tumor cells, both with and without previous administration of nanomolar concentrations of SP; the inhibition occurred in a dose-dependent manner. Moreover, CsA blocks SP-induced mitogen stimulation of tumor cells, suggesting that the NK-1 receptor is involved in such action. Following administration of CsA apoptosis was observed in the above seven tumor cell lines. These findings suggest that the antitumor action of CsA is at least due to its NK-1 receptor antagonist pharmacological profile, since the involvement of NK-2 receptors in the mentioned action must not be discarded, and that CsA has a broad-spectrum antitumor action. PMID- 20542067 TI - Circadian rhythms in gene expression: Relationship to physiology, disease, drug disposition and drug action. AB - Circadian rhythms (24h cycles) are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body. Components of this core clock mechanism regulate the circadian rhythms in genome wide mRNA expression, which in turn regulate various biological processes. Disruption of circadian rhythms can be either the cause or the effect of various disorders including metabolic syndrome, inflammatory diseases and cancer. Furthermore, circadian rhythms in gene expression regulate both the action and disposition of various drugs and affect therapeutic efficacy and toxicity based on dosing time. Understanding the regulation of circadian rhythms in gene expression plays an important role in both optimizing the dosing time for existing drugs and in the development of new therapeutics targeting the molecular clock. PMID- 20542070 TI - Calcium dependent modification of distal C-terminal sequences of glycine transporter GlyT1. AB - Glycine transporter GlyT1 plays important role in maintaining accurate glycine concentration in local brain microenvironment. Transporting efficiency of GlyT1 is strongly affected by the state of its distal C-terminus, which regulates transporter trafficking and cellular surface density. Using selected range of antibody epitopes against C-terminal region of GlyT1 we investigated its changes during calcium overload, the ubiquitous phenomena of several brain pathologies. We show that immunoreactivity against the last 12 amino acids of GlyT1C-terminal region exhibits robust calcium dependent decline, while the immunoreactivity of closely located region shows relatively small changes. Process is fully blocked by calcium chelation and inhibited by cysteine proteases inhibitors as well as inhibitors of protein kinase C. Distal GlyT1C-terminal end contains PDZ binding motif responsible for GlyT1 interaction with trafficking and clustering proteins. Its removal/modification could be part of the mechanism changing glycine homeostasis during physiological/pathological conditions characterized by elevated calcium. PMID- 20542071 TI - MSH5 is not a genetic predisposing factor for immunoglobulin A deficiency but marks the HLA-DRB1*0102 subgroup carrying susceptibility. AB - The etiology of selective IgA deficiency (IgAD) is clearly influenced by human leukocyte antigen (HLA) genetic composition, although the susceptibility observed has not been ascribed to any specific gene/s. A possible role of the MSH5 gene, mapping on this chromosomal region, has been proposed based on its function and on the association of some MSH5 polymorphisms (L85F/P786S and rs3131378) with the disease. However, the extensive linkage disequilibrium in the HLA region makes mandatory additional analyses. We aimed at evaluating the role of those MSH5 polymorphisms on IgAD susceptibility considering their linkage with other classically associated HLA markers, specifically DRB1*0102 and B*08-DRB1*03. We studied 146 trios composed by IgAD patient and parents to unambiguously establish the gametic phase. Association of those MSH5 variants with IgAD is observed but stratified analyses considering other HLA alleles rule out the role of MSH5 per se as a predisposing factor. However, the minor allele of one of the studied polymorphisms, 85F, defines the subgroup of DRB1*0102 haplotypes carrying susceptibility. The causal factor present on this haplotype (MSH5 85F-DRB1*0102) seems to be at the telomeric end of HLA class II or in Class I or III, as the allele composition in more centromeric markers is shared by all the haplotypes containing DRB1*0102. PMID- 20542072 TI - Prevalence of influenza vaccination and associated factors among pregnant women in Hong Kong. AB - A total of 568 pregnant women in Hong Kong were interviewed. Of them, 85.4% had heard of influenza vaccine, 21.3% had ever been vaccinated, 3.9% self-reported receiving influenza vaccination (IV) in the 2005/2006 flu season, and 33% were inclined toward receiving IV in the coming year. Multivariate analysis showed that those who had been recommended by health care professionals to receive IV during pregnancy were more likely than others to have received IV. Other variables related to the Health Belief Model were significantly associated with having ever been vaccinated or inclined toward receiving IV in the coming year. PMID- 20542073 TI - Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenil fish (Spaurus aurata). AB - Vitellogenin (Vtg) is a phospho-lipo-glycoprotein produced by oviparous animals in response to estrogen receptor (ER) binding. The presence of Vtg in juvenile and male fish liver and plasma has been used as biomarker to evaluate levels of environmental contaminants as dioxin and PCBs. Interaction of dioxins and PCBs with aryl hydrocarbon receptor (AhR) may affect reproduction by recruitment of estrogen receptor alpha (ERalpha). The aim of this study was to investigate the effects of PCB-126, a co-planar PCB prototypical AhR agonist, and of PCB-153, a non-coplanar PCB lacking dioxine-like activity, on Vtg expression in young fish (Spaurus aurata) after a 12 or 24h exposure to PCBs as well as 48h following PCBs removal. Vtg expression was evaluated by immunohistochemistry and by Western-blot analysis. Our results showed an increased Vtg expression following PCBs administration, with a maximum level after 12h of exposure to either PCB-126, PCB 153 or a mixture of both PCBs. Following this estrogenic activity, an anti estrogenic activity was detected after 24h of incubation with PCB-126 (alone or mixed with PCB-153), suggested by a decrease in Vtg expression likely through AhR, as a consequence of a hypothetic defence mechanism to endogenous or exogenous ligands. PMID- 20542074 TI - Effect of long-term optional ingestion of canola oil, grape seed oil, corn oil and yogurt butter on serum, muscle and liver cholesterol status in rats. AB - The aim of the present study was to determine the effect of long-term optional intake of vegetable oils (canola, grape seed, corn) and yogurt butter on the serum, liver and muscle cholesterol status. Twenty-five male Wistar rats were randomly categorized into five groups (n=5) as follows: control, canola oil, grape seed oil, corn oil and manually prepared yogurt butter. In each group, 24h two bottle choice (oil and water) tests were performed for 10 weeks. Serum cholesterol values showed a trend to decrease in grape seed oil, corn oil and yogurt butter groups compared to the control. Optional intake of yogurt butter made a significant increase in HDL-C values (42.34+/-9.98 mg/dL) yet decrease in LDL-C values (11.68+/-2.06 mg/dL) compared to the corresponding control (19.07+/ 3.51; 30.96+/-6.38 mg/dL, respectively). Furthermore, such findings were concomitant with a significant decrease in the liver TC levels (1.75+/-0.31 mg/g liver) and an increase in the muscle TC levels (1.85+/-0.32 mg/g liver) compared to the corresponding control (2.43+/-0.31; 0.94+/-0.14 mg/g liver, respectively). Optional intake of manually prepared yogurt butter has more beneficial effects on serum lipoprotein cholesterol values with some alterations in the liver and muscle cholesterol states than the vegetable oils. PMID- 20542075 TI - Mixture effects of imidazole fungicides on cortisol and aldosterone secretion in human adrenocortical H295R cells. AB - Exposure to chemicals commonly occurs in the form of mixtures. Methods and models are required to analyze and predict the effect of mixtures in order to improve risk assessment. The steroidogenesis and hormone production of the adrenal gland is a sensitive target for endocrine-disrupting chemicals including imidazoles. Here, we exposed human adrenocortical H295R cells to the individual imidazole fungicides prochloraz, ketoconazole, imazalil and their mixtures and analyzed the effects on secretion of cortisol and aldosterone and the effects on steroidogenic gene expression. The individual imidazole fungicides prochloraz, ketoconazole and imazalil and their mixtures inhibited cortisol secretion in a similar monotonic dose-response pattern with an EC(50) value of approximately 0.1 microM. Aldosterone secretion, in contrast, displayed a biphasic dose-response, with low dose stimulation of up to maximum twofold and high-dose inhibition. Biphasic dose responses were found following prochloraz and ketoconazole exposure and their mixtures, but not following imazalil exposure. The inhibition of cortisol secretion was equally well predicted with the concentration addition (CA) and independent action (IA) models, while the biphasic aldosterone response was partially predicted by a modified CA model and not predicted well by a modified IA model. Changes in expression levels of steroidogenic genes could not conclusively explain the different effects on the two hormone endpoints or the different specificities of the imidazoles. We conclude that single imidazoles and mixtures have specific effects on adrenal hormone secretion. These effects can only partly be predicted using current models and need to be further analyzed in terms of in vivo relevance and human risk assessment. PMID- 20542076 TI - Identification of key residues involved in fibril formation by the conserved N terminal region of Plasmodium falciparum merozoite surface protein 2 (MSP2). AB - Merozoite surface protein 2 (MSP2) from the human malaria parasite Plasmodium falciparum is expressed as a GPI-anchored protein on the merozoite surface. MSP2 is assumed to have a role in erythrocyte invasion and is a leading vaccine candidate. Recombinant MSP2 forms amyloid-like fibrils upon storage, as do peptides corresponding to sequences in the conserved N-terminal region, which constitutes the structural core of fibrils formed by full-length MSP2. We have investigated the roles of individual residues in fibril formation and local ordered structure in two peptides, a recombinant 25-residue peptide corresponding to the entire N-terminal domain of mature MSP2 and an 8-residue peptide from the central region of this domain (residues 8-15). Both peptides formed fibrils that were similar to amyloid-like fibrils formed by full-length MSP2. Phe11 and Ile12 have important roles both in stabilising local structure in these peptides and promoting fibril formation; the F11A and I12A mutants of MSP2(8-15) were essentially unstructured in solution and fibril formation at pH 7.4 and 4.7 was markedly retarded. The T10A mutant showed intermediate behaviour, having a less well defined structure than wild-type and slower fibril formation at pH 7.4. The mutation of Phe11 and Ile12 in MSP2(1-25) significantly retarded but did not abolish fibril formation, indicating that these residues also play a key role in fibril formation by the entire N-terminal conserved region. These mutations had little effect on the aggregation of full-length MSP2, however, suggesting that regions outside the conserved N-terminus have unanticipated importance for fibril formation in the full-length protein. PMID- 20542077 TI - Use of poly(amido)amine dendrimers in prevention of early non-enzymatic modifications of biomacromolecules. AB - Hyperglycaemia triggers the formation of both 'early' and advanced glycation end products, which are considered the major factors responsible for the complications of diabetes. Poly(amido)amine (PAMAM) dendrimers are relatively new class of materials with unique molecular structure predisposing them for the use as anti-glycation agents. The ability of poly(amido)amine (PAMAM) dendrimers G2 (MW 3256, 120 MUmol/l) and G4 (MW 14215, 30 MUmol/l) to inhibit the modification of proteins by high glucose (30 mmol/l, 37 degrees C, 72 h) was investigated using radiometric and spectrofluorometric assays. We monitored (a) non-enzymatic modifications of primary amino groups in BSA and polyamine compounds, and (b) the impact of anti-glycation agents on BSA conformation. Both PAMAM dendrimers and poly(L-lysine) (MW 70 kDa) effectively reduced BSA glycation, while undergoing the time-dependent modification themselves. Such a modification was a function of a number of available free amino groups per molecule, however, both dendrimers and poly(L-lysine) were equally effective in glucose scavenging. PAMAMs neither affected BSA conformation nor formed stable complexes with a protein, while non glycated poly(L-lysine) significantly quenched BSA fluorescence. Our results encourage raising the hypothesis that PAMAM dendrimers may be considered effective and safe chemical competitors for non-enzymatic modification by glucose, thus confirming the earlier in vivo study showing the inhibition of protein modification in experimental diabetes in the presence of PAMAM dendrimers. PMID- 20542078 TI - Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: a systematic review. AB - We conducted a systematic review and meta-regression analysis to quantify effects of exercise on brain hemodynamics measured by near-infrared spectroscopy (NIRS). The results indicate that acute incremental exercise (categorized relative to aerobic capacity (VO(2)peak) as low - <30% VO(2)peak; moderate - >=30% VO(2)peak to <60% VO(2)peak; hard - >=60% VO(2)peak to =VO(2)peak intensities) performed by 291 healthy people in 21 studies is accompanied by moderate-to-large increases (mean effect, dz+/-95% CI) in the prefrontal cortex of oxygenated hemoglobin (O(2)Hb) or other measures of oxygen level (O(2)Hbdiff) or saturation (SCO(2)) (0.92+/-0.67, 1.17), deoxygenated hemoglobin (dHb) (0.87+/-0.56, 1.19), and blood volume estimated by total hemoglobin (tHb) (1.21+/-0.84, 1.59). After peaking at hard intensities, cerebral oxygen levels dropped during very hard intensities. People who were aerobically trained attained higher levels of cortical oxygen, dHb, and tHb than untrained people during very hard intensities. Among untrained people, a marked drop in oxygen levels and a small increase in dHb at very hard intensities accompanied declines in tHb, implying reduced blood flow. In 6 studies of 222 patients with heart or lung conditions, oxygenation and dHb were lowered or unchanged during exercise compared to baseline. In conclusion, prefrontal oxygenation measured with NIRS in healthy people showed a quadratic response to incremental exercise, rising between moderate and hard intensities, then falling at very hard intensities. Training status influenced the responses. While methodological improvements in measures of brain oxygen are forthcoming, these results extend the evidence relevant to existing models of central limitations to maximal exercise. PMID- 20542079 TI - Posterior N1 asymmetry to English and Welsh words in Early and Late English-Welsh bilinguals. AB - We investigated the lateralization of the posterior event-related potential (ERP) component N1 (120-170 ms) to written words in two groups of bilinguals. Fourteen Early English-Welsh bilinguals and 14 late learners of Welsh performed a semantic categorization task on separate blocks of English and Welsh words. In both groups, the N1 was strongly lateralized over the left posterior sites for both languages. A robust correlation was found between N1 asymmetry for English and N1 asymmetry for Welsh words in both groups. Furthermore, in Late Bilinguals, the N1 asymmetry for Welsh words increased with years of experience in Welsh. These data suggest that, in Late Bilinguals, the lateralization of neural circuits involved in written word recognition for the second language is associated to the organization for the first language, and that increased experience with the second language is associated to a larger functional cerebral asymmetry in favor of the left hemisphere. PMID- 20542080 TI - Prefrontal, parietal and basal activation associated with the reordering of a two element list held in working memory. AB - A functional specialization in the prefrontal cortex along a dorsal-ventral gradient according to the type of processing in working memory, i.e. manipulation vs. maintenance, has been proposed based on previous neuroimaging studies. This seems particularly important for the further understanding of the functional architecture underlying working memory problems in patient populations. The current study examines the prefrontal involvement in the maintenance and manipulation of serial order of elements in working memory, with a task designed to be as simple as possible, to the aim of possible uses in clinical studies. Subjects held two-element ordered lists in memory and were presented with pseudo random sequences of "reorder" and "maintain" cues. Reorder cues were found to be associated with activation in the dorsal prefrontal cortex, parietal cortex and the basal ganglia. The results show that the simple task was indeed sufficient to evoke the prefrontal activation of interest, add to the information on functional dorsal-ventral specialization in prefrontal cortex and provide support for a prefrontal-parietal monitoring-manipulation network. PMID- 20542081 TI - The N400-concreteness effect reflects the retrieval of semantic information during the preparation of meaningful actions. AB - The present ERP study investigated when and how action semantics, i.e. the conceptual knowledge that we acquired over the course of our lives, is activated during the preparation of object-directed actions. Subjects were required to grasp one of two objects and were implicitly instructed to either perform a meaningful action (e.g. moving a cup towards the mouth) or a meaningless action with the object (e.g. moving a cup towards the eye). A larger anterior N400 was found for the preparation of meaningful compared to meaningless actions, likely reflecting the retrieval of action semantic information in case a meaningful action was required with the object. The distribution and the latency of the anterior N400-effect were strongly related to standard N400-repetition effects, thereby further corroborating the semantic nature of the effect. In sum, the present study provides new insight in the neural and temporal dynamics underlying semantics for action. PMID- 20542082 TI - Temporal dynamics of conflict monitoring and the effects of one or two conflict sources on error-(related) negativity. AB - The present electrophysiological study investigated the temporal development of response conflict and the effects of diverging conflict sources on error( related) negativity (Ne). Eighteen participants performed a combined stop-signal flanker task, which was comprised of two different conflict sources: a left-right and a go-stop response conflict. It is assumed that the Ne reflects the activity of a conflict monitoring system and thus increases according to (i) the number of conflict sources and (ii) the temporal development of the conflict activity. No increase of the Ne amplitude after double errors (comprising two conflict sources) as compared to hand- and stop-errors (comprising one conflict source) was found, whereas a higher Ne amplitude was observed after a delayed stop-signal onset. The results suggest that the Ne is not sensitive to an increase in the number of conflict sources, but to the temporal dynamics of a go-stop response conflict. PMID- 20542083 TI - (-)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, reduces dichlorodiphenyl-trichloroethane (DDT)-induced cell death in dopaminergic SHSY-5Y cells. AB - Results from epidemiological studies indicated that there exists an inverse correlation between consumption of green tea and neurodegenerative diseases including Parkinson's disease. We hypothesized that consumption of green tea would activate endogenous protective mechanisms against environmental toxin induced cell injury, which is believed to play a causative role in the etiology of Parkinson's disease. Here, we found that epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, concentration-dependently (1 microM, 3 microM and 10 microM) reduced dichlorodiphenyl-trichloroethane (DDT) (100 microM)-induced cell death in dopaminergic neuroblastoma SHSY-5Y cells. The cell viability was determined by trypan blue exclusion assays. We also found that preconditioning the SHSY-5Y cells with EGCG by multiple, brief, prior exposures of the cells to EGCG can subsequently protect the cells from DDT-induced cell death. The EGCG induced protective effect positively correlated with the number of exposures to EGCG. These results suggest that EGCG has a protective effect against DDT-induced cell death, and that prior exposures to EGCG activate an endogenous protective mechanism in the dopaminergic cells which can mitigate organochlorine pesticide induced cell injury. PMID- 20542084 TI - Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain. AB - Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain. PMID- 20542085 TI - Interleukin-2 as a neuromodulator possibly implicated in the physiopathology of sudden infant death syndrome. AB - Dysfunction in vital brainstem centers, including those controlling cardiorespiratory- and sleep/arousal pathophysiology, is reported in sudden infant death syndrome (SIDS). Biological mechanisms underlying SIDS, however, remain unclear. Cytokines are inter-cellular signaling chemicals. They can interact with neurotransmitters and might thus modify neural and neuroimmune functions. Cytokines could therefore act as neuromodulators. Interleukin (IL)-2 is a major immune-related cytokine. It has not been previously depicted in vital brainstem centers. We detected intense neuronal IL-2 immune-reactivity in the SIDS brainstem, namely in vital neural centers. This IL-2 overexpression might interfere with neurotransmitters in those critical brainstem centers, causing disturbed homeostatic control of cardiorespiratory and arousal responses, possibly leading to SIDS. PMID- 20542086 TI - Does somatosensory loss induce adaptation of the gait initiation process? AB - Gait initiation (GI) is the transient period between posture and movement. Its central programming takes into account the environmental constraints as well as the constraints induced by the body itself. Patients with peripheral sensory neuropathies display a severe proprioceptive deficit leading to balance and gait impairments and rely on a variety of compensatory mechanisms and are known to be dependent on vision. GI was studied on eight healthy subjects and five patients in order to assess the effect of somatosensory loss on the different phases of GI, combined with a manipulation of the visual inputs. Our main hypothesis is that the proprioceptive deficit would induce an adaptation of the GI process, especially when modifying the lower part of peripheral vision. The results show that the pathology induces some adaptations of the GI process, characterized by a decrease of the motor performance (assessed by the maximal anteroposterior velocity of the center of gravity at the end of the first step), a decrease in the spatial parameters (assessed by the peak amplitude of the backward shift of the center of foot pressure during the anticipation phase and the length of the first step), and a non-modification of the temporal parameters (assessed by the duration of the anticipation phase and of the first step). The suppression of the lower part of peripheral vision has no effect on the GI process. The role of the lower part of peripheral vision seems therefore to be less critical for GI, than for balance and locomotion. PMID- 20542087 TI - Acting performance and flow state enhanced with sensory-motor rhythm neurofeedback comparing ecologically valid immersive VR and training screen scenarios. AB - Actors were trained in sensory-motor rhythm (SMR) neurofeedback interfaced with a computer rendition of a theatre auditorium. Enhancement of SMR led to changes in the lighting while inhibition of theta and high beta led to a reduction in intrusive audience noise. Participants were randomised to a virtual reality (VR) representation in a ReaCTor, with surrounding image projection seen through glasses, or to a 2D computer screen, which is the conventional neurofeedback medium. In addition there was a no-training comparison group. Acting performance was evaluated by three experts from both filmed, studio monologues and Hamlet excerpts on the stage of Shakespeare's Globe Theatre. Neurofeedback learning reached an asymptote earlier as did identification of the required mental state following training in the ReaCTor training compared with the computer screen, though groups reached the same asymptote. These advantages were paralleled by higher ratings of acting performance overall, well-rounded performance, and especially the creativity subscale including imaginative expression, conviction and characterisation. On the Flow State scales both neurofeedback groups scored higher than the no-training controls on self-ratings of sense of control, confidence and feeling at-one. This is the first demonstration of enhancement of artistic performance with eyes-open neurofeedback training, previously demonstrated only with eyes-closed slow-wave training. Efficacy is attributed to psychological engagement through the ecologically relevant learning context of the acting-space, putatively allowing transfer to the real world otherwise achieved with slow-wave training through imaginative visualisation. The immersive VR technology was more successful than a 2D rendition. PMID- 20542088 TI - Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol. AB - Oxidative stress and secondary excitotoxicity, due to cellular energy deficit, are major factors playing roles in 3-nitropropionic acid (3-NPA) induced mitochondrial dysfunction. Acute or chronic exposure to 3-NPA also leads to neuronal degeneration in different brain regions. The present study quantitatively assessed peripheral neuropathy induced by chronic exposure to 3 NPA in rats. The neuroprotective abilities of two antioxidants, acetyl-l carnitine and resveratrol, were investigated as well. Rats were exposed for up to four weeks to 3-NPA alone or 3-NPA combined with acetyl-l-carnitine or resveratrol, administered peripherally. The experimental outcome was evaluated by neurophysiological, histological, and morphometric analyses. Rats exposed to 3 NPA developed hind limb paresis. Furthermore, a significant decrease in motor nerve conduction velocity (MCV) was detected in tail nerves and axonal degeneration in sciatic nerves (p<0.05). Treatment with resveratrol prevented the functional effects of 3-NPA exposure, whereas treatment with acetyl-l-carnitine, preventing paresis, was not effective to MCV and morphological changes. These data suggest that resveratrol is a good candidate for treatment of metabolic neuropathy. The experimental outcome of this study shows that chronic treatment with 3-NPA in rats is relevant in development of an experimental model of toxic neuropathy. PMID- 20542089 TI - The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction. AB - We use immunocytochemistry to show that the trophic molecule glial cell line derived neurotrophic factor (GDNF) and its receptor GDNF family receptor alpha-1 (GFRalpha-1) are present in both neonatal (P6) and adult (P45) rodent neuromuscular junctions (NMJ) colocalized with several synaptic markers. However, incubation with exogenous GDNF (10-200ng/ml, 1-3h), does not affect spontaneous ACh release. Moreover, GDNF does not change the size of the evoked ACh release from the weak and the strong axonal inputs on dually innervated postnatal endplates nor in the most developed singly-innervated synapses at P6 and P45. Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. PMID- 20542090 TI - Bulky high-mannose-type N-glycan blocks the taste-modifying activity of miraculin. AB - BACKGROUND: Miraculin (MCL) is a taste-modifying protein that converts sourness into sweetness. The molecular mechanism underlying the taste-modifying action of MCL is unknown. METHODS: Here, a yeast expression system for MCL was constructed to accelerate analysis of its structure-function relationships. The Saccharomyces cerevisiae expression system has advantages as a high-throughput analysis system, but compared to other hosts it is characterized by a relatively low level of recombinant protein expression. To alleviate this weakness, in this study we optimized the codon usage and signal-sequence as the first step. Recombinant MCL (rMCL) was expressed and purified, and the sensory taste was analyzed. RESULTS: As a result, a 2 mg/l yield of rMCL was successfully obtained. Although sensory taste evaluation showed that rMCL was flat in taste under all the pH conditions employed, taste-modifying activity similar to that of native MCL was recovered after deglycosylation. Mutagenetic analysis revealed that the N-glycan attached to Asn42 was bulky in rMCL. CONCLUSIONS: The high-mannose-type N-glycan attached in yeast blocks the taste-modifying activity of rMCL. GENERAL SIGNIFICANCE: The bulky N-glycan attached to Asn42 may cause steric hindrance in the interaction between active residues and the sweet taste receptor hT1R2/hT1R3. PMID- 20542092 TI - Ventilatory impairment in the dysmyelinated Long Evans shaker rat. AB - Although respiratory complications significantly contribute to morbidity/mortality in advanced myelin disorders, little is known concerning mechanisms whereby dysmyelination impairs ventilation, or how patients compensate (i.e. plasticity). To establish a model for studies concerning mechanisms of ventilatory impairment/compensation, we tested the hypotheses that respiratory function progressively declines in a model of CNS dysmyelination, the Long Evans shaker rat (les). The observed impairment is associated with abnormal inspiratory neural output. Minimal myelin staining was found throughout the CNS of les rats, including the brainstem and cervical bulbospinal tracts. Ventilation (via whole body plethysmography) and phrenic motor output were assessed in les and wild-type (WT) rats during baseline, hypoxia (11% O(2)) and hypercapnia (7% CO(2)). Hypercapnic ventilatory responses were similar in young adult les and WT rats (2 months old); in hypoxia, rats exhibited seizure-like activity with sustained apneas. However, 5-6 month old les rats exhibited decreased breathing frequencies, mean inspiratory flow (V(T)/T(I)) and ventilation (V (E)) during baseline and hypercapnia. Although phrenic motor output exhibited normal burst frequency and amplitude in 5-6 month old les rats, intra-burst activity was abnormal. In WT rats, phrenic activity was progressive and augmenting; in les rats, phrenic activity was decrementing with asynchronized, multipeaked activity. Thus, although ventilatory capacity is maintained in young, dysmyelinated rats, ventilatory impairment develops with age, possibly through discoordination in respiratory motor output. This study is the first reporting age-related breathing abnormalities in a rodent dysmyelination model, and provides the foundation for mechanistic studies of respiratory insufficiency and therapeutic interventions. PMID- 20542091 TI - Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat. AB - Ethanol exposure during postnatal days (PN) 4-6 in rats alters cerebellar development resulting in significant loss of Purkinje cells. There is little knowledge, however, on what happens to the neurons that survive. In this study, rat pups were treated with a daily dose of ethanol (either 3.6 or 4.5 g/kg body weight) delivered by intragastric intubation on PN4, PN4-6, or PN7-9. Then the interactions between climbing fibers and Purkinje cells were examined on PN14 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced in the PN4 and PN4-6 ethanol groups for the 4.5 g/kg dose level, compared to controls, indicating that the cerebellar circuitry was significantly altered following developmental ethanol exposure. Not only were there fewer Purkinje cells following ethanol exposure, but the surviving neurons had significantly fewer VGluT2-labeled synapses. These alterations in the synaptic integrity were both dose dependent and temporally dependent. PMID- 20542093 TI - Locus coeruleus neuronal activity during the sleep-waking cycle in mice. AB - Using extracellular single-unit recordings in nonanesthetized, head-restrained mice, we examined spontaneous and evoked discharges of noradrenaline-containing locus coeruleus (NA-LC) neurons across the sleep-waking cycle. The neurons were all characterized by triphasic broad action potentials. They discharged as either slow (<6 Hz) tonic, single spikes or phasic clusters of spikes specific to wakefulness (W), the discharge rate being highest during active waking and significantly lower during quiet waking. They remained totally silent during both slow-wave sleep (SWS) and paradoxical (or rapid eye movement (REM)) sleep. The phasic unit activity was related to abrupt activation of electromyographic activity occurring either spontaneously or elicited by alerting sensory stimuli. At the transition from waking to sleep, they ceased firing before the onset of cortical synchronization (deactivation), the first sign of electroencephalographic sleep, a significant decrease in firing rate preceding the onset of unit activity of sleep-specific neurons in the basal forebrain (BFB)/preoptic (POA) hypothalamus, as described previously [Takahashi K, Lin JS, Sakai K (2009) Neuroscience 161:269-292]. At the transition from SWS to waking, they fired before the onset of both cortical activation and a significant decrease in activity of sleep-specific neurons. These findings support the previous view that the NA-LC system is involved in both tonic and phasic processes of arousal, and further support our previous proposals that initiation of sleep is caused by decreased activity of waking-promoting neurons (disfacilitation) and that NA-LC neurons play an important role in the sleep/waking switch, that is from waking to sleep and from sleep to waking [Takahashi K, Lin JS, Sakai K (2009) Neuroscience 161:269-292]. PMID- 20542095 TI - Expression of a conditioned place preference or spatial navigation task following muscimol-induced inactivations of the amygdala or dorsal hippocampus: A double dissociation in the retrograde direction. AB - Previous work indicates an essential role of the basolateral amygdala in stimulus reward learning and the dorsal hippocampus in spatial learning and memory. The goal of the present, experiments was to examine the involvement of the amygdala and hippocampus in performance of tasks requiring stimulus-reward and spatial/relational learning and memory processes in the retrograde direction. Accordingly, this series of experiments tested the effects of temporary, inactivations directed at the basolateral nucleus of the amygdala or dorsal hippocampus on the, expression of a conditioned place preference (CPP) task or a spatial navigation water task. The results, of Experiments 1a and b showed that inactivations of the amygdala impaired the expression of a, previously acquired CPP but did not impair the expression of a learned spatial response required for, accurate performance of a spatial navigation task. The results of Experiments 2a and b showed that, inactivations of the dorsal hippocampus impaired expression of a learned response required for the, accurate performance of a spatial navigation task but did not impair the learned response required for, the expression of a CPP. Taken together, the results showed a functional dissociation between the, effects of amygdala or hippocampal dysfunction on the expression of these different classes of tasks. PMID- 20542094 TI - Relationship of cannabinoid CB1 receptor and cholecystokinin immunoreactivity in monkey dorsolateral prefrontal cortex. AB - Exposure to cannabis impairs cognitive functions reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC) and increases the risk of schizophrenia. The actions of cannabis are mediated via the brain cannabinoid 1 receptor (CB1R), which in rodents is heavily localized to the axon terminals of cortical GABA basket neurons that contain cholecystokinin (CCK). Differences in the laminar distribution of CB1R-immunoreactive (IR) axons have been reported between rodent and monkey neocortex, suggesting that the cell type(s) containing CB1Rs, and the synaptic targets of CB1R-IR axon terminals, may differ across species; however, neither the relationship of CB1Rs to CCK-containing interneurons, nor the postsynaptic targets of CB1R and CCK axon terminals, have been examined in primate DLPFC. Consequently, we compared the distribution patterns of CB1R- and CCK-IR structures, determined the proportions of CB1R and CCK neurons that were dual-labeled, and identified the synaptic types and postsynaptic targets of CB1R- and CCK-IR axon terminals in macaque monkey DLPFC. By light microscopy, CB1R- and CCK-IR axons exhibited a similar laminar distribution, with their greatest densities in layer 4. Dual-label fluorescence experiments demonstrated that 91% of CB1R-IR neurons were immunopositive for CCK, whereas only 51% of CCK-IR neurons were immunopositive for CB1R. By electron microscopy, all synapses formed by CB1R-IR axon terminals were symmetric, whereas CCK-IR axon terminals formed both symmetric (88%) and asymmetric (12%) synapses. The primary postsynaptic target of both CB1R- and CCK-IR axon terminals forming symmetric synapses was dendritic shafts (81-88%), with the remainder targeting cell bodies or dendritic spines. Thus, despite species differences in laminar distribution, CB1Rs are principally localized to CCK basket neuron axons in both rodent neocortex and monkey DLPFC. These axons target the perisomatic region of pyramidal neurons, providing a potential anatomical substrate for the impaired function of the DLPFC associated with cannabis use and schizophrenia. PMID- 20542096 TI - Nestmateship and body size do not influence mate choice in males and females: a laboratory study of a primitively eusocial wasp Ropalidia marginata. AB - We investigated the effect of nestmateship and body size on mate selection through a choice based assay in the primitively eusocial wasp Ropalidia marginata. A recent study has shown that male and female R. marginata mate with their nestmates and non-nestmates with equal probability if no choice is available. That study could also not detect any influence of body size on mating probability in the absence of choice. To confirm that the same results can be obtained even when the wasps have a choice, we offered a choice of two virgin partners either to a virgin test male or to a virgin test female and measured the probability that the test individual would mate with any particular partner based on nestmateship or body size. We show here that even when a choice is available, neither male nor female test wasps base their mate choice on the nestmateship or body size of the partner. We therefore suggest that the natural mating habit of these wasps is sufficiently promiscuous and not constrained by such factors as nestmateship and body size. PMID- 20542097 TI - Using video playback to study the effect of an audience on male mating behavior in the Sailfin molly (Poecilia latipinna). AB - Sexual conflict in poeciliid fishes is well-documented, particularly male sexual harassment and its effects on females. For instance, male attempts to force copulations influence female feeding, energy allocation, and preference for shoaling partners. However, there has been little research conducted to determine how the social environment shapes the occurrence and intensity of sexual harassment. In this study we ask whether an audience male influences the sexual behaviors of a focal male, the correlated feeding time reduction of female Poecilia latipinna, and if the size of the audience male (larger or smaller than the focal male) influences these behaviors. We presented a video of a male, either smaller or larger than the focal male, or an empty tank (control) to a female interacting with a male or female partner and measured feeding times and sexual behaviors. We found that male sexual behaviors increased in the presence of an audience male, especially if the audience male was larger than the focal male. Females fed more in the presence of a partner female than in the presence of a male, which was independent of the audience (i.e., video treatment). Focal female aggression towards the partner female increased with the size of the audience male. The present study shows that an audience male has multiple interacting influences on both male and female behavior. PMID- 20542098 TI - Observing responses: maintained by good news only? AB - Observing responses are those that produce stimuli correlated with the availability (S+) or non-availability (S-) of reinforcement but that has no influence on the actual delivery or timing of reinforcement. Prior research has shown that observing is maintained by the occasional production of the S+ ("good news") and not by production of the equally informative S- ("bad news"). However, for both humans and rats the S- maintains observing when it is at least implicitly correlated with good news. In the present study, pigeons could obtain both good and bad news by responding during the appropriate key color. In one condition, the bad news was actually more informative about reinforcement than was the good news. Nevertheless, a preponderance of the birds' responses was made on the nominally good-news option. The present results offer further support for the central role of good news in maintaining observing responses and are entirely consistent with the traditional conditioned-reinforcement (or classical conditioning) interpretation of observing. PMID- 20542099 TI - Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells. AB - Exposure to polycyclic aromatic hydrocarbons (PAHs) has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene (BaP), a potent mutagenic PAH, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. When analyzing the effect of BaP on the induction of CYP1 enzymes participating in the metabolic activation of PAHs in LNCaP cells, we found that BaP induced expression of CYP1A1 and CYP1A2, but not CYP1B1 enzyme. Despite a significant amount of DNA adducts being formed by BaP and, to a lesser extent also by another strong genotoxin, dibenzo[a,l]pyrene, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the phosphoinositide-3-kinase/Akt pro-survival pathway. The lack of apoptosis was not due a disruption of expression of pro-apoptotic and pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or checkpoint kinase-2. BaP did not activate p53, as evidenced by the lack of p53 accumulation, phosphorylation at Ser15, or induction of p53 transcriptional targets. Taken together, although genotoxic PAHs produced significant levels of DNA adducts in a model of human prostate carcinoma cells, they did not activate the mechanisms leading to elimination of cells with significant damage to DNA, presumably due to their failure to activate the p53 dependent DNA damage response. PMID- 20542100 TI - Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds. AB - OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients. METHODS: After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC. RESULTS: A total amount of 2269+/-1726 mg obidoxime was infused over 65 h+/-55 h resulting in a steady state plasma concentration of 14.5+/-7.3 microM. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32+/-0.1L/kg (V((1))) and 0.28+/-0.12 (V((2)))L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration. CONCLUSIONS: Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated. This result allows the recommendation of using this definite regimen for adults also in case of mass casualties. PMID- 20542101 TI - Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages. AB - The bioavailability of low molecular weight heparin (LMWH) has been increased by encapsulation in nanoparticles. As a complement to these results, the cytotoxicity and apoptosis induced by LMWH nanoparticles prepared by two methods [nanoprecipitation (NP) and double emulsion (DE)] using Eudragit RS (RS) and poly epsilon-caprolactone (PCL) have been analysed. Particle sizes varied from 54 to 400nm with zeta potential values between -65 and +63mV. Our results showed that the method of nanoparticle preparation affects their properties, especially in terms of drug incorporation and cell tolerance. Cell viability ranged from 6% to 100% depending on the preparation method and physicochemical properties of the particles and the type of toxicity assay. Particle diameter and zeta potential seemed to be the most valuable cytotoxicity markers when cell viability was measured by Trypan blue exclusion and MTT respectively. Nanoparticles prepared by DE were better tolerated than those of NP. LMWH encapsulation into the cationic nanoparticles reduces remarkably their toxicity. Apoptosis evaluation showed activated caspases in exposed cells. However, no nuclear fragmentation was detected in NR8383 cells whatever the tested nanoparticles. DE nanoparticles of RS and PCL can be proposed as a good LMWH delivery system due to their low toxicity (IC(50) approximately 2.33 and 0.96mg/mL, respectively). PMID- 20542102 TI - An in vitro study of epoetin beta intravenous injection site at the end of hemodialysis. AB - The aim of this study (SITEPO) is to evaluate the influence of the intravenous injection site (drip chamber injection site, venous injection site or venous fistula needle) on plasma concentration of epoetin beta (Neorecormon, Roche), a recombinant Human Erythropoietin (rHuEPO), at the end of in vitro hemodialysis sessions. No practical administration guidelines are available. Twenty 1-h dialysis sessions are performed. Before each dialysis, the circuit is filled with 270ml, of heparinized total human blood whose hematocrit is adjusted to 35%. A common dosage of epoetin beta in clinical practice (3000IU) is studied for the three injection sites and for reference experiments in which rHuEPO is not injected into the dialysis circuit. Plasma concentrations of erythropoietin are measured by ELISA. The physiologically endogenous erythropoietin concentration is systematically determined and removed from the total epoetin beta concentration. Average epoetin beta plasma levels returned are not significantly different between the three injection sites and no significant rHuEPO loss is observed after injection into the drip chamber, the venous injection site and the venous fistula needle compared with reference experiments. The three intravenous injection sites of rHuEPO can be used at the end of dialysis without significant epoetin beta loss. PMID- 20542103 TI - How does mismatch negativity reflect auditory motion? AB - Recent studies have shown that the mismatch negativity (MMN), a change-specific component of the auditory event-related potential (ERP), is accurately tracking the spatial location of the stationary sound source. The aim of the present study was to estimate the parameters of MMNs evoked by auditory motion and to compare the motion discrimination measured by MMN in normally hearing subjects with the psychophysical data obtained in the same group of subjects. The auditory motion was simulated by introducing variable interaural time differences (ITDs) into the deviant stimuli. The ERPs were recorded for frequently occurring stationary midline standards and for infrequent deviant sounds moving horizontally at different velocities. It was established that all the deviant stimuli elicited significant MMNs. The MMN increased monotonically in amplitude with growing angular distances travelled by the deviant stimuli. The deviants that travelled over the same angular distances at different velocities caused MMNs that agreed in magnitude but differed in latency. These results indicated that the angular distance rather than sound image velocity was the most essential cue involved in the MMN generation. To test the psychophysical performance, a two-interval forced choice task was employed, in which the ITD was the main dependent variable. The deviants that evoked significant MMNs at the minimal ITDs were not discriminated behaviorally, indicating that the motion discrimination of the hearing system may be better at a preattentive level. PMID- 20542104 TI - Wormwood (Artemisia absinthium L.)--a curious plant with both neurotoxic and neuroprotective properties? AB - The medical use of the wormwood plant Artemisia absinthium L. dates back to at least Roman times, while during the last century this tradition was seemingly on the decline due to fears of absinthism, a syndrome allegedly caused by the wormwood-flavoured spirit absinthe and more specifically as a result of thujone, a monoterpene ketone often present in the essential oil of wormwood. If threshold concentrations are exceeded, thujone does in fact exhibit neurotoxic properties leading to dose-dependent tonic-clonic seizures in animals, likely caused by GABA type A receptor modulation. Research has shown that the concentrations of thujone present in absinthe were not sufficient to exceed these thresholds, and the marketing of wormwood-flavoured alcoholic beverages has ultimately been reinstated. The declining fears of absinthism may have led to a revival of the medical uses of wormwood, evidenced by several experimental reports, e.g. on the treatment of Crohn's disease. Most recently in this journal, neuroprotective properties of wormwood were detected in rats, and the plant was suggested to be possibly beneficial in the treatment of strokes. While these results sound promising and worthwhile for further investigation, the well-defined profile of adverse properties of wormwood demands a more cautious interpretation of these results. It remained unclear in the studies, for example, if the threshold dose for thujone (e.g. as set by the European Medicines Agency) would be exceeded during therapeutic usage. Due to the colourful history of wormwood, its application in humans should be preceded by a thorough and careful risk-benefit analysis. PMID- 20542105 TI - In vitro antimicrobial, anthelmintic and cyclooxygenase-inhibitory activities and phytochemical analysis of Leucosidea sericea. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Leucosidea sericea is used as a vermifuge and in the treatment of ophthalmia by various tribes in southern African countries. AIM OF THE STUDY: The study aimed at screening leaves and stems of Leucosidea sericea for pharmacological activity and validating the plant's traditional use. A general phytochemical screening was also carried out. MATERIALS AND METHODS: Petroleum ether (PE), dichloromethane (DCM), ethanol (EtOH) and water extracts of the plant parts were investigated for antimicrobial, anthelmintic and cyclooxygenase (COX) inhibitory activities. Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and Candida albicans were used for the antimicrobial evaluation. Caenorhabditis elegans was used for the anthelmintic assay using the microdilution technique. Cyclooxygenase-1 and -2 (COX-1 and -2) were used to evaluate the anti-inflammatory potential of the plant extracts. Phytochemical analysis for phenolic compounds, including gallotannins, condensed tannins and flavonoids was done using 50% methanol extracts of the leaves and stems employing spectrophotometric methods. RESULTS: The leaf extracts exhibited broad spectrum antibacterial activity ranging from 0.025 to 6.25mg/ml. The most noteworthy minimum inhibitory concentration (MIC) of 0.025 mg/ml was exhibited by PE and DCM leaf extracts against Bacillus subtilis and Staphylococcus aureus, respectively. In the anthelmintic assay, the best minimum lethal concentration (MLC) value of 0.26 mg/ml was observed for the DCM and EtOH leaf extracts. Both leaf and stem organic solvent extracts exhibited high to moderate inhibition against COX-1 and 2 at a screening concentration of 250 microg/ml. At lower concentrations, the extracts displayed a dose-dependent inhibition, with the lowest IC(50) values of 0.06 microg/ml (COX-1) and 12.66 microg/ml (COX-2) exhibited by the PE extract of the leaves. Generally, the leaf extracts exhibited better pharmacological activities and contained higher amounts of phenolic compounds than the stem extracts. Alkaloids and saponins were only detected in the leaf and stem extracts, respectively. CONCLUSION: The reported results support the local use of Leucosidea sericea against eye infections and as a vermifuge. The pharmacological activities exhibited by the leaf extracts are probably due to their higher phenolic levels. PMID- 20542106 TI - Involvement of the PI3K/AKT pathway in ATP-induced proliferation of developing retinal cells in culture. AB - ATP induces the proliferation of chick retinal cells in culture through the activation of P2Y1 receptors, PKC and MAP kinases. Together with MAP kinases, the PI3K/AKT pathway has also been implicated as an important mediator in proliferative events during development. Here we investigated the participation of the PI3K/AKT signal pathway on ATP-induced proliferation of chick embryo retinal cells in culture. When retinal cultures obtained from 7-day-old embryos were cultivated for 1 day and treated with ATP, a transient and dose-dependent phosphorylation of both ERK and AKT was observed, an effect that could be mimicked by 500 microM ADP and blocked by 100 microM PPADS, a P2 receptor antagonist. Maximal stimulation of both enzymes was obtained with 100 microM ATP in 5 min, decreasing thereafter. Activation of these pathways by ATP seemed to be independent, since LY294002 and U0126, inhibitors of PI3K and MEK, did not block the activation of ERK and AKT, respectively, although each compound blocked its respective target. Moreover, when the cultures were incubated with ATP in the presence of LY294002, a decreased incorporation of [(3)H]-thymidine was observed, as compared to cultures treated only with ATP, a decline that was also obtained by incubating the cells with ATP plus 0.5 microM API-59CJ-Ome, an inhibitor of AKT. No decrease in cell viability was observed with this concentration of API 59CJ-Ome. An increase in cyclin D1 expression, that could be inhibited by 10 microM LY 294002 or 20 microM U0126, was observed when cells were incubated with 500 microM ADP. No effect of PI3K and MEK inhibitors was observed in the expression of p27kip1 in the cultures. These results suggest that, besides the involvement of the MAP kinases pathway, ATP-induced cell cycling of late developing retinal progenitors in culture also involves the activation of the PI3K/AKT pathway. PMID- 20542107 TI - Arginase 2 and nitric oxide synthase: Pathways associated with the pathogenesis of thyroid tumors. AB - We have previously shown that ARG2 expression was increased in most malignant thyroid tumors, but absent in benign lesions and normal tissues. Small interfering RNA knockdown was used to investigate the role of ARG2 in a thyroid carcinoma cell line. ARG2 knockdown decreased eNOS expression as well as the expression of eNOS-related genes (p21, Akt1, HIF-1, VEGF, and CAV1). ARG2 silencing changed tumor properties of thyroid cancer cells promoting apoptosis and reduced expression of cell proliferation markers. These results, coupled with enhanced nitric oxide production and elevated reactive oxygen species (ROS) levels, account for the altered intracellular redox environment. Genes related to either production (DUOX1 and NOX4) or catabolism (SODs) of ROS and reactive nitrogen species were negatively modulated by ARG2 knockdown. Additionally, a positive correlation of ARG2 with eNOS and related genes was investigated in thyroid tumors, further substantiating our in vitro findings. Our results suggest that ARG2 and eNOS may work in a coordinated manner and the underlying mechanism might be of major significance for thyroid tumorigenesis and/or tumor progression pathways. Fine modulation of ARG2, eNOS, and related genes may represent a potential source for targeted therapy of several cancer types. PMID- 20542108 TI - Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. AB - Epidemiological, as well as most in vivo, studies suggest that flavonoids have a positive influence on various cardiovascular diseases. Traditionally, these effects were only attributed to their antioxidant activity, which has been extensively studied. Apart from the direct antioxidant properties, which include direct reactive oxygen species scavenging activity and transient metal chelation, this review reports on many other effects that in pharmacologically achievable concentrations may also be responsible for their positive cardiovascular influence. These include direct inhibition of some radical-forming enzymes (xanthine oxidase, NADPH oxidase, and lipoxygenases), decreased platelet aggregation and leukocyte adhesion, and vasodilatory properties. For each of the aforementioned effects different structural features are necessary. Briefly, a catecholic B-ring is necessary for scavenging activity; hydroxyl groups in an ortho position, the 3-hydroxy-4-keto group, or the 5-hydroxy-4-keto group enable iron chelation; planar conformation with the 4-keto group and 2,3-double bond is essential for inhibition of leukocyte adhesion and platelet aggregation; specific hydroxy-methoxy ortho conformation in ring B is necessary for the inhibition of NADPH oxidase; and the 4-keto group is a requisite for vasodilatory action. This review shows that positive cardiovascular effects of flavonoids are achieved by various flavonoids via the interaction with different targets. PMID- 20542109 TI - Anti-phytopathogen potential of endophytic actinobacteria isolated from tomato plants (Lycopersicon esculentum) in southern Brazil, and characterization of Streptomyces sp. R18(6), a potential biocontrol agent. AB - Tomato plants (Lycopersicon esculentum) are highly susceptible to phytopathogen attack. The resulting intensive application of pesticides on tomato crops can affect the environment and health of humans and animals. The objective of this study was to select potential biocontrol agents among actinobacteria from tomato plants, in a search for alternative phytopathogen control. We evaluated 70 endophytic actinobacteria isolated from tomato plants in southern Brazil, testing their antimicrobial activity, siderophore production, indoleacetic acid production, and phosphate solubility. The actinomycete isolate with the highest antimicrobial potential was selected using the agar-well diffusion method, in order to optimize conditions for the production of compounds with antimicrobial activity. For this study, six growth media (starch casein-SC, ISP2, Bennett's, Sahin, Czapek-Dox, and TSB), three temperatures (25 degrees C, 30 degrees C, and 35 degrees C) and different pH were tested. Of the actinobacteria tested, 88.6% showed antimicrobial activity against at least one phytopathogen, 72.1% showed a positive reaction for indoleacetic acid production, 86.8% produced siderophores and 16.2% showed a positive reaction for phosphate solubility. Isolate R18(6) was selected due to its antagonistic activity against all phytopathogenic microorganisms tested in this study. The best conditions for production were observed in the SC medium, at 30 degrees C and pH 7.0. The isolate R18(6) showed close biochemical and genetic similarity to Streptomyces pluricolorescens. PMID- 20542110 TI - Comparing techniques for drug loading of shape-memory polymer networks--effect on their functionalities. AB - A family of oligo[(epsilon-caprolactone)-co-glycolide]dimethacrylate (oCG-DMA) derived networks of different glycolide contents as well as precursor molecular weights has been synthesized by crosslinking oCG-DMA, providing matrices of different hydrophilicity, network density, and morphology at body temperature. Such networks were loaded with a hydrophilic model drug, ethacridine lactate, either before crosslinking or afterwards by swelling in drug solution. Disadvantageous alterations of the shape-memory functionality and degradation characteristics were observed only in few loaded materials. Loading by swelling generally resulted in low payloads, which slightly increased for more hydrophilic polymer networks, and a substantial burst and fast subsequent release for all investigated materials. Loading before crosslinking gave almost no burst and higher subsequent release rates over longer periods of time. Overall, depending on the needs of a specific application, a material from this polymer family with the desired mechanical properties, shape-memory functionality, and degradation pattern can be selected and combined with drugs when considering that (i) loading by swelling is best suited for applications that require high initial doses and (ii) loading before crosslinking allows easy variation of payloads and low burst release for therapeutics that are non-sensitive to chemical alterations during crosslinking. PMID- 20542111 TI - Ternary biomolecular nanoparticles for targeting of cancer cells and anti angiogenesis. AB - To develop a targeted drug delivery system for cancer therapy and anti angiogenesis, amphiphilic heparin bioconjugates were synthesized by chemical conjugation of hydrophobic retinoic acid and a targeting ligand, folic acid, to the heparin backbone (HFR). The chemical structure of the HFR conjugates was confirmed by proton nuclear magnetic resonance ((1)H NMR). Various HFR conjugates with different retinoic acid coupling ratios were obtained by modulating the retinoic acid feed molar ratio. The anticoagulant activity of the HFR conjugates decreased to 30% of heparin levels as measured by anti-FXa chromogenic assay. The bioconjugates retained the anti-angiogenic effect, showing a significant decrease in endothelial tubular formation using a Matrigel model. In aqueous solutions, the bioconjugates readily self-assembled to form nanoparticles via the hydrophobic interaction among retinoic acid. The HFR nanoparticles were spherical and ranged from 150 to 300 nm, depending on the degree of retinoic acid coupling. The presence of folic acid efficiently enhanced the cellular uptake of the HFR nanoparticles in folate receptor-positive cells. Furthermore, the internalized HFR nanoparticles demonstrated greater cytotoxicity against folate receptor positive cells compared to free retinoic acid. These results indicate that specific delivery of retinoic acid with ternary biomolecular nanoparticles targeting folate receptor-positive tumors is a promising strategy to enhance chemotherapy efficacy with minimal side effects. PMID- 20542112 TI - In vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB(2)) in rat liver microsomes. AB - The in vitro metabolism of an inverse agonist of the peripheral cannabinoid receptor (CB(2)), indomethacin morpholinylamide (BML-190), has been characterized using rat liver microsomal incubation. BML-190 was found to yield at least 15 metabolic products as identified by HPLC-MS/MS analysis. Four major phase one metabolic pathways either individually, or in combination, were proposed to account for the identified metabolic products: (1) loss of the p-chlorobenzyl group, (2) hydroxylation on the indole or on the morpholine ring, (3) morpholinyl ring opening, and (4) demethylation of the methoxyl group on the indole ring. PMID- 20542113 TI - COX-2 inhibitor nimesulide analogs are aromatase suppressors in breast cancer cells. AB - Cyclooxygenase-2 (COX-2) inhibitor nimesulide derivatives compounds A and B decreased aromatase activity in breast cancer cells via a novel mechanism different to aromatase inhibitors (AIs), and were defined as "aromatase suppressors". Breast carcinoma cells (MCF-7aro and T47Daro) transfected with aromatase full gene were used to explore the mechanisms of the two compounds. They dose and time-dependently suppressed aromatase activity in MCF-7aro and T47Daro cells in the nanomole range. However, they neither directly inhibited aromatase, nor improved aromatase degradation even at much higher concentrations. They could also suppress androgen stimulated cell growth, but did not affect estrogen enhanced cell proliferation. These results suggest that compounds A and B selectively interfere with aromatase in breast cancer cells, but not estrogen receptor (ER) downstream to disrupt androgen mediated cell growth. Interestingly, compound B effectively inhibited LTED (long-term estrogen deprived MCF-7aro cell) cell growth, which is a model for AIs resistance, with an IC(50) of 4.68 +/- 0.54 MUM. The results indicate that compound B could potentially overcome AI resistance in breast cancer cell and could be used as a lead to design more potent derivatives. PMID- 20542114 TI - A gut-specific chitinase gene essential for regulation of chitin content of peritrophic matrix and growth of Ostrinia nubilalis larvae. AB - Chitinases belong to a large and diverse family of hydrolytic enzymes that break down glycosidic bonds of chitin. However, very little is known about the function of chitinase genes in regulating the chitin content in peritrophic matrix (PM) of the midgut in insects. We identified a cDNA putatively encoding a chitinase (OnCht) in European corn borer (ECB; Ostrinia nubilalis). The OnCht transcript was predominately found in larval midgut but undetectable in eggs, pupae, or adults. When the larvae were fed on an artificial diet, the OnCht transcript level increased by 4.4-fold but the transcript level of a gut-specific chitin synthase (OnCHS2) gene decreased by 2.5-fold as compared with those of unfed larvae. In contrast, when the larvae were fed with the food and then starved for 24h, the OnCht transcript level decreased by 1.8-fold but the transcript level of OnCHS2 increased by 1.8-fold. Furthermore, there was a negative relationship between OnCht transcript level and chitin content in the midgut. By using a feeding-based RNAi technique, we were able to reduce the OnCht transcript level by 63-64% in the larval midgut. Consequently, these larvae showed significantly increased chitin content (26%) in the PM but decreased larval body weight (54%) as compared with the control larvae fed on the diet containing GFP dsRNA. Therefore, for the first time, we provide strong evidence that OnCht plays an important role in regulating chitin content of the PM and subsequently affecting the growth and development of the ECB larvae. PMID- 20542115 TI - Juvenile hormone and allatostatins in the German cockroach embryo. AB - Levels of juvenile hormone III (JH), FGLamide allatostatin peptides (ASTs), ASTs precursor (preproAST) mRNA and methyl farnesoate epoxidase (CYP15A1) mRNA were measured in embryos of the cockroach Blattella germanica. JH starts to rise just after dorsal closure, reaches maximal levels between 60% and 80% of embryogenesis, and decrease subsequently to undetectable levels. ASTs show low levels during the first two thirds of embryogenesis, increase thereafter and maintain high levels until hatching. PreproAST mRNA shows quite high levels during the two days following oviposition, thus behaving as a maternal transcript, the levels then become very low until mid embryogenesis, and increase afterwards, peaking towards the end of embryo development. CYP15A1 transcripts were detected around 25% embryogenesis and the levels tended to increase through embryogenesis, although differences amongst the days studied were not statistically significant. The opposite patterns of JH and AST towards the end of embryo development, along with the detection of AST immunoreactivity in corpora allata from late embryos, suggest that JH decline is caused by the increase of AST. Moreover, the uncorrelated patterns of JH concentration and CYP15A1 mRNA levels suggest that CYP15A1 expression does not modulate JH production. PMID- 20542116 TI - A fatty acyl-CoA reductase highly expressed in the head of honey bee (Apis mellifera) involves biosynthesis of a wide range of aliphatic fatty alcohols. AB - Honey bees (Apis mellifera) are social insects which have remarkable complexity in communication pheromones. These chemical signals comprise a mixture of hydrocarbons, wax esters, fatty acids, aldehydes and alcohols. In this study, we detected several long chain aliphatic alcohols ranging from C18-C32 in honey bees and the level of these alcohols varied in each body segment. C18:0Alc and C20:0Alc are more pronounced in the head, whereas C22:0Alc to C32Alc are abundant in the abdomen. One of the cDNAs coding for a fatty acyl-CoA reductase (AmFAR1) involved in the synthesis of fatty alcohols was isolated and characterized. AmFAR1 was ubiquitously expressed in all body segments with the predominance in the head of honey bees. Heterologous expression of AmFAR1 in yeast revealed that AmFAR1 could convert a wide range of fatty acids (14:0-22:0) to their corresponding alcohols, with stearic acid 18:0 as the most preferred substrate. The substrate preference and the expression pattern of AmFAR1 were correlated with the level of total fatty alcohols in bees. Reconstitution of the wax biosynthetic pathway by heterologous expression of AmFAR1, together with Euglena wax synthase led to the high level production of medium to long chain wax monoesters in yeast. PMID- 20542118 TI - Quercetin attenuates Monocyte Chemoattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-kappaB and AP-1. AB - Monocyte Chemoattractant Protein-1 (MCP-1) is involved in the diapedesis of blood monocytes into the arterial intima, an early critical event in atherogenesis. Modulating MCP-1 expression can be a key strategy to decrease the risk for atherosclerosis in diabetes. We hypothesized that quercetin, an anti-inflammatory molecule could modulate high glucose concentration (HG) induced MCP-1 expression in aortic endothelial cells in vitro because of its regulatory effects on Activator Protein-1 (AP-1) and Nuclear Factor-kappaB (NF-kappaB). Rat aortic endothelial cells (RAECs) were exposed to HG in the presence or absence of quercetin. Quercetin attenuated HG induced MCP-1 mRNA (42%) and protein synthesis (45%) when estimated using real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Western blot analysis found quercetin to maintain cytosolic p65 protein levels to that seen in control. Quercetin was found to attenuate HG induced increased NF-kappaB and AP-1 DNA binding activity in electrophoretic mobility shift assay. Immunofluorescence studies revealed quercetin to prevent HG induced nuclear localization of p65 and c-jun. Quercetin was also found to decrease HG induced activation of NF-kappaB (71%+/-14%), AP-1 (69%+/-24%) and MCP-1 promoter (79%+/-25%) in EA.hy926 cells when analyzed using luciferase reporter assay. We conclude that quercetin attenuates MCP-1 expression in HG treated RAECs, probably by regulating both NF kappaB and AP-1 pathways. The findings provide new insights into HG induced MCP-1 gene regulation in aortic endothelial cells and the potential of quercetin in abating the risk for atherosclerosis in diabetes. PMID- 20542117 TI - Hydrogen sulfide and ischemia-reperfusion injury. AB - Gasotransmitters are lipid soluble, endogenously produced gaseous signaling molecules that freely permeate the plasma membrane of a cell to directly activate intracellular targets, thus alleviating the need for membrane-bound receptors. The gasotransmitter family consists of three members: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H(2)S). H(2)S is the latest gasotransmitter to be identified and characterized and like the other members of the gasotransmitter family, H(2)S was historically considered to be a toxic gas and an environmental/occupational hazard. However with the discovery of its presence and enzymatic production in mammalian tissues, H(2)S has gained much attention as a physiological signaling molecule. Also, much like NO and CO, H(2)S's role in ischemia/reperfusion (I/R) injury has recently begun to be elucidated. As such, modulation of endogenous H(2)S and administration of exogenous H(2)S has now been demonstrated to be cytoprotective in various organ systems through diverse signaling mechanisms. This review will provide a detailed description of the role H(2)S plays in different model systems of I/R injury and will also detail some of the mechanisms involved with its cytoprotection. PMID- 20542119 TI - Whole-genome DNA methylation profiling using MethylCap-seq. AB - MethylCap-seq is a robust procedure for genome-wide profiling of DNA methylation. The approach consists of the capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation sequencing of eluted DNA. Elution of the captured methylated DNA is done in steps using a salt gradient, which stratifies the genome into fractions with different CpG density. The enrichment reached within the individual eluates allows for cost-effective deep sequence coverage. The profiles together yield a detailed genome-wide map of methylated regions and readily allows detection of DNA methylation in known and novel regions. Here, we describe principles and details of the MethylCap-seq procedure using different sources of starting material. PMID- 20542120 TI - Prospective motion correction of high-resolution magnetic resonance imaging data in children. AB - Motion artifacts pose significant problems for the acquisition and analysis of high-resolution magnetic resonance imaging data. These artifacts can be particularly severe when studying pediatric populations, where greater patient movement reduces the ability to clearly view and reliably measure anatomy. In this study, we tested the effectiveness of a new prospective motion correction technique, called PROMO, as applied to making neuroanatomical measures in typically developing school-age children. This method attempts to address the problem of motion at its source by keeping the measurement coordinate system fixed with respect to the subject throughout image acquisition. The technique also performs automatic rescanning of images that were acquired during intervals of particularly severe motion. Unlike many previous techniques, this approach adjusts for both in-plane and through-plane movement, greatly reducing image artifacts without the need for additional equipment. Results show that the use of PROMO notably enhances subjective image quality, reduces errors in Freesurfer cortical surface reconstructions, and significantly improves the subcortical volumetric segmentation of brain structures. Further applications of PROMO for clinical and cognitive neuroscience are discussed. PMID- 20542122 TI - Cost function masking during normalization of brains with focal lesions: still a necessity? AB - Although normalization of brain images is critical to the analysis of structural damage across individuals, loss of tissue due to focal lesions presents challenges to the available normalization algorithms. Until recently, cost function masking, as advocated by Brett and colleagues (2001), was the accepted method to overcome difficulties encountered when normalizing damaged brains; however, development of the unified segmentation approach for normalization in SPM5 (Ashburner & Friston, 2005) offered an alternative. Crinion et al. (2007) demonstrated this approach produced normalization results without cost function masking that appeared to be robust to lesion effects when tested using the same simulated lesions studied by Brett et al. (2001). The present study sought to confirm the validity of this approach in brains with focal damage due to vascular events. To do so, we examined outcomes of normalization using unified segmentation with and without cost function masking in 49 brain images with chronic stroke. Lesion masks were created using two approaches (precise and rough drawings of lesion boundaries), and normalization was implemented with both smoothed and unsmoothed versions of the masks. We found that failure to employ cost function masking produced less accurate results in real and simulated lesions, compared to masked normalization, both in terms of deformation field displacement and voxelwise intensity differences. Additionally, unmasked normalization led to significant underestimation of lesion volume relative to all four masking conditions, especially in patients with large lesions. Taken together, these findings suggest cost function masking is still necessary when normalizing brain images with chronic infarcts. PMID- 20542121 TI - The effect of arousal on the emotional memory network depends on valence. AB - Some suggest that arousal is the essential element needed to engage the amygdala. However, the role of arousal in the larger emotional memory network may differ depending on the valence (positive, negative) of the to-be-remembered information. The goal of the current study was to determine the influence of arousal-based changes in amygdalar connectivity for positive and negative items. Participants were shown emotional and neutral pictures while they underwent a functional magnetic resonance imaging (fMRI) scan. The emotional pictures varied by valence (positive or negative) and arousal (high or low). Approximately 90minutes later, outside of the scanner, participants took a surprise recognition test. Effective connectivity analysis examined how arousal affected successful encoding activity. For negative information, arousal increased the strength of amygdala connections to the inferior frontal gyrus and the middle occipital gyrus, while for positive information arousal decreased the strength of these amygdala efferents. Further, while the effect of arousal on memory for positive information was restricted to amygdalar efferents, arousal had a more widespread effect for negative items, enhancing connectivity between other nodes of the emotional memory network. These findings emphasize that the effect of arousal on the connectivity within the emotional memory network depends on item valence. PMID- 20542123 TI - Estimating complex cortical networks via surface recordings- a critical note. AB - We discuss potential caveats when estimating topologies of 3D brain networks from surface recordings. It is virtually impossible to record activity from all single neurons in the brain and one has to rely on techniques that measure average activity at sparsely located (non-invasive) recording sites. Effects of this spatial sampling in relation to structural network measures like centrality and assortativity were analyzed using multivariate classifiers. A simplified model of 3D brain connectivity incorporating both short- and long-range connections served for testing. To mimic M/EEG recordings we sampled this model via non-overlapping regions and weighted nodes and connections according to their proximity to the recording sites. We used various complex network models for reference and tried to classify sampled versions of the "brain-like" network as one of these archetypes. It was found that sampled networks may substantially deviate in topology from the respective original networks for small sample sizes. For experimental studies this may imply that surface recordings can yield network structures that might not agree with its generating 3D network. PMID- 20542124 TI - Automatic classification of patients with Alzheimer's disease from structural MRI: a comparison of ten methods using the ADNI database. AB - Recently, several high dimensional classification methods have been proposed to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls (CN) based on T1-weighted MRI. However, these methods were assessed on different populations, making it difficult to compare their performance. In this paper, we evaluated the performance of ten approaches (five voxel-based methods, three methods based on cortical thickness and two methods based on the hippocampus) using 509 subjects from the ADNI database. Three classification experiments were performed: CN vs AD, CN vs MCIc (MCI who had converted to AD within 18 months, MCI converters - MCIc) and MCIc vs MCInc (MCI who had not converted to AD within 18 months, MCI non-converters - MCInc). Data from 81 CN, 67 MCInc, 39 MCIc and 69 AD were used for training and hyperparameters optimization. The remaining independent samples of 81 CN, 67 MCInc, 37 MCIc and 68 AD were used to obtain an unbiased estimate of the performance of the methods. For AD vs CN, whole-brain methods (voxel-based or cortical thickness-based) achieved high accuracies (up to 81% sensitivity and 95% specificity). For the detection of prodromal AD (CN vs MCIc), the sensitivity was substantially lower. For the prediction of conversion, no classifier obtained significantly better results than chance. We also compared the results obtained using the DARTEL registration to that using SPM5 unified segmentation. DARTEL significantly improved six out of 20 classification experiments and led to lower results in only two cases. Overall, the use of feature selection did not improve the performance but substantially increased the computation times. PMID- 20542125 TI - Leukemia lineage-specific chimerism analysis and molecular monitoring improve outcome of donor lymphocyte infusions. AB - A retrospective analysis was performed of 118 patients with hematologic malignancies who received donor lymphocyte infusions (DLIs) after allogeneic stem cell transplantation (ASCT). Treatment was either given because of hematologic relapse (n = 44), molecular/cytogenetic relapse (n = 52), or other causes (n = 22). Molecular relapse was in most cases based on leukemia lineage-specific chimerism analysis. Patients with acute leukemia and myelodysplastic syndrome showed a 3-year survival of 42% if DLI treatment was given because of molecular relapse, compared to 16% in hematologic relapse (P < .006). In multivariate analysis, there was a correlation between response to DLI and nonhematologic relapse (risk ratio [RR] 3.36, P = .001), chronic graft-versus-host disease (cGVHD) (RR = 1.51, P = .005), and late relapse (RR = 2.06, P = .017). The overall incidences of acute GVHD (aGVHD) grades I-II and grades III-IV aGVHD were 33% and 8.5%, respectively. Probability of cGVHD was 33%. The development of aGVHD or cGVHD did not significantly influence the response of DLI in patients with molecular/cytogenetic relapse. However, the development of cGVHD was significantly associated with a better response in patients with hematologic relapse because only 4 of 29 patients without cGVHD responded compared to 7 of 12 with cGVHD (P = .007). The development of cGVHD increased significantly if DLI was given >12 months after ASCT (46% versus 27%, P = .04). In contrast, time between ASCT and start of DLI treatment had no significant influence on the risk of developing aGVHD. To conclude, monitoring of leukemia lineage-specific chimerism is of utmost importance for DLI response after ASCT. PMID- 20542126 TI - Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenone-induced hemiparkinsonian rats. AB - Several studies have shown functional improvements, neuroprotective, and neuroregenerative effects after mesenchymal stem cells transplantation to parkinsonian animal models. However, questions remain about the safety, feasibility, and long-term efficacy of this approach. In this study, we investigated migration, therapeutic, tumorigenesis, and epileptogenic effects of human umbilical cord mesenchymal stromal cells (HUMSCs) 1 year after transplantation into rotenone-induced hemiparkinsonian rats. Our data indicated that DiI-labeled HUMSCs migrated in the lesioned hemisphere, from corpus striatum (CPu) to substantia nigra. By integrating with host cells and differentiating into NSE, GFAP, Nestin, and tyrosine hydroxylase-positive cells, HUMSCs prevented 48.4% dopamine neurons from degeneration and 56.9% dopamine terminals from loss, both correlating with improvement of apomorphine-induced rotations. The CD50 and CD97 value of pentylenetetrazol and semiquantitative immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), beta-catenin, C-myc, and NF-kappaB expression showed no significant difference between HUMSCs transplanted and untransplanted groups, whereas the expressions of Bcl-2 and P53 in the grafted CPu were upregulated by 281% and 200% compared to ungrafted CPu. The results of this long-term study suggest that HUMSCs transplantation, 1 of the most potential treatments for Parkinson's disease, is an effective and safe approach. PMID- 20542128 TI - The therapeutic approach to non-tuberculous mycobacterial infection of the lung. AB - Non-tuberculous mycobacteria (NTM) are a group of alcohol fast, aerobic, nonmotile bacteria that are found in the environment. Recent reports indicate that their incidence and prevalence is increasing and guidelines have been developed laying down criteria for diagnosis. The treatment of these mycobacteria may be difficult, in many cases involving complex regimens containing multiple drugs. While traditional anti-tuberculosis medications are frequently used, specific therapeutic regimens depend on the organism isolated, in vitro susceptibility testing, drug tolerance and toxicity and concomitant medical disorders. In this review, we describe the diagnosis and treatment of the more important lung pathogens, describing complexities and controversies surrounding treatment with traditional, adjunctive and the newer and more experimental agents. PMID- 20542127 TI - Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchymal stem cells: implications for cell-based therapies in Parkinson's disease. AB - It is thought that the ability of human mesenchymal stem cells (hMSC) to deliver neurotrophic factors might be potentially useful for the treatment of neurodegenerative disorders. The aim of the present study was to characterize signals and/or molecules that regulate brain-derived neurotrophic factor (BDNF) protein expression/delivery in hMSC cultures and evaluate the effect of epigenetically generated BDNF-secreting hMSC on the intact and lesioned substantia nigra (SN). We tested 4 different culture media and found that the presence of fetal bovine serum (FBS) decreased the expression of BDNF, whereas exogenous addition of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to serum-free medium was required to induce BDNF release (125 +/- 12 pg/day/106 cells). These cells were called hM(N)SC. Although the induction medium inhibited the expression of alpha smooth muscle actin (ASMA), an hMSC marker, and increased the nestin-positive subpopulation of hMSC cultures, the ability to express BDNF was restricted to the nestin-negative subpopulation. One week after transplantation into the SN, the human cells integrated into the surrounding tissue, and some showed a dopaminergic phenotype. We also observed the activation of Trk receptors for neurotrophic factors around the implant site, including the BDNF receptor TrkB. When we transplanted these cells into the unilateral lesioned SN induced by striatal injection of 6-hydroxydopamine (6 OHDA), a significant hypertrophy of nigral tyrosine hydroxylase (TH)(+) cells, an increase of striatal TH-staining and stabilization of amphetamine-induced motor symptoms were observed. Therefore, hMSC cultures exposed to the described induction medium might be highly useful as a vehicle for neurotrophic delivery to the brain and specifically are strong candidates for future therapeutic application in Parkinson's disease. PMID- 20542129 TI - Adherence to inhaled corticosteroids: comparison of available therapies. AB - Adherence to daily anti-inflammatory therapy, the cornerstone being inhaled corticosteroids (ICSs), is critical for the control of persistent asthma. Many factors, both behavioral and treatment-related, can affect treatment adherence. In the pediatric population, adherence is often the responsibility of parents/caregivers. Thus, parents may need improved awareness of the major asthma controller medications, especially regarding the efficacy and safety of ICSs; their beliefs or concerns regarding asthma therapy have a bearing on their diligence in encouraging adherence with the prescribed treatment regimen. Dosing complexity and factors relating to inhaler use are also important components of adherence. There are currently 6 ICSs (excluding nebulized ICSs) approved for children in the United States. The purpose of this review is to examine and compare the features of the available ICSs that may influence adherence in the treatment of pediatric asthma. PMID- 20542130 TI - The effect of plant protein-based diet supplemented with dipeptide or free amino acids on digestive tract morphology and PepT1 and PepT2 expressions in common carp (Cyprinus carpio L.). AB - Common carp (Cyprinus carpio) of average body mass 0.07+/-0.02 g were fed three formulated diets: wheat gluten protein-based diet supplemented with Lys-Gly dipeptide (PP), wheat gluten protein-based diet supplemented with free lysine and glycine (AA), and a wheat gluten protein-based control diet without lysine supplementation (CON), frozen zooplankton (Z) (restricted diet), and a commercial starter food Aglo Norse (AN). After 4 weeks of experimental feeding, fish fed AN diet showed the highest body mass and length. Significantly lower mass occurred in groups fed PP, AA, CON, and Z. Fish fed CON diet showed the lowest intestinal folds and the highest number of mucous cells. Fish fed PP diet showed a significantly higher number of gastrin/cholecystokinin (CCK) positive cells. The diameter of lipid vacuoles in hepatocyte cytoplasm of fish fed formulated diets (PP, AA and CON) was significantly higher than in fish fed zooplankton (Z) and the commercial diet (AN). Hepatocytes of fish fed AA and CON showed a higher nucleus proliferation rate than in the other experimental groups. The quantitative analysis of the number of proliferating cell nuclear antigen (PCNA) and caspase-3(rabbit polyclonal antibody CPP-32)-positive cells showed that the highest proliferation rate was accompanied by the high apoptosis in the intestine of fish fed AA and CON. After 4 weeks of experimental feeding the highest relative expression of PepT1 gene was observed in fish fed PP diet, while the lowest expression occurred in fish fed CON. Feeding carp plant protein-based diet supplemented with Lys-Gly dipeptide (PP) had a beneficial influence on fish growth and metabolism in the digestive tract as compared to fish fed control diet without lysine supplementation (CON). PMID- 20542131 TI - Identification, mRNA expression and characterization of proliferating cell nuclear antigen gene from Chinese mitten crab Eriocheir japonica sinensis. AB - The sliding clamp proliferating cell nuclear antigen (PCNA) plays important roles in nucleic acid metabolism. In this work, we isolated a PCNA gene (designated as EjsPCNA, accession: FJ483830) by rapid amplification of cDNA ends approach from the Chinese mitten crab Eriocheir japonica sinensis. The full-length cDNA of EjsPCNA consists of 1123 nucleotides with an open-reading frame of 780bp encoding 259 amino acids (28.62kDa) and containing an interdomain connecting loop, C terminal tail, and center loop. Sequence alignment, phylogenetic analyses, and structure comparison revealed that EjsPCNA is a member of the PCNA family. Real time RT-PCR results indicate that EjsPCNA is expressed throughout three developmental stages. EjsPCNA mRNA expression levels at the first crab stage are significantly higher than that of the other two stages. Present data showed that the expression levels of EjsPCNA in E. j. sinensis are likely related to proliferation activity of tissues, and suggested that EjsPCNA gene is probably involved in the crabs' early developmental regulation. PMID- 20542132 TI - Malaria exacerbates experimental mycobacterial infection in vitro and in vivo. AB - Tuberculosis (Mtb) and malaria are among the most important infectious causes of morbidity and mortality worldwide, causing an estimated 1.5 million and 1 million deaths every year, respectively. Here we demonstrate a biological interaction between malaria and mycobacteria in vitro and in vivo. Murine macrophages co incubated with Plasmodium falciparum parasitized erythrocytes demonstrated impaired control of intracellular Mtb replication, and reduced production of reactive nitrogen species in response to mycobacteria. Infection of C57BL/6 mice with Plasmodium species exacerbated the course of acute mycobacterial infection (57% increase in peak splenic CFU, p = 0.043 for difference over time course of infection), induced disruption of the structural integrity of established granulomas, and caused reactivation of latent mycobacterial infection (2.6-fold increase in peak splenic CFU, p = 0.016 for difference over time course of reactivation). Malaria pigment deposition within the granulomas of co-infected mice suggested that the influx of dysfunctional hemozoin-laden monocytes into the locus of mycobacterial control may contribute to impaired containment of mycobacteria. Collectively, these results point to malaria-induced dysregulation of innate and adaptive anti-mycobacterial defences, and suggest that the interaction of these globally important pathogens may potentiate Mtb infection and transmission. PMID- 20542133 TI - Protective cellular responses to Burkholderia mallei infection. AB - Burkholderia mallei is a Gram-negative bacillus causing the disease glanders in humans. During intraperitoneal infection, BALB/c mice develop a chronic disease characterised by abscess formation where mice normally die up to 70 days post infection. Although cytokine responses have been investigated, cellular immune responses to B. mallei infection have not previously been characterised. Therefore, the influx and activation status of splenic neutrophils, macrophages and T cells was examined during infection. Gr-1+ neutrophils and F4/80+ macrophages infiltrated the spleen 5 h post-infection and an increase in activated macrophages, neutrophils and T cells occurred by 24 h post-infection. Mice depleted of Gr-1+ cells were acutely susceptible to B. mallei infection, succumbing to the infection 5 days post-infection. Mice depleted of both CD4 and CD8 T cells did not succumb to the infection until 14 days post-infection. Infected MUMT (B cell) and CD28 knockout mice did not differ from wildtype mice whereas iNOS-2 knockout mice began to succumb to the infection 30 days post infection. The data presented suggests that Gr-1+ cells, activated early in B. mallei infection, are essential for controlling the early, innate response to B. mallei infection and T cells or nitric oxide are important during the later stages of infection. PMID- 20542134 TI - Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells. AB - Helicobacter pylori (H. pylori) is a major human pathogenic bacterium in gastric mucosa. However, the regulatory mechanism of H. pylori-induced immune response is not clear. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression, and their role in H. pylori infection is just beginning to be explored. Here, we first reported that H. pylori infection up regulated the expression of miR-146a in gastric epithelial cells as well as in gastric mucosal tissues in NF-kappaB-dependent manner. In turn, miR-146a may downregulate the expression of target genes, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). Furthermore, miR 146a negatively regulated H. pylori-triggered interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and macrophage inflammatory protein (MIP) -3alpha through diminishing NF-kappaB activity. In conclusion, H. pylori-induced miR-146a plays a potential role in a negative feedback loop to modulate the inflammation by targeting IRAK1 and TRAF6. PMID- 20542135 TI - Th2 immune response against Schistosoma mansoni infection. AB - Schistosoma mansoni eggs - or more specifically, secreted products thereof - are potent inducers of a Th2 response in the host. Here we review current knowledge on the Th2-promoting effects of egg-derived components and the consequences for the host. PMID- 20542137 TI - MicroRNAs, a superimposed regulatory network important for development and disease. PMID- 20542136 TI - Three dimensional optical coherence tomography imaging: advantages and advances. AB - Three dimensional (3D) ophthalmic imaging using optical coherence tomography (OCT) has revolutionized assessment of the eye, the retina in particular. Recent technological improvements have made the acquisition of 3D-OCT datasets feasible. However, while volumetric data can improve disease diagnosis and follow-up, novel image analysis techniques are now necessary in order to process the dense 3D-OCT dataset. Fundamental software improvements include methods for correcting subject eye motion, segmenting structures or volumes of interest, extracting relevant data post hoc and signal averaging to improve delineation of retinal layers. In addition, innovative methods for image display, such as C-mode sectioning, provide a unique viewing perspective and may improve interpretation of OCT images of pathologic structures. While all of these methods are being developed, most remain in an immature state. This review describes the current status of 3D-OCT scanning and interpretation, and discusses the need for standardization of clinical protocols as well as the potential benefits of 3D-OCT scanning that could come when software methods for fully exploiting these rich datasets are available clinically. The implications of new image analysis approaches include improved reproducibility of measurements garnered from 3D-OCT, which may then help improve disease discrimination and progression detection. In addition, 3D OCT offers the potential for preoperative surgical planning and intraoperative surgical guidance. PMID- 20542139 TI - Mutagenicity of oxidized DNA precursors in living cells: Roles of nucleotide pool sanitization and DNA repair enzymes, and translesion synthesis DNA polymerases. AB - The base moieties of DNA precursors in the nucleotide pool are subjected to oxidative damage, and the formation of damaged DNA precursors is an important source of mutagenesis. 8-Hydroxy-2'-deoxyguanosine 5'-triphosphate, also known by the name of its keto-enol tautomer as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5' triphosphate, and 2-hydroxy-2'-deoxyadenosine 5'-triphosphate have been identified as the major products of in vitro oxidation reactions. The mutagenicities of these damaged precursors in living cells will be summarized in this review. In addition, the roles of the nucleotide pool sanitization and DNA repair enzymes, and the translesion synthesis DNA polymerases will be described. PMID- 20542138 TI - The glomerulus--a view from the outside--the podocyte. AB - In the past decade, podocyte research has been greatly aided by the development of powerful new molecular, cellular and animal tools, leading to elucidation of an increasing number of proteins involved in podocyte function and identification of mutated genes in hereditary glomerulopathies. Accumulating evidence indicates that podocyte disorders may not only underlie these hereditary glomerulopathies but also play crucial role in a broad spectrum of acquired glomerular diseases. Genetic susceptibility, environmental influence and systemic responses are all involved in the mediation of the pathogenesis of podocytopathies. Injured podocytes may predisopose to further injury of other podocytes and other adjacent/distant renal cells in a vicious cycle, leading to inexorable progression of glomerular injury. The classic view is that podocytes have a limited ability to proliferate in the normal mature kidney. However, recent research in rodents has provided suggestive evidence for podocyte regeneration resulting from differentiation of progenitor cells within Bowman's capsule. PMID- 20542140 TI - DNA polymerases involved in the incorporation of oxidized nucleotides into DNA: their efficiency and template base preference. AB - Genetic information must be duplicated with precision and accurately passed on to daughter cells and later generations. In order to achieve this goal, DNA polymerases (Pols) have to faithfully execute DNA synthesis during chromosome replication and repair. However, the conditions under which Pols synthesize DNA are not always optimal; the template DNA can be damaged by various endogenous and exogenous genotoxic agents including reactive oxygen species (ROS), and ROS oxidize dNTPs in the nucleotide pool from which Pols elongate DNA strands. Both damaged DNA and oxidized dNTPs interfere with faithful DNA synthesis by Pols, inducing various cellular abnormalities, such as mutations, cancer, neurological diseases, and cellular senescence. In this review, we focus on the process by which Pols incorporate oxidized dNTPs into DNA and compare the properties of Pols: efficiency, i.e., k(cat)/K(m), k(pol)/K(d) or V(max)/K(m), and template base preference for the incorporation of 8-oxo-dGTP, an oxidized form of dGTP. In general, Pols involved in chromosome replication, the A- and B-family Pols, are resistant to the incorporation of 8-oxo-dGTP, whereas Pols involved in repair and/or translesion synthesis, the X- and Y-family Pols, incorporate nucleotides in a relatively efficient manner and tend to incorporate it opposite template dA rather than template dC, though there are several exceptions. We discuss the molecular mechanisms by which Pols exhibit different template base preferences for the incorporation of 8-oxo-dGTP and how Pols are involved in the induction of mutations via the incorporation of oxidized nucleotides under oxidative stress. PMID- 20542141 TI - A comprehensive screening system for damaged nucleotide-binding proteins. AB - To identify novel nucleotide pool sanitizing enzymes, we have established a comprehensive screening system for damaged nucleotide-binding proteins based on proteomics technology. In the screening system, affinity chromatography with resins carrying various damaged nucleotides is used for the purification of binding proteins, and the purified proteins are identified by mass-spectrometry. Inosine triphosphate (ITP) is a deleterious damaged nucleotide, and can be generated by nitrosative deamination of ATP or phosphorylation of inosine monophosphate (IMP). Using the above system, we performed screens for ITP-binding proteins from mouse and human cell extracts, and identified several ITP-binding enzymes. We identified both mouse inosine triphosphatase (ITPA) and human ITPA, well-known ITP hydrolyzing enzymes, as ITP-binding proteins. These results support the validity of this screening system. In addition to ITPA, we identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein as an ITP-binding protein. Biochemical analysis revealed that NUDT16 selectively hydrolyzes deoxyinosine diphosphate (dIDP) and IDP to deoxyinosine monophosphate (dIMP) and IMP, respectively. dITP and ITP are also hydrolyzed by NUDT16 to a lesser extent. The knockdown of NUDT16 in HeLa MR cells suppressed cell proliferation, and was accompanied by a significantly increased accumulation of strand breaks in nuclear DNA, suggesting that NUDT16 has an essential role in the maintenance of genome stability. RS21-C6, another ITP-binding protein identified in our screen, binds not only to ITP, but also to ATP. RS21-C6 hydrolyzes dCTP and 5-halo-dCTP, but does not hydrolyze ITP or ATP. It is likely that RS21-C6 may control dCTP levels or eliminate 5-halo-dCTP in the nucleotide pools. In conclusion, the results of these studies show that our screening system is applicable in studying the health effects of damaged nucleotides and cellular sanitizing systems for nucleotide pools. PMID- 20542143 TI - Development of a reverse transcription-loop-mediated isothermal amplification (RT LAMP) for clinical detection of Plasmodium falciparum gametocytes. AB - Plasmodium falciparum gametocytes are usually present in peripheral blood at a very low level, thus requiring a sensitive assay detection method. In this study, reverse transcription-loop-mediated isothermal amplification (RT-LAMP) was developed for clinical detection of P. falciparum gametocytes. Transcripts of Pfs16 of sexually committed ring and Pfs25 of mature gametocytes were detected by RT-LAMP in 82 clinical blood samples using nested RT-PCR as a gold standard. RT LAMP demonstrated a detection limit of 1 parasitized red blood cell (RBC)/500microl of blood for both Pfs16 and Pfs25 transcripts. For Pfs16 transcript, RT-LAMP detected all 30 samples positive by nested RT-PCR (100% sensitivity) and 1 in 52 samples negative by nested RT-PCR (98.1% specificity). For Pfs25 transcript, RT-LAMP detected all 15 samples positive by nested RT-PCR (100% sensitivity) and none of 67 samples negative by nested RT-PCR (100% specificity). Negative predictive value (NPV) and positive predictive value (PPV) of RT-LAMP for detection of Pfs16 transcript were 100% and 96.8%, respectively, and 100% for both when employing Pfs25 transcript. Detection rate of Pfs16 and Pfs25 transcripts by RT-LAMP in microscopically gametocyte-negative samples was 91.7% and 29.2%, respectively. Compared with nested RT-PCR, RT-LAMP had a higher sensitivity but similar specificity, with the advantage of a shorter assay time. As RT-LAMP requires very basic instruments and the results can be obtained by visual inspection, this technique provides a simple and reliable tool for epidemiological studies of malaria transmission and in gametocyte-targeted control programmes. PMID- 20542142 TI - Programmed cell death triggered by nucleotide pool damage and its prevention by MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase. AB - Accumulation of oxidized bases such as 8-oxoguanine in either nuclear or mitochondrial DNA triggers various cellular dysfunctions including mutagenesis, and programmed cell death or senescence. Recent studies have revealed that oxidized nucleoside triphosphates such as 8-oxo-dGTP in the nucleotide pool are the main source of oxidized bases accumulating in the DNA of cells under oxidative stress. To counteract such deleterious effects of nucleotide pool damage, mammalian cells possess MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase and related enzymes, thus minimizing the accumulation of oxidized bases in cellular DNA. Depletion or increased expression of the MTH1 protein have revealed its significant roles in avoiding programmed cell death or senescence as well as mutagenesis, and accumulating evidences indicate that MTH1 is involved in suppression of degenerative disorders such as neurodegeneration. PMID- 20542144 TI - Advances in polymeric micelles for drug delivery and tumor targeting. AB - A plethora of formulation techniques have been reported in the literature for targeting drugs to specific sites. Polymeric micelles (PMs) can be targeted to tumor sites by passive as well as active mechanisms. Some inherent properties of PMs, including size in the nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor allow PMs to be targeted to the tumor site by a passive mechanism called the enhanced permeability and retention effect. PMs formed from an amphiphilic block copolymer are suitable for encapsulation of poorly water-soluble, hydrophobic anticancer drugs. Other characteristics of PMs such as separate functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. PMs can be conjugated with many ligands such as antibody fragments, epidermal growth factors, alpha(2) glycoprotein, transferrin, and folate to target micelles to cancer cells. Application of heat or ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be directed toward tumor angiogenesis, which is a potentially promising target for anticancer drugs. PMs have been used for the delivery of many anticancer agents in preclinical and clinical studies. This review summarizes recently available information regarding targeting of anticancer drugs to the tumor site using PMs. PMID- 20542145 TI - Sequence and phylogenetic analysis of the VP6 and NSP4 genes of human rotavirus strains: evidence of discordance in their genetic linkage. AB - NSP4 and VP6 genes of a total of 118 rotavirus strains detected in adolescent and adult cases of acute gastroenteritis (AGE) in 1993-1996 and 2004-2007 were characterized to determine their diversity and genetic linkage. Eighty-two percent and 89% of the strains showed amplification of NSP4 and VP6 genes respectively in RT-PCR. Sequencing and phylogenetic analysis of the VP6 genes showed distribution of genogroups in the lineages I-1 (1.4%), I-2 (50.7%) and II 4 (47.9%) in the 1990s and I-2 (73.5%) and II-4 (26.5%) in 2000s, indicating diversity in genogroups at both time points. Amino acid divergence within the genogroup II strains from 1990s and genogroup I strains from the 2000s was noteworthy (4.7-6.7%). Sequencing and phylogenetic analysis of the NSP4 genes showed almost equal distribution (45.0-55.0%) of genotypes A and B however, higher amino acid divergence within the genotype B strains (up to 9.3%) than in genotype A strains (up to 2.9%) at the two-time points. Nearly 70% of the strains showed NSP4-A-VP6-I or NSP4-B-VP6-II genetic linkage. The discordance in the linkage noted in 29.7% of the strains was predominated by NSP4-B and VP6-I combination and appeared strikingly high in the infections caused by unusual and mixed rotavirus strains. This is the first report to describe the phylogenetic analysis of rotavirus NSP4 and VP6 genes and their discordance in adolescent and adult cases with AGE from India. The extensive diversity within the rotavirus genes and their relationship revealed by this study emphasizes the need for evaluation of the rotavirus vaccines being used currently. PMID- 20542146 TI - How early is the atherosclerotic risk in rheumatoid arthritis? AB - Rheumatoid arthritis is a systemic disease characterized by a reduced life expectancy mainly due to cardiovascular disease. In long-standing disease, it has been widely demonstrated that both traditional cardiovascular risk factors than chronic inflammation and immune-mediated mechanisms play a relevant role in atherosclerosis. Recently, it has been shown that the increased cardiovascular risk appears to precede rheumatoid arthritis onset and that particular immune and inflammatory factors, predating disease presentation, in association with a well defined genetic background, may be associated with increased risk of accelerated atherosclerosis in patients with early disease. However, the effect of early immunosuppressive treatment on cardiovascular disease outcome remains uncertain. A multidisciplinary cardiovascular risk management is required to provide the better care of patients with RA at disease onset. PMID- 20542147 TI - The neural influence on the occurrence of locomotor-respiratory coordination. AB - This study focused on the neurogenic mechanisms of coordination between locomotor and respiratory rhythms. The aim of the present study was to investigate the influence of peripheral neurogenic drive from moving limbs, and the level of consciousness, on locomotor-respiratory coordination. Subjects performed movement for 20 min in a supine position using a bicycle ergometer. The movement comprised three types of leg movements: active (loadless) movement, passive movement while awake and passive movement during sleep. We found no difference between active and passive movement in the degree of coordination. However, the degree of coordination during sleep was significantly lower than that while awake (p<0.05). We conclude that peripheral neurogenic drive from moving limbs is able to generate locomotor-respiratory coordination, and that the level of consciousness may influence the degree of coordination. PMID- 20542149 TI - Phenotypic and molecular characterization of a novel case of dyssegmental dysplasia, Silverman-Handmaker type. AB - Dyssegmental dysplasia, Silverman-Handmaker type (DDSH; #MIM 224410) is an autosomal recessive form of lethal dwarfism characterized by a defect in segmentation and fusion of vertebral bodies components ("anisospondyly") and by severe limb shortening. It is caused by mutations in the perlecan gene (HSPG2), but so far, only three molecularly confirmed cases have been reported. We report a novel case of DDSH in a fetus that presented at 15 weeks gestation with encephalocele, severe micromelic dwarfism and narrow thorax. After termination of pregnancy, radiographs showed short ribs, short and bent long bones and anisospondyly of two vertebral bodies. The fetus was homozygous for a previously undescribed null mutation in HSPG2. PMID- 20542148 TI - An integrative model of respiratory and cardiovascular control in sleep disordered breathing. AB - While many physiological control models exist in the literature, none thus far has focused on characterizing the interactions among the respiratory, cardiovascular and sleep-wake regulation systems that occur in sleep-disordered breathing. The model introduced in this study integrates the autonomic control of the cardiovascular system, chemoreflex and state-related control of respiration, including respiratory and upper airway mechanics, along with a model of circadian and sleep-wake regulation. The integrative model provides realistic predictions of the physiological responses under a variety of conditions including: the sleep wake cycle, hypoxia-induced periodic breathing, Cheyne-Stokes respiration in chronic heart failure, and obstructive sleep apnoea (OSA). It can be used to investigate the effects of a variety of interventions, such as isocapnic and hypercapnic and/or hypoxic gas administration, the Valsalva and Mueller maneuvers, and the application of continuous positive airway pressure on OSA subjects. By being able to delineate the influences of the various interacting physiological mechanisms, the model is useful in providing a more lucid understanding of the complex dynamics that characterize state-cardiorespiratory control in the different forms of sleep-disordered breathing. PMID- 20542150 TI - Additional cryptic CNVs in mentally retarded patients with apparently balanced karyotypes. AB - Apparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental for detecting small abnormalities because it only identifies genomic imbalances larger than 5-10 Mb. In contrast, high-resolution whole-genome arrays enable the detection of submicroscopic abnormalities in patients with apparently balanced rearrangements. Here, we report on the whole-genome analysis of 13 MR patients with previously detected balanced chromosomal abnormalities, five de novo, four inherited, and four of unknown inheritance, using Single Nucleotide Polymorphism (SNP) arrays. In all the cases, the patient had an abnormal phenotype. In one familial case and one unknown inheritance case, one of the parents had a phenotype which appeared identical to the patient's phenotype. Additional copy number variants (CNVs) were identified in eight patients. Three patients contained CNVs adjacent to one or either breakpoints. One of these patients showed four and two deletions near the breakpoints of a de novo pericentric inversion. In five patients we identified CNVs on chromosomes unrelated to the previously observed genomic imbalance. These data demonstrate that high-resolution array screening and conventional karyotyping is necessary to tie complex karyotypes to phenotypes of MR patients. PMID- 20542151 TI - Snake venomics and antivenomics of Crotalus durissus subspecies from Brazil: assessment of geographic variation and its implication on snakebite management. AB - We report the comparative proteomic and antivenomic characterization of the venoms of subspecies cascavella and collilineatus of the Brazilian tropical rattlesnake Crotalus durissus. The venom proteomes of C. d. collilineatus and C. d. cascavella comprise proteins in the range of 4-115 kDa belonging to 9 and 8 toxin families, respectively. Collilineatus and cascavella venoms contain 20-25 main toxins belonging to the following protein families: disintegrin, PLA(2), serine proteinase, cysteine-rich secretory protein (CRISP), vascular endothelial growth factor-like (VEGF), L-amino acid oxidase, C-type lectin-like, and snake venom metalloproteinase (SVMP). As judged by reverse-phase HPLC and mass spectrometry, cascavella and collilineatus share about 90% of their venom proteome. However, the relative occurrence of the toxin families departs among the two C. durissus subspecies venoms. The most notable difference is the presence of the myotoxin crotamine in some C. d. collilineatus specimens (averaging 20.8% of the total proteins of pooled venom), which is absent in the venom of C. d. cascavella. On the other hand, the neurotoxic PLA(2) crotoxin represents the most abundant protein in both C. durissus venoms, comprising 67.4% of the toxin proteome in C. d. collilineatus and 72.5% in C. d. cascavella. Myotoxic PLA(2)s are also present in the two venoms albeit in different relative concentrations (18.1% in C. d. cascavella vs. 4.6% in C. d. collilineatus). The venom composition accounts for the clinical manifestations caused by C. durissus envenomations: systemic neurotoxicity and myalgic symptoms and coagulation disturbances, frequently accompanied by myoglobinuria and acute renal failure. The overall compositions of C. d. subspecies cascavella and collilineatus venoms closely resemble that of C. d. terrificus, supporting the view that these taxa can be considered geographical variations of the same species. Pooled venom from adult C.d. cascavella and neonate C.d. terrificus lack crotamine, whereas this skeletal muscle cell membrane depolarizing inducing myotoxin accounts for approximately 20% of the total toxins of venom pooled from C.d. collilineatus and C.d. terrificus from Southern Brazil. The possible relevance of the observed venom variability among the tropical rattlesnake subspecies was assessed by antivenomics using anti-crotalic antivenoms produced at Instituto Butantan and Instituto Vital Brazil. The results revealed that both antivenoms exhibit impaired immunoreactivity towards crotamine and display restricted ( approximately 60%) recognition of PLA(2) molecules (crotoxin and D49-myotoxins) from C. d. cascavella and C. d. terrificus venoms. This poor reactivity of the antivenoms may be due to a combination of factors: on the one hand, an inappropriate choice of the mixture of venoms for immunization and, on the other hand, the documented low immunogenicity of PLA(2) molecules. C. durissus causes most of the lethal snakebite accidents in Brazil. The implication of the geographic variation of venom composition for the treatment of bites by different C. durissus subspecies populations is discussed. PMID- 20542152 TI - Complex regional pain syndrome after musculoskeletal trauma: who owns the monkey? PMID- 20542153 TI - Classification and staging of endometrial sarcomas: one disease or two different tumor types? PMID- 20542154 TI - Moving cancer up the global health agenda. PMID- 20542155 TI - Focusing on children's mental health. PMID- 20542156 TI - Rational use of medicines. PMID- 20542157 TI - A blow to the fight against snakebite. PMID- 20542159 TI - Anne Mills--nurturing a generation of health economists. PMID- 20542160 TI - Health care in the Czech Republic. PMID- 20542161 TI - Getting research in the NHS started. PMID- 20542162 TI - Wiring a nation. PMID- 20542164 TI - Unilateral pleural effusion--but where from? PMID- 20542163 TI - The passage of a colonic cast. PMID- 20542165 TI - Bullous lesion of the newborn scalp. PMID- 20542166 TI - Atypical methotrexate-induced ultraviolet recall phenomenon during the treatment of ectopic pregnancy. PMID- 20542167 TI - Vulvitis plasmacellularis circumscripta in pre-existing lichen sclerosus: treatment with imiquimod 5% cream. PMID- 20542168 TI - Dermal hypersensitivity reaction as a prodrome to Hodgkin lymphoma. PMID- 20542169 TI - Imatinib mesylate-induced pseudoporphyria. PMID- 20542170 TI - Recurrent generalized indeterminate cell histiocytosis: a case report. PMID- 20542171 TI - Varenicline-induced drug eruption with resulting palmar/plantar hyperhidrosis and dysesthesia. PMID- 20542172 TI - Subungal traumatic neuroma. PMID- 20542173 TI - Antidesmocollin-1 antibody-positive, antidesmoglein antibody-negative pemphigus herpetiformis. PMID- 20542174 TI - The group of epidermal nevus syndromes Part I. Well defined phenotypes. AB - The epidermal nevus syndromes represent a group of distinct disorders that can be distinguished by the type of associated epidermal nevus and by the criterion of presence or absence of heritability. Well defined syndromes characterized by organoid epidermal nevi include Schimmelpenning syndrome, phacomatosis pigmentokeratotica, nevus comedonicus syndrome, angora hair nevus syndrome, and Becker nevus syndrome. The molecular basis of these disorders has so far not been identified. By contrast, the group of syndromes characterized by keratinocytic nevi comprises three phenotypes with a known molecular etiology in the form of CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, type 2 segmental Cowden disease, and fibroblast growth factor receptor 3 epidermal nevus syndrome (Garcia-Hafner-Happle syndrome), whereas Proteus syndrome is still of unknown origin. From this overview, it is clear that a specific type of these disorders cannot be classified by the name "epidermal nevus syndrome" nor by the terms "organoid nevus syndrome" or "keratinocytic nevus syndrome." LEARNING OBJECTIVES: After completing this learning activity, participants should be able to distinguish nine different epidermal nevus syndromes by their characteristic features, understand the practical significance of avoiding terms like "epidermal nevus syndrome" or "keratinocytic nevus syndrome" to define any specific entity within this group of disorders, and differentiate between nonhereditary traits and those bearing a genetic risk because of either Mendelian or non-Mendelian inheritance. PMID- 20542175 TI - The group of epidermal nevus syndromes Part II. Less well defined phenotypes. AB - In addition to the well established epidermal nevus syndromes, such as Schimmelpenning, Becker, Proteus, CHILD, or nevus comedonicus syndromes, the group of less well defined phenotypes associated with epidermal nevi presently includes nevus trichilemmocysticus syndrome, didymosis aplasticosebacea, SCALP syndrome (sebaceous nevus, central nervous system malformations, aplasia cutis congenita, limbal dermoid,and pigmented nevus), Gobello syndrome, Bafverstedt syndrome, NEVADA syndrome (nevus epidermicus verrucosus with angio-dysplasia and aneurysms), and CLOVE syndrome (congenital lipomatous overgrowth, vascular malformations, and epidermal nevus). These syndromes can thus far be regarded as being in limbo. Future clinical and molecular research may show which of these disorders can be added to the list of well defined nosologic entities. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to understand why the list of distinct epidermal nevus syndromes can thus far not be regarded as being complete; why clinicians, when seeing a patient with an epidermal nevus syndrome that is difficult to categorize, should bear in mind the group of less well defined epidermal nevus syndromes; and how practical dermatologists can help recognize rare forms of epidermal nevus syndromes and categorize them appropriately. PMID- 20542176 TI - An analysis of pain and analgesia after Mohs micrographic surgery. AB - BACKGROUND: Pain characteristics and analgesia in patients undergoing Mohs micrographic surgery have not been systematically studied. It is important to know about pain after Mohs micrographic surgery to better serve patient needs. OBJECTIVE: We sought to measure pain in patients after Mohs micrographic surgery, and to investigate the relationship among postoperative pain, surgical characteristics, patient characteristics, and analgesics used. METHODS: The Wong Baker 0-to-10 pain scale was prospectively administered postoperatively to all patients presenting for Mohs micrographic surgery in a private practice setting between October 1, 2007, and December 31, 2008. Patients recorded their pain level from the day of surgery through postoperative day 4. The age, sex, location of surgery, number of lesions operated on, postoperative size, type of repair, severity of pain, and oral analgesics consumed and dosages used were recorded. RESULTS: A total of 433 patients were included in the final analysis. The highest pain scores were found on the day of surgery and steadily declined until postoperative day 4 (P < .000). In all, 52% of patients took pain medication on the day of surgery, which declined successively with each postoperative day. The highest mean pain scores were statistically significantly associated with repair type (flaps), age (<66 years), number of lesions, and consumption of narcotics for pain relief. No statistically significant differences existed for sex or postoperative defect size. LIMITATIONS: The instrument used to measure pain relied on patient self-report in a private practice surgery center. Only the validated Wong-Baker pain scale was used to assess pain in this study. CONCLUSION: Approximately half of the patients after Mohs micrographic surgery take medication for pain control. Type of closure, location of surgery, age, and type of pain medication taken were significantly associated with postoperative pain. PMID- 20542177 TI - Refractory ulcers: the role of tumor necrosis factor-alpha. PMID- 20542178 TI - Trachyonychia and sarcoidosis. PMID- 20542179 TI - High responses of peripheral lymphocytes to mosquito salivary gland extracts in patients with Wells syndrome. PMID- 20542180 TI - The role of Fc gamma receptors polymorphisms in bullous pemphigoid. PMID- 20542181 TI - Preliminary evidence for a role of mast cells in epidermal growth factor receptor inhibitor-induced pruritus. PMID- 20542182 TI - Cutaneous Crohn disease mimicking anal condylomata in a child. PMID- 20542183 TI - Acute generalized exanthematous pustulosis induced by Rhus (lacquer). PMID- 20542184 TI - Ingestion of a dietary supplement resulting in selenium toxicity. PMID- 20542185 TI - Molluscum contagiosum folliculitis mimicking tinea barbae in a lung transplant recipient. PMID- 20542186 TI - Refractory cutaneous lichenoid sarcoidosis treated with tranilast. PMID- 20542187 TI - Twenty nail onychomadesis: an unusual finding in Cronkhite-Canada syndrome. PMID- 20542188 TI - JAAD grand rounds quiz*: Dusky intertriginous plaques and acral erythema after bone marrow transplant. AB - LEARNING OBJECTIVES: At the conclusion of this learning activity, physician participants should be able to assess their own diagnostic and patient management skills and use the results of this exercise to help determine personal learning needs that can be addressed through subsequent CME involvement. Instructions for claiming CME credit appear in the front advertising section. See last page of Contents for page number. INSTRUCTIONS: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence. PMID- 20542189 TI - JAAD grand rounds quiz*: Renal transplant patient with vegetative plaque on the cheek. PMID- 20542190 TI - JAAD grand rounds quiz*: Erythematous keratotic papules in a patient with Fabry disease. PMID- 20542191 TI - Smoking habits of students of nursing: a questionnaire survey (2004-2006). AB - AIM: To determine changes in the prevalence of tobacco use among students of nursing and associated factors. BACKGROUND: The prevalence and distribution of smokers among nursing students varies according to the country and period of study. METHOD: Transversal descriptive study by self-answered questionnaire. Eight hundred and fifty four subjects (94.9%) were questioned in the period 2004 2006. FINDINGS: Twenty eight percent of the students declared themselves to be smokers. The habit began before the students started university. The tendency of prevalence by year of survey and by graduation year was downward. The students shown a low nicotine dependency according to Fagerstrom and little motivation to give up. The average age at the onset of consumption was 14.6 (1.8) years. From the logistical regression analysis, the model best explaining the prevalence of tobacco consumption included the variable of year surveyed and academic background, those coming from the baccalaureate showing a lesser prevalence and tendency to smoke. CONCLUSIONS: Tobacco consumption among students of health sciences was less than in the general population of the same age but high given their future profession. The tendency to smoke is decreasing and most started smoking before joining the university. We recommend an intensification of actions directed at teenagers and the promotion of anti-tobacco campaigns in universities. PMID- 20542192 TI - [Introduction. Chronic thromboembolic pulmonary hypertension]. PMID- 20542193 TI - [Epidemiological aspects in chronic thromboembolic pulmonary hypertension]. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious disease with a very poor prognosis and extremely low survival in untreated patients or in those treated with anticoagulation alone. The true incidence and prevalence of CTEPH is currently unknown and the disease is probably underdiagnosed. Current data indicate that the incidence ranges from 0.1% to 3.8%. The latest research and reported studies reveal the need to determine not only the incidence of CTEPH in symptomatic patients but also in asymptomatic patients who subsequently develop the disease, as well as in the remaining patients with an asymptomatic venous thromboembolic event. Several risk factors are associated with a greater predisposition to CTEPH (advanced age, extensive obstruction, elevated systolic pulmonary pressure, and numerous clinical conditions). Due to advances made in the management of CTEPH in the last few years, the clinical course and prognosis and of this disease may be undergoing a major change and CTEPH may become a chronic, treatable disease. PMID- 20542194 TI - [Etiopathogenesis and physiopathology in chronic thromboembolic pulmonary hypertension]. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the organization of thrombotic material within the pulmonary arteries. The lack of correlation between the proportion of obliterated pulmonary arteries and pulmonary hypertension values suggest that an exclusively mechanical theory could be too simplistic. Acute pulmonary embolism could be the initial event, but disease progression probably results from progressive vascular remodelling of the small vessels. Unresolved pulmonary arterial thrombosis may be a decisive factor in initiating endothelial-to-mesenchymal transition. The present article analyzes the genetic features, inflammatory mechanisms and clinical factors influencing the physiopathological mosaic of this complex entity. PMID- 20542195 TI - [Risk factors in chronic thromboembolic pulmonary hypertension]. AB - Although preoccupation with chronic thromboembolic pulmonary hypertension (CTEPH) among the scientific community is constantly increasing, the pathogenesis of this disease has not been completely elucidated and factors predisposing to its development are not precisely known. Some patients may be genetically conditioned to develop CTEPH, but only a few fibrinogen mutations and an increase in the frequency of polymorphisms of human leukocyte antigens have been described. Hereditary coagulation defects are no more prevalent in patients with CTEPH than in controls, except for factor VIII and antiphospholipid antibodies. Some studies have analyzed differences in the expression of type 1 tissue plasminogen activator inhibitor in the thrombus of patients with CTEPH (compared with thrombi of acute pulmonary thromboembolism [PTE]) and suggest that thrombosis in situ can contribute to the persistence of the coagulum and disease progression. Some characteristics of acute PTE have been associated with its progression to CTEPH, such as idiopathic PTE, large perfusion defects, massive PTE, recurrent PTE and pulmonary hypertension persisting at 5 weeks after the thrombotic event. Several clinical factors that increase the risk of CTEPH have been described, such as splenectomy, ventricular shunts, and chronic inflammatory diseases. Thyroid replacement therapy and cancer have also emerged as new predictors of CTEPH. Identification of new predisposing factors will provide clues to the pathogenic mechanisms of the disease and will facilitate early diagnosis and more effective treatment. PMID- 20542196 TI - [Clinical and hemodynamic diagnosis in chronic thromboembolic pulmonary hypertension]. AB - Diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is based on the clinical picture, the presence of obstructive lesions in the pulmonary arteries and hemodynamic evaluation. The diagnostic process encompasses distinct elements ranging from clinical suspicion to definitive confirmation through complex examinations including angiography and pulmonary hemodynamic studies. Patients with an established diagnosis of CTEPH should be evaluated for pulmonary endarterectomy, requiring additional studies and multidisciplinary assessment, which should be performed in centers with experience of this type of surgery. The present article reviews the procedures used to establish the diagnosis of CTEPH, as well as the procedures that allow candidates for surgical treatment of this disease to be identified. PMID- 20542197 TI - [Imaging tests in chronic thromboembolic pulmonary hypertension]. AB - Imaging tests are the cornerstone of the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). A series of imaging tests of unquestionable utility is currently available: ventilation-perfusion scintigraphy, echocardiography, multislice computed tomography (CT), magnetic resonance imaging, and pulmonary arteriography. However, not all of these techniques are routinely indicated in all patients. Scintigraphy and echography are used to screen for CTEPH after an acute pulmonary thromboembolism. Multidetector CT is effective in the study of CTEPH since this procedure reveals the localization, extension and characteristics of the central and peripheral arterial thrombi as well as providing data on the vessel distal to the obstruction. Other findings that can affect medical or surgical treatment can be assessed with this technique, such as collateral systemic circulation, concurrent parenchymatous abnormalities, and coronary or cardiac disease. Multidetector CT is a non invasive method that is well tolerated by patients and consequently can be used in the follow-up of the disease or to evaluate postsurgical results. Pulmonary arteriography predated other imaging techniques and was the technique of choice for the diagnosis of CTEPH for many years. Because of limited access to this procedure, a low but nevertheless present risk, and the development of non invasive diagnostic techniques, mainly multidetector CT, the main indication of pulmonary arteriography is currently assessment of surgical accessibility in candidates for pulmonary thromboendarterectomy. When performed by expert hemodynamists using a standardized technique in the hemodynamic laboratory, this procedure is safe even in patients with severe pulmonary hypertension. PMID- 20542198 TI - [Surgical treatment in patients with chronic thromboembolic pulmonary hypertension]. AB - Chronic thromboembolic pulmonary hypertension (CTEPH), which has a natural history with low long-term survival, is increasingly being diagnosed. Pulmonary endarterectomy (PE) is the treatment of choice, which can be curative. This technique consists of a true endarterectomy through a midline sternotomy with extracorporeal circulation and periods of hypothermic circulatory arrest. The following procedures should be performed before surgery: transesophageal echocardiogram, ventilation-perfusion pulmonary scintigraphy, right cardiac catheterism, pulmonary angiography and helicoidal computed tomography. Surgery should be indicated in CTEPH as soon as the diagnosis is made, before arteriopathy develops in the non-obstructed regions and CTEPH becomes severe. The only absolute contraindication to PE is the presence of obstructive or restrictive, severe underlying pulmonary disease. There are no inaccessible grades of embolic obstruction, or grade of right ventricular failure or level of pulmonary vascular resistance (PVR) that are inoperable. However, prognosis worsens with greater preoperative pulmonary pressure and greater postoperative PVR. Mortality in PE is 4-10% and the main cause of postoperative death is the persistence of high pulmonary pressures and PVR, followed by reperfusion edema, which requires prolongation of mechanical ventilation, the use of pulmonary vasodilators and, sometimes, extracorporeal respiratory support. In the long term, 75% of patients undergoing PE show good functional results and half recover adequate exercise tolerance. Pulmonary transplantation is an alternative for patients unsuitable for PE, although with worse results and greater mortality. PMID- 20542199 TI - [Medical treatment in patients with chronic thromboembolic pulmonary hypertension]. AB - Pulmonary thromboendarterectomy is the treatment of choice in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, specific medical treatment of pulmonary hypertension (PH) can be an alternative or play a complementary role to surgery. Thus, in patients unsuitable for surgery due to distal thrombotic obstruction, residual or persistent PH after surgery or very severe PH and a high-risk hemodynamic profile, medical treatment may improve their clinical course and the outcome of thromboendarterectomy. Patients with distal obstruction in the pulmonary tree and those with residual PH after surgery show clinical and hemodynamic deterioration due to progression of the pulmonary vascular disease in the smallcaliber arterioles. Conventional treatment with diuretics, anticoagulants and oxygen therapy has been demonstrated to have little effectiveness. In the last decade, numerous drugs have been developed for the treatment of PH: prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors acting principally in vascular remodelling of small-caliber arterioles. Although evidence of the effectiveness of these drugs in PH and the histological similarity of small-vessel vasculopathy in CTEPH to that of other forms of PH provide the main rationale for the use of these drugs in patients with CTEPH, the evidence from clinical trials is still limited. PMID- 20542200 TI - Membrane interacting peptides--towards the understanding of biological membranes. PMID- 20542201 TI - Detection of Helicobacter pylori and clarithromycin resistance in gastric biopsies of pediatric patients by using a commercially available real-time polymerase chain reaction after NucliSens semiautomated DNA extraction. AB - The aim of this study was to evaluate a commercially available kit, MutaREAL Helicobacter pylori (Inmundiagnostik, Bensheim, Germany) real-time polymerase chain reaction (PCR), for detection of H. pylori infection and point mutations in the 23S rRNA genes responsible for clarithromycin resistance in gastric biopsies. METHODS: Gastric biopsies were obtained by endoscopy from pediatric patients with gastric symptoms, cultured according to standard microbiologic procedures, and clarithromycin resistance was determined by E-test. DNA extraction was performed by NucliSens platform with the NucliSens magnetic extraction reagents (bioMerieux, Marcy-l'Etoile, France) according to the manufacturer's instructions. MutaREAL kit was used according to manufacturer recommendations in a LightCycler (Roche Diagnostics Gmbh, Mannheim, Germany) for the detection of H. pylori infection and clarithromycin susceptibility. RESULTS: Amplification was positive for H. pylori in 62 and negative in 44 biopsies out of 106 biopsies. All negative biopsies were positive for human beta-globin gene. This real-time PCR assay showed sensitivity of 93.33% (negative predictive value, 90.90%) and specificity of 86.95% (positive predictive value, 90.32%) for H. pylori detection. Clarithromycin resistance was detected in 26 cases by PCR with a sensitivity and specificity of 90.62 and 95.83, respectively. CONCLUSIONS: MutaREAL kit was able to detect H. pylori and its clarithromycin susceptibility with high efficacy. This method is quicker than culture and is suitable to be done in 1 h after DNA extraction. The new system of automatic extraction will lead to reduction in the total time. PMID- 20542203 TI - Clinical, microbiologic, and genetic determinants of persistent methicillin resistant Staphylococcus aureus bacteremia. AB - Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite full susceptibility to vancomycin; therefore, associated factors were assessed. A retrospective cohort analysis of 222 patients with MRSAB treated with vancomycin was conducted; patients with persistent MRSAB (pMRSAB) were compared to those with nonpersistent bacteremia (NPB). Incidence of pMRSAB was 9%. More patients with vancomycin MIC = 2 mg/L had pMRSAB (16%) compared to patients with vancomycin MIC <2 mg/L (5%), P = 0.012. SCCmec type and Panton-Valentine leukocidin production were similar between patients with pMRSAB and NPB. There was no difference in vancomycin troughs, time to first dose, or area under the concentration-time curve/MIC between groups. More metastatic complications were observed in pMRSAB 63% versus NPB 32% (P = 0.005). Multivariate analysis found endocarditis (odds ratio [OR], 2.3; P = 0.021), complicated MRSAB (OR, 2.6; P = 0.009), vancomycin MIC = 2 (OR, 2.6; P = 0.009), and septic shock (OR 2.2 P = 0.031), which were independent predictors of pMRSAB. PMID- 20542204 TI - Identification of acid-fast bacilli using pyrosequencing analysis. AB - Pyrosequence identification of 117 isolates of acid-fast bacilli (AFB) was compared to both routine phenotypic methods and Sanger sequencing. Two (2) vendor provided pyrosequencing primers specific for AFB were used for the study. Pyrosequence analysis correctly identified 114 (98%) of the tested 117 AFB isolates. Among the test Mycobacterium spp., 18 of 20 Mycobacterium spp. were identified correctly to the species level. All rapidly growing mycobacteria were correctly identified to species by pyrosequencing. Other slowly growing mycobacteria such as Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium-intracellulare, and others were easily identified by pyrosequencing. Only Mycobacterium simiae and Mycobacterium scrofulaceum were not identifiable by the pyrosequence method. Among the 25 Nocardia isolates, all were correctly identified to the genus level. Identification of AFB by pyrosequence analysis provides both a rapid and accurate method for this group of organisms. PMID- 20542202 TI - Campylobacter jejuni and Campylobacter coli in children from communities in Northeastern Brazil: molecular detection and relation to nutritional status. AB - This study determined the prevalence of Campylobacter jejuni/coli and its relation with nutritional status in children from Northeastern Brazil. This was a case-control study design. Stool samples were evaluated for hipO (C. jejuni), ask (C. coli), and cdtABC (C. jejuni's cytolethal distending toxin) genes. The nutritional status from these children was assessed by anthropometric measures and z-scores. C. jejuni and C. coli were detected in 9.6% (8/83) and 6.0% (5/83) in the diarrhea group and in 7.2% (6/83) and 1.2% (1/83) of the nondiarrhea group, respectively. Children with positive molecular detection of C. jejuni showed significantly lower z-scores than children without C. jejuni. The cdtABC operon was found in 57% of hipO(+) samples. C. jejuni/coli prevalence was similar in diarrhea and nondiarrhea groups. There was a significant association of C. jejuni infection with lower nutritional status. PMID- 20542205 TI - Performance of diagnostic tests to detect respiratory viruses in older adults. AB - The performance of 4 laboratory methods for diagnosis of viral respiratory tract infections (RTI) in older adults was evaluated. Seventy-four nasopharyngeal (NP) swab specimens were obtained from 60 patients with RTI at a long-term care facility over 2 respiratory seasons. Sixteen specimens were positive for a respiratory virus by at least 1 method. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) by the Luminex xTAG Respiratory Viral Panel (RVP) detected 16 (100%) of the positive specimens, RVP of 24-h culture supernatant detected 8 (50%), direct fluorescent antibody testing detected 4 (25%), rapid culture detected 2 (12.5%), and rapid antigen testing detected none. For a comparison group, RVP was performed on NP swabs from 20 outpatient children with RTI. The mean fluorescence intensity by RVP was significantly lower for positive adult patients than pediatric patients (P = 0.0373). Our data suggest that older adult patients shed lower titers of viruses, necessitating a highly sensitive assay such as RT-PCR to reliably detect respiratory viral pathogens. PMID- 20542207 TI - First report of Actinobaculum schaalii urinary tract infection in North America. AB - A recurrent urinary tract infection with Actinobaculum schaalii, a fastidious, facultative anaerobic, and emerging pathogen, is described. Diagnosis was delayed when routine urine cultures were initially performed yielding recurrently negative results. Resolution of symptoms occurred after anaerobic cultures were done to allow organism isolation, identification, and appropriate antimicrobial treatment. PMID- 20542208 TI - Rapid detection of vancomycin-resistant enterococci from rectal swabs by the Cepheid Xpert vanA/vanB assay. AB - The detection of vancomycin-resistant enterococci using a novel commercial multiplex real-time polymerase chain reaction assay (Xpert vanA/vanB, Cepheid, Sunnyvale, CA) was evaluated on 804 rectal swab specimens. Compared to enriched culture, sensitivity and negative predictive value of this method were 100%. Many false-positive results were recovered (sensitivity, 85.4%; positive predictive value, 8.7%), especially for the vanB gene. PMID- 20542209 TI - In vitro synergistic/additive activity of levofloxacin with meropenem against Stenotrophomonas maltophilia. AB - Synergy testing of levofloxacin and meropenem by Etest and time-kill assay (TKA) was performed against 30 genetically unique clinical Stenotrophomonas maltophilia isolates. Synergy was demonstrated in 18/30 (60%) isolates by Etest and in 13/30 (43%) by TKA; the remaining isolates were indifferent. Methods showed agreement for 25/30 (83%) of isolates. PMID- 20542210 TI - Direct detection of methicillin-resistant Staphylococcus aureus from blood cultures using an immunochromatographic immunoassay-based MRSA rapid kit for the detection of penicillin-binding protein 2a. AB - Using an EZ-Step MRSA rapid kit, a novel screening test for methicillin-resistant Staphylococcus aureus (MRSA) that detects penicillin-binding protein 2a, 34 of 36 MRSA-positive clinical blood culture samples were positive on direct testing (sensitivity, 94.4%), whereas 21 of 21 methicillin-susceptible S. aureus-positive samples were negative (specificity, 100%). PMID- 20542211 TI - Detection of toxigenic Clostridium difficile in diarrheal stools by rapid real time polymerase chain reaction. AB - The Cepheid Xpert polymerase chain reaction assay (Sunnyvale, CA) had a sensitivity of 100%, specificity of 96.7%, and positive and negative predictive values of 90.5% and 100%, respectively, compared with toxigenic culture for the laboratory diagnosis of Clostridium difficile in diarrheal stool samples. This test appears to be a significant improvement to poorly performing enzyme immunoassays. PMID- 20542206 TI - Comparative in vitro activity of cefditoren and other antimicrobials against Enterobacteriaceae causing community-acquired uncomplicated urinary tract infections in women: a Spanish nationwide multicenter study. AB - Cefditoren is a third-generation orally administered cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacterial species. After an oral 400-mg single dose, the mean concentrations in urine are 186.5 mg/L at 2 to 4 h and 12.7 mg/L at 8 to 12 h, and it is a potential drug to be used in the treatment of urinary tract infection (UTI). We performed a multicenter nationwide study in Spain in order to determine the in vitro activity of cefditoren and other comparative agents against Enterobacteriaceae causing community-acquired uncomplicated UTI in women. From June 2008 to March 2009, 89 institutions participated in the study. A total of 2152 Enterobacteriaceae were collected and sent to a coordinating laboratory where identification and antimicrobial susceptibility testing was performed against 20 antimicrobials using an automated microdilution method (MicroScan; Siemens, Sacramento, CA). Cefditoren MICs were determined by the broth microdilution method (Clinical and Laboratory Standards Institute guidelines) using the same inoculum. Microorganisms isolated were Escherichia coli (81.8%), Klebsiella pneumoniae (7.9%), Proteus mirabilis (5.2%), and others (5.1%). A total of 51 isolates (2.4%) were extended-spectrum beta-lactamase (ESBL) producers, 3 (0.1%) produced plasmidic AmpC enzymes, and 64 (2.9%) produced chromosomal AmpC. The MIC(50)/MIC(90) (mg/L) of cefditoren against all isolates was 0.12/0.5. Cefditoren inhibited 96.5% of isolates at 1 mg/L and was uniformly active against all isolates with the exception of strains producing ESBLs or AmpC enzymes. The MIC(50)/MIC(90) of other antimicrobials were ampicillin (AMP) >16/>16, amoxicillin/clavulanic acid (A/C) 2, trimethoprim/sulfamethoxazole (SxT) 4/76, and fosfomycin (FOS) A, resulting in premature stop codon (Y399X). Same mutation was previously identified in a Scottish family, however, phenotypic differences suggest the role of additional factors modifying the disease course. Although it does not change therapeutic strategy, accurate molecular diagnosis allows genetic counselling in family members. Autoimmunity remains the major cause of adrenal failure; however, other rare conditions should always be considered. PMID- 20542259 TI - The expression of estrogen receptors in rat genioglossus muscle-derived satellite cells and its relationship to intracellular Ca(2+) mobilization. AB - Genioglossus (GG) is the most important pharyngeal dilator muscle in maintaining upper airway (UA) patency in human; therefore, its dysfunction plays an important role in pathogenesis of sleep-related breathing disorder. Recently, the expression of estrogen receptors (ERs) on mRNA and protein level has been evidenced in GG muscle; however, the cellular localization of two subtypes of ER in GG myoblasts remains unclear. The present study was designed to clarify the expression and cellular distribution of ERs in rat GG muscle-derived satellite cells (MDSCs) and further probe the effect of ERs expression on regulation of intracellular Ca(2+). The immunocytochemistry revealed positive staining for both ERalpha and ERbeta in nuclei and cytoplasm of GG MDSCs. Noticeably, positive signals for ERalpha and ERbeta were comparable in cytoplasm, whereas the positive staining of ERalpha in nuclear was obviously strong than that of ERbeta. More intriguingly, by using Fluo 4-AM as a fluorescent Ca(2+) indicator and 17beta estradiol (E2) as a stimulant, we observed that the level of intracellular Ca(2+) was not affected by E2 application, which implied that Ca(2+) signaling may not be involved in ER-mediated estrogenic effects on GG MDSCs. Taken together, the present study clearly indicates the differential cellular localization of ERs in rat GG MDSCs; moreover, ER-mediated estrogenic effect in rat GG MDSCs bears no relationship to intracellular Ca(2+) mobilization. In addition, the GG MDSCs express both ERalpha and ERbeta and therefore, provide a suitable and convenient in vitro cell model for investigating the molecular mechanisms of estrogenic effects on rat GG muscle. PMID- 20542260 TI - [Primary epiploic appendicitis: a cause of non-surgical acute abdomen]. PMID- 20542261 TI - Thinking about false belief: it's not just what children say, but how long it takes them to say it. AB - We examined 240 children's (3.5-, 4.5-, and 5.5-year-olds) latency to respond to questions on a battery of false-belief tasks. Response latencies exhibited a significant cross-over interaction as a function of age and response type (correct vs. incorrect). 3.5-year-olds'incorrect latencies were faster than their correct latencies, whereas the opposite pattern emerged for 4.5- and 5.5-year olds. Although these results are most consistent with conceptual change theories of false-belief reasoning, no extant theory fully accounts for our data pattern. We argue that response latency data provide new information about underlying cognitive processes in theory of mind reasoning, and can shed light on concept acquisition more broadly. PMID- 20542262 TI - Testing the theory of embodied cognition with subliminal words. AB - In the current study, we tested the embodied cognition theory (ECT). The ECT postulates mandatory sensorimotor processing of words when accessing their meaning. We test that prediction by investigating whether invisible (i.e., subliminal) spatial words activate responses based on their long-term and short term meaning. Masking of the words is used to prevent word visibility and intentional elaboration of the words' semantic content. In this way, masking specifically isolates mandatory sensorimotor processing of words as predicted by the ECT. Do spatial subliminal words activate responses nonetheless? In Experiment 1, we demonstrate a spatial congruence effect of the invisible words if they precede visible target words. In Experiment 2, we show that masked words activate responses based on their long-term meaning. In Experiment 3, we demonstrate that masked words are also processed according to their short-term response meaning. We conclude that the ECT is supported by our findings and discuss implications of our results for embodied theories of semantic word processing and masked priming experiments. PMID- 20542263 TI - Dynamic infrared imaging for analysis of fingertip temperature after cold water stimulation and neurothermal modeling study. AB - The human hand is considered to be the terminus of the nervous system. It contains numerous capillary vessels, and it plays an important role in the regulation of the autonomic nervous system. We have used infrared thermography and ultrasound Doppler flowmetry to investigate characteristics of the temperature variation of the hand and the blood flow after cold stimuli. We have also developed an image processing algorithm to measure temperature of various parts of the hand via sequential thermal images. Measured results show that local cold stimuli will induce oscillation of temperature, which may be due to neuroregulation during rewarming. Finally, in order to explain the mechanism of autonomic nervous system (ANS) regulation we have developed an ANS regulation model on the basis of the knowledge of the physiology and bioheat transfer. The results computed using our model are in good agreement with the experimental results. PMID- 20542264 TI - A feasibility study to evaluate pelvic peritoneal anatomy with a saline intraperitoneal sonogram (SIPS). AB - OBJECTIVE: To prove the safety and feasibility of evaluating pelvic anatomy with a new imaging technique called saline intraperitoneal sonogram (SIPS). DESIGN: Prospective clinical case series. SETTING: Outpatient fertility clinic. PATIENT(S): Ten women with unexplained infertility and normal hysterosalpingograms (HSG). Five women with no known risk factors and five women with known risk factors for adhesive disease were enrolled. INTERVENTION(S): Step 1 required performing a sonohysterogram. Step 2 involved directing a 17-g oocyte retrieval needle into a pocket of peritoneal fluid under ultrasound guidance and infusing normal saline. The pelvic anatomy was evaluated with the three dimensional and four-dimensional mode on pelvic ultrasound. MAIN OUTCOME MEASURE(S): Technical feasibility, safety, time, fluid infusion, and deficit volumes. RESULT(S): All 10 patients successfully completed the protocol. One of the five women with no risk factors for adhesive disease and a normal HSG was discovered to have a unilateral hydrosalpinx and filmy adhesive disease on SIPS. Both findings were confirmed on laparoscopy. Three out of the five women with known risk factors had abnormal SIPS imaging and were confirmed on laparoscopy to have significant adhesive disease. The average procedure time was 45 minutes (+/ 15 minutes). CONCLUSION(S): This study demonstrates that SIPS is a safe, quick, and potentially cost-effective method for evaluating pelvic adhesive disease in an outpatient facility in women with unexplained infertility and a normal HSG. PMID- 20542265 TI - Influence of embryo transfer on blastocyst viability. AB - OBJECTIVE: To investigate the impact of injection speeds of the transferred load on embryo viability. DESIGN: Laboratory model for in vitro simulation of embryo transfer (ET). SETTING: Academic research institutes of reproduction biotechnology and private centers of reproductive medicine. ANIMAL(S): Mouse hybrid F1 females, C57bl/10J * CBA-H (N = 15), aged 2 to 3 months. INTERVENTION(S): In vitro exposure of mouse blastocysts to either fast ET with an ejection speed of the transferred load of >1 m/s or slow ET with an ejection speed of <0.1 m/s. MAIN OUTCOME MEASURE(S): Morphologic changes and apoptotic index of blastocysts. RESULT(S): Morphologic changes in response to ET were most prevalent in blastocysts exposed to fast ET. The mean apoptotic index was 52% in the group exposed to fast ET, 25% in the group exposed to slow ET, and 12.8% in control group. CONCLUSION(S): Fast ejection of the transferred load can trigger both morphologic changes and apoptosis in mouse blastocysts. A reduction of the ejection speed of the transferred load minimizes injury to the embryos. Therefore, embryos should be transferred at the lowest possible speed. PMID- 20542266 TI - The effect of age on the expression of apoptosis biomarkers in human spermatozoa. AB - OBJECTIVE: To evaluate the impact of age on the expression of apoptotic biomarkers in human spermatozoa. DESIGN: Cross sectional, prospective study. SETTING: Academic centers. PATIENT(S): Healthy volunteers with proven fertility, stratified by age (n = 25, range: 20-68 years). INTERVENTION(S): Examination of serum hormone levels and basic semen parameters, and assessment of early (plasma membrane translocation of phosphatidylserine) and late (DNA fragmentation) sperm apoptotic markers by flow cytometry (using Annexin-V binding and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). MAIN OUTCOME MEASURE(S): Apoptosis markers. RESULT(S): Advancing male age was significantly and positively correlated with Annexin-V binding results. Although not significant, there was a clear trend for increased DNA fragmentation in the older groups. The age threshold for these observations appears to be 40 years. Advancing male age was positively correlated with FSH and sex hormone-binding globulin (SHBG) levels, and negatively correlated with sperm concentration. CONCLUSION(S): Advancing male age is associated with the expression of early apoptotic markers as evidenced by significantly increased plasma membrane translocation of phosphatidylserine, as well as with a more subtle proportion of sperm carrying DNA fragmentation. This study confirmed that male age is also associated with a decline in sperm concentration. PMID- 20542267 TI - Heparin inhibits interferon-gamma signaling in human endometrial stromal cells by interference with the cellular binding of interferon-gamma. AB - OBJECTIVE: To examine the impact of heparins on interferon-gamma (IFN-gamma) signaling in human endometrial stromal cells (ESCs) in vitro. DESIGN: In vitro experiment. SETTING: Research laboratory at a medical university center. PATIENT(S): Premenopausal women undergoing hysterectomy for benign reasons. INTERVENTION(S): The ESCs were isolated from hysterectomy specimens, decidualized in vitro using P and 17beta-E(2), and incubated with recombinant IFN-gamma, unfractionated heparin, and low molecular weight heparins (LMWHs). MAIN OUTCOME MEASURE(S): Interferon response factor 1 (IRF-1) and N-myc interactor (Nmi) messenger RNA (mRNA) were measured using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Phosphorylation of signal transducer and activator of transcription 1 (STAT-1) was detected by an in-cell Western assay, expression of the IFN-gamma receptor by flow cytometry. Cell-bound IFN-gamma was determined in lysates by an ELISA. RESULT(S): Heparin and LMWHs inhibit the IFN gamma-mediated induction of IRF-1, but not Nmi in undifferentiated and decidualized ESCs. The phosphorylation of signal transducer and activator of transcription 1 STAT-1 upon IFN-gamma stimulation is inhibited as well. Heparin has no effect on the IFN-gamma receptor in ESCs, but inhibits the binding of IFN gamma to the cells. CONCLUSION(S): Unfractionated heparin, as well as LMWHs, are able to inhibit IFN-gamma signaling in human ESCs and therefore might be clinically interesting agents to modulate the actions of this proinflammatory cytokine at the implantation site. PMID- 20542268 TI - Multiple sensor fault diagnosis for dynamic processes. AB - Modern industrial plants are usually large scaled and contain a great amount of sensors. Sensor fault diagnosis is crucial and necessary to process safety and optimal operation. This paper proposes a systematic approach to detect, isolate and identify multiple sensor faults for multivariate dynamic systems. The current work first defines deviation vectors for sensor observations, and further defines and derives the basic sensor fault matrix (BSFM), consisting of the normalized basic fault vectors, by several different methods. By projecting a process deviation vector to the space spanned by BSFM, this research uses a vector with the resulted weights on each direction for multiple sensor fault diagnosis. This study also proposes a novel monitoring index and derives corresponding sensor fault detectability. The study also utilizes that vector to isolate and identify multiple sensor faults, and discusses the isolatability and identifiability. Simulation examples and comparison with two conventional PCA-based contribution plots are presented to demonstrate the effectiveness of the proposed methodology. PMID- 20542269 TI - Characterization and quenching of friction-induced limit cycles of electro hydraulic servovalve control systems with transport delay. AB - This paper develops a systematic and straightforward methodology to characterize and quench the friction-induced limit cycle conditions in electro-hydraulic servovalve control systems with transport delay in the transmission line. The nonlinear friction characteristic is linearized by using its corresponding describing function. The delay time in the transmission line, which could accelerate the generation of limit cycles is particularly considered. The stability equation method together with parameter plane method provides a useful tool for the establishment of necessary conditions to sustain a limit cycle directly in the constructed controller coefficient plane. Also, the stable region, the unstable region, and the limit cycle region are identified in the parameter plane. The parameter plane characterizes a clear relationship between limit cycle amplitude, frequency, transport delay, and the controller coefficients to be designed. The stability of the predicted limit cycle is checked by plotting stability curves. The stability of the system is examined when the viscous gain changes with respect to the temperature of the working fluid. A feasible stable region is characterized in the parameter plane to allow a flexible choice of controller gains. The robust prevention of limit cycle is achieved by selecting controller gains from the asymptotic stability region. The predicted results are verified by simulations. It is seen that the friction induced limit cycles can be effectively predicted, removed, and quenched via the design of the compensator even in the case of viscous gain and delay time variations unconditionally. PMID- 20542270 TI - Prehospital factors associated with severe injury in older adults. AB - INTRODUCTION: Globally, injury is amongst the leading causes of death and disability in all age groups. Despite the use of prehospital trauma triage guidelines, identification of older persons with severe,potentially life threatening injuries has been problematic. The purpose of this paper is to review prehospital factors associated with severe injuries amongst older adults. SEARCH STRATEGY: MEDLINE, CINAHL, Embase, and Cochrane databases were searched using key word searches of natural language and MeSH vocabulary. Criteria for final retention of the articles included: a focus on adults 50 years and older, single or multisystem injury and identification of prehospital (injury scene) factors associated with severe injury. Severe injury was defined as a maximum Abbreviated Injury Score (MAIS) >= 3 or an injury severity score >= 16, including fatal injury. RESULTS: The database searches yielded 469 unduplicated citations. Snowball searching yielded an additional 17 citations. Of these 486 citations, 19 research studies and 2 reviews with practice guidelines met the retention criteria. All of the research studies were secondary analyses, involving the use of hospital trauma registries, injury databases, patient medical records, and statewide hospital discharge data. These studies were conducted in the United States (US), Canada, and the United Kingdom (UK).Factors associated with severe injury included age, sex, systolic blood pressure, pulse, Glasgow ComaScale (GCS) score, use of anticoagulant and antiplatelet agents, angle of impact, restraint systems,occupant mobility at the scene, and number of persons injured. DISCUSSION AND CONCLUSIONS: The literature has two significant limitations: the lack of prospective studies of older trauma patient triage indicators and a lack of clarity in many published discussions related to the cause of injury mortality, i.e., whether deaths resulted from the direct effects of the injury or from complications, the effect of comorbidities, or a combination of these. The strongest evidence available at this time consists of retrospective analyses. There might be additional unidentified prehospital factors associated with severe injury in this population that have greater sensitivity, specificity, and predictive validity than current indicators. Seeking and validating such factors and validating existing triage indicators must assume priority amongst investigators and funding agencies. PMID- 20542271 TI - Chronic kidney disease in pregnancy requiring first-time dialysis. AB - OBJECTIVE: To report on the treatment and outcome of pregnancy in 29 women with chronic kidney disease (CKD), 24 of whom had moderate or severe renal dysfunction. METHODS: Renal dysfunction at the onset of pregnancy was stratified: serum creatinine <=1.4 mg/dL was defined as mild; 1.5-2.5 mg/dL was defined as moderate; and >2.5 mg/dL was defined as severe renal insufficiency. Clinical complications and perinatal outcomes were evaluated. RESULTS: The average serum creatinine level at the beginning of pregnancy was 3.32 mg/dL (range, 1.2-7.1 mg/dL), and the average urine protein level was 1.51 g in 24 hours (range, 0.1 5.6g in 24 hours). Dialysis therapy was necessary for 1 woman with mild renal dysfunction, 4 patients with moderate renal dysfunction, and 17 patients with severe renal dysfunction. CONCLUSION: The use of dialysis in pregnancy among women with moderate or severe renal dysfunction proved to be useful, but many patients became dependent on dialysis. It is not known whether this was due to the interaction between pregnancy and advanced CKD. PMID- 20542272 TI - Metformin compared with glyburide for the management of gestational diabetes. AB - OBJECTIVE: To assess blood glucose control and neonatal outcomes when women with gestational diabetes mellitus (GDM) were treated with metformin or glyburide. METHODS: When an appropriate diet was insufficient to control their blood glucose levels, women with GDM were randomized to a glyburide or a metformin treatment group. If the maximum dose was reached, the assessed drug was replaced by insulin. The primary outcome measures analyzed were maternal glucose levels during pregnancy, birth weight, and neonatal glucose levels. RESULTS: The only significant difference in outcome between the 2 treatment drugs was that maternal weight gain during pregnancy was less in the metformin (n=40) than in the glyburide group (n=32) (10.3 kg vs 7.6 kg; P=0.02). No differences were found in treatment failure, mean level of fasting or postprandial plasma glucose, rate of participants with glycated hemoglobin, birth weight, rate of large-for gestational-age newborns, or newborns with hypoglycemia. CONCLUSION: The treatment of GDM with metformin or glyburide was found to be equivalent for both women and newborns. PMID- 20542273 TI - Safety is an interpretive act: a hermeneutic analysis of care in childbirth. AB - OBJECTIVE: To explore the interpretive nature of safety through a hermeneutic analysis of women's stories of feeling unsafe. DESIGN: This is a re interpretation of data from a study completed in 1998 that explored the meaning of being safe in childbirth. Three stories are interpreted from that study using a hermeneutic phenomenological methodological approach. The analysis seeks to reveal what lies behind the simple, taken-for-granted stories of experience towards recognising the interpretive nature of safety. SETTING: New Zealand maternity services. PARTICIPANTS: Stories from 3 women are profiled, with glimpses from the stories of other participants. FINDINGS: Women may experience unsafe events but when they seek help struggle to get the unsafety of the situation recognised. This is because there is nothing to see 'now', the woman has difficulty describing what is happening, or the practitioner does not follow through to investigate further. There is a sense that women can feel 'not believed'. Further, the woman may not understand that what she is experiencing is not normal. CONCLUSIONS: Safety reveals itself as lost or found in interpretation. Listening, watching and responding are the hallmarks of safe practice. PMID- 20542275 TI - Scaffold microarchitecture determines internal bone directional growth structure: a numerical study. AB - A number of successful results have been reported in bone tissue engineering, although the routine clinical practice has not been reached so far. One of the reasons is the poor understanding of the role of each scaffold design parameter in its functional performance, which yields an uncertain outcome of each clinical application. Specifically, the role of internal scaffold microarchitectural shape on the regeneration rate and distribution of newly formed bone is still unknown. This work is focused on the in-silico determination of the role of scaffold microstructural anisotropy in bone tissue regeneration. A multiscale approach of the problem is established distinguishing between macroscopic region domain (bone organ and scaffold) and microscopic domain (scaffold microstructure). Results show that, once the scaffold microstructure is properly interconnected and the porosity is sufficiently high, similar rates of bone regeneration are found. However, the main conclusion of the work is that initial scaffold microstructural anisotropy has important consequences since it determines the spatial distribution of the newly formed tissue. PMID- 20542274 TI - In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate. AB - OBJECTIVES: We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model. METHODS: AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of the AAAs was also quantified endovascularly. RESULTS: A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration. CONCLUSIONS: We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications. PMID- 20542276 TI - An alternative route to dye-polymer complexation study using asymmetrical flow field-flow fractionation. AB - The goal of the present work is to apply the versatile asymmetrical flow field flow fractionation (AF4) coupled to UV and light scattering detection for the characterization of hyperbranched poly(ethylene imine) decorated with maltose shell (PEI-Mal) and the polar dye Rose Bengal (RB) in respect to their complexation behaviour. The quantitative determination of the non-complexed dye was carried out using the ultra-filtration effect of AF4 during the focussing phase, whereas the non-bound RB is filtrated and transported out of the channel while the complex of RB and PEI-Mal remains inside. A calibration with UV detector (550 nm) was established and different parameters (e.g. membrane material, molecular weight cut-off and stability of both, pure RB and RB@PEI-Mal complexes in solution) were investigated and verified. Successful reproducibility tests were performed. First complexation studies with the developed method were applied successfully with different mixture compositions of RB and PEI-Mal. PMID- 20542277 TI - Colloidal crystal growth monitored by Bragg diffraction interference fringes. AB - We monitored the crystal growth kinetics of crystallization of a shear melted crystalline colloidal array (CCA). The fcc CCA heterogeneously nucleates at the flow cell wall surface. We examined the evolution of the (1 1 1) Bragg diffraction peak, and, for the first time, quantitatively monitored growth by measuring the temporal evolution of the Bragg diffraction interference fringes. Modeling of the evolution of the fringe patterns exposes the time dependence of the increasing crystal thickness. The initial diffusion-driven linear growth is followed by ripening-driven growth. Between 80 and 90 microM NaCl concentrations the fcc crystals first linearly grow at rates between 1.9 and 4.2 microm/s until they contact homogeneously nucleated crystals in the bulk. At lower salt concentrations interference fringes are not visible because the strong electrostatic interactions between particles result in high activation barriers, preventing defect annealing and leading to a lower crystal quality. The fcc crystals melt to a liquid phase at >90 microM NaCl concentrations. Increasing NaCl concentrations slow the fcc CCA growth rate consistent with the expectation of the classical Wilson-Frenkel growth theory. The final thickness of wall nucleated CCA, that is determined by the competition between growth of heterogeneously and homogenously nucleated CCA, increases with higher NaCl concentrations. PMID- 20542278 TI - Amino-functionalized Fe(3)O(4)@SiO(2) core-shell magnetic nanomaterial as a novel adsorbent for aqueous heavy metals removal. AB - A novel amino-functionalized Fe(3)O(4)@SiO(2) magnetic nanomaterial with a core shell structure was developed, aiming to remove heavy metal ions from aqueous media. The structural, surface, and magnetic characteristics of the nanosized adsorbent were investigated by elemental analysis, FTIR, N(2) adsorption desorption, transmission electron microscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, vibrating sample magnetometry, thermogravimetric analysis, and zeta-potential measurement. The amino-functionalized Fe(3)O(4)@SiO(2) nanoadsorbent exhibited high adsorption affinity for aqueous Cu(II), Pb(II), and Cd(II) ions, resulting from complexation of the metal ions by surface amino groups. Moreover, the adsorption affinity for heavy metal ions was not much impacted by the presence of a cosolute of humic acid (10.6mg/L) or alkali/earth metal ions (Na(+), K(+), Mg(2+)) (0.025-0.30mmol/L). The metal loaded Fe(3)O(4)@SiO(2)-NH(2) nanoparticles could be recovered readily from aqueous solution by magnetic separation and regenerated easily by acid treatment. Findings of the present work highlight the potential for using amino functionalized Fe(3)O(4)@SiO(2) magnetic nanoparticles as an effective and recyclable adsorbent for the removal of heavy metal ions in water and wastewater treatment. PMID- 20542279 TI - Monolayers of mixture of alkylaminomethyl rutin and lecithin at the air/water interface. AB - A compound of flavonol-based biosurfactant, as C(8)-substituted alkylaminomethyl rutin (DAMR) for a potential pharmaceutical or agrochemical use, was prepared experimentally. The surface behavior of DAMR and its mixture with lecithin from soybean (SL) had been studied. DAMR, regarded as a pseudo-amphoteric character, exhibits both liquid-condensed (LC) and liquid-expanded (LE) phases while SL is in the form of the LE phase only. The phase parameters of DAMR (including A(limt), pi(coll)) are observed to strongly depend on both the subphase temperature and the pH, which regulate the degree of ionization. In addition, the observed positive deviation calculated from excess Gibbs free energies of the DAMR-SL system suggests a repulsive interaction between DAMR and SL at all X(DAMR) values. Also the interaction parameter is found to increase linearly with surface pressure, regardless of composition. Notably, the relationship of logarithmic activity coefficient vs. X(DAMR)(2) reveals that the molecular interaction of DAMR-SL can be adequately simulated using a simple regular mixture model. Importantly, lower C(S)(-1) values of this mixture than those with pure DAMR and SL denote weak elasticity of mixed monolayers with values of X(DAMR) of 0.2-0.8, indicating that the direct addition of DAMR may exert a somewhat adverse influence on SL membranes. PMID- 20542280 TI - Competing effects of silanol surface concentration and solvent dielectric constant on electrostatic layer-by-layer assembly of silica nanoparticles on gold. AB - Two types of silica nanoparticles having differing concentrations of ionizable surface groups are used to investigate the interplay between nanoparticle surface charge and solvent dielectric constant in nanostructure development during layer by-layer assembly with a cationic polyacrylamide. Zeta (zeta) potential measurements are used to determine the extent of silanol dissociation with pH. For 19-nm-diameter X-Tec 3408 silica nanoparticles from Nano-X GmbH (NanoX), complete dissociation yields a zeta-potential value of about -44mV and occurs between pH 5 and 6 in 50% ethanol-in-water mixture by volume. By contrast, 65-nm diameter polishing silica from Electron Microscopy Supply (EMS) has a zeta potential that does not equilibrate even up to pH 7 with a value of -59mV under otherwise similar solution conditions. The more negative zeta potential at a given pH is found to substantially reduce nanoparticle adsorption. This behavior is opposite that observed when the dielectric constant of the suspension is decreased, independent of particle size. Nanoparticle surface chemical heterogeneity is discussed as a plausible explanation for such seriously discrepant behavior and the effects on multilayer electrical contact resistance for proton-exchange membrane (PEM) fuel-cell coating applications are presented. PMID- 20542281 TI - Bipolar leads obtained from the unipolar precordial leads for noise filtering. PMID- 20542282 TI - A happy story: Developmental changes in children's sensitivity to facial expressions of varying intensities. AB - Using 20 levels of intensity, we measured children's thresholds to discriminate the six basic emotional expressions from neutral and their misidentification rates. Combined with the results of a previous study using the same method (Journal of Experimental Child Psychology, 102 (2009) 503-521), the results indicate that by 5 years of age, children are adult-like, or nearly adult-like, for happy expressions on all measures. Children's sensitivity to other expressions continues to improve between 5 and 10 years of age (e.g., surprise, disgust, fear) or even after 10 years of age (e.g., anger, sad). The results indicate that there is a slow development of sensitivity to the expression of all basic emotions except happy. This slow development may impact children's social and cognitive development by limiting their sensitivity to subtle expressions of disapproval or disappointment. PMID- 20542283 TI - Combined central precocious puberty and primary gonadal failure after treatment of childhood malignancy in two boys: a diagnostic and therapeutic conundrum. AB - Central precocious puberty and primary gonadal failure are known sequelae of childhood cancer or its treatment. Here we report two boys with coexistent central precocious puberty and primary gonadal failure after treatment for childhood malignancies. PMID- 20542284 TI - Relationship between whole grain and fiber consumption and body weight measures among 6- to 18-year-olds. AB - OBJECTIVES: To examine the relationship between whole grain and fiber consumption and body weight measures in children 6 to 12 (n=3868) and adolescents 13 to 18 (n=4931) years old. STUDY DESIGN: Combined 1999 to 2004 National Health and Nutrition Examination Survey data were analyzed. Mean body mass index (BMI), BMI percentile, BMI z-score, waist circumference, and prevalence of overweight/obesity were compared across categories of whole grain consumption (0 to <0.6, >or=0.6 to <1.5, >or=1.5 to <3, and >or=3 servings) with (1) a sex, ethnicity, and total energy intake-adjusted model and (2) a cereal fiber plus model 1 covariates profile. RESULTS: Mean whole grain intake was 0.59 and 0.63 servings/d among children 6 to 12 years and adolescents 13 to 18 years, respectively. In children, consumption of >or=3 servings of whole grain was not associated with body weight measures; however, consumption of 1.5 to <3 servings was positively associated with all weight measures. In adolescents, BMI z-score was significantly lower in the highest whole grain consumption group compared with the lowest 2 groups; BMI percentile and waist circumference (model 1 only) were also significantly lower in the highest whole grain consumption group. CONCLUSIONS: Overall consumption of whole grain was below current recommendations of at least 3 servings per day. Only in adolescents was this level of whole grain intake associated with lower BMI z-scores. PMID- 20542285 TI - Fatness, fitness, and increased cardiovascular risk in young children. AB - OBJECTIVES: To investigate the relationships between cardiorespiratory fitness and adiposity among young children, and their influence on a comprehensive cardiovascular risk profile. STUDY DESIGN: The sample included 95 healthy weight, 54 overweight, and 31 obese children (n=180, 10.9+/-2.1 years). All children had a medical assessment that included a physical examination and fasting investigations including glycated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, insulin and glucose levels. Body mass index and waist circumference z-scores were calculated. Children's fitness level was measured with the Queens College step test. RESULTS: Although low fitness was independently associated with cardiovascular risk, multi-level analysis demonstrated that waist circumference z-score was the only significant predictor of cardiovascular risk factors including SBP (beta=3.29, P<.001), DBP (beta=1.88, P<.005), high-density lipoprotein (beta=-0.12, P<.001), and triglyceride levels (beta=0.14, p<.001), fasting insulin (beta=2.83, P<.001), C peptide (beta=0.11, P<.001), and HOMA-IR (beta=0.34, P<.001), with increasing waist circumference z-score associated with increasing cardiovascular risk. Within the healthy weight children, high fitness was associated with significantly reduced triglyceride levels, and lower fasting glucose, insulin and HOMA-IR. CONCLUSIONS: Young children's health may be influenced more by body fatness, and in particular, the distribution of body fat than by cardiorespiratory fitness. However, within the healthy weight children, high fitness was associated with a favorable metabolic profile, suggesting that cardiorespiratory fitness may exert a protective effect on metabolic risk in children whose risk is not confounded by fatness. PMID- 20542286 TI - Congenital cytomegalovirus infection: screening and treatment. PMID- 20542288 TI - Prebiotic effect of lactulose in preterm infants. PMID- 20542289 TI - Maternal depression and child growth: definitional issues, longitudinal trajectories, and analytic considerations. PMID- 20542287 TI - Endothelial abnormalities in adolescents with type 1 diabetes: a biomarker for vascular sequelae? AB - OBJECTIVE: To evaluate whether counts of circulating colony forming unit endothelial cells (CFU-ECs), cells co-expressing CD34, CD133, and CD31 (CD34+CD133+CD31+), and CD34+CD45- cells are altered in adolescents with type 1 diabetes and if the changes in counts correlate with endothelial dysfunction. STUDY DESIGN: Adolescents with diabetes (ages 18 to 22 years) and race- and sex matched control subjects were studied. We assessed circulating CFU-ECs, using colony assays, and CD34+CD133+CD31+ and CD34+CD45- cells, using poly-chromatic flow cytometry. CFU-ECs and CD34+CD133+CD31+ are hematopoietic-derived progenitors that inversely correlate with cardiovascular risk in adults. CD34+CD45- cells are enriched for endothelial cells with robust vasculogenic potential. Vascular reactivity was tested by laser Doppler iontophoresis. RESULTS: Subjects with diabetes had lower CD34+CD133+CD31+ cells, a trend toward reduced CFU-ECs, and increased CD34+CD45- cells compared with control subjects. Endothelium-dependent vasodilation was impaired in subjects with diabetes, which correlated with reductions in circulating CD34+CD133+CD31+ cells. CONCLUSIONS: Long-term sequelae of type 1 diabetes include vasculopathies. Endothelial progenitor cells promote vascular health by facilitating endothelial integrity and function. Lower CD34+CD133+CD31+ cells may be a harbinger of future macrovascular disease risk. Higher circulating CD34+CD45- cells may reflect ongoing endothelial damage. These cells are potential biomarkers to guide therapeutic interventions to enhance endothelial function and to prevent progression to overt vascular disease. PMID- 20542290 TI - Improved diagnosis of mild hypothyroidism using time-of-day normal ranges for thyrotropin. AB - OBJECTIVE: To assess clinical utility of time-of-day-based thyrotropin (TSH) ranges. STUDY DESIGN: Ranges for TSH at 8 am, 4 pm, and am/pm TSH ratio were developed from prior data in 94 typical children (age, 5 to 18 years). Data for these values in 227 short children (1.5 to 18 years) were compared with those in typical children. RESULTS: Short children included idiopathic short stature (ISS, n=153), central hypothyroidism (Central, n=42), and mild primary hypothyroidism (Primary, n=32), referred for evaluation of growth. In typical children, ISS, and Primary, 8 am TSH was greater than 4 pm TSH (P<.05). In Primary, 8 am TSH was greater than normal. Only 4 with Primary had elevated 4 pm TSH (using usual laboratory range of 0.5 to 4 mU/L). In contrast, only 63% of 4 pm TSHs in Primary were elevated. compared with 95% confidence limits in typical children. In Central, 8 am TSH and 4 pm TSH were within normal time-of-day range, and FT4 was in lowest one-third of normal. am/pm TSH ratio was less than 95% confidence limits in 76% of those with Central. CONCLUSIONS: Either 8 am TSH or 4 pm TSH (compared with time-of-day normal range) can identify TSH elevation. Low am/pm TSH ratio (FT4 in lowest one-third of normal) confirms central hypothyroidism. Thus, time-of-day TSH ranges should be used for accurate diagnosis and more appropriate cost-effective treatment of mild hypothyroidism. PMID- 20542291 TI - Underestimation of influenza viral infection in childhood asthma exacerbations. AB - Bocavirus was found in 11.6% of hospitalized children and 13% of ambulatory patients with exacerbations of asthma, and respiratory syncytial virus was found in 13.5% and 17.7%, respectively. In addition, influenza A virus was detected in 2.6% of hospitalized children and 14.1% (P<.001) of ambulatory-treated patients. Thus, the influenza burden in asthma may be underestimated. PMID- 20542292 TI - Smoking and brain development in preterm infants. PMID- 20542293 TI - Do self- or parent-reported dietary, physical activity, and sedentary behaviors predict worsening obesity in children? AB - OBJECTIVE: To determine whether information gathered during routine healthcare visits regarding obesity related risk factors and risk behaviors predicts increases in BMI z-score over time among overweight and obese children. STUDY DESIGN: Medical records from 168 overweight and 441 obese patients seen for repeated visits between September 2003 and April 2006 were examined for reported dietary, physical activity, and sedentary behaviors, family history of obesity and diabetes mellitus, documented Acanthosis nigricans, and BMI values. Random effects regression analysis was done to determine whether demographic, familial, or behavioral data predicted changes in BMI z-score over time. RESULTS: The presence of A nigricans and a family history of obesity were associated with an increase in BMI z-score (beta=0.56, SE=0.09, P<.001 and beta=0.31, SE=0.13, P=.021). These risk factors explained 8% and 7% of the variation in BMI z-score respectively. Self- or parent-reported dietary and physical activity behaviors did not predict change in BMI z-score. CONCLUSIONS: Our findings suggest that the risk factors and self- or parent-reported risk behaviors routinely assessed by pediatric clinicians have limited ability to predict future growth trends, demonstrating the difficulty in determining which patients have the greatest risk of progression of obesity. PMID- 20542295 TI - Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. AB - OBJECTIVES: To evaluate the beneficial effects of Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation. STUDY DESIGN: A double blind, placebo-controlled, randomized study was conducted from January 2008 to December 2008 in 44 consecutive infants at least 6 months old (mean age+/-SD, 8.2+/-2.4 SD; male/female, 24/20) admitted to the Gastrointestinal Endoscopy and Motility Unit of the Department of Pediatrics, University "Federico II" of Naples, with a diagnosis of functional chronic constipation. The 44 infants with chronic constipation were randomly assigned to 2 groups: group A (n=22) received supplementation with the probiotic L reuteri (DSM 17938) and group B (n=22) received an identical placebo. Primary outcome measures were frequency of bowel movements per week, stool consistency, and presence of inconsolable crying episodes, recorded in a daily diary by parents. RESULTS: Infants receiving L reuteri (DSM 17938) had a significantly higher frequency of bowel movements than infants receiving a placebo at week 2 (P=.042), week 4 (P=.008), and week 8 (P=.027) of supplementation. In the L reuteri group, the stool consistency was reported as hard in 19 infants (86.4%) at baseline, in 11 infants (50%) at week 2, and in 4 infants (18.2%) at weeks 4 and 8. However, there was no significant difference between L reuteri and placebo groups in the stool consistency at all weeks (P=.63, week 2; P=.38, week 4; P=.48, week 8). Similarly, there was no statistically difference in the 2 groups in the presence of inconsolable crying episodes. No adverse effects were reported. CONCLUSIONS: The administration of L reuteri (DSM 17938) in infants with chronic constipation had a positive effect on bowel frequency, even when there was no improvement in stool consistency and episodes of inconsolable crying episodes. Because of their safety profile, probiotics may be an attractive option in the treatment of functional constipation. PMID- 20542296 TI - The development of sucking patterns in preterm, small-for-gestational age infants. AB - OBJECTIVE: To determine whether the development of sucking patterns in small-for gestational age (SGA) preterm infants differs from appropriate-for-gestational age (AGA) preterm infants. STUDY DESIGN: We assessed sucking patterns in 15 SGA and 34 AGA preterms (gestational age70 m depth), in southern West Bengal, India. In the deep aquifer, concentrations of As did not change over time despite increases in the concentration of Fe in two wells. The shallow aquifer occurs in two sedimentological settings: palaeo-channel and palaeo-interfluve. At the top of the shallow aquifer of the palaeo-channel, decreases in all constituent concentrations with time, and an (3)H/(3)He age of 1.4 years, proves that the aquifer is beginning to be flushed of pollutants. In As-polluted groundwater (>50 microg/L As) tapped from deeper grey sands of the shallow, palaeo-channel, aquifer, concentrations of As were mostly stable over time, but both increases and decreases occurred with time in response to downward migration of the chemically-stratified water column. In groundwater tapped from Pleistocene brown sands, the concentration of As remained either low and stable (<2 microg/L As), or increased at rates up to 34 microg/L per year. The increases were caused by the flow of As-rich groundwater either downward into brown sand at the base of palaeo-channels, or laterally into a confined, unpolluted, palaeo-interfluvial, aquifer of brown sand that lies regionally beneath a palaeosol. Under the present pumping regime, the prognosis for As-pollution in the shallow aquifer is complex. Wells in brown sand may become polluted over timescales of as little as 2 years, whilst some wells tapping As-polluted groundwater from grey sand will become fit for potable use (<50 microg/L) within a few decades. The evidence of flushing, and of declining As in some of the groundwater from palaeo-channels, which are conduits for recharge of the confined, As-free, palaeo-interfluve aquifer, and probably also the deeper aquifer, offers hopes that the spread of As-pollution will be limited. PMID- 20542312 TI - Application of the gas tracer method for measuring oxygen transfer rates in subsurface flow constructed wetlands. AB - The oxygen transfer rate (OTR) has a significant impact on the design, optimal operation and modelling of constructed wetlands treating wastewater. Oxygen consumption is very fast in wetlands and the OTR cannot be determined using an oxygen mass balance. This problem is circumvented in this study by applying the gas tracer method. Experiments were conducted in an unplanted gravel bed (dimensions L x W x d 125 x 50 x 35 cm filled with a 30-cm layer of 10-11-mm gravel) and a planted horizontal subsurface flow constructed wetland (HSSFCW) (L x W x d 110 x 70 x 38 cm filled with a 30-cm layer of 3.5-mm gravel with Phragmites australis). Tap water saturated with propane as gas tracer (pure or commercial cooking gas, depending on the test) was used. The mass transfer ratio between oxygen and commercial propane gas was quite constant and averaged R = 1.03, which is slightly lower than the value of R = 1.39 that is usually reported for pure propane. The OTR ranged from 0.31 to 5.04 g O(2) m(-2) d(-1) in the unplanted gravel bed and from 0.3 to 3.2 g O(2) m(-2) d(-1) in the HSSFCW, depending on the hydraulic retention time (HRT). The results of this study suggest that the OTR in HSSFCW is very low for the oxygen demand of standard wastewater and the OTR calculations based on mass balances and theoretical stoichiometric considerations overestimate OTR values by a factor that ranges from 10 to 100. The gas tracer method is a promising tool for determining OTR in constructed wetlands, with commercial gas proving to be a viable low-cost alternative for determining OTR. PMID- 20542313 TI - Organic micropollutant removal from wastewater effluent-impacted drinking water sources during bank filtration and artificial recharge. AB - Natural treatment systems such as bank filtration (BF) and artificial recharge (via an infiltration basin) are a robust barrier for many organic micropollutants (OMPs) and may represent a low-cost alternative compared to advanced drinking water treatment systems. This study analyzes a comprehensive database of OMPs at BF and artificial recharge (AR) sites located near Lake Tegel in Berlin (Germany). The focus of the study was on the derivation of correlations between the removal efficiencies of OMPs and key factors influencing the performance of BF and AR. At the BF site, shallow monitoring wells located close to the Lake Tegel source exhibited oxic conditions followed by prolonged anoxic conditions in deep monitoring wells and a production well. At the AR site, oxic conditions prevailed from the recharge pond along monitoring wells to the production well. Long residence times of up to 4.5 months at the BF site reduced the temperature variation during soil passage between summer and winter. The temperature variations were greater at the AR site as a consequence of shorter residence times. Deep monitoring wells and the production well located at the BF site were under the influence of ambient groundwater and old bank filtrate (up to several years of age). Thus, it is important to account for mixing with native groundwater and other sources (e.g., old bank filtrate) when estimating the performance of BF with respect to removal of OMPs. Principal component analysis (PCA) was used to investigate correlations between OMP removals and hydrogeochemical conditions with spatial and temporal parameters (e.g., well distance, residence time and depth) from both sites. Principal component-1 (PC1) embodied redox conditions (oxidation-reduction potential and dissolved oxygen), and principal component-2 (PC2) embodied degradation potential (e.g., total organic carbon and dissolved organic carbon) with the calcium carbonate dissolution potential (Ca(2+) and HCO(3)(-)) for the BF site. These two PCs explained a total variance of 55% at the BF site. At the AR site, PCA revealed redox conditions (PC1) and degradation potential with temperature (PC2) as principal components, which explained a total variance of 56%. PMID- 20542314 TI - Contaminant immobilization and nutrient release by biochar soil amendment: roles of natural organic matter. AB - Contamination of soil interstitial waters by labile heavy metals such as Cu(II), Cd(II), and Ni(II) is of worldwide concern. Carbonaceous materials such as char and activated carbon have received considerable attention in recent years as soil amendment for both sequestering heavy metal contaminants and releasing essential nutrients like sulfur. Information is currently lacking in how aging impacts the integrity of biochars as soil amendment for both agricultural and environmental remediation purposes. Major contributors to biochar aging in soils are: sorption of environmental constituents, especially natural organic matter (NOM), and oxidation. To investigate the impact of NOM and organic fractions of chars, we employed broiler litter-derived chars and steam-activated carbons that underwent varying degrees of carbonization, in the presence and absence of NOM having known carboxyl contents. For aging by oxidation, we employed phosphoric acid activated carbons that underwent varying degrees of oxidation during activation. The results suggest that the organic fractions of biochars, and NOM having high carboxyl contents can mobilize Cu(II) retained by alkaline soil. Base treatment of broiler litter-derived char formed at low pyrolysis temperature (350 degrees C) improved the immobilization of all heavy metals investigated, and the extent of immobilization was similar to, or slightly greater than pecan shell-derived phosphoric acid activated carbons. Portions of total sulfur were released in soluble form in soil amended with broiler litter-derived carbons, but not pecan shell-derived phosphoric acid activated carbons. PMID- 20542315 TI - Dissolved nutrients and atrazine removal by column-scale monophasic and biphasic rain garden model systems. AB - Rain gardens are bioretention systems that have the potential to reduce peak runoff flow and improve water quality in a natural and aesthetically pleasing manner. We compared hydraulic performance and removal efficiencies of nutrients and atrazine in a monophasic rain garden design versus a biphasic design at a column-scale using simulated runoff. The biphasic rain garden was designed to increase retention time and removal efficiency of runoff pollutants by creating a sequence of water saturated to unsaturated conditions. We also evaluated the effect of C substrate availability on pollutant removal efficiency in the biphasic rain garden. Five simulated runoff events with various concentrations of runoff pollutants (i.e. nitrate, phosphate, and atrazine) were applied to the monophasic and biphasic rain gardens once every 5d. Hydraulic performance was consistent over the five simulated runoff events. Peak flow was reduced by approximately 56% for the monophasic design and 80% for the biphasic design. Both rain garden systems showed excellent removal efficiency of phosphate (89-100%) and atrazine (84-100%). However, significantly (p<0.001) higher removal of nitrate was observed in the biphasic (42-63%) compared to the monophasic rain garden (29-39%). Addition of C substrate in the form of glucose increased removal efficiency of nitrate significantly (p<0.001), achieving up to 87% removal at a treatment C/N ratio of 2.0. This study demonstrates the importance of retention time, environmental conditions (i.e. saturated/unsaturated conditions), and availability of C substrate for bioremediation of pollutants, especially nitrates, in rain gardens. PMID- 20542317 TI - Ultrasound assisted photocatalytic degradation of diclofenac in an aqueous environment. AB - Diclofenac (DF) is an anti-inflammatory drug found in aqueous environments as a pollutant due to its widespread use. The sonolytic, photocatalytic and sonophotocatalytic degradation of DF using three photocatalysts (TiO(2), ZnO and Fe-ZnO) were studied. The degradation of DF followed first-order like kinetics. The sonophotocatalytic degradation using TiO(2) under UV-vis radiation showed a slight synergistic enhancement in the degradation of the parent compound, whereas a detrimental effect was observed for the mineralization process. In the case of Fe-ZnO, both degradation and mineralization showed near additive effects. A number of degradation products were identified. PMID- 20542316 TI - Simulated geochemical weathering of a mineral ash-rich biochar in a modified Soxhlet reactor. AB - Although there are many studies on the characterization of C in biochar and its C sequestration potential, there is little knowledge on the mineral fraction in biochar and its weathering. The latter, however, can have powerful implications on nutrient availability. In the present study, a modified Soxhlet reactor was used to simulate the long-term geochemical weathering of an ash-rich biochar produced from sewage sludge of a non-industrial area in New Zealand. The weathering process took place during a period of 300 h, with and without the addition of humic acid (1.00 g added to 20.00 g of biochar), and the treatments were referred to as treatment BC-HA and BC-B, respectively. Both the leaching kinetics and the transformations within the solid phase were studied. The results revealed that substantial amounts of K (8.5-10.2%) and S (20.2-28.3%) were recovered in the weathering solutions. Noticeable Ca (17.9-20.7%) and P (15.4%) in the solid were released but only a few were recovered in the weathering solutions because of the precipitation. The presence of humic acids increased this dissolution and thus the availability of K, S, Ca, Mg and P, but induced N immobilization. Nitrogen availability was already very low (<1.0% of the total N) due to the probable recalcitrant heterocyclic N structure. The pH of the biochar samples dropped from 8.4 to 7.5; this was mainly attributed to loss of base cations through leaching and probable carbonation of the system. The XPS spectra evidenced the oxidation of C in biochar during the weathering process with the formation of carbonyl and carboxylic functional groups. The results obtained in this study showed some promise for the positive use of modified Soxhlet extractor in simulating the geochemical weathering in ash-rich biochars and providing a better understanding on the kinetics of nutrient release. This will be key information in assessing the added value of biochars as soil amendments. PMID- 20542318 TI - Complications with remediation strategies involving the biodegradation and detoxification of recalcitrant contaminant aromatic hydrocarbons. AB - Environmentally persistent aromatic hydrocarbons known as unresolved complex mixtures (UCMs) derived from crude oil can be accumulated by, and elicit toxicological responses in, marine organisms (e.g. mussels, Mytilus edulis). Comprehensive two-dimensional gas chromatography time-of-flight mass-spectrometry (GCxGC-ToF-MS) previously revealed that these UCMs included highly branched alkylated aromatic hydrocarbons. Here, the effects of biodegradation on the toxicity and chemical composition of an aromatic UCM hydrocarbon fraction isolated from Tia Juana Pesado (TJP) crude oil were examined. 48h exposure of mussels to the aromatic hydrocarbon fraction (F2) resulted in tissue concentrations of 900microgg(-1) (dry wt.) and approximately 45% decrease in clearance rate. Over 90% of the hydrocarbon burden corresponded to an UCM. Following a 5day recovery period, GCxGC-ToF-MS analysis of the tissues indicated depuration of most accumulated hydrocarbons and clearance rates returned to those observed in controls. To assess the potential of biodegradation to reduce UCM toxicity, TJP F2 was exposed to bacteria isolated from Whitley Bay, UK, for 46days. Mussels exposed to the undegraded TJP F2 from the abiotic control exhibited a reduction in clearance rate comparable with values for the pure crude oil TJP F2. Clearance rates of mussels exposed to biodegraded TJP F2 were statistically similar to seawater controls, suggesting biodegradation had reduced the TJP F2 toxicity. GCxGC-ToF-MS analysis revealed the same compound groups in the tissue of mussels exposed to pure TJP F2, undegraded TJP F2 and biodegraded TJP F2 samples; however >300 fewer compounds were observed in the biodegraded (954 compounds) compared to the undegraded TJP F2 (1261). The compound distributions were markedly different, possibly accounting for the decrease in toxicity. Extraction and analysis of pelleted bacterial cell material revealed that a significant proportion of the TJP F2 had adsorbed onto the cells. Thus extreme care must be taken in interpreting biodegradation data from recalcitrant UCM hydrocarbons. PMID- 20542319 TI - Hospice enrollment for terminally ill patients with gynecologic malignancies: impact on outcomes and interventions. AB - OBJECTIVE: To determine survival and interventions for patients with non-curative gynecologic malignancies based on supportive care enrollment. METHODS: An IRB approved retrospective review identified patients with recurrent/persistent gynecologic cancers from 2002 to 2008. Demographics, therapy, clinicopathologic data, hospice utilization, surgical/invasive procedures and survival were collected. Patients were considered hospice enrollees if they enrolled following recommendation from their provider (HOSPICE); however, patients that declined hospice when recommended were considered (NO HOSPICE), regardless if they ultimately received supportive care. Standard statistical tests including: t-test and Kaplan-Meier with Log Rank were used. RESULTS: Eighty-one patients were identified: 29 patients (36%) NO HOSPICE and 52 (64%) HOSPICE. Mean age was 61. Most patients had ovarian cancer (54.3%), were white (61.7%) and had disease recurrence (72%). Patients utilized a median of 3 anti-neoplastic therapies (range 0-10) for recurrent or progressive/persistent disease. Median time receiving hospice care was 1week for NO HOSPICE patients versus 8weeks HOSPICE patients (p<0.0005). In a subset of patients with recurrent disease, median overall survival for NO HOSPICE patients was 9months (95% CI 5.9-12.1months) versus 17months (95% CI 11.1-22.9months) for HOSPICE patients (p=0.002). NO HOSPICE patients were more likely to have a procedure performed (55% vs. 31%) within 4weeks of their death, including the administration of chemotherapy OR 2.4 (95% CI 1.1-7.1, p=0.036). CONCLUSIONS: While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients. Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization. PMID- 20542320 TI - Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase. AB - BACKGROUND: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. METHODS: In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. RESULTS: Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. CONCLUSION: Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT. PMID- 20542321 TI - Low-dose, but not high-dose, cyclosporin A promotes regulatory T-cell induction, expansion, or both. PMID- 20542322 TI - Immune deficiency caused by impaired expression of nuclear factor-kappaB essential modifier (NEMO) because of a mutation in the 5' untranslated region of the NEMO gene. AB - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key transcription factor that regulates both innate and adaptive immunity as well as ectodermal development. Mutations in the coding region of the IkappaB kinase gamma/NF-kappaB essential modifier (NEMO) gene cause X-linked ectodermal dysplasia with immunodeficiency. OBJECTIVE: To determine the genetic cause of recurrent sinopulmonary infections and dysgammaglobulinemia in a patient with a normal NEMO coding sequence and his affected brother. METHODS: TNF-alpha and IFN-alpha production in response to Toll like receptor (TLR) stimulation was analyzed by ELISA, NEMO mRNA levels were measured by quantitative PCR, and NEMO protein expression was measured by Western blotting. NF-kappaB activation was assessed by nuclear translocation of p65 and luciferase reporter gene assays. RESULTS: TLR-induced TNF-alpha and IFN-alpha production by PBMCs was impaired in the patient and his brother. Sequencing of the patient's NEMO gene revealed a novel mutation in the 5' untranslated region, which was also present in the brother, resulting in abnormally spliced transcripts and a 4-fold reduction in mRNA levels. NEMO protein levels in EBV transformed B cells and fibroblasts from the index patient were 8-fold lower than normal controls. NF-kappaB p65 nuclear translocation in the patient's EBV B cells after TLR7 ligation was defective. NF-kappaB-dependent luciferase gene expression in IL-1-stimulated fibroblasts from the patient was impaired. CONCLUSION: This is the first description of immune deficiency resulting from low expression of a normal NEMO protein. PMID- 20542323 TI - Mepolizumab does not alter levels of eosinophils, T cells, and mast cells in the duodenal mucosa in eosinophilic esophagitis. PMID- 20542324 TI - Oral peanut immunotherapy in children with peanut anaphylaxis. AB - BACKGROUND: The only treatment option for peanut allergy is strict avoidance. OBJECTIVE: To investigate efficacy and safety of oral immunotherapy (OIT) in peanut allergy. METHODS: Twenty-three children (age, 3.2-14.3 years) with IgE mediated peanut allergy confirmed by positive double-blind, placebo-controlled food challenge (DBPCFC) received OIT following a rush protocol with roasted peanut for 7 days. If a protective dose of at least 0.5 g peanut was not achieved, patients continued with a long-term buildup protocol using biweekly dose increases up to at least 0.5 g peanut. A maintenance phase for 8 weeks was followed by 2 weeks of peanut avoidance and a final DBPCFC. Immunologic parameters were determined. RESULTS: After OIT using the rush protocol, patients tolerated a median dose of only 0.15 g peanut. Twenty-two of 23 patients continued with the long-term protocol. After a median of 7 months, 14 patients reached the protective dose. At the final DBPCFC, patients tolerated a median of 1 g (range, 0.25-4 g) in comparison with 0.19 g peanut at the DBPCFC before OIT (range, 0.02-1 g). In 2.6% of 6137 total daily doses, mild to moderate side effects were observed; in 1.3%, symptoms of pulmonary obstruction were detected. OIT was discontinued in 4 of 22 patients because of adverse events. There was a significant increase in peanut-specific serum IgG(4) and a decrease in peanut specific IL-5, IL-4, and IL-2 production by PBMCs after OIT. CONCLUSION: Long term OIT appears to be safe and of some benefit in many patients with peanut allergy. With an increase in threshold levels and a reduction of peanut-specific T(H)2 cytokine production, the induction of tolerance may be feasible in some patients. PMID- 20542325 TI - Mutations in CCR3 render it missing in action. PMID- 20542327 TI - Microtensile bond strength of a resin cement to a novel fluorcanasite glass ceramic following different surface treatments. AB - OBJECTIVES: This study evaluated the effect of surface treatments on the bond strength of fluorcanasite and lithium disilicate glass-ceramics, with the possibility of eliminating HF etching of these ceramics. METHODS: Fifteen blocks of an experimental fluorcanasite and a lithium disilicate glass-ceramic (IPS e.max CAD) were assigned to one of the following three surface treatments: (1) machined with 60 microm finish, (2) machined and grit blasted, (3) machined and HF etched. The ceramic blocks were duplicated in composite resin (Spectrum) and cemented together with a resin luting agent (Variolink II). Thirty microbars per group (1.0 x 1.0 x 20 mm) were obtained and subjected to a tensile force at a crosshead speed of 0.5 mm/min using a universal testing machine until failure. The mode of failure was determined using scanning electron microscopy. The appropriate bonding procedure was assessed for durability by storing in water at 100 degrees C for 24 h. Statistical analyses were performed with ANOVA and Tukey's test (P<0.05). RESULTS: Machining alone significantly increased the bond strength (MPa) of the fluorcanasite (27.79+/-6.94) compared to the lithium disilicate (13.57+/-4.52) (P<0.05). HF etching resulted in the lowest bond strength (8.79+/-2.06) for the fluorcanasite but the highest for the lithium disilicate (24.76+/-9.38). Regarding durability, the machined fluorcanasite (15.24+/-5.46) demonstrated significantly higher bond strength than the machined and HF etched lithium disilicate (12.28+/-3.30). SIGNIFICANCE: The fitting surface of the fluorcanasite glass-ceramic should retain the machined finish and be directly treated with silane. The use of HF acid is contraindicated. PMID- 20542328 TI - Microfluidic dissociation and clearance of Alzheimer's beta-amyloid aggregates. AB - The abnormal aggregation of beta-amyloid peptide (Abeta) in the brain is a major histopathological feature of Alzheimer's disease. Herein, we first report on microfluidic dissociation and clearance analysis of pre-formed Abeta aggregates for parallel screening of aggregate destabilizers. As a proof of the concept for the microfluidic platform, we investigated (1) microfluidics-based clearance of metal ion-induced Abeta aggregates using different types of metal chelators, (2) the clearance effect of deferoxamine on Abeta aggregates within microchannels, (3) comparison between destabilized Abeta dissociated from pre-formed Abeta aggregates and remaining deposits within the microchannels both before and after the clearance, and (4) secondary structure change in Abeta deposits by the clearance treatment. The microfluidics-based clearance system should be suitable for efficient screening of chemical candidates to enhance the clearance of Abeta deposits prior to their in vivo evaluation. PMID- 20542329 TI - The biocompatibility and antibacterial properties of waterborne polyurethane silver nanocomposites. AB - Nanocomposites from a polyester-type waterborne polyurethane (PU) containing various low concentrations (15-75 ppm) of silver nanoparticles (nano Ag, size approximately 5 nm) were prepared. The PU-Ag nanocomposites exhibited good nanoparticle dispersion up to 30 ppm of nano Ag, confirmed by the transmission electron microscopy. Distinct surface morphology at different concentrations of nano Ag was shown by the atomic force microscopy. The oxidative degradation of PU Ag was inhibited in all concentrations of nano Ag tested, especially at 30 ppm ("PU-Ag 30 ppm"). This may be related to the free radical scavenging ability observed for the nanocomposites. PU-Ag 30 ppm showed enhanced fibroblast attachment and endothelial cell response, as well as reduced monocyte and platelet activation, relative to PU alone or nanocomposites at the other silver contents. The rat subcutaneous implantation confirmed the better biocompatibility of the nanocomposites. The adhesion of Bacillus subtilis, Escherichia (E.) coli or Ag(+)-resistant E. coli on PU-Ag nanocomposites was significantly lower at all concentrations of nano Ag tested. Besides, the nanocomposites demonstrated microbiostatic effect while pure PU did not. The commercial catheters coated with PU-Ag 30 ppm were inserted into rat jugular veins for evaluation. The results showed milder inflammation for PU-Ag after 3 months compared to the non-coated catheters or pure PU-coated catheters. The enhanced performance of PU-Ag over that of pure PU was a result of extensively modified surface morphology in the presence of a very small amount of nano Ag. The dispersion of nano Ag was highly associated with the overall performance. PMID- 20542330 TI - The performance of a hydrogel nucleus pulposus prosthesis in an ex vivo canine model. AB - A nucleus pulposus prosthesis (NPP) made of the hydrogel N-vinyl-2-pyrrolidinone copolymerized with 2-(4'-iodobenzoyl)-oxo-ethyl methacrylate has recently been developed. The special features of this NPP, i.e. intrinsic radiopacity and its ability to swell in situ to fill the nucleus cavity and restore disc height, were investigated ex vivo in canine spinal specimens. L7-S1 intervertebral discs were isolated from three canine spinal specimens, and the dimensions of the nuclei pulposi were measured. Based on these averaged measurements, the NPP prototype was made and inserted in its dry form (xerogel) into a canine cadaveric spinal segment and allowed to swell overnight at 38 degrees C. The integrity of the NPP and the filling of the nucleus cavity were assessed before and after swelling, using radiography, computed tomography, and magnetic resonance imaging. The ability of the NPP to restore disc height was assessed on radiographs of 10 spinal specimens. Thereafter the NPP was macroscopically assessed in situ by dissection of the spinal specimen. Both on imaging and macroscopically, 9/10 NPPs appeared to have a near perfect fit and disc height was restored in 8/10 spinal segments. The NPP may thus be an acceptable treatment option for low back patients meeting the requirements for NPP treatment. PMID- 20542331 TI - pH-Dependent biodegradable silica nanotubes derived from Gd(OH)3 nanorods and their potential for oral drug delivery and MR imaging. AB - We report a pH dependence of degradable silica nanotubes, which dissolved to the biodegradation product monosilicic acid, Si(OH)(4). The silica nanotubes, potentially acting as oral-based administration carriers, were resistant to dissolution in the extreme acidic condition of pH 1, but degraded quickly at pH 8, and the degradation rate can be tuned by tailoring the thickness of silica nanotubes with thicker nanotubes dissolving more slowly. Because Gd(OH)(3) nanorods were used as templates, the silica nanotubes could be further developed as MR imaging contrast agents as well as drugs carriers. The released Gd(3+) ions resulting from the etching of Gd(OH)(3) nanorods were chelated by the pre modified DOTA, yielding Gd-DOTA complexes grafted onto silica nanotubes. The Gd DOTA grafted silica nanotubes loaded with doxorubicin revealed enhanced T(1) imaging contrast and anticancer activity. PMID- 20542332 TI - The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFbeta1-induced chondrogenesis of human mesenchymal stem cells. AB - Human bone marrow-derived mesenchymal stem cells (hMSCs) are promising cell candidates for cartilage regeneration. Building the appropriate microenvironment for cell differentiation in response to exogenous stimuli is a critical step towards the clinical utilization of hMSCs. In this study, the effects of RGD peptide immobilization onto macro-porous alginate scaffolds on TGF-beta1-induced hMSC chondrogenesis were evaluated. The results revealed different cell morphology, viability and proliferation extent in the RGD-immobilized vs. un modified scaffolds. The TGF-beta1-induced activation of both Smad-dependent (SMAD2) and Smad-independent (ERK1/2) signaling pathways was stronger and persisted for over 3 weeks in the RGD-immobilized scaffolds, indicating greater accessibility of the cells to the inducer. By contrast, in the un-modified alginate scaffolds, the cells aggregated into compacted clusters resulting in lesser effects of TGF-beta1. The efficient and prolonged exposure to the chondrogenic inducer in the RGD-modified scaffolds ensured the appropriate progression of MSC differentiation from the initial phase of cell condensation until the appearance of committed chondrocytes, at 3 weeks of cultivation. Taken together, our results highlight the fundamental importance of the microenvironment design of the scaffold as well as the presentation of the inductive cue for inducing efficient stem-cell controlled differentiation. PMID- 20542333 TI - Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta. AB - DLX3, a member of the large homeobox gene family of transcription factors, is necessary for normal placentation. Targeted deletion of dlx3 in mouse resulted in embryonic death due to placental failure. This study demonstrates the presence of DLX3 mRNA expression in human first trimester and term placental tissue, cultured trophoblast-like cell lines and in isolated primary villous and extravillous trophoblast cells. Using an ovine polyclonal antibody, the spatial distribution was identified for DLX3 in human placental tissues, trophoblast cell lines and in freshly isolated primary trophoblast cells. A 50 kDa immunoreactive DLX3 protein was detected in the human placenta, in trophoblast cell lines and in primary trophoblast cells. Nuclear expression for DLX3 was observed in villous cytotrophoblasts, syncytiotrophoblast and extravillous cytotrophoblast in the proximal regions of the cytotrophoblast cell columns in first trimester placental tissues. Immunoreactivity was also detected in few stromal cells and microvascular endothelial cells surrounding the fetal capillaries. In the first trimester placental bed, DLX3 expression was predominantly observed in the cytoplasm of the endovascular and interstitial trophoblasts. We conclude that the cellular expression of DLX3 was extensive in the human placenta and propose that DLX3 may play an important role in normal placental development. PMID- 20542334 TI - The gold compound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-kappaB activity. AB - Constitutive activation of NF-kappaB and STAT3 plays an important role in the cellular proliferation and survival of multiple myeloma cells. We first found that auranofin (AF), a coordinated gold compound, induced a significant level of cell cycle arrest at G1 phase and subsequent apoptosis of myeloma cells. Further, AF inhibited constitutive and IL-6-induced activation of JAK2 and phosphorylation of STAT3 followed by the decreased expression of Mcl-1. AF down-regulated the activation of NF-kappaB, and the combination of AF and a specific NF-kappaB inhibitor resulted in a marked decrease of Mcl-1 expression. These results suggest that AF inhibits both IL-6 induced-JAK/STAT pathway and NF-kappaB activation in myeloma cells. PMID- 20542335 TI - Synthesis, characterization, and protein tyrosine phosphatases inhibition activities of oxovanadium(IV) complexes with Schiff base and polypyridyl derivatives. AB - Seven new mixed-ligand vanadyl complexes, [V(IV)O(5-Br-SAA)(NN)] and [V(IV)O(2-OH NAA)(NN)] (1-7) (5-Br-SAA for 5-bromosalicylidene anthranilic acid, 2-OH-NAA for 2-hydroxy-1-naphthaldehyde anthranilic acid and NN for N,N'-donor heterocyclic base, namely, 2,2'-bipyridine (bpy, 1 and 5), 1,10-phenanthroline (phen, 2 and 6), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3 and 7), dipyrido[3,2-a:2',3' c]phenazine (dppz, 4)), were synthesized and characterized. X-ray crystal structure of [V(IV)O(5-Br-SAA)(phen)] revealed a distorted octahedral geometry with the Schiff base ligand coordinated in a tridentate ONO-fashion and the phenanthroline ligand in a bidentate fashion. Density-functional theory (DFT) calculations suggest a similar structure and the same coordination mode for all the other oxovanadium complexes synthesized. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), with IC(50) values approximately 41-75 nM. Kinetics assays suggest that the complexes inhibit PTP1B in a competitive manner. Notably, they had moderate selectivity of PTP1B over T-cell protein tyrosine phosphatase (TCPTP) (about 2-fold) and good selectivity over Src homology phosphatase 1 (SHP-1) (about 4 approximately 7-fold). Thus, these mixed-ligand complexes represent a promising class of PTP1B inhibitors for future development as anti-diabetic agents. PMID- 20542336 TI - Genetic and functional study of the IPO5 gene in schizophrenia. AB - The present work reported on a weak association of the importin 5 (IPO5) gene with schizophrenia in combined family and case-control samples and also investigated a possible mechanism by which the IPO5 gene may contribute to the development of the disease in a Chinese population. Our results suggest that abnormal expression and alternative splicing of the IPO5 gene may be involved in the pathophysiology of schizophrenia. PMID- 20542337 TI - Gene expression profiling in nerve biopsy of vasculitic neuropathy. AB - To investigate molecular mechanisms of peripheral nerve vasculitis, gene expression patterns in archived frozen sural nerve biopsies from patients with vasculitic neuropathy were compared to control nerves by DNA microarray technology. There was a striking upregulation of mRNA of genes involved in immune system processes. Of special interest was the activation of immunoglobulin genes, such as IGLJ3, IGHG3, IGKC, and IGL, and of several chemokines, such as CXCL9 or CCR2. Genes involved in vascular proliferation or remodelling such as CXC31 and AIF were also upregulated. Among the downregulated genes were the Kruppel-Like Transcription Factors KLF2, KLF4 and the nuclear orphan receptor NR4A1 genes known to be involved in endothelial cell activation. Thus, this gene expression profile analysis revealed that in peripheral nerve vasculitis a prominent activation of immune response related genes as well as genes involved in vascular proliferation is taken place, while genes inhibiting endothelial cell activation are down regulated. These data point to interesting mechanistic clues to the molecular pathogenesis of vasculitic neuropathies. PMID- 20542338 TI - Histopathological morphometric study of cochleosaccular dysplasia in Dalmatian dogs. AB - OBJECTIVE: To analyze temporal bones of deaf Dalmatian dogs from 5 days after birth to adulthood to better understand the pathogenesis of cochleosaccular dysplasia. METHODS: This is an experimental animal histopathological temporal bone study that included two groups of temporal bones. Group I consisted of 41 temporal bones from deaf Dalmatian dogs and group II of 25 temporal bones from 15 "normal" aged-matched, hearing Black Labradors. Morphometric analysis included: stria vascularis and spiral ligament area measurements, and cell counts of spiral ganglion, Scarpa's ganglion, and hair cells of saccular macula. RESULTS: The following findings were significantly less in deaf Dalmatian group compared to hearing Labradors: (1) cellular area of the stria vascularis in all cochlear turns; (2) cellular area of spiral ligament in the inferior part of the basal turn; (3) cellular density of spiral ganglion cells within segments III and IV; (4) number of Scarpa's ganglion cells; and (5) density of saccular hair cells types I and II. A borderline negative correlation was found between average density of spiral ganglion cells of segments III and IV and age in group I. Young deaf animals showed some cochlear hair cells, however in adult dogs all hair cells were replaced by supporting cells. CONCLUSION: General pattern of cochleosaccular dysplasia is variable, even when only one etiology, the genetic one, is involved. The gradual degeneration of inner ear elements in the cochleosaccular degeneration might indicate that early intervention might be crucial to stop the progression of cochleosaccular dysplasia. PMID- 20542339 TI - Screening for overt diabetes by oral glucose tolerance test: stratification by fasting blood glucose and patients' age improve practicability of guidelines in cardiological routine. AB - BACKGROUND/OBJECTIVES: Guidelines recommend screening all patients with cardiovascular disease by oral glucose tolerance test (OGTT). Due to its time consuming protocol, costs and overall inconvenience performance of OGTT is limited in cardiological routine. Thus, we aimed to identify easily available parameters that could help to reduce the numbers of OGTT needed. METHODS: OGTTs (n=1215) were performed in all patients without known type 2 diabetes mellitus (T2DM) that were submitted to the heart center Wuppertal with known or suspected coronary artery disease for an elective coronary angiography from January to October 2007. RESULTS: 31.4% had normal glucose tolerance; prediabetes was present in 50.7%, whereas 17.9% were newly diagnosed with T2DM. Thus, 998 OGTTs did not result in the new diagnosis of so far undiagnosed T2DM. Multiple logistic regression and receiver operated characteristic analyses demonstrated that fasting blood glucose (FBG)>= 90 mg/dl and age >= 55 years were predictive for so far undiagnosed T2DM. Considering these two parameters 81.1% (=sensitivity) of so far undiagnosed T2DM patients would have been identified (specificity=63.4%) and the number of OGTTs could have been reduced from 1215 to 541. CONCLUSIONS: About 70% of patients were newly diagnosed with impaired glucose metabolism. FBG >= 90 mg/dl and age >= 55 years were predictive for so far undiagnosed T2DM and OGTTs could be reduced by 55.5%. This should alleviate the implementation of the current guidelines in daily cardiological practice. PMID- 20542340 TI - The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans. AB - BACKGROUND: The R820W mutation in the MYBPC3 gene has been associated with the development of hypertrophic cardiomyopathy (HCM) in rag-doll cats, but had not been described in humans. AIMS: To describe the phenotype associated with the R820W mutation identified in a human family. METHODS: The R820W was identified by direct sequencing of the MYBPC3 gene in a 47 year old woman with HCM and left ventricular non-compaction (LVNC). Clinical and genetic studies of the R820W mutation were performed in her family. RESULTS: The index patient was homozygous for the mutation and had no additional mutations in the main sarcomeric genes (MYH7, TNNT2, TNNI3, and TPM1). She had HCM with LVNC and normal systolic function. One brother had died suddenly at age 43 years. Another brother diagnosed of LVNC with severe systolic dysfunction and a cardiac arrest was also homozygous for the mutation. One heterozygous 31 year old sister, and three heterozygous sons of the index (ages 14, 20 and 23 years old) were clinically unaffected. The father of the index was apparently healthy and her mother had atrial fibrillation and an electrocardiographic diagnosis of left ventricular hypertrophy at age 86 years. CONCLUSION: The R820W mutation in the MYBPC3 gene, previously associated with HCM in rag-doll cats, causes both HCM and LVNC in homozygous human carriers, with mild or null clinical expression in heterozygous carriers. PMID- 20542341 TI - Hyperuricemia predicts adverse outcomes in patients with heart failure. AB - BACKGROUND: Hyperuricemia is associated with worse outcomes of patients with chronic heart failure (HF). However, it is unknown in an unselected HF patients encountered in routine clinical practice. We thus assessed the impact of hyperuricemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with worsening HF. METHODS: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of hospitalized HF patients and the outcomes were followed for 2.1 years after discharge. Study cohorts (n=1869) were divided into 2 groups according to serum uric acid (UA) at discharge; >= 7.4 mg/dL (n=908) and <7.4 mg/dL (n=961). RESULTS: Of the total cohort of HF patients, 56% had hyperuricemia defined as UA >= 7.0mg/dl. Patients with UA >= 7.4 mg/dL had higher rates of all-cause death, cardiac death, rehospitalization, and all-cause death or rehospitalization due to worsening HF. After multivariable adjustment, higher UA levels were a significant and independent predictor for all cause death (adjusted hazard ratio [HR] 1.413, 95% confidence interval [CI] 1.094 1.824, P=0.008) and cardiac death (adjusted HR 1.399, 95% CI 1.020-1.920, P=0.037). CONCLUSIONS: Hyperuricemia was common in patients with HF encountered in clinical practice and higher UA was independently associated with long-term adverse outcomes in these patients. PMID- 20542342 TI - Competition and quality in health care markets: a differential-game approach. AB - We investigate the effect of competition on quality in health care markets with regulated prices taking a differential game approach, in which quality is a stock variable. Using a Hotelling framework, we derive the open-loop solution (health care providers set the optimal investment plan at the initial period) and the feedback closed-loop solution (providers move investments in response to the dynamics of the states). Under the closed-loop solution competition is more intense in the sense that providers observe quality in each period and base their investment on this information. If the marginal provision cost is constant, the open-loop and closed-loop solutions coincide, and the results are similar to the ones obtained by static models. If the marginal provision cost is increasing, investment and quality are lower in the closed-loop solution (when competition is more intense). In this case, static models tend to exaggerate the positive effect of competition on quality. PMID- 20542343 TI - Trend analysis of radiation therapy incidents over seven years. AB - PURPOSE: To examine incident rates in external beam radiation therapy (RT) as significant changes in technology were introduced. MATERIALS AND METHODS: From 2001 to 2007, several technological and practice enhancements were made. All treatment incident reports, including near misses (from 2004), were classified, under a research ethics board approval, according to type (prescription or geometry), cause (location, documentation, non-compliance, laterality, prescribed change, human error, planning/dosimetry, software/hardware malfunction, and accessory), and clinical impact (none, minor, moderate, and severe). Trend analysis was performed retrospectively. RESULTS: One thousand and sixty three reports were analyzed. The average incident rate per 100 RT course was 1.7+/-0.4; excluding near misses, this rate fell to 1.4+/-0.3. Both rates showed a downward trend. The occurrence of events due to treatment accessories (0.75-0.28), prescribed changes to treatment parameters (0.17-0.03), and location (0.41-0.17) have decreased, while documentation-related incidents have risen (0.03-0.37). The proportion of incidents is highest at the planning and treatment stages. CONCLUSION: Our analysis has shown that while technological and process enhancements can reduce certain error pathways, others can be created. Trends in incident rates have been assessed, indicating robustness of our practice in view of these changes. PMID- 20542344 TI - Evaluation of the radiobiological impact of anatomic modifications during radiation therapy for head and neck cancer: can we simply summate the dose? AB - BACKGROUND AND PURPOSE: Adaptive strategies in radiotherapy (RT) require the knowledge of the total dose given to every organ of the body. Because of anatomical changes and setup errors non-rigid registration is necessary to map the different dose fractions to a common reference. This study evaluates practically if the accumulation of all of these registered dose fractions must take radiobiology into account in a classical clinical setting. MATERIALS AND METHODS: Ten patients with head and neck tumors treated by chemo-RT were used. Contrast-enhanced CT scans were acquired prior and during RT following delivery of mean doses of 14.2, 24.5, 35.0 and 44.9 Gy and the planned pre-treatment helical tomotherapy sinograms were applied on the per-treatment CTs to create a series of per-treatment dose distributions corresponding to each per-treatment CT image. In order to calculate the cumulative dose distribution, the per-treatment dose maps were non-rigidly deformed by using the deformation map computed by a non-rigid registration. The deformed dose maps were then summed in two ways: one while taking radiobiology into account and one without. These two strategies were compared using clinical surrogates in the target volumes (TV) and in surrounding organs at risk (OAR). RESULTS: The differences between the strategies, while statistically significant (p<0.05), are clinically irrelevant. In the OARs, the mean differences stay in the 0.01-0.07 Gy range for the total dose. In the targets, all mean differences stay in the 0.001-0.012 Gy range. However, some local high difference spots appear leading to punctual errors as high as 2.5 Gy. CONCLUSION: If using current radiotherapy practices and clinical recommendations based on dose surrogates computed globally on OARs and TVs, one does not need to take radiobiological effects into account while accumulating total dose as these lead to very small differences compared to a simple accumulation technique consisting of a linear sum of the dose fractions. However, care must be taken if other adaptive strategies, based on local rather than global information, are used. PMID- 20542345 TI - Correlating quantitative MR measurements of standardized tumor lines with histological parameters and tumor control dose. AB - PURPOSE: To correlate non-invasively acquired radiobiologically relevant magnetic resonance (MR) parameters with functional histology and tumor control doses (TCD(50)). MATERIALS AND METHODS: The MR parameters relative perfusion, re oxygenation and lactate (Lac) concentration from eight human xenograft squamous tumor lines were compared with the histologically acquired pimonidazole hypoxic fraction, the perfused vessel area and TCD(50). RESULTS: Good spatial correlation in the parameter maps could be observed between the pimonidazole staining and tumor regions, which can be reoxygenated when breathing carbogen. A strong positive correlation (R=0.74) was found between whole tumor pimonidazole hypoxic fraction and re-oxygenation, as one would expect. A good correlation was also observed between Lac concentration and re-oxygenation (R=0.71) and between TCD(50) and re-oxygenation (R=0.64), whereas Lac and TCD(50) showed a moderate relation (R=0.44). The in vivo measurement of relative perfusion could be validated to reflect the perfused vessel area (R=0.63). No correlation was detected between perfusion and re-oxygenation or TCD(50). CONCLUSIONS: Lac and re oxygenation were shown to be pretreatment predictive markers independent from the pathophysiological changes induced during a fractionated course of radiotherapy. These parameters hold promise to be acquired non-invasively with results just a few minutes after measurement and to tailor radiotherapy to individual patterns of a tumor microenvironment. PMID- 20542346 TI - Phase I dose escalation trial of hypofractionated limited-field external beam thoracic radiotherapy for limited-stage small cell carcinoma of the lung. AB - PURPOSE: To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer. MATERIALS AND METHODS: Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose. RESULTS: Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules. CONCLUSIONS: The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions. PMID- 20542347 TI - Center-of-pressure regularity as a marker for attentional investment in postural control: a comparison between sitting and standing postures. AB - Postural control is a highly automatized basic activity that requires limited attentional investments. These investments have been shown to increase from balancing experts to controls, and from controls to persons with impaired postural control. Such between-subject comparisons led to a proposed direct relation between the regularity of center-of-pressure (COP) fluctuations and the amount of attention invested in posture. This study aims to expand this relation to a within-subject comparison of conditions that differ in balance demands. Specifically, more regular COP fluctuations were expected for standing than sitting, as stimulus-response reaction-time studies showed that the required attentional demands are lower for sitting than standing. COP registrations were made for fifteen healthy young adults in seated and standing postures. COP regularity was quantified with sample entropy. As expected, COP fluctuations were found to be more regular for standing than sitting, as evidenced by significantly lower sample entropy values. These findings expand the relation between COP regularity and the amount of attention invested in posture to postural tasks that vary in balance demands. An assessment of COP regularity may thus not only be instrumental in the examination of attentional investment in posture in between subject designs, but also for different postures in within-subjects designs. PMID- 20542349 TI - Non-Fickian transport in porous media with bimodal structural heterogeneity. AB - Tracer tailing in breakthrough curves in porous media with two distinct porosities is analyzed in terms of the dynamic responses of experimental fixed bed columns filled either with solid or porous beads. The flow is fast in the column interstitial space between beads (for both solid and porous beads) but slow within the porous beads that act as controlled 'traps' constituting an immobile zone. The transport is quantified using a Continuous Time Random Walk (CTRW) framework, which accounts for domains with controlled structural and flow heterogeneity associated with two distinct spatial and time spectra. We first demonstrate that breakthrough curves for a column containing solid glass beads exhibit non-Fickian transport, quantifiable both in fitting and validation mode by a CTRW based on a power law transition time distribution. We then examine breakthrough curves in the porous bead case, obtaining fits with a two-scale CTRW model that accounts explicitly for the two time spectra. Because the porous beads are uniform, tracer trapping within them is described by a simple first-order approximation trap model, with relatively weak capture and relatively faster release rates. The extent of tailing apparent in the porous bead breakthrough curves, due to the traps, can be quantitatively distinguished from the contribution to tailing due to mobile zone non-Fickian transport. A parameter study of the two-scale CTRW adds further insight into the dynamics of the process, showing the interaction between the advective non-Fickian transport and the mass exchange to immobile regions. PMID- 20542350 TI - In situ testing of metallic iron nanoparticle mobility and reactivity in a shallow granular aquifer. AB - This paper describes the results of a series of single well push-pull tests conducted to evaluate the in situ transport of carboxymethyl cellulose (CMC) stabilized nanoscale zero-valent iron (ZVI) particles in saturated sediments and their reactivity toward chlorinated ethenes. CMC-stabilized nanoscale ZVI particles were synthesized on site by reducing ferrous ions with borohydride in water in the presence of CMC. Nanoscale ZVI and bimetallic ZVI-Pd nanoparticle suspensions were prepared and injected into depth-discrete aquifer zones during three push-pull tests. The injected nanoparticle suspensions contained a conservative tracer (Br(-)) and were allowed to reside in the aquifer pore space for various time periods prior to recovery by groundwater extraction. The comparison between Br(-) and Fe concentrations in extracted groundwater samples indicated that the CMC-stabilized nanoscale ZVI particles were mobile in the aquifer but appeared to lose mobility with time, likely due to the interactions between particles and aquifer sediments. After 13 h in the aquifer, the nanoscale ZVI particles became essentially immobilized. During the push-pull test with injection of Fe-Pd nanoparticles, ethane concentrations increased from non detectable to 65 microg/L in extracted groundwater within less than 2 h of reaction time, indicating the rapid abiotic degradation of chlorinated ethenes. The amount of total chlorinated ethene mass destroyed was low presumably because the injected solutions "pushed" the dissolved chlorinated ethenes away from the injection well, without substantial mixing, and because stationary (sorbed) chlorinated ethene mass on the aquifer sediments was low. In situ remediation programs using highly reactive metallic nanoparticles should incorporate delivery methods that maintain high groundwater pore velocities during injection to increase advective transport distances (e.g. groundwater circulation wells). Also, source zones with abundant stationary contaminant mass that is accessible by advective transport should be targeted for remediation with the nanoparticles, as opposed to portions of dissolved plumes, in order to maximize the in situ destruction of contaminants. PMID- 20542351 TI - Effect of foliar application of antitranspirant on photosynthesis and water relations of pepper plants under different levels of CO2 and water stress. AB - Strategies such as foliar application of antitranspirants have the potential to regulate transpiration, but often, the limitation of CO(2) exchange as a result of reduced stomatal conductance can impair this beneficial effect. Elevated ambient [CO(2)] could significantly improve CO(2) diffusion while effectively reducing transpiration. In this experiment, we examined the response of sweet pepper (Capsicum annuum L.) to the foliar application of antitranspirant (AT) under two [CO(2)] (380 and 2000 micromol mol(-1)) and two drought intensities (4 or 8d without irrigation). The results showed that stomatal conductance and transpiration were reduced, while AT impaired photosynthesis at standard, but not at elevated [CO(2)] of fully irrigated plants. This effect was already apparent after 4d of drought. Drought had a minor impact on chlorophyll fluorescence (F(v)/F(m)). Additionally, root respiration was increased at elevated [CO(2)] but, after 8d of drought, it was higher for plants treated with AT than for non sprayed plants. Leaf water potential was affected more by drought at ambient compared to elevated [CO(2)], and, especially after 8d of drought, AT minimized the reductions in leaf water potential. Leaf concentrations of proline and starch were affected by both [CO(2)] and AT, especially after 8d of drought. Moreover, increasing [CO(2)] promoted the accumulation of starch, but led to decreases in the tissue concentrations of the soluble organic osmolytes, and hence diminished osmotic adjustment after 8d of water withholding, relative to ambient [CO(2)]. This study indicates that, in addition to the reported beneficial effect of elevated [CO(2)] on drought stress, AT could significantly improve drought tolerance in sweet pepper plants. PMID- 20542352 TI - Artificial neural networks modeling the in vitro rhizogenesis and acclimatization of Vitis vinifera L. AB - This study employs artificial neural networks (ANNs) to create a model to identify relationships between variables affecting the in vitro rhizogenesis and acclimatization of two cultivars of Vitis vinifera L. Albarino and Mencia. The effects of three factors (inputs), the type of cultivar, concentration and exposure time to indolebutyric acid (IBA), on the success of in vitro rhizogenesis and acclimatization were evaluated. The developed model, using ANNs software, was assessed using a separate set of validation data and was in good agreement with the observed results. Exposure time to IBA was found to have the dominant role in influencing the height of acclimatized plantlets. ANNs can be a useful tool for modeling different complex processes and data sets, in plant tissue cultures or, more generally, in plant biology. PMID- 20542353 TI - Screening at admission for carrier prevalence of multidrug-resistant organisms in resource-constrained settings: a hospital-based observational study. PMID- 20542354 TI - Clinical and economic outcomes of decreased fluconazole susceptibility in patients with Candida glabrata bloodstream infections. AB - BACKGROUND: The impact of reduced fluconazole susceptibility on clinical and economic outcomes in patients with Candida glabrata bloodstream infections (BSI) is unknown. METHODS: A retrospective cohort study was conducted to evaluate 30 day inpatient mortality and postculture hospital charges in patients with C glabrata BSI with decreased fluconazole susceptibility (minimum inhibitory concentration [MIC] >= 16 MUg/mL) versus fluconazole-susceptible C glabrata BSI (MIC <= 8 MUg/mL). These analyses were adjusted for demographics, comorbidities, and time at risk. Secondary analyses limited the C glabrata group with decreased fluconazole susceptibility to MIC >= 64 MUg/mL. RESULTS: There were 45 (31%) deaths among 144 enrolled patients: 19 deaths (25%) among 76 patients with C glabrata BSI with decreased fluconazole susceptibility and 26 deaths (38%) among 68 patients with fluconazole-susceptible C glabrata BSI. Decreased fluconazole susceptibility was not independently associated with increased 30-day inpatient mortality (adjusted odds ratio, .60; 95% confidence interval (CI): .26-1.35; P = 0.22) or hospital charges (multiplicative change in hospital charges, .93; 95% CI: .60-1.43; P = 0.73). Older age was associated with increased mortality and increased time at risk was associated with increased hospital charges. CONCLUSION: Crude mortality rates remain high in patients with C glabrata BSI. However, decreased fluconazole susceptibility was not associated with increased mortality or hospital charges. PMID- 20542355 TI - [Pneumorrhachis: a rare complication of an asthma episode]. PMID- 20542356 TI - [T(H)17 lymphocytes: induction, phenotype, functions, and implications in human disease and therapy]. AB - Differentiation of naive CD4(+) T helper (T(H)) cells is a major step of the adaptative immune response. When activated by pathogens in a specific cytokine environment, CD4(+) T cells differentiate into different subsets of T(H) cells with specific effector functions. T(H)1 lymphocytes orchestrate cellular immune response by producing interferon-gamma and stimulating cytotoxic cells whereas T(H)2 cells orchestrate humoral immune response by producing interleukin-4 (IL 4), IL-5 and IL-10, leading to immunoglobulin production. Conversely, regulatory T cells (Treg) are capable of inhibiting immune response. Recently discovered, T(H)17 cells are characterized by their ability to produce IL-17 and play an important role in anti-infectious and inflammatory immune responses. This review focuses on present knowledge about T(H)17 cells: their induction, phenotype, functions, implications in host defense and human disease, and their potential to represent possible therapeutic targets. PMID- 20542357 TI - [Nephrogenic systemic fibrosis]. AB - Nephrogenic systemic fibrosis is a recently described entity that occurs in patients with advanced renal failure. Its cause is probably toxic. The patients develop skin thickening, which is usually symmetrical on the limbs and sometimes extend to the trunk. Joint contractures and muscle sclerosis confine the patients to wheelchair. Systemic involvement may occur and includes cardiomyopathy, pulmonary fibrosis and diaphragmatic paralysis. The diagnosis is confirmed by the association of skin fibrosis and a cellular infiltration composed of CD34+ fibrocytes. Prognosis is severe with many deaths, rarely directly related to the disease. An improvement of lesions is possible, especially in case of resolution of the renal insufficiency. Several treatments have been evaluated, but none has shown consistent benefit. The toxic culprit is likely to be the gadolinium ions (Gd(+++)), released from some contrast agents used in nuclear magnetic resonance imaging. Evidence of the responsibility of Gd(+++) is based on epidemiologic, biochemical and experimental data. Recommendations have been published for patients with renal insufficiency requiring a nuclear magnetic resonance imaging. If they are followed and efficient, it is likely that nephrogenic systemic sclerosis will disappear. PMID- 20542358 TI - Cesium-137 contamination of oak (Quercus petrae Liebl.) from sub-mediterranean zone in South Bulgaria. AB - This study focuses on the cesium-137 ((137)Cs) contamination in grass and in different compartments of oak trees growing in ecosystems, located in the zone with sub-mediterranean climate in South Bulgaria, characterized with high summer temperatures, low precipitation and often periods of drought. In 2008, three experimental sites - PP1, PP2, PP3 - were sampled in oak ecosystems from Maleshevska Mountain at 900 m above sea level. Samples from grass species and oak tree leaves, branches with different diameter, wood disks and bark were analyzed for (137)Cs activity with gamma-spectrometry. The soil-to-plant transfer factor (TF) values for (137)Cs were estimated differentiating different tree compartments. Our findings showed relatively high activity concentrations of (137)Cs in oak trees even 22 years after the Chernobyl accident. The grass under oak was less contaminated compared with the oak trees. The different organs of oak trees could be distinguished according to the (137)Cs contamination as follows: bark>branches (d<1 cm)>leaves>branches (d>3 cm)>wood. The relatively higher contamination of bark compared with the new-formed biomass suggested that a significant part of (137)Cs was accumulated as a result of direct adsorption at the time of the main contamination event. The TF values obtained and the presence of (137)Cs in the branches, leaves and in the wood formed after 1986 confirmed that 22 years after the contamination, the main mechanism of (137)Cs entrance in tree biomass was the root uptake. PMID- 20542359 TI - The relationship between first-time mothers and care providers in the early postnatal phase: an ethnographic study in a Swiss postnatal unit. AB - OBJECTIVE: to consider the relationship between first-time mothers and care providers in an organisational context. DESIGN: an ethnographic approach was used to study the views and behaviours of providers and recipients of postnatal care. Fieldwork involved mainly conversations or qualitative interviews and observation. SETTING: a postnatal unit in a tertiary referral hospital in Switzerland. PARTICIPANTS: 10 child-bearing women and the care providers assigned to them. ANALYSIS: analysis of the data was organised using the women's expectations of care and the maternity unit's mission statement. Thematic analysis centred around two main themes: the experience of 'being on a postnatal journey' and 'caring relationships'. FINDINGS: the findings presented fall within the framework of the second theme. A caring relationship was established through 'weaving the net'. This relationship was then maintained through 'keeping the thread'. The relationship was eventually ended through 'finishing off'. KEY CONCLUSIONS: the quality of the caring relationship between a woman and a care provider influences satisfaction with received care. It determines the extent to which women feel in control of their situation at discharge. Organisational and professional factors influence this relationship, which in turn can influence a nurse's level of job satisfaction. IMPLICATIONS FOR PRACTICE: changes in the provision of postnatal care may involve organisational as well as clinical interventions to ensure continuous and consistent care. PMID- 20542360 TI - Dissipation gradients of phenanthrene and pyrene in the Rice rhizosphere. AB - An experiment was conducted to reveal the effects of rice cultivation as well as polycyclic aromatic carbohydrates (PAHs) degrading bacterium (Acinetobacter sp.) on the dissipation gradients of two PAHs (PHE and PYR) in the rhizosphere. The results showed that the presence of rice root and bacteria significantly accelerated the dissipation rate of PHE and PYR. The root exudates contributed to the formation of dissipation gradients of PHE and PYR along the vertical direction of roots, with a higher dissipation rate in the rhizosphere and near rhizosphere zone than the soil far away the rhizosphere. PMID- 20542361 TI - Effects of root anatomy and Fe plaque on arsenic uptake by rice seedlings grown in solution culture. AB - Hydroponic experiments were carried out to investigate the effects of root anatomy, induced by aeration and stagnation, and Fe plaque on arsenic (III&V) uptake and translocation by rice plants. The results showed that As uptake in rice plants (Gui Chao-2) treated by aeration was decreased due to lower root specific surface area. Rice roots with larger specific surface area tended to form more Fe plaque, and Fe plaque affected As uptake kinetics by changing As influx curves from linear to hyperbolic for As(III) and from hyperbolic to S curve for As(V). Fe plaque increased As(III&V) adsorption and minimized the effects of root anatomy characteristics on As uptake into roots and subsequently translocation to shoots. Fe plaque increased As(III) uptake rate at As(III) concentrations of 0.5 to approximately 8 mg L(-1), reduced As(V) uptake rate at low As(V) concentrations (<2 mg L(-1)), but increased As uptake rate at high As(V) concentrations (>6 mg L(-1)). PMID- 20542362 TI - Policy implications of a financial incentive programme to retain a physician workforce in underserved Japanese rural areas. AB - Existing evidence supports the effectiveness of a financial incentive policy for medical students and early-career physicians in return for obligatory rural service. But whether the experience of contractual rural service affects the physician's choice of practice location after the service is completed remains unknown. This study analysed the practice location of Jichi Medical University (JMU) graduates. JMU is a Japanese medical education programme with a contract system under which all graduates have an obligation to serve in underserved areas for about six years in exchange for a 6-year undergraduate tuition waiver. 484 JMU graduates who were under rural service in 2000 and had completed the service by 2006 were included in the study. The rurality of the communities was determined by population density quintiles. The proportion of those practicing in the communities with the highest rurality quintile in 2000 (30.8%) decreased dramatically (8.7%) in 2006, but the geographic distribution of the participants after contract was still biased toward rural areas compared with the distribution pattern of all Japanese physicians. The flow of participants from rural to urban communities was largely unidirectional. In 2006, 452 (93.4%) practiced in places with the same or lower rurality than in 2000, while only 32 (6.6%) practiced in places with higher rurality as compared to the placements of 2000. Multivariate analysis showed that service experience in the communities of the first and second highest quintiles of rurality was associated with choosing such places after contract, independent of known predictors of rural practice, such as having a rural background and primary care specialty choice. Although the effect of contractual rural service substantially decreased after finishing the service, the experience of rural service early in the physician's career had a positive impact on the later choice of a rural practice. The results from this study support the use of a policy that attracts early-career physicians to practice in rural areas. PMID- 20542363 TI - From targeted exemptions to user fee abolition in health care: experience from rural Zambia. AB - Poor access to health care is one of the greatest impediments to improved health in Africa. In Zambia, user fees are considered to be partly responsible for substantial disparities in access to health care. When the Government introduced user fees in 1993, considerable concern was expressed about the adverse effects on utilisation and access. A national exemption policy was designed to protect the poorest sections of the population. However, this was largely ineffective in reaching the majority of the eligible population. On January 13th, 2006, the President of Zambia announced a policy to abolish user fees at primary health care facilities in designated rural districts. This was a major policy shift from targeted exemptions to free primary health care across the board. This study reviewed the performance of free health care in Zambia, following 15 months of implementation. Using a comprehensive national facility-based dataset, we found that utilisation increased among the rural population aged at least five years by 55%. Importantly, utilisation increases were greatest in the districts with the highest levels of poverty and material deprivation. Further, our patient exit interview survey at facilities in two rural districts reveals that although there is some evidence of a strain on drug supplies, perceptions of quality of health care remain fairly positive. This is in contrast to the experience in other countries that have removed user fees. Our findings strongly suggest that fee removal is more effective than fragmented efforts to target exemptions to certain groups in providing protection against the financial consequences of using health services. PMID- 20542364 TI - Resource mobilization for health advocacy: Afro-Brazilian religious organizations and HIV prevention and control. AB - Brazil's national response to AIDS has been tied to the ability to mobilize resources from the World Bank, the World Health Organization, and a variety of donor agencies. The combination of favorable political economic opportunities and the bottom-up demands from civil society make Brazil a particularly interesting case. Despite the stabilization of the AIDS epidemic within the general Brazilian population, it continues to grow in pockets of poverty, especially among women and blacks. We use resource mobilization theories to examine the role of Afro Brazilian religious organizations in reaching these marginalized populations. From December 2006 through November 2008, we conducted ethnographic research, including participant observation and oral histories with religious leaders (N = 18), officials from the National AIDS Program (N = 12), public health workers from Rio de Janeiro (N = 5), and non-governmental organization (NGO) activists who have worked with Afro-Brazilian religions (N = 5). The mobilization of resources from international donors, political opportunities (i.e., decentralization of the National AIDS Program), and cultural framings enabled local Afro-Brazilian religious groups to forge a national network. On the micro level, in Rio de Janeiro, we observed how macro-level structures led to the proliferation of capacity-building and peer educator projects among these religious groups. We found that beyond funding assistance, the interrelation of religious ideologies, leadership, and networks linked to HIV can affect mobilization. PMID- 20542365 TI - Accurate reconstruction of discontinuous mandible using a reverse engineering/computer-aided design/rapid prototyping technique: a preliminary clinical study. AB - PURPOSE: To improve the reconstructive surgical outcome of a discontinuous mandibular defect, we used reverse engineering (RE), computer-aided design (CAD), and rapid prototyping (RP) technique to fabricate customized mandibular trays to precisely restore the mandibular defects. Autogenous bone grafting was also used to restore the bony continuity for occlusion rehabilitation. PATIENTS AND METHODS: Six patients who had undergone block resection of the mandible underwent reconstruction using a custom titanium tray combining autogenous iliac grafts. The custom titanium tray was made using a RE/CAD/RP technique. A virtual 3 dimensional model was obtained by spiral computed tomography scanning. The opposite side of the mandible was mirrored to cover the defect area to restore excellent facial symmetry. A bone grafting tray was designed from the mirrored image and manufactured using RP processing and casting. The mandibular defects were restored using the trays in combination of autologous iliac grafting. An implant denture was made for 1 of the 6 patients at 24 weeks postoperatively for occlusion rehabilitation. RESULTS: The trays fabricated using this technique fit well in all 6 patients. The reconstructive procedures were easy and time saving. Satisfactory facial symmetry was restored. No severe complications occurred in the 5 patients without occlusion rehabilitation during a mean 50-month follow-up period. The reconstruction in the patient with occlusion lasted for only 1 year and failed eventually because of bone resorption and infection. CONCLUSIONS: Mandibular reconstruction was facilitated using the RE/CAD/RP technique. Satisfactory esthetic results were achieved. However, the rigidity of the cast tray could cause severe stress shielding to the grafts, which could lead to disuse atrophy. Therefore, some modification is needed for functional reconstruction. PMID- 20542366 TI - Quality of life of patients with tongue cancer 1 year after surgery. AB - PURPOSE: To study the changes and factors affecting the quality of life (QOL) of patients with tongue cancer 1 year after primary surgery. PATIENTS AND METHODS: A total of 289 consecutive patients with tongue cancer who had undergone primary surgery from 2003 to 2008 at our hospital were recruited. Patient QOL was evaluated using the University of Washington Quality of Life Questionnaire, version 4. Statistical analysis was conducted using a paired-samples t test and multiple stepwise linear regression with Statistical Package for Social Sciences, version 11.5 (SPSS, Chicago, IL). RESULTS: At 1 year after surgery, the appearance, activity, speech, swallowing, shoulder function, salivary, and taste domain scores were significantly lower than the preoperative scores (P < .05). However, the pain, anxiety, and mood scores were significantly better 1 year after surgery (P < .05). The overall QOL had increased greatly 1 year after surgery but did not reach the pretreatment level. Multiple stepwise linear regression analysis showed that the main factors affecting QOL were radiotherapy, advanced clinical stage (P < .05), socioeconomic status, and patient age. Radiotherapy, advanced clinical stage (P < .05), socioeconomic status, and age (P < .05) were independently associated with QOL. CONCLUSIONS: The patients with tongue cancer who have been diagnosed and treated early might have a better QOL. A greater socioeconomic status can also improve the QOL of patients with tongue cancer after primary surgery. PMID- 20542367 TI - Histomorphologic and bone-to-implant contact evaluation of dual acid-etched and bioceramic grit-blasted implant surfaces: an experimental study in dogs. AB - PURPOSE: The objective of this study was to histologically evaluate a bioceramic grit-blasted and acid-etched surface (presenting calcium and phosphorous incorporation within the surface and its oxide) versus a dual acid-etched (no calcium and phosphorous, control) moderately rough implant surface in a dog tibia model. MATERIALS AND METHODS: Implants 3 x 10 mm were placed bilaterally along the proximal tibia of 6 Doberman dogs and remained for 2 and 4 weeks in vivo. After the dogs were euthanized, the implants were nondecalcified processed to approximately 30-microm-thick plates. Transmitted light optical microscopy was used to evaluate healing patterns and bone-to-implant contact. Statistical analysis was performed by 1-way analysis of variance at the 95% level of significance and by Tukey post hoc tests. RESULTS: At 2 weeks, histologic evaluation showed woven bone formation throughout the perimeter of both implant surfaces. However, replacement of woven bone by lamellar bone was only observed around the test surface at 4 weeks in vivo. No significant differences in bone-to implant contact were observed for the different groups (P > .27). CONCLUSION: Despite nonsignificant differences between bone-to-implant contact for the different surfaces and times in vivo, higher degrees of bone organization were observed for the test implants. Biomechanical testing is warranted to verify potential differences in biomechanical fixation effectiveness between surfaces. PMID- 20542368 TI - Expression of TGF-beta1, osteonectin, and BMP-4 in mandibular distraction osteogenesis with compression stimulation: reverse transcriptase-polymerase chain reaction study and biomechanical test. AB - PURPOSE: This study compared the levels of transforming growth factor-beta1 (TGF beta1), osteonectin, and bone morphogenetic protein-4 (BMP-4) expression in regenerated bone in a rabbit mandible that had undergone conventional distraction osteogenesis (DO) with those in regenerated bone from a modified DO technique with compression stimulation. MATERIALS AND METHODS: A total of 42 rabbits were used in this reverse transcriptase-polymerase chain reaction study. In the control group, distraction was performed at 1 mm/day for 8 days. In the experimental group, overdistraction was performed for 10 days, followed by a 3 day latency period and 2 days of compression to achieve the same amount of DO. Three rabbits per subgroup were killed at 0, 5, 13, 20, 27, 34, and 41 days after the initial osteotomy. The levels of TGF-beta1, osteonectin, and BMP-4 in the bone regenerates were measured by reverse transcriptase-polymerase chain reaction. A biomechanical microhardness test was also performed in 8 rabbits as a separate experiment. RESULTS: Reverse transcriptase-polymerase chain reaction revealed a greater level of TGF-beta1 in the experimental group immediately after applying the compression force that continued for 2 weeks. The level then decreased to that of the control group at 3 weeks. The greater level of osteonectin in the experimental group after compression than that in the control group continued for 3 weeks. In the experimental group, the level of BMP-4 increased immediately after compression. However, the level in the control group decreased. The microhardness ratio of distracted bone to normal bone on the cortex was statistically different at 0.47 in the control group and 0.80 in the experimental group (P = .049) at 55 days after osteotomy. CONCLUSION: The effectiveness of the new DO technique with compression stimulation was confirmed by the gene expression study and the biomechanical test findings. PMID- 20542369 TI - Applications of 3-dimensional virtual computerized tomography technology in oral and maxillofacial surgery: current therapy. AB - With the recent introduction of in-office cone-beam volumetric tomography scanners and the development of computed tomographic-based proprietary third party 3-dimensional dental implant software programs, the field of implant dentistry is moving toward the 3-dimensional evaluation and placement of dental implants according to a restoratively driven treatment plan. The goal is to place the dental implant according to where the final dental restoration will be fabricated. The precision, accuracy, and 3-dimensional visualization capabilities of these technologies open avenues for the oral and maxillofacial surgeon in the diagnosis, planning, and surgical management of many nonimplant-related cases. The combination of these technologies is useful in expanding our information in dentoalveolar, preprosthetic, trauma, pathology and reconstruction, orthognathic and craniofacial, and cosmetic esthetic implant surgical cases. This article discusses the use of these technologies in the practice of oral and maxillofacial surgery. PMID- 20542370 TI - White matter integrity and pictorial reasoning in high-functioning children with autism. AB - The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response times (RT) on a pictorial reasoning task under three conditions: visuospatial, V, semantic, S, and V+S, a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion weighted images were collected from HFA and CTRL participants, matched on age and IQ, and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (S) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL. Performance in visuospatial reasoning (V, V+S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL. Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically developing children, whereas autistic cognition may rely more on visuospatial processing networks. PMID- 20542372 TI - A numerical study of the evolution of the blast wave shape in tunnels. AB - When the explosion of condensed materials occurs in a tunnel, the subsequent blast wave reveals two patterns. The region close to the explosive charge exhibits a free-field overpressure decay pattern and the region far from the explosion, which undergoes much less overpressure decay, exhibits a quasi-one dimensional pattern. Well-known overpressure decay laws that are applicable in each region already exist. In order to assess the validity range of each of these laws, the blast wave due an explosion inside a typical confined geometry is examined in order to determine the position of the transition zone from the free pattern to the one-dimensional pattern. To this end, the detonation of different quantities of explosive charges was simulated inside a tunnel with a constant cross-sectional area, and the wave aspect was determined for each region. This paper proposes a correlation law that defines the transition distance according to the explosive charge's weight and material and the geometry of the propagating domain. The validity of the proposed correlation law is corroborated by experimental results. In the authors' opinion, this law may be helpful for rapidly and efficiently drawing up the blast wave damage map. PMID- 20542371 TI - What can solid state NMR contribute to our understanding of protein folding? AB - Complete understanding of the folding process that connects a structurally disordered state of a protein to an ordered, biochemically functional state requires detailed characterization of intermediate structural states with high resolution and site specificity. While the intrinsically inhomogeneous and dynamic nature of unfolded and partially folded states limits the efficacy of traditional X-ray diffraction and solution NMR in structural studies, solid state NMR methods applied to frozen solutions can circumvent the complications due to molecular motions and conformational exchange encountered in unfolded and partially folded states. Moreover, solid state NMR methods can provide both qualitative and quantitative structural information at the site-specific level, even in the presence of structural inhomogeneity. This article reviews relevant solid state NMR methods and their initial applications to protein folding studies. Using either chemical denaturation to prepare unfolded states at equilibrium or a rapid freezing apparatus to trap non-equilibrium, transient structural states on a sub-millisecond time scale, recent results demonstrate that solid state NMR can contribute essential information about folding processes that is not available from more familiar biophysical methods. PMID- 20542373 TI - Voltammetric monitoring photodegradation of EDTA based on carbon nanotubes modified electrode. AB - This work described a fast and sensitive voltammetric method developed for monitoring the photodegradation of ethylenediaminetetraacetic acid (EDTA). Due to the unique properties of carbon nanotubes (CNTs) such as negative charges, large surface area and excellent electron transfer ability, metal ion namely Fe(3+) showed a pair of well-defined redox response peaks on the CNTs-modified electrode. When EDTA was present in the solution, the voltammetric response of Fe(3+) was suppressed due to the chelating interaction between Fe(3+) and EDTA. In acetate buffer solution, the concentration of EDTA was found to be inversely proportional to the decreased cathodic peak current in the range of 1.0x10(-6) to 1.0x10(-4) mol/L with a detection limit (3S/N) of 6.5x10(-7) mol/L. While EDTA was degraded by UV irradiation, the voltammetric response on the CNTs-modified electrode was enhanced due to the reduced amount of EDTA species chelating with Fe(3+). Accordingly, the concentration variation of EDTA during the photodegradation was analyzed. The effects of H(2)O(2) and pH on the photodegradation of EDTA were investigated. Thus, the proposed CNTs-based voltammetry provided a useful analytical tool for studying the degradation of EDTA. PMID- 20542374 TI - The separation of uranium ions by natural and modified diatomite from aqueous solution. AB - In this work the natural and the surfactant modified diatomite has been tested for ability to remove uranium ions from aqueous solutions. Such controlling factors of the adsorption process as initial uranium concentration, pH, contact time and ionic strength have been investigated. Effect of ionic strength of solution has been examined using the solutions of NaCl, Na(2)CO(3) and K(2)SO(4). The pseudo-first order and the pseudo-second order models have been used to analyze the adsorption kinetic results, whereas the Langmuir and the Freundlich isotherms have been used to the equilibrium adsorption data. The effects of the adsorbent modification as well as uranium adsorption on the diatomite surface have been studied using X-ray powder diffraction, scanning electron microscopy and FTIR spectroscopy. The maximum adsorption capacities of the natural and the modified diatomite towards uranium were 25.63 micromol/g and 667.40 micromol/g, respectively. The desorptive solutions of HCl, NaOH, Na(2)CO(3), K(2)SO(4), CaCO(3), humic acid, cool and hot water have been tested to recover uranium from the adsorbent. The highest values of uranium desorption (86%) have been reached using 0.1M HCl. PMID- 20542375 TI - Photocatalytic dechlorination of PCB 138 using leuco-methylene blue and visible light; reaction conditions and mechanisms. AB - A study of dechlorination of PCB 138, under visible light employing methylene blue (MB) and triethylamine (TEA) in acetonitrile/water has been conducted to investigate the details of the mechanism of dechlorination and to determine the efficiency of the process for this representative congener. Two other amines, N methyldiethanolamine (MEDA) and (triethanolamine) TEOA also replaced TEA and two other solvents, methanol and ethanol replacing acetonitrile were examined for effects on reaction rates. The results show that PCB 138 can be dechlorinated efficiently in this photocatalytic reaction. Clarifying ambiguities in several previous reports, the reduced form of MB, leuco-methylene blue (LMB) was identified as responsible for the photoreaction with its excited state transferring an electron to PCBs; oxidized LMB (i.e. MB) is reduced back to LMB by the excess amine present. The reaction depends on a cycle driven by the amine as a sacrificial electron donor. MEDA proved to be the most efficient electron donor; apparently in consequence of the most favourable steady state concentration of LMB. Methanol and ethanol may be used to replace acetonitrile with little change in the efficiency of the reaction. PMID- 20542376 TI - Selective separation of radio-cesium from acidic solutions using supported liquid membrane containing chlorinated cobalt dicarbollide (CCD) in phenyltrifluoromethyl sulphone (PTMS). AB - A supported liquid membrane method was developed using chlorinated cobalt dicarbollide (CCD) in phenyltrifluoromethyl sulphone (PTMS) as the carrier, impregnated in PTFE flat sheet membranes for the selective separation of Cs(I) from nitric acid feed solution. Solvent extraction studies were carried out for optimizing the feed as well as strip conditions. >95% Facilitated transport of Cs(I) was observed in about 3h when 1M HNO(3) and 8M HNO(3) were used as the feed and strip solutions, respectively while 0.025M CCD in PTMS was used as the carrier extractant. Selectivity studies, carried out using a mixture of radiotracers viz. (51)Cr, (59)Fe, (99)Mo, (99m)Tc, (106)Ru, (137)Cs, (152)Eu and (241)Am, indicated selective transport of Cs(I) with DF values >100. Though reproducibility of the transport data was excellent when carried out in two successive transport experiments with freshly loaded carrier solvent, the stability of the membrane was poor which restricts its long term use. PMID- 20542377 TI - Effects of three amendments on extractability and fractionation of Pb, Cu, Ni and Sb in two shooting range soils. AB - Contamination of shooting range soils with toxic trace elements, in particular Pb and Sb, is of increasing environmental concern worldwide. We studied the extractability of Sb, and other metals in two shooting range soils: a calcareous soil (pH 8) with low organic carbon (0.5%) and a non-calcareous soil (pH 6.3) with elevated organic carbon content (5%). Both soils contained total concentrations of around 500 mg kg(-1) Pb, 65 mg kg(-1) Cu, 100 mg kg(-1) Zn and 20 mg kg(-1) Sb. We tested the effects of Ca(OH)(2), phosphate and sodium humate amendments on metals and Sb extractability. Extracts with H(2)O and NaNO(3) contained 0.02-0.05% of the total Zn and Pb; 0.1-0.5% of total Ni and Cu and approximately 1% of total Sb. Sequential extraction procedure of Zeien and Brummer resulted in similar percentages for the sum of the two most labile fractions (F1+F2) in two soils: 10% Pb, and 15-20% Sb. Water and NaNO(3) extractable Sb concentrations increased after phosphate addition, but were not affected by the addition of sodium humate. The results show that leaching of Sb from shooting ranges into ground and surface waters may generate a serious environmental risk under widely different soils conditions. PMID- 20542378 TI - Simultaneous removal of heavy-metal ions in wastewater samples using nano-alumina modified with 2,4-dinitrophenylhydrazine. AB - 2,4-Dinitrophenylhydrazine (DNPH) immobilized on sodium dodecyl sulfate coated nano-alumina was developed for the removal of metal cations Pb(II), Cd(II), Cr(III), Co(II), Ni(II) and Mn(II) from water samples. The research results displayed that adsorbent has the highest adsorption capacity for Pb(II), Cr(III) and Cd(II) in ions mixture system. Optimal experimental conditions including pH, adsorbent dosage and contact time have been established. Langmuir and Freundlich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data was given by the Freundlich adsorption isotherm equation for Mn(II), Pb(II), Cr(III) and Cd(II) ions and by Langmuir isotherm equation for Ni(II) and Co(II) ions. Desorption experiments by elution of the adsorbent with a mixture of nitric acid and methanol show that the modified alumina nanoparticles could be reused without significant losses of its initial properties even after three adsorption-desorption cycles. Thus, modified nano-alumina with DNPH is favorable and useful for the removal of these metal ions, and the high adsorption capacity makes it a good promising candidate material for Pb(II),Cr(III) and Cd(II) removal. PMID- 20542379 TI - TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. AB - Somatosensory neurons detect environmental stimuli, converting external cues into neural activity that is relayed first to second-order neurons in the spinal cord. The detection of cold is proposed to be mediated by the ion channels TRPM8 and TRPA1. However, there is significant debate regarding the role of each channel in cold-evoked pain, complicating their potential as drug targets for conditions such as cold allodynia and hyperalgesia. To address this debate, we generated mice lacking functional copies of both channels and examined behaviors and neural activity in response to painful cold and noxious cooling compounds. Whereas normal mice display a robust preference for warmth over cold, both TRPM8-null (TRPM8(-/-)) and TRPM8/TRPA1 double-knockout mice (DKO) display no preference until temperatures reach the extreme noxious range. Additionally, in contrast to wildtype mice that avoid touching cold surfaces, mice lacking TRPM8 channels display no such avoidance and explore noxious cold surfaces, even at 5 degrees C. Furthermore, nocifensive behaviors to the cold-mimetic icilin are absent in TRPM8(-/-) and DKO mice, but are retained in TRPA1-nulls (TRPA1(-/-)). Finally, neural activity, measured by expression of the immediate-early gene c-fos, evoked by hindpaw stimulation with noxious cold, menthol, or icilin is reduced in TRPM8( /-) and DKO mice, but not in TRPA1(-/-) animals. Thus our results show that noxious cold signaling is exclusive to TRPM8, mediating neural and behavioral responses to cold and cold-mimetics, and that TRPA1 is not required for acute cold pain in mammals. PMID- 20542380 TI - Nanometer-resolution electron microscopy through micrometers-thick water layers. AB - Scanning transmission electron microscopy (STEM) was used to image gold nanoparticles on top of and below saline water layers of several micrometers thickness. The smallest gold nanoparticles studied had diameters of 1.4 nm and were visible for a liquid thickness of up to 3.3 microm. The imaging of gold nanoparticles below several micrometers of liquid was limited by broadening of the electron probe caused by scattering of the electron beam in the liquid. The experimental data corresponded to analytical models of the resolution and of the electron probe broadening as function of the liquid thickness. The results were also compared with Monte Carlo simulations of the STEM imaging on modeled specimens of similar geometry and composition as used for the experiments. Applications of STEM imaging in liquid can be found in cell biology, e.g., to study tagged proteins in whole eukaryotic cells in liquid and in materials science to study the interaction of solid:liquid interfaces at the nanoscale. PMID- 20542381 TI - Epidemiological survey and molecular characterization of Echinococcus granulosus in cattle in an endemic area of eastern Turkey. AB - Cystic echinococcosis (CE) is a zoonotic disease affecting mainly various species of livestock and humans. A survey of cystic echinococcosis in cattle was conducted from December 2008 to April 2009 in an endemic area of eastern Turkey. A total of 1758 cattle were examined and hydatid cysts were found in 33.9% of the cattle (595/1758). Most of the cattle (75.8%) had hydatid cysts only in the lungs, 10.9% only in the liver, 12.4% in the both liver and lungs, 0.7% in the spleen and 0.2% in the heart. 220 of these cysts were examined by PCR of 12S rRNA gene and sequencing of mt-CO1 gene. 147 of 220 cattle isolates showed the same band pattern with 12S rRNA analyses and were identified as G1-G3 complex (Echinococcus granulosus sensu stricto) and also 28 of these were confirmed by mitochondrial CO1 sequencing as G1 genotype. The other 73 samples that did not amplified with 12S rRNA gene specific primers were analyzed for mt-CO1 gene and only 7 samples yielded 446bp product and after the CO1 sequencing these were identified as G3 genotype. This study confirms the predominance of the sheep strain (G1 genotype) in Turkey and this is the most comprehensive genetic survey of cattle CE in Turkey. PMID- 20542382 TI - A Bayesian evaluation of two dip-stick assays for the on-site diagnosis of infection in calves suspected of clinical giardiasis. AB - The objective of the present study was to evaluate two commercially available dip stick assays for the diagnosis of Giardia infections in faecal samples from calves suspected of clinical giardiasis. The dip-stick assays provide an on-site and hence quick alternative to laboratory diagnosis. A three-test Bayesian model was used, including the test results of the Coris Giardia strip (Coris Bioconcept, Gembloux, Belgium), the Speed Giardia or BVT dip-stick (Bio Veto Test/Virbac, La Seyne sur Mer, France), and the Meridian immunofluorescence assay (IFA: Meridian Diagnostics Inc., Cincinnati, OH). In total, 421 faecal samples were examined with the three diagnostic assays between October 2008 and November 2009. Overall, the number of positive samples was markedly higher using the IFA compared to both dip-stick assays, resulting in a high sensitivity (se: 88%, with a 95% probability interval (PI) 60-99%) compared to the Coris dip-stick assay (se: 28%; PI: 16-41%) and the BVT dip-stick assay (se: 26%, PI: 16-35). The specificities of all the three assays were very high (IFA sp: 94%, PI: 90-99%; Coris sp: 92%, PI 86-98%; BVT sp: 93%, PI 88-98%). A positive diagnosis by the dip-stick assays was significantly correlated with a higher cyst excretion level, as measured by IFA. The majority (76%) of the positive samples in the present study contained less than 5000cyst per gram of faeces, even though all these animals displayed clinical symptoms of diarrhea potentially due to Giardia. The low level of cyst excretion in these samples might in part explain the poor sensitivity of both dip-stick assays. Although multiple samplings might be an option to increase the sensitivity of the dip-stick assays, the laboratory based IFA seems at current to be the best option for clinical diagnosis of Giardia in calves. PMID- 20542383 TI - Temporal changes of smoking status and motivation among Chinese heroin-dependent, methadone-maintained smokers. AB - INTRODUCTION: The rates of cigarette smoking remain extremely high in active heroin users and methadone-maintained patients. It remains undetermined whether smoking status and motivation would be differentially affected by heroin and methadone administration. METHODS: Heroin-dependent, methadone-maintained patients were recruited in the present studies. A battery of self-report questionnaires was used in the current study, in order to assess smoking status and motivations before first heroin use, during active heroin use and after Methadone Maintenance Treatment (MMT) admission. RESULTS: An extremely high portion of participants started smoking before first heroin use. The highest level of cigarette smoking was found during the period of active heroin use, and cigarette consumption was reported to decrease after MMT admission. A wide range of smoking motivations were found before first heroin use. Moreover, "maintaining heroin pleasure" was the primary motivation for the increase in cigarette consumption during the period of active heroin use and 1h after heroin administration, while "habitual smoking" was the primary smoking motivation before first heroin use and after MMT admission respectively. CONCLUSIONS: The present study first demonstrated that the prolonged rewarding effect of heroin following cigarette smoking may account for the increase of nicotine consumption found in the heroin-dependent patients. It appears that heroin and methadone differentially influenced smoking status and motivation among heroin-dependent, methadone-maintained patients. PMID- 20542385 TI - Dose-volume histogram parameters and clinical factors associated with pleural effusion after chemoradiotherapy in esophageal cancer patients. AB - PURPOSE: To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT). METHODS AND MATERIALS: Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose >= 50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving >= 10-60 Gy (Heart-V(10) to V(60) and Lung-V(10) to V(60), respectively) were analyzed in relation to pleural effusion. RESULTS: The median follow-up time was 26.9 months (range, 6.7-70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V(10) to V(60), and Lung-V(50) to V(60) were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age >= 65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V(50) as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V(50) <20%, 20%<= Heart V(50) <40%, and Heart-V(50) >= 40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01). CONCLUSION: Heart-V(50) is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion. PMID- 20542386 TI - Regional nodal involvement and patterns of spread along in-transit pathways in children with rhabdomyosarcoma of the extremity: a report from the Children's Oncology Group. AB - PURPOSE: To evaluate the incidence and prognostic factors for regional failure, with attention to the in-transit pathways of spread, in children with nonmetastatic rhabdomyosarcoma of the extremity. METHODS AND MATERIALS: The Intergroup rhabdomyosarcoma studies III, IV-Pilot, and IV enrolled 226 children with rhabdomyosarcoma of the extremity. Failure at the in-transit (epitrochlear/brachial and popliteal) and proximal (axillary/infraclavicular and inguinal/femoral) lymph nodes was evaluated. The median follow-up for the surviving patients was 10.4 years. RESULTS: Of the 226 children, 55 (24%) had clinical or pathologic evidence of either in-transit and/or proximal lymph node involvement at diagnosis. The actuarial 5-year risk of regional failure was 12%. The prognostic factors for poor regional control were female gender and lymph node involvement at diagnosis. In the 116 patients with a distal extremity primary tumor, 5% had in-transit lymph node involvement at diagnosis. The estimated 5-year incidences of in-transit and proximal nodal failure was 12% and 8%, respectively. The in-transit failure rate was 0% for patients who underwent radiotherapy and/or underwent lymph node sampling of the in-transit nodal site but was 15% for those who did not (p = .07). However, the 5-year event-free survival rate did not differ between these two groups (64% vs. 55%, respectively, p = .47). CONCLUSION: The high incidence of regional involvement necessitates aggressive identification and treatment of regional lymph nodes in patients with rhabdomyosarcoma of the extremity. In patients with distal extremity tumors, in transit failures were as common as failures in more proximal regional sites. Patients who underwent complete lymph node staging with appropriate radiotherapy to the in-transit nodal site, if indicated, were at a slightly lower risk of in transit failure. PMID- 20542387 TI - In regards to Barkati et al. (Int J Radiat Oncol Biol Phys 2010;76:410-416). PMID- 20542388 TI - Obesity increases the risk of chest wall pain from thoracic stereotactic body radiation therapy. AB - PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat thoracic tumors. We attempted here to identify dose-volume parameters that predict chest wall toxicity (pain and skin reactions) in patients receiving thoracic SBRT. PATIENTS AND METHODS: We screened a database of patients treated with SBRT between August 2004 and August 2008 to find patients with pulmonary tumors within 2.5 cm of the chest wall. All patients received a total dose of 50 Gy in four daily 12.5-Gy fractions. Toxicity was scored according to the NCI CTCAE V3.0. RESULTS: Of 360 patients in the database, 265 (268 tumors) had tumors within <2.5 cm of the chest wall; 104 (39%) developed skin toxicity (any grade); 14 (5%) developed acute pain (any grade), and 45 (17%) developed chronic pain (Grade 1 in 22 cases [49%] and Grade 2 or 3 in 23 cases [51%]). Both skin toxicity and chest wall pain were associated with the V30, or volume of the chest wall receiving 30 Gy. Body mass index (BMI) was also strongly associated with the development of chest pain: patients with BMI>=29 had almost twice the risk of chronic pain (p=0.03). Among patients with BMI>29, diabetes mellitus was a significant contributing factor to the development of chest pain. CONCLUSION: Safe use of SBRT with 50 Gy in four fractions for lesions close to the chest wall requires consideration of the chest wall volume receiving 30 Gy and the patient's BMI and diabetic state. PMID- 20542389 TI - Response to "The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population-based study on 17,845 patients." (Int J Radiat Oncol Biol Phys 2010;76:342-348). PMID- 20542391 TI - Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial. AB - BACKGROUND: Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting. METHODS: Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date. RESULTS: The difference in weight at 26 weeks post quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs +/- 8.94 vs placebo: 9.7 lbs +/- 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43). CONCLUSIONS: For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence. PMID- 20542392 TI - Longitudinal serological and virological study on porcine torovirus (PToV) in piglets from Spanish farms. AB - A study was performed to evaluate porcine torovirus (PToV) seroprevalence and infection in three multi-site farms from the North-eastern region of Spain. Serum samples from 120 piglets and faecal samples from 36 piglets were longitudinally collected at 1, 3, 7, 11 and 15 weeks of age. Serum samples from their dams (n=30) were also taken 1-week post-farrowing. PToV antibodies in serum were monitored by ELISA, while viral infection was assessed by real-time RT-PCR in faeces. A high seroprevalence (about 100%) was observed in animals older than 11 weeks and in adult sows. Moreover, all 1-week-old animals were seropositive, indicating maternal antibody transference through colostrum. The antibody titers declined to close to or below the ELISA cut-off value by the age of weaning (3 weeks of age). Development of a significant antibody response to PToV occurred before 7 weeks of age in about 50% of piglets, and the remaining animals developed the response by weeks 11 or 15. These results indicate that PToV infection occurred soon after weaning. Although the prevalence of infection in suckling piglets varied among the studied farms, PToV prevalences in 7 and 11 week-old pigs were between 50-67% and 58-75%, respectively, in all farms. Sequencing results indicated that more than one PToV strains were circulating in the studied farms. Present data suggest that PToV was endemic on the studied farms, and provide new insights on the epidemiology of PToV. PMID- 20542393 TI - Genetic diagnosis and acetazolamide treatment of familial hemiplegic migraine. AB - A female patient presented with horizontal gaze nystagmus, mild cerebellar ataxia, recurrent headache and hemiplegia since childhood with cerebellar atrophy on magnetic resonance imaging. Genetic analysis revealed a CACNA1A gene mutation, leading to a diagnosis of familial hemiplegic migraine (FHM1). FHM is very rare, but should be considered as a differential diagnosis for childhood cerebellar symptoms and/or cerebellar atrophy. To avoid missing FHM1, a detailed clinical history including headache or hemiplegia is essential. Oral acetazolamide during the aura phase, comprising mild headache and abnormal leg sensation, relieved these symptoms in this patient, suggesting that acetazolamide could represent a first line of treatment. PMID- 20542394 TI - A humanoid mouse model of autism. AB - Even now fruit of the human genome project is available, we have difficulties to approach neuropsychiatric disorders at the molecular level. Autism is a complex psychiatric illness but has received considerable attention as a developmental brain disorder not only from basic researchers but also from society. Substantial evidence suggests that chromosomal abnormalities contribute to autism risk. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We succeeded to generate mice with a 6.3-Mb wide interstitial duplication in mouse chromosome 7c that is highly syntenic to human 15q11-13 by using a Cre-loxP-based chromosome-engineering technique. The only paternally duplicated mice display autistic behavioral features such as poor social interaction and stereotypical behavior, and exhibit a developmental abnormality in ultrasonic vocalizations as well as anxiety. The detailed analysis focusing on a non-coding small nucleolar RNA, MBII52, within the duplicated region, revealed that the paternally duplicated mice alter the editing ratio of serotonin (5-HT) 2c receptor pre-mRNA and intracellular calcium responses by a 5 HT2c receptor specific agonist are changed in neurons. This result may explain one of molecular mechanisms of abnormal behaviors in the paternal duplicated mice. The first chromosome-engineered mouse model for human chromosome 15q11-13 duplication fulfills not only face validity of human autistic phenotypes but also construct validity based on human chromosome abnormality. This model will be a founder mouse for forward genetics of autistic disease and an invaluable tool for its therapeutic development. PMID- 20542395 TI - Frequent association of autism spectrum disorder in patients with childhood onset epilepsy. AB - Autism spectrum disorder (ASD) has a close relationship with epilepsy. This study retrospectively examined patients with epilepsy associated with ASD. Among the 519 patients with epilepsy, 79 patients (15.2%) had ASD. Sixty-two patients had idiopathic ASD and 17 had secondary ASD. The epilepsy patients with idiopathic ASD were retrospectively analyzed. There were 47 males and 15 females, ranging from 2 to 43 years of age (median 11 years). The most frequent age at the onset of seizures was 4 years, and 85% occurred before 10. ASD was detected after the onset of epilepsy in 29 cases (46.8%), and eight of them had been overlooked for more than five years. Most of these were high-functioning ASD cases. The most frequent type of seizure was a complex partial seizure (CPS; 68%). Paroxysmal activities on EEG were localized in the frontal area in about half of the cases. Multiple anti-epileptic drugs were used in 33.8% cases (two in 17.7%, three in 16.1%), and 67.3% of the patients were seizure-free for more than two years. An amelioration of the autistic symptoms occurred after epilepsy treatment in five cases (8%). CPS with frontal paroxysms occurring from one to nine years of age seems to be characteristic of epilepsy associated with ASD. PMID- 20542396 TI - Development of a LC-MS/MS method for the determination of antrodin B and antrodin C from Antrodia camphorata extract in rat plasma for pharmacokinetic study. AB - A selective and sensitive liquid chromatography-tandem mass spectrometry (LC MS/MS) method was developed and validated for the determination of antrodin B and antrodin C in rat plasma. Both target compounds, together with the internal standard (diazepam), were extracted from rat plasma samples by liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an Agilent XDB-C(8) column with an isocratic mobile phase consisting of acetonitrile and water (70:30, V/V) at a flow rate of 0.5 mL/min. The mass spectrometric detection was performed by selected reaction monitoring (SRM) mode via atmospheric pressure chemical ionization (APCI) source operating in positive ionization mode. The assay exhibited a linear dynamic range of 47.6-4760 ng/mL for antrodin B and 56.6-5660 ng/mL for antrodin C. The intra- and inter-day precision was less than 5.3% and the accuracy was less than 2.7% for both analytes. The validated method has been applied to the pharmacokinetic study of antrodin B and antrodin C in rats following oral administration of Antrodia camphorata extract. PMID- 20542397 TI - Pneumopericardium with cardiac tamponade as a complication of cardiac pacemaker insertion one year after procedure. AB - BACKGROUND: Lead dislodgement has been shown to be the most common complication in the first 30 days after pacemaker insertion. Although it is rare, pneumopericardium with tamponade can also result. OBJECTIVES: We present a case of an extremely rare delay from cardiac pacemaker insertion to lead migration with resulting pneumopericardium and cardiac tamponade. CASE REPORT: A 65-year old woman with a past medical history significant for congestive heart failure, chronic obstructive pulmonary disease, and third-degree heart block, requiring pacemaker insertion 2 years prior with a revision 1 year prior, presented to the Emergency Department complaining of sudden-onset pleuritic chest pain. Her work up revealed a pneumopericardium with atrial pacemaker lead migration into the right middle lobe of the lung. She suddenly developed hypotension and respiratory distress and required pericardiocentesis and, ultimately, surgical repair for a perforated right atrium. CONCLUSION: Pacemaker migration can lead to pneumopericardium and tamponade, even up to 1 year after placement. PMID- 20542398 TI - The effects of incorporating a pneumonia severity index into the admission protocol for community-acquired pneumonia. AB - BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for admissions in the emergency department (ED). However, patient disposition is not always standardized. OBJECTIVE: To evaluate the effect of incorporating a pneumonia severity index (PSI) on admission rates and medical costs in CAP patients presenting to the ED. METHODS: From April 2008 to March 2009, CAP patients presenting to the ED were prospectively screened and low-risk CAP patients (PSI I, II, or III) were enrolled (after group). Discharge and outpatient care were recommended for this group in the absence of other medical conditions requiring hospitalization. Data from low-risk CAP patients from May 2003 to October 2006 were also collected for comparative analysis (before group). RESULTS: There were 365 and 174 patients in the before and after groups, respectively. The admission rate of the after group was significantly lower than that of the before group (30.4% vs. 68.2%, p < 0.01). The subsequent admission rates after ED discharge due to CAP were similar (3.2% vs. 7.7%, p = 0.10). The ultimate admission rate in the after group was significantly lower than that in the before group (32.5% vs. 70.7%, p < 0.01). Direct medical costs per patient for the before and after groups were $US 1532 and $US 1186, respectively (p = 0.03). CONCLUSIONS: Incorporation of the PSI into the admission protocol for ED patients with CAP significantly reduced the admission rates and medical costs. PMID- 20542399 TI - Abnormal coagulation tests obtained in the emergency department are associated with mortality in patients with suspected infection. AB - BACKGROUND: Early recognition of acute organ dysfunction in emergency department (ED) patients with suspected infection may help select patients at increased risk of mortality. The hematologic system is often overlooked in the evaluation and management of patients with infection because it is poorly circumscribed and serves a multitude of functions. STUDY OBJECTIVES: We examine the hypothesis that abnormalities in commonly and easily obtained markers of coagulation function (international normalized ratio [INR], partial thromboplastin time [PTT], and platelet count [PLT]) are associated with mortality in ED patients admitted to the hospital with suspected infection. METHODS: DESIGN: Secondary analysis of a prospective observational cohort study. SETTING: Urban tertiary care university hospital with 50,000 annual ED visits. PATIENTS: Included patients: adults (age 18 >= years) evaluated in the ED for a suspected infection, had an INR, PTT, and PLT obtained during the ED stay, admitted to the hospital. Excluded patients: on oral anticoagulant therapy, received heparin, or pre-existing severe liver disease. RESULTS: There were 1688 patients included. The in-hospital mortality rate was 5.9%. After adjusting for elderly status, comorbid illness burden, and severity of illness, elevated INR was associated with a 2.9 (95% confidence interval [CI] 1.6-5.2) increased odds of death, and a low platelet count (< 150,000/uL) was associated with 2.0 (95% CI 1.2-3.3) increased odds of death. The C-statistic for the model was 0.80. CONCLUSION: We found an independent association between abnormalities in the coagulation system and mortality in ED patients with suspected infection. These findings underscore the close interaction between inflammation and coagulation and provide evidence that these simple laboratory tests should be routinely considered during the early evaluation of the infected patient. PMID- 20542400 TI - Potential complications of combining intramuscular olanzapine with benzodiazepines in emergency department patients. AB - BACKGROUND: Olanzapine (Eli Lilly and Company, Indianapolis, IN) is starting to be used with more frequency in emergency departments (EDs) for agitated patients. The potential complications of the use of olanzapine in combination with a benzodiazepine have not been well characterized in ED patients with undifferentiated agitation. OBJECTIVES: The measurement of vital signs, repeat medication dosage, and ethanol levels in patients who received parenteral (intramuscular [IM]) olanzapine either alone or concurrently with benzodiazepines. METHODS: This is a structured retrospective chart review of all patients who met the criteria of having received IM olanzapine for agitation and having vital signs documented both before medication administration and within 4 h afterwards. RESULTS: Twenty-five patients were identified as meeting the inclusion criteria. Ten patients received olanzapine and benzodiazepine, and 15 patients received olanzapine alone. Regardless of whether or not they received benzodiazepines, patients who had ingested significant amounts of alcohol before arrival in the ED had decreased oxygen saturations after olanzapine administration. Oxygen saturations decreased more in patients who had ingested alcohol and then received olanzapine + benzodiazepines. Two patients (20%) who received olanzapine + benzodiazepines and who had ingested significant amounts of alcohol exhibited hypoxia, defined as lowest O(2) saturation <= 92%. CONCLUSIONS: In this relatively small sample, olanzapine plus benzodiazepines seems to be safe in patients who have not ingested alcohol, but may produce potentially significant oxygen desaturations in patients who have. Future, prospective studies should explore the benefits vs. potential risks of adding a benzodiazepine to olanzapine for agitated patients in the ED. PMID- 20542401 TI - Unintentional non-adherence and belief in medicines in older adults. AB - OBJECTIVE: To determine whether beliefs in medicines are associated with forgetfulness and carelessness in taking medications. METHODS: Using a survey research design, baseline data (N=1220) and follow-up data (N=1024) were collected through an Internet survey using a convenience sample from Medicare enrollees aged 65 and older and who were Internet users. Logistic regression models were used to determine if patient's beliefs about the necessity of taking prescribed medications and their concern beliefs regarding the potential consequences of taking medications were significant in predicting forgetfulness and carelessness in taking medications. RESULTS: Concern beliefs in medicines were a significant predictor of forgetfulness and carelessness in taking medications. CONCLUSION: If all cases of forgetfulness and carelessness in taking medications are considered as unintentional non-adherence with no reference to the patient's beliefs in medicines; using cue based interventions such as phone reminders or alarms are not likely to reduce non-adherence. There was a strong association between patient belief in medications and non-adherence in older adults who were Medicare enrollees. PRACTICAL IMPLICATIONS: It is important that researchers consider the influence that patient medication beliefs have on patient adherence to develop better interventions to reduce non-adherence. PMID- 20542402 TI - Learning clinical communication skills: outcomes of a program for professional practitioners. AB - OBJECTIVE: To assess the effects of a communication skills program on professional practitioners' performance and self-confidence in clinical interviewing. METHODS: Twenty-five health professionals took 3 months of basic communication skills followed by 3 months of advanced communication skills. An additional quarter dealt with self-awareness and communication in special situations. Participants' performances were evaluated in clinical interviews with standardized patients before, during and after the program by external observers and standardized patients, using standardized instruments. Participants assessed their own confidence in their communication skills before and after the program. Data were analysed using GLM repeated-measures procedures in SPSS. RESULTS: Basic communication skills and self-confidence improved throughout the 6 months; competencies declined but self-confidence continued to increase 4 months later. Compared with taking no course, differences were statistically significant after the 6 months (external observers only) and 4 months later (external observers and participants). CONCLUSION: The program effectively improved communication skills, although significantly only when assessed by external observers. Four months later, effects were significant in communication skills (external observers), despite the decline and in self-confidence. PRACTICE IMPLICATIONS: While periodical enrollment in programs for the practice of communication skills may help maintain performance, more knowledge on communication and self-awareness may enhance self-confidence. PMID- 20542403 TI - Shared decision making in medicine: the influence of situational treatment factors. AB - OBJECTIVE: Although shared decision making (SDM) has become increasingly important in bioethical discussions and clinical practice, it is not clear in which treatment situations SDM is suitable. We address this question by investigating social norms on the appropriateness of SDM in different situations. METHODS: We conducted qualitative expert interviews with patients, general practitioners, and health administration and research professionals. RESULTS: SDM was considered to be most important in severe illness and chronic condition. Furthermore, SDM was indicated to be required if there is more than one therapeutic option, especially if it is not clear which option is best. Interviewees classified end-of-life decisions and decisions about prevention as those that primarily should be made by informed patients. On the other hand a paternalistic decision was considered most appropriate in emergency situations and when the patient does not want to participate in decision making. CONCLUSION: This study demonstrates that multiple situational factors and their interactions must be considered regarding the scope of SDM in medical consultation. PRACTICE IMPLICATIONS: Research addressing this question will help physicians adjust their consultation style and allow implementations of SDM and decision aids to be tailored more appropriately to complex treatment situations. PMID- 20542404 TI - Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults. AB - OBJECTIVES: The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC). METHODS: From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p=0.032), for DFS, margins after surgery (p=0.007), for DSS, regional or distant metastasis at diagnosis (p=0.002), initial AJCC and MSKCC stage (p=0.018 and p=0.048) and margins after surgery (p=0.042). On multivariate analysis, margins remained statistically significant for DFS (p=0.039) when there was a trend with the initial AJCC stage (p=0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system. CONCLUSIONS: Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients. PMID- 20542405 TI - Continuous non-invasive arterial pressure measurement: evaluation of CNAP device during vascular surgery. AB - OBJECTIVE: Standard non-invasive blood pressure (BP) monitoring is an intermittent, discontinuous procedure. Beat-to-beat BP monitoring requires invasive measurement via an arterial catheter and may be associated with serious complications. The Infinity CNAP SmartPod (Drager Medical AG & Co. KG, Lubeck, Germany) has recently been proposed for non-invasive continuous beat-to-beat BP measurements. The present study was designed to compare BP obtained with the CNAP and with an invasive method in the operating room. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: Twenty-five patients undergoing major vascular surgery were included. Systolic, mean and diastolic BP were monitored invasively (SAP, MAP and DAP respectively) and not invasively using the CNAP (CNAP-S, CNAP-M and CNAP-D respectively). Measurements were performed intraoperatively every minute during 1 hour. RESULTS: One thousand and five hundred pairs of simultaneous CNAP and invasive BP measurements were obtained and 148 were eliminated. The range of BP measurements was 63-205 mmHg for SAP and 57-187 mmHg for CNAP-S, 38-143 mmHg for MAP and 43-142 mmHg for CNAP-M, 29-126 mmHg for DAP and 33-121 mmHg for CNAP-D. Bias and 95% limit of agreement between CNAP and invasive BP measurements were respectively 7.2 and -17.7 to 32.2 mmHg for SAP, 1.8 and -22.0 to 18.3 mmHg for MAP, and -7.5 and -27.3 to 12.4 mmHg for DAP. The percentage of CNAP measurements with a bias <10% with the arterial line was 69%, 86% and 91% for systolic, diastolic and mean pressures, respectively. CONCLUSION: Despite low accuracy for SAP and DAP measurements, CNAP system seems more accurate for MAP measurement in patients undergoing vascular surgery. PMID- 20542406 TI - Specific eating disorder clusters based on social anxiety and novelty seeking. AB - While social avoidance and distress (SAD), a key aspect of social phobia related to behavioral inhibition, is high in different eating disorders (EDs), novelty seeking (NS) is mainly linked to bulimic disorders. Since heterogeneity in NS levels (low/high) exists in social phobia and in about 55% of ED with a highly disturbed personality, we examined ED types based on SAD and NS and their relationships to eating and comorbid features. Scores of 825 ED women on SAD and NS were submitted to cluster analysis. Five clinically differentiated ED clusters emerged: two without SAD (45%) and three with high SAD and low (13%), mid (34%), high NS (8%) levels. High vs. low SAD groups showed greater eating and social impairment, ineffectiveness, ascetism, suicide attempts, and lower education. Among SAD clusters, "SAD-low NS" had the lowest rate of binge eating, vomit, substance use, stealing and compulsive buying, whereas "SAD-high NS" presented the opposite pattern. However, no differences across SAD clusters were found with regard to ED diagnostic category distribution or history of treatment. Findings show that SAD-ED types present heterogeneity of NS and greater severity. PMID- 20542407 TI - Deformation of log-likelihood loss function for multiclass boosting. AB - The purpose of this paper is to study loss functions in multiclass classification. In classification problems, the decision function is estimated by minimizing an empirical loss function, and then, the output label is predicted by using the estimated decision function. We propose a class of loss functions which is obtained by a deformation of the log-likelihood loss function. There are four main reasons why we focus on the deformed log-likelihood loss function: (1) this is a class of loss functions which has not been deeply investigated so far, (2) in terms of computation, a boosting algorithm with a pseudo-loss is available to minimize the proposed loss function, (3) the proposed loss functions provide a clear correspondence between the decision functions and conditional probabilities of output labels, (4) the proposed loss functions satisfy the statistical consistency of the classification error rate which is a desirable property in classification problems. Based on (3), we show that the deformed log-likelihood loss provides a model of mislabeling which is useful as a statistical model of medical diagnostics. We also propose a robust loss function against outliers in multiclass classification based on our approach. The robust loss function is a natural extension of the existing robust loss function for binary classification. A model of mislabeling and a robust loss function are useful to cope with noisy data. Some numerical studies are presented to show the robustness of the proposed loss function. A mathematical characterization of the deformed log-likelihood loss function is also presented. PMID- 20542408 TI - Information-theoretic methods for studying population codes. AB - Population coding is the quantitative study of which algorithms or representations are used by the brain to combine together and evaluate the messages carried by different neurons. Here, we review an information-theoretic approach to population coding. We first discuss how to compute the information carried by simultaneously recorded neural populations, and in particular how to reduce the limited sampling bias which affects the calculation of information from a limited amount of experimental data. We then discuss how to quantify the contribution of individual members of the population, or the interaction between them, to the overall information encoded by the considered group of neurons. We focus in particular on evaluating what is the contribution of interactions up to any given order to the total information. We illustrate this formalism with applications to simulated data with realistic neuronal statistics and to real simultaneous recordings of multiple spike trains. PMID- 20542409 TI - Beneficial effect of epilepsy surgery in a case of childhood non-paraneoplastic limbic encephalitis. AB - This 15-year-old girl had subacute onset of secondary generalized seizures, confusion, and subsequent memory decline. MRI showed bilateral hippocampal swelling progressing to unilateral mesial temporal sclerosis (MTS) within 12 months. Epilepsy surgery was performed, and laboratory data were consistent with non-paraneoplastic limbic encephalitis. 18 months after epilepsy surgery, the patient is seizure-free with stable cognitive functions. PMID- 20542410 TI - Diffusion tensor imaging in patients with focal epilepsy due to cortical dysplasia in the temporo-occipital region: electro-clinico-pathological correlations. AB - PURPOSE: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (anisotropy, FA) of water diffusion. We explored the characteristics of pathology-proven cortical dysplasia (CD) in the posterior quadrant in a case series of three patients using DTI measures, to assess associated alterations in subcortical connectivity and correlate with in situ epileptogenicity, seizure propagation and functional outcome. METHODS: The FA maps were visually inspected by a Neuroradiologist blinded to clinical data and conventional MRI (PR) and tractography was performed to assess connectivity of the dysplastic cortex and correlate with seizure propagation on invasive EEG. RESULTS: Analysis of FA maps revealed reduced connectivity with reduced arborization and thinning of the fiber bundles between the subcortical WM and the dysplastic cortex in patients 1 and 2, confirmed on tractography. Fiber tracts reconstructed from regions underlying the ictal onset help explain ictal propagation patterns. In the two patients without preexisting visual field deficit, resections spared the optic radiation visible on the FA map. CONCLUSIONS: Diffusivity measures and visualization of tracts provide complementary information on white matter changes accompanying CD and may assist to explain ictal spread patterns. Careful correlation with measures of function will allow the assessment of the functional significance of various dysplastic lesions and may help to design resective strategies. PMID- 20542411 TI - Schizophrenia and obesity: addressing obesogenic environments in mental health settings. PMID- 20542412 TI - The Cognitive Assessment Interview (CAI): development and validation of an empirically derived, brief interview-based measure of cognition. AB - BACKGROUND: Practical, reliable "real world" measures of cognition are needed to supplement neurocognitive performance data to evaluate possible efficacy of new drugs targeting cognitive deficits associated with schizophrenia. Because interview-based measures of cognition offer one possible approach, data from the MATRICS initiative (n=176) were used to examine the psychometric properties of the Schizophrenia Cognition Rating Scale (SCoRS) and the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS). METHOD: We used classical test theory methods and item response theory to derive the 10-item Cognitive Assessment Interview (CAI) from the SCoRS and CGI-CogS ("parent instruments"). Sources of information for CAI ratings included the patient and an informant. Validity analyses examined the relationship between the CAI and objective measures of cognitive functioning, intermediate measures of cognition, and functional outcome. RESULTS: The rater's score from the newly derived CAI (10 items) correlate highly (r=.87) with those from the combined set of the SCoRS and CGI-CogS (41 items). Both the patient (r=.82) and the informant (r=.95) data were highly correlated with the rater's score. The CAI was modestly correlated with objectively measured neurocognition (r=-.32), functional capacity (r=-.44), and functional outcome (r=-.32), which was comparable to the parent instruments. CONCLUSIONS: The CAI allows for expert judgment in evaluating a patient's cognitive functioning and was modestly correlated with neurocognitive functioning, functional capacity, and functional outcome. The CAI is a brief, repeatable, and potentially valuable tool for rating cognition in schizophrenia patients who are participating in clinical trials. PMID- 20542413 TI - Inpatient mother-and-child postpartum psychiatric care: factors associated with improvement in maternal mental health. AB - PURPOSE: This study assessed the underexplored factors associated with significant improvement in mothers' mental health during postpartum inpatient psychiatric care. METHODS: This study analyzed clinical improvement in a prospective cohort of 869 women jointly admitted with their infant to 13 psychiatric Mother-Baby Units (MBUs) in France between 2001 and 2007. Predictive variables tested were: maternal mental illness (ICD-10), sociodemographic characteristics, mental illness and childhood abuse history, acute or chronic disorder, pregnancy and birth data, characteristics and mental health of the mother's partner, and MBU characteristics. RESULTS: Two thirds of the women improved significantly by discharge. Admission for 25% was for a first acute episode very early after childbirth. Independent factors associated with marked improvement at discharge were bipolar or depressive disorder, a first acute episode or relapse of such an episode. Schizophrenia, a personality disorder, and poor social integration (as measured by occupational status) were all related to poor clinical outcomes. DISCUSSION: Most women improved significantly while under care in MBUs. Our results emphasize the importance of the type of disease but also its chronicity and the social integration when providing postpartum psychiatric care. PMID- 20542414 TI - Surface alumina species on modified titanium dioxide: A solid-state (27)Al MAS and 3QMAS NMR investigation of catalyst supports. AB - (27)Al MAS and 3QMAS NMR have been used to study Al(2)O(3)/TiO(2) catalyst supports synthesized via excess-solution impregnation and surface sol-gel methods. Temperature and alumina loading level strongly affect chemical states of aluminum oxide species observed. Surface cations, Al(H2O)6(3+), a surface alumina monolayer, and disordered transitional aluminas (multilayers) and alpha-alumina, coexist on the TiO(2) surface. Chemical shift and quadrupole coupling constants are reported for the major species identified in 3QMAS experiments. Gold particle catalysts prepared from supports calcined at 500 degrees C have optimum catalytic activity in CO oxidation, and smallest gold particle size for supports, which show maximum monolayer type octahedral alumina on the titania surface. PMID- 20542415 TI - Characterization of and biomolecule immobilization on the biocompatible multi walled carbon nanotubes generated by functionalization with polyamidoamine dendrimers. AB - Polyamidoamine (PAMAM) dendrimers were covalently tethered onto the surface of multi-walled carbon nanotubes (MWCNTs). The morphology and dispersive properties of the MWCNT-PAMAM hybrids were characterized and the peripheral functional groups were identified. Cytotoxicity to human osteosarcoma MG-63 cells, and protein and DNA immobilization ability of the hybrids were evaluated in detail. The dendrimers were present on the surface of MWCNTs in high density. The MWCNT PAMAM hybrids exhibited good dispersibility and stability in aqueous solution. We showed that the hybrids are biocompatible, with no obvious cytotoxicity at concentration <25 microgmL(-1) over 24h. They possess excellent biomolecule immobilization ability (bovine serum albumin and 5'-Fam-CAAggTCgTgTAAAggTCAg-3' were used as models). The functionalization of MWCNTs with PAMAM dendrimers improved the biomolecule-immobilization ability 70-fold and simultaneously decreased the cellular toxicity by about 30%. It is expected that the MWCNT-PAMAM hybrids will find promising applications in biosensors and biomolecule delivery systems in gene or protein therapy. PMID- 20542416 TI - [Breastfeeding in a population of preterm infants: a prospective study in a university-affiliated hospital]. AB - AIMS: To evaluate mothers' breastfeeding intention at birth and the breastfeeding rate at hospital discharge and at 3 months of life in a population of preterm infants. To study the relation between gestational age and the breastfeeding rate at birth. To analyze sociodemographic and neonatal factors that could influence breastfeeding rate. METHODS: We present a prospective study concerning preterm infants born between November 1st 2006 and April 20th 2007 at Brest University Hospital. Exclusion criteria were: death during hospitalization and neurological or digestive diseases not allowing enteral feeding. The following data were extracted from medical charts: birth weight, gestational age, medical care in the neonatal period, delivery circumstances, and feeding mode at hospital discharge. Mothers were asked their sociodemographic status and their intention to breastfeed. Parents were contacted 3 months later to determine the feeding mode at that time. Risk factors were studied for single births through univariate and multivariate analysis. RESULTS: We recruited 149 mother-infant dyads. There were 9 lost to follow-up at 3 months. Breastfeeding rates were: 69.13% (range: 61.7 76.5) at birth, 57.82% (range: 49.8-65.8) at hospital discharge, and 33.57% (range: 25.9-41.7) at 3 months. There was an inverse relation between breastfeeding rate and gestational age: OR=0.07 (0; 0.50). Other factors significantly associated with a high breastfeeding rate were: mother's high level of education: OR=3.19 (1.39; 7.33) and low birth weight: OR=0.20 (0.08; 0.53). CONCLUSION: Our breastfeeding rates are lower than recommended by WHO. Mothers of late preterm infants or with a low socioeconomic status should benefit from supportive care. PMID- 20542417 TI - Who should treat thyroid cancer? A UK surgical perspective. PMID- 20542418 TI - Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid. AB - Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor alpha-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation. PMID- 20542419 TI - Liposomal encapsulation improves the duration of soft tissue anesthesia but does not induce pulpal anesthesia. AB - STUDY OBJECTIVE: To compare the topical and the pulpal anesthesia efficacy of liposomal and plain benzocaine formulations. DESIGN: Double-blinded, randomized crossover study. SETTING: University ambulatory dental center. PATIENTS: 30 ASA physical status I volunteers. INTERVENTIONS: Volunteers received, in three different sessions, topical application of liposome-encapsulated 10% benzocaine (LB10), 10% benzocaine gel (B10), and 20% benzocaine gel (B20) in the right maxillary canine mucobuccal fold. MEASUREMENTS: Pain associated with the needle insertion was rated by visual analog scale (VAS) and the duration of topical anesthesia was recorded. Pulpal anesthesia was evaluated using an electric pulp tester. MAIN RESULTS: VAS values (median, 1st - 3rd quartiles) were 17 cm (11 - 25), 14 cm (3 - 22), and 21 cm (9 - 21) for B10, LB10, and B20, respectively. No differences were noted among the groups (Friedman test; P = 0.58). Soft tissue anesthesia was also not different. The LB10 [10 (8 - 12) min] showed longer soft tissue anesthesia (Friedman test; P < 0.01) than the other agents [B10 = 8 (5 - 10) min, and B20 = 7 (6 - 9) min]. None of the topical benzocaine formulations tested induced pulpal anesthesia. CONCLUSIONS: The encapsulation of benzocaine into liposome increased the duration of soft tissue anesthesia. However, it did not induce pulpal anesthesia. PMID- 20542420 TI - Nanoparticle decorated anodes for enhanced current generation in microbial electrochemical cells. AB - The development of highly efficient anode materials is critical for enhancing the current output of microbial electrochemical cells. In this study, Au and Pd nanoparticle decorated graphite anodes were developed and evaluated in a newly designed multi-anode microbial electrolysis cell (MEC). The anodes decorated with Au nanoparticles produced current densities up to 20-fold higher than plain graphite anodes by Shewanella oneidensis MR-1, while those of Pd-decorated anodes with similar morphologies produced 50-150% higher than the control. Significant positive linear regression was obtained between the current density and the particle size (average Feret's diameter and average area), while the circularity of the particles showed negative correlation with current densities. On the contrary, no significant correlation was evident between the current density and the particle density based on area fraction and particle counts. These results demonstrated that nano-decoration can greatly enhance the performance of microbial anodes, while the chemical composition, size and shape of the nanoparticles determined the extent of the enhancement. PMID- 20542421 TI - Trastuzumab in gastric cancer. AB - Trastuzumab is a fully humanised monoclonal antibody directed at the human epidermal growth factor receptor-2 (HER-2) which has been a component of standard therapy for advanced and resected HER-2-positive breast cancers for almost a decade. HER-2 over-expression, defined as HER-2 protein over-expression using immunohistochemistry scored as 3+ and/or erbB-2 amplification detected by fluorescent in situ hybridisation, was detected in 22.1% of 3807 patients with advanced gastric and oesophagogastric junction (OGJ) adenocarcinoma screened for eligibility for the phase III ToGA study. The validated scoring system for HER-2 positivity in gastric cancers differs from that recommended for breast cancer due to an increased frequency of incomplete membranous immunoreactivity and heterogeneity of HER-2 expression in gastric cancers. The highest rates of HER-2 over-expression are observed in patients with OGJ rather than gastric tumours and intestinal-type rather than diffuse or mixed histology. The international multicentre randomised phase III ToGA study assessed the addition of trastuzumab to a cisplatin plus fluoropyrimidine (FP) chemotherapy doublet for patients with HER-2-positive advanced gastric or OGJ adenocarcinoma. The investigators reported a clinically and statistically significant benefit in terms of response rate (47.3% versus 34.5%, p=0.0017), median progression-free survival (6.7 versus 5.5 months, p=0.0002) and median overall survival (13.8 versus 11.1 months, p=0.0046). Trastuzumab plus FP chemotherapy is now the standard of care for patients with advanced gastric and OGJ cancers which over-express HER-2. Further research to evaluate trastuzumab delivered beyond progression, in combination with alternative first-line chemotherapy regimens, and in the perioperative and adjuvant setting is urgently needed. Additionally, research into mechanisms of resistance and strategies to overcome primary or acquired resistance to trastuzumab must now be expedited, using lessons learnt over the past decade in HER-2-positive breast cancer to maximise the benefit from this agent. PMID- 20542422 TI - Improving the lipid accumulation properties of the yeast cells for biodiesel production using molasses. AB - In this article the high lipid accumulation potential of Candida lipolytica, Candida tropicalis and Rhodotorula mucilaginosa cells were shown in molasses medium. Four different pH values were examined (4-7) to discover the optimum lipid accumulation medium. Varied concentrations of (NH4)2SO4 (0.5, 1.0, 1.5 g/L) and molasses (6%, 8%, 10%) were tested to find the optimum carbon and nitrogen amounts for the highest cellular lipid production. It is shown that the maximum lipid content could be achieved in the medium containing 8% molasses solution and 1.0 g/L (NH4)2SO4 at pH 5 after four days of incubation time. The maximum lipid contents and methyl ester yields were measured as 59.9% and 84.9% for C. lipolytica, 46.8% and 93.2% for C. tropicalis, 69.5% and 92.3% for R. mucilaginosa. Because of the dominant fatty acids were C16 and C18 in the lipids of yeast cells, these crude lipids could be promising feedstock for biodiesel production. PMID- 20542423 TI - Simultaneous enzymatic synthesis of FAME and triacetyl glycerol from triglycerides and methyl acetate. AB - In the presence of methyl acetate triglycerides such as vegetable oils are transformed simultaneously into the corresponding fatty acid methyl esters and triacetyl glycerol (triacetin). The reaction, catalyzed by lipases, was studied as a function of some critical parameters, such as type of catalyst, enzyme hydration and immobilization support. The aim of the work was to achieve a conversion of the triglyceride as high as possible and to maximize the yield of the triacetin, the reaction end point. It was found that by using the immobilized lipase from Candida antarctica yields as high as 80% of both fatty acid esters and triacetin could be achieved. These results were obtained by carefully controlling the amount of water present in the reaction medium and the hydration level of the enzyme macromolecule. PMID- 20542424 TI - Hydroxysafflor Yellow A suppresses thrombin generation and inflammatory responses following focal cerebral ischemia-reperfusion in rats. AB - Hydroxysafflor Yellow A has been demonstrated to attenuate pressure overloaded hypertrophy in rats and inhibit platelet aggregation. Herein we found that Hydroxysafflor Yellow A prevented cerebral ischemia-reperfusion injury by inhibition of thrombin generation. In addition, treatment with Hydroxysafflor Yellow A significantly inhibited NF-kappaB p65 nuclear translation and p65 binding activity, both mRNA and protein levels of ICAM-1 and the infiltration of neutrophils. Mean while, Hydroxysafflor Yellow A had the capacity to improve neurological deficit scores, increase the number of the surviving hippocampal CA1 pyramidal cells and decrease the plasma angiotensin II level. These results illustrated that anti-cerebral ischemic mechanism of Hydroxysafflor Yellow A may be due to its suppression of thrombin generation and inhibition of thrombin induced inflammatory responses by reducing angiotensin II content. PMID- 20542425 TI - Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. Herein, we describe an efficient synthesis of a novel isosteric selenium analog of the highly specific PPARbeta/delta ligand 2-methyl-4-((4-methyl-2-(4 trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (GW501516; 1). The study examined the efficiency of the novel selenium analog 2 methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-selenazol-5-yl) methylsulfanyl)phenoxy-acetic acid (2) to activate PPARbeta/delta and the effect of ligand activation of PPARbeta/delta on cell proliferation and target gene expression in human HaCaT keratinocytes. The results showed that similar to GW501516, the Se-analog 2 increased expression of the known PPARbeta/delta target gene angiopoietin-like protein 4 (ANGPTL4); the compound 2 was comparable in efficacy as compared to GW501516. Consistent with a large body of evidence, the Se-analog inhibited cell proliferation in HaCaT keratinocytes similar to that observed with GW501516. In summary, the novel Se-analog 2 has been developed as a potent PPARbeta/delta ligand that may possess additional anti-cancer properties of selenium. PMID- 20542426 TI - Monastrol analogs: a synthesis of pyrazolopyridine, benzopyranopyrazolopyridine, and oxygen-bridged azolopyrimidine derivatives and their biological screening. AB - A synthesis of novel pyrazolopyridine, benzopyranopyrazolopyridine, and oxygen bridged pyrazolo-, tetrazolo-, benzimidazo-, and thiazolopyrimidines via Hantzsch and Biginelli-like condensations has been developed. The ability of these compounds to inhibit Eg5 activity has been examined. The results indicate that synthetic manipulations in the monastrol thiourea moiety are inefficient. PMID- 20542427 TI - Synthesis and biological activity of glycosyl-1H-1,2,3-triazoles. AB - Glycosyl 1,2,3-triazoles with alpha-D-gluco, beta-D-gluco, alpha-D-galacto, beta D-galacto and beta-2-acetamido-2-deoxygluco (GlcNAc) stereochemistry were prepared by reaction of the corresponding azides with vinyl acetate under microwave irradiation. The deprotected glucosyl and galactosyl triazoles did not display inhibitory activity against the tested glycosidases at 1 mM. Of the four fungal glycosidases evaluated, GlcNAc-triazole was found to be hydrolyzed by Talaromyces flavus CCF 2686 beta-N-acetylhexosaminidase. Beta-GlcNAc-triazole was furthermore established to act as a strong ligand of rat and human natural killer cell activating receptors. PMID- 20542428 TI - Antitumor agents 273. Design and synthesis of N-alkyl-thiocolchicinoids as potential antitumor agents. AB - As a part of our continuing study of colchicinoids as therapeutically useful antitumor drugs, thiocolchicine derivatives, including their phosphate and other water soluble salts, were synthesized and evaluated for inhibition of tubulin polymerization and for in vitro cytotoxicity. Three compounds, 7, 10, and 11, showed potent inhibition of tubulin assembly (IC(50)=0.88-1.1 microM). In addition, compound 7, a water soluble succinic acid salt of N deacetylthiocolchicine (4), showed potent cytotoxicity against a panel of tumor cell lines, suggesting it might be a potential lead to be developed as a therapeutic antitumor agent. Compound 8, a water soluble succinic acid salt of N,N-dimethyl-N-deacetylthiocolchicine (5), showed selective activities against HCT-8 and SK-BR-3 cells. N,N-Diethyl-N-deacetylthiocolchicine (6) seemed not to be a substrate for the P-gp efflux pump, based on the similar ED(50) values obtained against P-gp over-expressing KBvin (0.0146 microg/mL) cells and the parent KB (0.0200 microg/mL) cell line. PMID- 20542429 TI - Antitumor agents 278. 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs as potent in vitro anti-cancer agents. AB - 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs were designed, synthesized, and evaluated for cytotoxic activity. Among all 4-substituted ABO analogs, cyclohexyl (12), N-methoxy-N-methylacetamide (14), and various aromatic derivatives (15-25 and 27) exhibited promising cell growth inhibitory activity with ED(50) values of 0.01-5.8 microM against all tested tumor cell lines. The 4'-methoxyphenyl derivative (18) and 3'-methylphenyl derivative (24) showed the most potent antitumor activity against a broad range of cancer cell lines with ED(50) values of 0.01-76 microM. Preliminary SAR results indicated that substitutions on nitrogen are critical to the antitumor potency. PMID- 20542430 TI - Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. AB - Based on the favorable antiviral profiles of 4'-substituted nucleosides, novel 1 (2'-deoxy-2'-fluoro-4'-C-ethynyl-beta-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC(50) values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug. PMID- 20542431 TI - Effects of maximal oxygen uptake test and prolonged cycle ergometer exercise on the quiet standing control. AB - This work aims at testing the influence of peripheral and central fatigue, after maximal oxygen uptake test (Test1) and prolonged (Test2) cycle ergometer exercises, respectively, on sway density curve (SDC) parameters of postural control. Sixteen healthy male subjects were submitted to stabilometric tests, before and after the exercises. The Test1 was started at 12.5W, with 12.5W/min increments and 50rpm cadence until exhaustion. From the respiratory gas exchange signals, the first ventilatory threshold was obtained by the v-slope method. After a minimum of 72h, the subjects performed the Test2 for 60min, at a power output corresponding to 70% of such threshold. Before and just after these exercises, a set of 10 stabilometric trials of 50s was performed, alternating the eyes open and closed conditions, intercalated by a 10s resting period. The resulting signals were used to obtain the SDC. The Test1 caused decrease of the mean of peaks duration in SDC (p<0.05), decreasing the stability level, with small changes in the rates of central nervous system (CNS) and muscular torque controls. Conversely, Test2 increased the mean of time intervals between peaks in SDC (p<0.05), thus decreasing the CNS commands rate with minor changes in the stability level. Visual privation had a greater effect on body sway than these exercises, which were applied to muscles that are not the main actuators in body sway control. Concluding, this study allowed discriminating the effects of exercise intensities on body sway control. PMID- 20542432 TI - Friederich Nietzsche and the seduction of Occam's razor. AB - Friedrich Nietzsche developed dementia at the age of 44 years. It is generally assumed that the cause of his dementia was neurosyphilis or general pareisis of the insane (GPI). Others have proposed frontal-based meningioma as the underlying cause. We have reviewed Nietzsche's medical history and evaluated the evidence from the medical examinations he underwent by various physicians. We have viewed the possible diagnosis of GPI or meningioma in light of present neuro-ophthalmic understanding and found that Nietzsche did not have the neurological or neuro ophthalmic symptoms consistent with a diagnosis of GPI. The anisocoria which was assumed to be Argyll Robertson pupil was present since he was six years of age. He did not have tongue tremor, lacked progressive motor features and lived at least 12 years following the onset of his neurological signs. Furthermore, the headaches that have been attributed to a frontal-based tumour were present since childhood and the pupil abnormality that has been interpreted as an "afferent pupillary defect" had the characteristics of an abnormality of the efferent pupillary innervation. None of the medical records or photographs suggest there was any ocular misalignment. We concluded that neither diagnosis of GPI nor frontal-based meningioma is convincing. It is likely that Nietzsche suffered from migraines, his blindness in his right eye was a consequence of high progressive myopia associated with retinal degeneration, his anisocoria explained by unilateral tonic pupil, and his dementia by an underlying psychiatric disease. PMID- 20542433 TI - Metastasis of renal cell carcinoma to a haemangioblastoma of the medulla oblongata in von Hippel-Lindau syndrome. AB - We describe a patient with von Hippel-Lindau (VHL) syndrome with metastasis of renal cell carcinoma (RCC) to a haemangioblastoma (HAB) of the medulla oblongata. Histological examination revealed cells with clear cytoplasm arranged in alveolar or tubular patterns in most fields of view. In a small area, the tumor showed abundant thin-walled vessels and clear cells. Immunohistochemically, staining for cytokeratin, epithelial membrane antigen and CD10 was typically positive in the tumor portion that contained RCC but not in the HAB. The HAB was immunopositive for inhibin-alpha and CD34. Detailed histological analysis and immunohistochemistry should allow differentiation of HAB and RCC. PMID- 20542434 TI - Lennox-Gastaut syndrome and idiopathic intracranial hypertension. AB - Lennox-Gastaut Syndrome is a severe childhood epilepsy syndrome characterised by the diagnostic triad of a slow spike and wave pattern on electroencephalogram, multiple seizure types and developmental delay. Idiopathic intracranial hypertension is a syndrome characterised by raised cerebrospinal fluid pressure in the absence of an intracranial mass lesion or ventricular dilatation and often headache. We present the first reported case of Lennox-Gastaut Syndrome associated with symptomatic idiopathic intracranial hypertension in a 15 year old male, requiring cerebrospinal fluid diversion by means of ventriculoperitoneal shunting. PMID- 20542435 TI - MRI safety: nephrogenic systemic fibrosis and other risks. AB - Magnetic resonance imaging (MRI) is now a commonly used imaging modality in many neurosurgical and neurological conditions. Although generally regarded as safe, there are a number of important safety considerations. These include a recently recognised, rare condition termed nephrogenic systemic fibrosis (NSF) that occurs in patients with significant renal impairment who receive gadolinium based contrast. Currently, NSF remains poorly understood and there is no universally effective treatment beyond the avoidance of contrast in patients with significant renal impairment. Other safety considerations include MRI contraindicated devices and the role of MRI in pregnancy. PMID- 20542436 TI - How are ion pumps and agrin signaling integrated? AB - Na(+),K(+)-ATPase (NKA) has a fundamental role in ion transport across the plasma membrane of animal cells and uses approximately 50% of brain energy consumption. Recent work has uncovered additional roles for NKA in signal transduction. How might such different functions of the sodium-potassium pump be connected and regulated? We envision an integrated model of ion pumping and signaling, considering in particular the recently discovered regulation of the sodium potassium pump by agrin, a protein that is cleaved specifically by neurotrypsin at the synapse. Based on the recently solved structure of NKA and sequence analysis, we propose a molecular model for the agrin-NKA interaction, in which agrin displaces the NKA beta-subunit and exploits the ouabain-binding pocket. PMID- 20542437 TI - Sensitivity of knee soft-tissues to surgical technique in total knee arthroplasty. AB - Restricted range of motion and excessive laxity are both potential complications of total knee arthroplasty (TKA). During TKA surgery, the surgeon is frequently faced with the question of how tightly to implant the prosthesis. The most common method of altering implantation tightness is to vary the thickness of the polyethylene inlay after the bone cuts have been made and the trial components inserted. We have sought to quantify how altering the polyethylene thickness may affect post-operative soft tissue tension for a range of prosthetic designs. Four different prosthetic designs were implanted into fresh-frozen cadaveric knee joints. All four designs were implanted in the standard manner, with a 100 Newton distraction force used to set soft tissue balance. The tibiofemoral force was then recorded at 15 degrees intervals throughout the passive flexion range. After the standard implantation of each prosthesis, the tibial component was raised or lowered to mimic increasing and decreasing the polyethylene thickness by 2mm and the force measurements repeated. Tibiofemoral force in extension correlated with implantation tightness for all prosthesis designs. Between 15 degrees and 90 degrees of knee flexion, all four designs were insensitive to changes in implantation tightness. Beyond 90 degrees the effect was more notable in rotating platform mobile-bearing and cruciate-retaining prostheses than in posterior-stabilised mobile-bearing designs. The findings of this research may be useful in assisting surgical decision-making during the implantation of TKA prostheses. PMID- 20542438 TI - Discovery of orally available spirodiketopiperazine-based CCR5 antagonists. AB - Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti HIV activity. Full details of structure-activity relationship (SAR) study are presented. PMID- 20542439 TI - Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626. AB - A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4 (4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4 iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D2 versus D3 receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D2 binding affinity and the D2 versus D3 selectivity. PMID- 20542440 TI - Gametophyte morphology of Platycerium andinum Baker and Platycerium wandae Racif. AB - This paper describes the morphology of the sexual phase and spores of Platycerium andinum and Platycerium wandae. Spores were sown in Thompson's media and the cultures were kept at 24-25 degrees C, with 12h light/darkness photoperiod. Developmental phases were fixed in FAA and processed for observation with the scanning electron microscope. Spores of both species are monolete; Vittaria-type germination and Aspidium-type prothallial development were observed. In the phase of development, the gametophytes develop unicellular secretory and as they mature, develop bifurcated or branched pluricellular trichomes, both in the cushion and near the meristematic zone. Adult gametophytes in culture are cordiform-spatulate to cordiform-reniform, most are unisexual and a few are bisexual. Gametangia belong to the leptosporangiate fern type. Archegonial morphology is uniform, with an elongate, thin neck curved toward the base of the gametophyte. Antheridia have a basal cell, an annular cell and an undivided opercular cell. Three hundred days after the spores were sown, sporophytes still had not developed. In both species, some spores germinate inside the sporangial capsule (intra-sporangial germination). We provide new information on morphogenesis in the genus Platycerium. PMID- 20542441 TI - Incoherent scattering of gamma photons for non-destructive tomographic inspection of pipeline. AB - A scanner system, operating in a non-destructive and non-invasive way, is presented for pipeline to determine its location in land soil, wall thickness, type of liquid flowing and crack/blockage position. The present experiment simulates a real case where pipe corrosion (wall thinning) under insulation can be known from the study of incoherent scattering of 662 keV gamma photons. The incoherent scattered intensity, obtained by unfolding (deconvolution) the experimental pulse-height distribution of NaI(Tl) scintillation detector with the help of inverse response matrix, provides the desired information. The method is quite sensitive for small change (approximately 1 mm) in the thickness of pipe wall, locating a defect of 1mm width under insulation and a small change (approximately 0.1 gm cm(-3)) in the density of liquid flowing through pipe. PMID- 20542442 TI - Origin of fine dust in urban environmental zones--Evidence from element patterns received by dichotomous collection and INAA. AB - In order to fulfil the EU-limitations of fine dust and traffic-produced gases Cologne installed 2008 one of the first German environmental zones, from which stepwise vehicles with too high emissions will be locked out. Verification of effectiveness and the research on further strategies to reduce fine dust are studied as promising applications of a method on discrimination of aerosol components from different origins (Weckwerth, 2001). New measurements in Cologne gave several implications on supports, especially in connection with traffic abrasion from brakes, tires and rails. PMID- 20542443 TI - Response to copper excess in Arabidopsis thaliana: Impact on the root system architecture, hormone distribution, lignin accumulation and mineral profile. AB - Growth, in particular reorganization of the root system architecture, mineral homeostasis and root hormone distribution were studied in Arabidopsis thaliana upon copper excess. Five-week-old Arabidopsis plants growing in hydroponics were exposed to different Cu(2+) concentrations (up to 5 muM). Root biomass was more severely inhibited than shoot biomass and Cu was mainly retained in roots. Cu(2+) excess also induced important changes in the ionome. In roots, Mg, Ca, Fe and Zn concentrations increased, whereas K and S decreased. Shoot K, Ca, P, and Mn concentrations decreased upon Cu(2+) exposure. Further, experiments with seedlings vertically grown on agar were carried out to investigate the root architecture changes. Increasing Cu(2+) concentrations (up to 50 muM) reduced the primary root growth and increased the density of short lateral roots. Experiment of split-root system emphasized a local toxicity of Cu(2+) on the root system. Observations of GUS reporter lines suggested changes in auxin and cytokinin accumulations and in mitotic activity within the primary and secondary root tips treated with Cu(2+). At toxic Cu(2+) concentrations (50 muM), these responses were accompanied by higher root apical meristem death. Contrary to previous reports, growth on high Cu(2+) did not induce an ethylene production. Finally lignin deposition was detected in Cu(2+)-treated roots, probably impacting on the translocation of nutrients. The effects on mineral profile, hormonal status, mitotic activity, cell viability and lignin deposition changes on the Cu(2+) induced reorganization of the root system architecture are discussed. PMID- 20542444 TI - Ideal proportions in full face front view, contemporary versus antique. AB - AIM: To compare the facial proportions of contemporary harmonious faces with those of antiquity, to validate classical canons and to determine new ones useful in orthofacial surgery planning. MATERIAL AND METHODS: Contemporary beautiful faces were retrieved from yearly polls of People Magazine and FHM. Selected B/W frontal facial photographs of 31 men and 74 women were ranked by 20 patients who had to undergo orthofacial surgery. The top-15 female faces and the top-10 male faces were analyzed with Scion Image software. The classical facial index, the Bruges facial index, the ratio lower facial height/total facial height and the vertical tri-partite of the lower face were calculated. The same analysis was done on pictures of classical sculptures representing seven goddesses and 12 gods. RESULTS: Harmonious contemporary female faces have a significantly lower classical facial index, indicating that facial height is less or facial width is larger than in male and even than in antique female faces. The Bruges index indicates a similar difference between ideal contemporary female and male faces. The contemporary male has a higher lower face (48%) compared to total facial height than the contemporary female (45%), although this is statistically not significant (P=0.08). The lower facial thirds index remained quite stabile for 2500 years, without gender difference. A good canon for both sexes today is stomion-gnathion being 70% of subnasale-stomion. CONCLUSION: The average ideal contemporary female face is shorter than the male face, given the fact that interpupillary distance is similar. The Vitruvian thirds in the lower face have to be adjusted to a 30% upper lip, 70% lower lip-chin proportion. The contemporary ideal ratios are suitable to be implemented in an orthofacial planning concept. PMID- 20542445 TI - Editorial comment. PMID- 20542446 TI - Effect of bilateral versus unilateral exertion tests on maximum voluntary activity and within-participant reproducibility in the shoulder. AB - Normalized surface EMG requires known muscle activity from a well defined reference contraction, often a maximum voluntary isometric exertion (MVIE). One factor that may impact the activity obtained during a MVIE is the use of a bilateral or unilateral version of the test. The objective of this work was to investigate how performing MVIE tests unilaterally or bilaterally affects maximum voluntary electrical activity (MVE) for selected shoulder muscles. Further, we examined if within-participant reproducibility could be improved with the use of bilateral or unilateral MVIE tests. Sixteen participants completed five repetitions of a palm press, empty can, and external rotation MVIE tests both bilaterally and unilaterally. Muscle activity was recorded from seven muscles acting at the glenohumeral joint during the performance of each test. Repeated measures ANOVAs were used to determine within-participant differences on muscle specific MVEs and hand force measures between the two versions of the test. Gender was compared as a between participants factor. Within-participant reproducibility in muscle activity between bilateral and unilateral MVIEs was compared using coefficients of variation. Performing a bilateral empty can MVIE test elicited significantly higher MVEs for the upper trapezius (14%) and supraspinatus muscles (15%) than a unilateral test in this study population. MVEs during the palm press and external rotation were not affected by performing the tests bilaterally or unilaterally. Reliability was similar between unilateral and bilateral exertions across MVIE tests. Hence, we recommend that the empty can MVIE test be performed bilaterally, while either bilateral or unilateral configurations are equivalent during the palm press and external rotation MVIE tests. PMID- 20542447 TI - A comparison of characteristics and resource use between in-hospital and admitted patients with stroke. AB - BACKGROUND: Although in-hospital stroke is not a common occurrence, it is important to identify what components of stroke care these patients receive. The aims of this study were to estimate the clinical characteristics, process of stroke care, and mortality in patients admitted to hospital with stroke compared with patients with in-hospital strokes. METHODS: Data from a community-based stroke register (1995-2004) in an inner city multiethnic population of 271,817 in South London, United Kingdom, were analyzed. RESULTS: From a total of 2402 patients, 291 (12.1%) had in-hospital strokes. Patients with in-hospital strokes were more likely to be incontinent, be dysphagic, have a motor deficit, and have a low level of consciousness (P < .001) compared with admitted patients with stroke. Brain imaging was carried out more frequently in admitted patients with stroke (P < .001). Access to stroke unit care was higher in admitted patients with stroke (P < .001). In-hospital patients with stroke had a longer mean length of stay (55.9 days) compared with admitted patients with stroke (37.9 days, P < .001). There were no significant differences between the groups for receipt of physiotherapy or occupational therapy after discharge (P=.232) or receipt of speech and language therapy (P=.345). After adjustment of case mix variables, in hospital patients with stroke were less likely to undergo imaging (odds ratio [OR]=0.54, 95% confidence interval [CI]=0.33-0.89, P=.015). In-hospital patients with stroke were less likely to be treated in a stroke unit (OR=0.33, 95% CI=0.22 0.50, P < .001) and prescribed antiplatelet therapy at 3 months (OR=0.51, 95% CI=0.30-0.88, P=.015). By 3 months, in-hospital patients with stroke were more likely to have died (P < .001), although this was not significant after case mix adjustment (OR=1.39, 95% CI=0.90-2.15, P=.135). CONCLUSION: This study demonstrated that in-hospital patients with stroke had worse stroke severity, and poorer access to a number of components of stroke care compared with admitted patients with stroke. All hospitals should include, in their stroke policies and guidelines, evidence-based pathways that prioritize the needs of patients who have a stroke while in hospital. PMID- 20542448 TI - Frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic tumor physiology in an individual patient. AB - RATIONALE AND OBJECTIVES: Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients. MATERIALS AND METHODS: Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 x 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period. RESULTS: A composite index, the Tissue Optical Index (TOI), showed a significant ( approximately 50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery. CONCLUSION: This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy. PMID- 20542449 TI - Lung growth in infants and toddlers assessed by multi-slice computed tomography. AB - RATIONALE AND OBJECTIVES: Postnatal lung growth and development have primarily been evaluated from a very limited number of autopsied lungs, but it remains unclear whether alveolarization of the lung is complete during infancy and whether the conducting airways grow proportionately. The purpose of this study was to evaluate lung growth and development in vivo in infants and toddlers using multislice computed tomography. MATERIALS AND METHODS: Thirty-eight subjects (14 male, 24 female) aged 17 to 142 weeks underwent low-dose volumetric high resolution computed tomographic imaging at an inflation pressure of 20 cm H(2)O during an induced respiratory pause. Lung volume and weight were determined, as well as airway dimensions (inner and outer area and wall area) for the trachea and the next three to four generations. RESULTS: Lung volume, air volume, and tissue volume increased linearly with body length. The air and tissue components of the lung parenchyma increased at a constant rate with each other. In addition, airway caliber decreased with increasing generation from the trachea into each lobe. Airway caliber was also correlated with body length; however, there was no interaction effect between airway generation and body length on transformed airway size. CONCLUSIONS: In vivo assessment suggests that the growth of the lung parenchyma in infants and toddlers occurred with a constant relationship between air volume and lung tissue, which is consistent with lung growth occurring primarily by the addition of alveoli rather than the expansion of alveoli. In addition, the central conducting airways grow proportionately in infants and toddlers. This information may be important for evaluating subjects with arrested lung development. PMID- 20542450 TI - Validation of a new reference standard for the diagnosis of vasospasm. AB - RATIONALE AND OBJECTIVES: The purpose of our study is to perform an internal validation of a new reference standard for vasospasm diagnosis in aneurysmal subarachnoid hemorrhage (A-SAH) patients. MATERIALS AND METHODS: A retrospective study was performed on A-SAH patients between January 2002 and May 2009. All patients were applied to this new reference standard using a multistage hierarchical approach incorporating clinical and imaging criteria. An internal validation method was performed in two phases to compare the new reference standard with digital subtraction angiography (DSA) and to assess accuracy. In Phase I, the diagnostic outcomes from DSA at the primary level were compared with the secondary/tertiary levels in the reference standard. In Phase II, the new reference standard was compared with chart diagnosis. Accuracy test characteristics, agreement rates, kappa values, and bias indices were calculated. RESULTS: In Phase I (n = 85), there was 87% agreement rate, 0.674 kappa, and 0.12 bias index. However, there was 100% agreement in patients diagnosed with vasospasm by DSA. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 61%, 83%, and 100% respectively. In Phase II (n = 137), there was 91% agreement rate, 0.824 kappa, and 0.04 bias index. Sensitivity, specificity, PPV, and NPV were 88%, 95%, 96%, and 87%, respectively. CONCLUSION: Performing validation methods for a new reference standard is an evolving and ongoing process because limitations and bias in the reference standard are identified. Based on the results of this internal validation, a modification in the new reference standard is made at the primary level, resulting in improvement in its accuracy and classification of A-SAH patients. PMID- 20542451 TI - Post-CABG coronary CT angiography: radiation dose and graft image quality in retrospective versus prospective ECG gating. AB - RATIONALE AND OBJECTIVES: The aim of this study was to compare effective radiation doses between prospective and retrospective electrocardiographic gating during coronary computed tomographic angiography for coronary artery bypass grafting evaluation. MATERIALS AND METHODS: Fifty consecutive coronary computed tomographic angiographic exams for coronary artery bypass grafting evaluation, 25 prospectively gated and 25 retrospectively gated, were reviewed from January 8, 2008, to June 16, 2009. Body mass index and image quality were also compared between the two groups. To minimize the potential bias introduced by differences in torso length, the effective radiation dose from each exam was measured and normalized to a 24-cm z-axis scan length for all patients. Pooled t tests were used to compare the prospectively and retrospectively gated groups. RESULTS: The average effective doses delivered in the retrospective and prospective groups were 40.8 mSv (standard error [SE], 1.8 mSv) and 8.6 mSv (SE, 0.7 mSv), respectively. When normalized to the average z-axis scan length of 24 cm, the effective dose in the retrospective group, 38.4 mSv (SE, 1.3 mSv), was still >4 times greater than that in the prospective group, 9.1 mSv (SE, 0.7 mSv) (P < .0001). There was no significant difference in body mass index or image quality between the groups. CONCLUSIONS: Effective radiation dose in coronary computed tomographic angiography for coronary artery bypass grafting evaluation is very high because of long scan lengths. Prospective electrocardiographic gating significantly reduces effective radiation dose by an average of 76% compared to retrospectively gated scans (9.1 vs 38.4 mSv). In the coronary artery bypass grafting population, prospective electrocardiographic gating should be used whenever ventricular functional assessment is not required. PMID- 20542452 TI - CT colonography computer-aided polyp detection: Effect on radiologist observers of polyp identification by CAD on both the supine and prone scans. AB - RATIONALE AND OBJECTIVES: To determine whether the display of computer-aided detection (CAD) marks on individual polyps on both the supine and prone scans leads to improved polyp detection by radiologists compared to the display of CAD marks on individual polyps on either the supine or the prone scan, but not both. MATERIALS AND METHODS: The acquisition of patient data for this study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act-compliant. Subsequently, the use of the data was declared exempt from further institutional review board review. Four radiologists interpreted 33 computed tomography colonography cases, 21 of which had one adenoma 6-9 mm in size, with the assistance of a CAD system in the first reader mode (ie, the radiologists reviewed only the CAD marks). The radiologists were shown each case twice, with different sets of CAD marks for each of the two readings. In one reading, a true-positive CAD mark for the same polyp was displayed on both the supine and prone scans (a double-mark reading). In the other reading, a true-positive CAD mark was displayed either on the supine or prone scan, but not both (a single-mark reading). True-positive marks were randomized between readings and there was at least a 1-month delay between readings to minimize recall bias. Sensitivity and specificity were determined and receiver operating characteristic (ROC) and multiple-reader multiple-case analyses were performed. RESULTS: The average per polyp sensitivities were 60% (38%-81%) versus 71% (52%-91%) (P = .03) for single-mark and double-mark readings, respectively. The areas (95% confidence intervals) under the ROC curves were 0.76 (0.62-0.88) and 0.79 (0.58-0.96), respectively (P = NS). Specificities were similar for the single-mark compared with the double-mark readings. CONCLUSION: The display of CAD marks on a polyp on both the supine and prone scans led to more frequent detection of polyps by radiologists without adversely affecting specificity for detecting 6-9 mm adenomas. PMID- 20542453 TI - Setting up, maintaining and evaluating an evidence based radiology journal club: the University of Michigan experience. AB - The authors outline the steps involved in setting up, maintaining, and evaluating an evidence-based imaging journal club, using their collective experience at the University of Michigan. The article opens with a background to journal clubs in general and describes their changing purpose or role in recent decades. This should act as a useful framework or "how-to" guide to get things started. Different journal club formats are discussed, and the pros and cons of each are outlined. Suggestions for obtaining feedback from residents and for performing evaluation are also provided. In addition, useful information, references and links to useful resources are also given throughout the article. Finally, the authors share the positive (and negative) experiences of setting up, maintaining, and evaluating the University of Michigan's journal club, now in its third year. The authors welcome feedback from readers who have been involved in evidence based imaging journal clubs to share their experiences, good and bad. PMID- 20542454 TI - Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus. AB - BCL11A is a major regulator of fetal hemoglobin production. Reduced levels of BCL11A have been shown to delay switching from fetal to adult hemoglobin, suggesting that it acts as a stage-specific repressor of gamma globin expression. We have carried out a survey of BCL11A binding in the globin, BCL11A and GATA1 loci by ChIP-on-chip analysis in primary human erythroid cells. We found strong occupancy in both alpha and beta globin upstream regulatory regions as well as in regions involved in switching and hereditary persistence of fetal hemoglobin. Genetic studies have identified a restricted 14kb region in BCL11A intron 2 as being highly associated with HbF levels. Strong GATA-1 binding and acetylated histone H3 was found in this area, which could be indicative of a regulatory element, changes in which might be responsible for the overall regulation of BCL11A. We also observed BCL11A and GATA-1 binding in a known auto-regulatory promoter element of the GATA1 locus. PMID- 20542455 TI - The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. AB - Canine cognitive dysfunction (CCD) is an age-related neurobehavioural syndrome which, although common, is severely under-diagnosed in community-based dogs. Using data from a large cross-sectional survey of older dogs (n=957), this study aimed to develop a clinical scale for assessing CCD. Data-driven analytical techniques were used to distil 27 significant behavioural items (previously identified as relevant to CCD) into an assessment tool with maximal cognito behavioural breadth whilst maintaining clinical utility. The resulting CCD rating scale (CCDR) comprised 13 behavioural items, of which three were sensitive to the severity of the disease stage. When tested on an independent survey sample, the CCDR had an overall 98.9% diagnostic accuracy with a 77.8% positive predictive value and a 99.3% negative predictive value. Test-re-test reliability of the CCDR over 2months was also high (r=0.73, P<0.0001). In conjunction with veterinary assessment, the CCDR could be a valuable tool in research and clinical settings for both the assessment and longitudinal tracking of cognitive change. PMID- 20542457 TI - Back pain in older male Italian-born immigrants in Australia: the importance of socioeconomic factors. AB - Back pain is common in older people and is associated with functional disability and poor self-rated health. Older persons are under-represented in back pain research, and research on back pain in older persons from ethnic minorities is particularly sparse. We investigated differences in back pain characteristics, effects and medication use in a population-based sample of 335 Italian-born immigrants and 849 Australian-born men aged 70 years and over. There were 189 (62%) Italian-born men and 507 (63%) Australian-born men who reported experiencing back pain in the past 12 months. Despite no difference in the reported prevalence of back pain between the two groups of men, Italian-born men were more likely to report that their pain was frequent, severe and chronic. Italian-born men were also more likely to report having other sites of pain and that they had limited their activities in the past 12 months due to back pain. Despite these differences, the use of analgesic medication was the same in both groups. Multivariate analyses showed that differences in pain characteristics and effects between the two groups of men were explained by socioeconomic factors such as years of education and occupation history. PMID- 20542456 TI - Cytotoxicity and cytokine production by bovine alveolar macrophages challenged with wild type and leukotoxin-deficient Mannheimia haemolytica. AB - Leukotoxin (LKT) is a virulence factor for Mannheimia haemolytica. In this study, bovine alveolar macrophages (BAMs) were challenged with wild type (wt) and LKT deficient (lkt(-)) M. haemolytica at a concentration of 1 bacterium/BAM and the cytokine response was quantified by ELISA and real-time reverse transcriptase PCR. Significant increases in protein concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were observed in supernatants obtained from BAMs challenged with the lkt(-) strain of M. haemolytica compared with wt challenged BAMs. There were no significant differences in mRNA expression of TNFalpha, IL-1beta, IL-6, IL-8 or IL-10 between BAMs challenged with the lkt(-) strain of M. haemolytica compared with wt challenged BAMs. BAMs challenged with the wt strain exhibited, on average, 43% more cytotoxicity than lkt(-) challenged BAMs (P<0.01). PMID- 20542458 TI - Extended phase graphs with anisotropic diffusion. AB - The extended phase graph (EPG) calculus gives an elegant pictorial description of magnetization response in multi-pulse MR sequences. The use of the EPG calculus enables a high computational efficiency for the quantitation of echo intensities even for complex sequences with multiple refocusing pulses with arbitrary flip angles. In this work, the EPG concept dealing with RF pulses with arbitrary flip angles and phases is extended to account for anisotropic diffusion in the presence of arbitrary varying gradients. The diffusion effect can be expressed by specific diffusion weightings of individual magnetization pathways. This can be represented as an action of a linear operator on the magnetization state. The algorithm allows easy integration of diffusion anisotropy effects. The formalism is validated on known examples from literature and used to calculate the effective diffusion weighting in multi-echo sequences with arbitrary refocusing flip angles. PMID- 20542459 TI - Influence of heredity and environment on peak bone density: a parent-offspring study. AB - The aim of the study was to determine the relative influence of heredity and environment on peak bone density and also to estimate the risk of having low peak bone density if the bone density of parents is low. The study comprised 83 families (48 daughters and 35 sons and their parents). The children were at an age when bone density is at its peak at most skeletal sites (22.2+/-1.8 girls; 23.1+/-1.2 boys). Bone mineral density (BMD; g/cm(2)) was determined by dual energy X-ray absorptiometry. Anthropometric measurements were made, and calcium intake and physical activity were assessed. Heredity accounted for 22-42% of the variation in BMD of the children, depending on the skeletal site. Heritability for cortical BMD of mid-radius was considerably lower than that for spinal trabecular BMD. Children whose parents had low BMDs (T-score< or =-1) were 1.1 times more likely to inherit low BMD. Child BMD depended significantly on parent BMD and also on physical activity. In our study, heredity accounted for the total BMD variation more than the environmental factors. This influence was lower in the cortical than in the trabecular parts of the skeleton. Optimal environmental factors, such as physical activity, may influence the risk of inheriting low BMD. PMID- 20542460 TI - Previous treatment in predicting drug-resistant tuberculosis in an area bordering East London, UK. AB - OBJECTIVES: To determine the utility of 'risk assessment' in selecting Mycobacterium tuberculosis isolates for rifampin resistance or rpoB genotyping compared to 'non-selectively' genotyping all isolates. Secondly, we examined the association between past treatment and drug resistance. METHODS: From January 2003 to December 2006, demographic, clinical, and laboratory data were prospectively collected on patients with laboratory-confirmed tuberculosis (TB). On the basis of past treatment for active TB infection or known exposure to drug resistant TB, selected samples were sent to a mycobacterial reference laboratory for rpoB genotyping. A multivariable logistic regression model was developed to examine the association between past treatment and drug resistance, adjusted for other factors. Sensitivity, specificity, and negative and positive predictive values of past treatment as a predictor for drug resistance were determined. RESULTS: There were 392 patient episodes of culture-proven TB. Thirty-three drug resistant isolates were cultured from 30 patients: 29 (87.9%) were isoniazid resistant, three (9.1%) were multidrug-resistant (MDR), and one (3.0%) was rifampin mono-resistant. One patient with isoniazid resistance developed recurrent disease, and two isolates, initially isoniazid-resistant, mutated and became MDR TB. Based on risk assessment, rpoB genotyping was performed on 19 samples, and two (10.5%) had mutations that predicted multiple drug resistance. Although for MDR TB, a past history of treatment predicted two out of three patients with acquired resistance, adjusted analysis did not demonstrate a significant association between previous treatment of active TB and drug resistance (odds ratio 1.5, 95% confidence interval (CI) 0.4-5.6). The positive predictive value of past treatment as a predictor for drug resistance was 12.0% (95% CI 2.6-31.2%). CONCLUSION: Although numbers of MDR TB were too small to draw meaningful conclusions, past treatment may be useful in selecting samples for rpoB genotyping. Overall, previous treatment had a low positive predictive value for drug resistance in an area bordering East London. PMID- 20542462 TI - What to believe: Bayesian methods for data analysis. AB - Although Bayesian models of mind have attracted great interest from cognitive scientists, Bayesian methods for data analysis have not. This article reviews several advantages of Bayesian data analysis over traditional null-hypothesis significance testing. Bayesian methods provide tremendous flexibility for data analytic models and yield rich information about parameters that can be used cumulatively across progressive experiments. Because Bayesian statistical methods can be applied to any data, regardless of the type of cognitive model (Bayesian or otherwise) that motivated the data collection, Bayesian methods for data analysis will continue to be appropriate even if Bayesian models of mind lose their appeal. PMID- 20542461 TI - Physical activity as a mediator of the associations between neighborhood walkability and adiposity in Belgian adults. AB - This study examined whether physical activity (PA) and sedentary behavior mediated the relationship of neighborhood walkability with two measures of adiposity: body mass index (BMI) and waist-to-height ratio (WHTR). Twenty-four neighborhoods in Ghent, Belgium were selected, stratified by objectively assessed walkability and by socio-economic status. Participants (1200 adults aged 20-65 years) completed the International Physical Activity Questionnaire and wore an accelerometer for 7 days. Weight and height were self-reported and waist circumference was objectively measured. Accelerometer-assessed moderate-to vigorous PA and self-reported cycling for transport mediated the associations of walkability with BMI and WHTR. Moreover, walking for transport and recreational walking significantly mediated the relationship between walkability and BMI. Sedentary behavior did not mediate associations of walkability with BMI or WHTR. These findings suggest that PA, but not sedentary behavior, is a mechanism by which walkability may affect adults' adiposity. Planning for neighborhoods to be high in walkability could have favorable effects on physical activity and weight status. PMID- 20542463 TI - External quality assessment for molecular detection of human papillomaviruses. AB - BACKGROUND: The United Kingdom National External Quality Assessment Service (UK NEQAS) distributes clinically relevant and educational specimens for external quality assessment (EQA). OBJECTIVES: The aim of this report was to assess the suitability of using liquid based cytology (LBC) samples for the EQA of molecular methods and to review the methods used by participants to detect the presence of high risk (HR) human papillomavirus (HPV) genotypes. STUDY DESIGN: Three pilot distributions were dispatched between January 2008 and January 2009 with each distribution consisting of four different specimens. RESULTS: Performance was good with over 90% of participants reporting correctly on the presence or absence of high risk genotypes in all but one specimen, specimen 9006 (82.1%). Specimen 9006 was a pooled specimen, negative for HR genotypes but containing low risk (LR) genotypes 61, 70 and 81. The most commonly used assay for the detection of the presence of HR HPV was the Digene Hybrid Capture II assay. The in-house PCR assays were most commonly associated with incorrect results, and the use of these assays decreased during the 13 month pilot study. CONCLUSIONS: The UK NEQAS molecular detection of HPV scheme provides a standardised, homogeneous and characterised clinical specimen, however this study has shown that genotyping results reported by participants were still varied. Inclusion of available HPV standards will help to standardise assays. Robust EQA of HPV molecular screening programmes will be essential for monitoring the impact of the HPV vaccine. PMID- 20542464 TI - VZV meningitis following varicella vaccine. AB - Live attenuated varicella zoster virus is administered to prevent varicella in children and herpes zoster in the elderly. We report a case of disseminated herpes zoster in a previously healthy elderly woman hours after Oka strain vaccination. PCR and restriction enzyme analysis revealed that symptoms were caused by wild type virus. PMID- 20542465 TI - Brainstem lesions may be important in the development of epilepsy in multiple sclerosis patients: an evoked potential study. AB - OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with epileptic seizures sometimes observed in the same patients. In this study, we used evoked responses to study the pathogenesis of epilepsy in MS. METHODS: Patients with a diagnosis of definite MS and who had EPs performed (visual (VEP), brainstem auditory (BAEP) and short latency somatosensory (upper (USSEP) and lower (LSSEP))) were retrospectively included in this study. They were divided into three groups; Group I: Patients with no epilepsy and who were not taking anti-epileptic drugs (AED); Group II: Patients with epilepsy and taking AEDs; and Group III: Patients with no epilepsy who were taking AEDs for symptoms related to neuropathic pain. RESULTS: Three hundred and fifty-five patients were included in this study; Group I: 229 patients (64.5%), Group II: 20 patients (5.6%) and Group III: 106 patients (29.9%). The proportion of patients with abnormal BAEP and USSEP was higher in Group II. CONCLUSIONS: A positive association exists between the presence of epilepsy in MS patients and BAEP and USSEP abnormalities. Analysis of Group III ruled out AED use as a factor. SIGNIFICANCE: Brainstem lesions may be the cause of epileptogenicity in MS. PMID- 20542466 TI - Contemporary results following surgical repair of acute type a aortic dissection (AAAD): a single centre experience. AB - OBJECTIVES: The study aims to define predictors of neurological dysfunction, 30 day mortality, long-term survival and quality of life following repair of acute type A aortic dissection (AAAD). METHODS: Between 2000 and 2008, 65 patients underwent repair of AAAD. Sixty-four pre-, intra- and post-operative variables were studied. Mean follow-up was 26.6 months. RESULTS: The mean age was 61years; 60% were male and five had Marfan's syndrome. At presentation, ischaemic ECG changes were seen in 45%, malperfusion syndrome in 59%, moderate-severe aortic regurgitation in 48% and tamponade in 16%. EF was <40% in 17%. There was a delay of >12hours between diagnosis and operation in 64%. Axillary cannulation was performed in 37%. Cerebral protection was by hypothermic arrest (HCA) alone (19%), HCA with retrograde cerebral perfusion (RCP) (11%), or HCA with antegrade cerebral perfusion (ACP) (46%). The procedure was performed on cross-clamp in 24%. Full arch replacement was performed in 14% and concomitant coronary artery grafting was performed in 11%. Post-operative neurological dysfunction was present in 33.8%. The only significant predictor of poor neurological outcome was full arch replacement (p=0.04) on univariate analysis. In-hospital OR 30 mortality was 23.53%. Significant predictors of mortality were low ejection fraction (p=0.017) and post-operative renal failure (p=0.012). Long-term survival was 70% at two years, 50% at five years and 25% at nine years. Functional outcomes and long-term quality of life were assessed in 69% of patients who were alive at last follow-up. Ninety percent of patients reported minimal limitation on functional scores. Quality of life was assessed using the EQ-5D questionnaire. Forty-eight percent of patients recorded full health with an overall mean index of 0.854 (where the best possible score is 1) using the US preference weighted index score. CONCLUSIONS: Discharged patients have reasonable long-term survival and good quality of life. PMID- 20542467 TI - Transcatheter coil embolisation: a novel definitive treatment option for intralobar pulmonary sequestration. AB - Pulmonary sequestrations have been conventionally treated surgically with removal of the tissue mass and ligation of its feeding vessels. There is established evidence to support the use of transcatheter arterial coil embolisation as an effective definitive treatment option for extralobar sequestration especially in the paediatric literature describing good long-term clinical outcomes. We present a case of an adult with intralobar sequestration in whom the diagnosis was established with multi-detector computed tomography (MDCT) and in whom transcatheter arterial coil embolisation was successfully performed as a definitive treatment option to support the growing body of evidence of transcatheter arterial coil embolisation as a safe and effective treatment option for both form of pulmonary sequestrations. PMID- 20542468 TI - Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. AB - BACKGROUND: Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta analysis of randomised controlled trials of these drugs. METHODS: We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61,590 patients from five trials. Data on common types of solid organ cancers were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials. FINDINGS: Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183). INTERPRETATION: This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation. PMID- 20542469 TI - Angiotensin-receptor blockers and cancer: urgent regulatory review needed. PMID- 20542470 TI - Airway luminal T cells: a newcomer on the stage of TB vaccination strategies. AB - Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in the lung interstitium and spleen before Mycobacterium tuberculosis exposure and protection. In contrast, respiratory mucosal immunization leads to distribution of T cells not only in the lung interstitium and spleen, but also in the airway lumen, and the presence of these cells correlates well with protection. Furthermore, airway luminal recruitment of parenteral vaccine-induced T cells in peripheral tissues prior to M. tuberculosis challenge restores protection. We propose that understanding the biology of airway luminal T cells holds important implications for developing effective TB vaccination strategies. PMID- 20542471 TI - Preventing infective complications relating to induced abortion. AB - Infective complications following induced abortions are still a common cause of morbidity and mortality. This review focusses on defining the strategies to improve care of women seeking an induced abortion and to reduce infective complications. We have considered the evidence for screening and cost effectiveness for antibiotic prophylaxis. Current evidence suggests that treating all women with prophylactic antibiotics in preference to screening and treating is the most cost-effective way of reducing infective complications following induced abortions. The final strategy to prevent infective complications should be individualized for each region/area depending on the prevalence of organisms causing pelvic infections and the resources available. PMID- 20542472 TI - Reduction of postoperative pain after lumbar microdiscectomy with DuraSeal Xact Adhesion Barrier and Sealant System. AB - BACKGROUND CONTEXT: An excessive amount of scar tissue after lumbar microdiscectomy may increase postoperative pain. Several fibrosis inhibitors have been used in the past in an endeavor for better functional outcome. PURPOSE: The goal of this study was to evaluate DuraSeal Xact Adhesion Barrier and Sealant System (DSX), a polyethylene glycol-based synthetic fibrosis inhibitor, for its ability to reduce postoperative pain after lumbar microdiscectomy. STUDY DESIGN: This is a prospective randomized controlled study. PATIENT SAMPLE: Twenty patients between 19 and 71 years of age about to undergo elective lumbar single level discectomy were randomized into two groups of 10. OUTCOME MEASURES: Assessments included the visual analog scale (VAS) pain score, the short form (SF)-36 questionnaire, and the Oswestry low back pain scale, preoperatively and at discharge, and 30, 90, and 180 days after surgery. METHODS: One group was treated with DSX, and the control group received the local standard of care. DSX was applied as a thin layer on the nerve root and surrounding area after microdiscectomy. RESULTS: The VAS pain scale was lower at all time points in the DSX treatment group than in the control group. The reductions at 30, 90, and 180 days for DSX and control groups, respectively, were 43.9% versus 35.6%, 64.3% versus 44.8%, and 75.4% versus 59.6%. The SF-36 scores in the DSX treatment group showed more improvement than in the control group as soon as 30 days for physical functioning, general health, vitality, social functioning, mental health, and emotional patterns, and by 90 days for bodily pain and general health. The Oswestry pain score was lower at all time points in the DSX treatment group than in the control group. The reductions at 30, 90, and 180 days for DSX and control groups, respectively, were 41.5% versus 34.3%, 68.2% versus 42.4%, and 73.3% versus 55.4%. Wound healing was normal in the DSX treatment group, there were no complications related to DSX use, and no patient in either group required reoperation. CONCLUSIONS: Although this study is too small to have conclusions of efficacy and will need confirmation by larger trials, treatment of a microdiscectomy site with DSX for fibrosis prevention shows promising results in terms of safety, reduction of postoperative pain and functional results when compared to control with the additional advantage of being suitable for use in the presence of a dural tear. PMID- 20542473 TI - Central orexin-A changes the gastrointestinal motor pattern from interdigestive to postprandial in rats. AB - Orexin-A, also described as hypocretin-I, was discovered in the extracts of the rat brain. OXA is implicated in a wide variety of physiological functions, such as feeding, arousal, behavioral activity, energy homeostasis and gastrointestinal motility. Orexin receptor type-1 is highly expressed in the dorsal motor nucleus of vagus. Although peripherally administered OXA abolishes small intestinal interdigestive contractions in rats, it still remains unclear whether central OXA affects interdigestive GI motility in rats. Two strain gauge transducers were attached on the antrum and duodenum to record circular muscle contractions. Spontaneous gastroduodenal contractions were recorded in freely moving conscious rats. OXA (1-20 ug) was administered intracerebroventricularly (i.c.v.). Atropine pretreatment (1 mg/kg, i.p.) and truncal vagotomy were performed to elucidate the neural pathways of central OXA. OXA (1-20 ug) dose-dependently disrupted the interdigestive phase III-like contractions and induced an irregular postprandial like motility pattern in the stomach and duodenum. The stimulatory effect of OXA on gastroduodenal postprandial-like motility pattern was abolished by atropine and truncal vagotomy. Central administration (i.c.v.) of selective OXA receptor antagonist, SB-334867 (16 ug), enhanced gastric spontaneous phase III-like contractions. It is suggested that central OXA changes GI motor pattern from interdigestive to postprandial via the vagal cholinergic pathways. Endogenous OXA may have an inhibitory role in interdigestive GI motility in rats. PMID- 20542474 TI - Current and emerging techniques of fetal cell separation from maternal blood. AB - Intense research has been carried out in recent years into methods that aim to harvest fetal genetic material from maternal blood as substitutes to amniocentesis and chorionic villus sampling. Just over 30 years have past since the first fetal cells were separated from maternal blood using flow cytometry highlighting the prospect of non-invasive prenatal diagnosis of fetal abnormalities. The aim of this review paper is to describe the most commonly used cell separation methods with emphasis on the isolation of fetal cells from maternal blood. The most significant breakthroughs and advances in fetal cell separation are reviewed and critically analyzed. Although much has been accomplished using well established techniques, a rapid and inexpensive method to separate fetal cells with great accuracy, sensitivity and efficiency to maximize cell yield is still required. In the past decade MEMS (Micro Electro Mechanical Systems) technologies have enabled the miniaturization of many biological and medical laboratory processes. Lab-on-chip systems have been developed and encompass many modules capable of processing different biological samples. Such chips contain various integrated components such as separation channels, micropumps, mixers, reaction and detection chambers. This article will also explore new emerging MEMS based separation strategies, which hope to overcome the current limitations in fetal cell separation. PMID- 20542475 TI - Simultaneous determination of cytosine arabinoside, daunorubicin and etoposide in human plasma. AB - A method for simultaneous bioanalysis of the three cytotoxic drugs cytosine arabinoside, daunorubicin and etoposide in human plasma was developed and validated. A HPLC method with ultra-violet and fluorescence detection, preceded by mixed-mode cation-exchange solid phase extraction sample preparation, was used for the quantification of the analytes. The assay was used for the simultaneous measurement of cytosine arabinoside, daunorubicin and etoposide with linearity in the ranges of 13-1500 ng/mL, 15-1000 ng/mL and 52.5-3500 ng/mL, respectively. The chromatographic run-time was 15.5 min. The overall precision (% relative standard deviation) was within 0.2-13.5% and the recovery ranged between 86.1% and 110.1% for the three drugs at all concentrations tested. Plasma samples were stable for at least two months when stored at -20 degrees C. The method was successfully applied to quantification of the three drugs in blood samples from patients undergoing induction treatment for acute myeloid leukaemia, thus demonstrating its suitability for clinical studies. PMID- 20542476 TI - Determination and pharmacokinetics of gastrodin in human plasma by HPLC coupled with photodiode array detector. AB - In present study, an HPLC method coupled with photodiode array detector (HPLC PDA) was established for determination and pharmacokinetics of gastrodin (GAS) in human plasma after an oral administration of GAS capsule. In the method, ethanol and dichloromethane were respectively used for deproteinization and purification during the sample preparation procedure. Separation of GAS was achieved on an AichromBond-AQ C18 column (5 microm, 150 mm x 4.6 mm) with the mobile phase of methanol-0.1% phosphoric acid solution (2:98, v/v) at a flow rate of 0.8 ml/min. The wavelength was set at 220 nm and the injection volume was 20 microl. Under the conditions, the calibration curve was linear within the concentration range of 50-4000 ng/ml with the correlation coefficient (r) of 0.99554 (weight=1/X(2)) and the lower limit of quantification (LLOQ) was 50 ng/ml. The inter- and intra day precisions were less than 11% and the accuracies (%) were within the range of 95.55-103.78%. The extraction recoveries were over 65% with RSDs less than 5.50%. The GAS was proved to be stable under tested conditions. Thus, the method was valid enough to be applied for pharmacokinetic study of GAS in human plasma. The pharmacokinetic parameters of GAS in human plasma after an oral administration of 200 mg GAS capsule were described as: C(max), 1484.55+/-285.05 ng/ml; T(max), 0.81+/-0.16 h; t(1/2alpha), 3.78+/-2.33 h; t(1/2beta), 6.06+/-3.20 h; t(1/2Ka), 0.18+/-0.53 h; K(12), 0.18+/-0.41/h; K(21), 0.20+/-0.16/h; K(10), 4.11+/-15.81/h; V1/F, 180.35+/-89.44 L; CL/F, 62.50+/-140.03 l/h; AUC(0-->t), 5619.41+/-1972.88 (ng/ml) h; and AUC(0-->infinity), 7210.26+/-3472.74 (ng/ml) h, respectively. These will be useful for the clinical application of GAS. PMID- 20542477 TI - Analysis by LC/ESI-MS of iophenoxic acid derivatives and evaluation as markers of oral baits to deliver pharmaceuticals to wildlife. AB - Iophenoxic acid and its derivatives (methyl, ethyl, and propyl) are organic chemicals used as markers in baiting campaigns to deliver vaccines, pharmaceuticals, contraceptives or poisons to wildlife. In this study we develop a method of detection of IPA derivatives by LC/ESI-MS (using butyl-IPA as internal standard) obtaining a limit of detection and quantification in wild boar (Sus scrofa) serum of 0.037 microg/ml and 0.123 microg/ml, respectively. The average recovery of IPA derivatives was 88% at levels >0.2 microg/ml, with coefficients of variation <15%. Wild boars in captivity were orally treated with 5 mg/kg b.w. (three adults) or 15 mg/kg b.w (two piglets and three adults) of methyl-, ethyl- and propyl-IPA and the serum levels of these were monitored during 18 months after dosing. Ethyl- and propyl-IPA were detected up to 18 months after a single oral dose in wild boar, especially at 15 mg/kg. Methyl-IPA was detected until 9 months after dosing. Half-lives of methyl-, ethyl- and propyl-IPA were (mean+/-SD) 41+/-5, 183+/-85 and 165+/-45 days, respectively. One control piglet not exposed to IPA, but housed in the same facility than treated animals showed detectable IPA levels in serum. Piglets born from mothers exposed to marked baits also showed detectable IPA levels in serum. The high persistence of Et- and Pr-IPA must be considered in the field trials, because the presence of the product at low levels in one animal may not reflect a real ingestion of the marked bait. PMID- 20542478 TI - Development and validation of a sensitive ultra performance liquid chromatography tandem mass spectrometry method for the analysis of fentanyl and its major metabolite norfentanyl in urine and whole blood in forensic context. AB - Fentanyl and its major metabolite norfentanyl often occur in low doses in biological samples. Therefore, a highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and fully validated. Sample preparation was performed on a mixed-mode cation exchange solid phase extraction (SPE) cartridge with an additional alkaline wash step to decrease matrix effects and thus increase sensitivity. Ionization of fentanyl and norfentanyl with electrospray ionization (ESI) was more efficient than atmospheric pressure chemical ionization (APCI). The use of a mobile phase of high pH resulted in higher ESI signals than the conventional low pH mobile phases. In the final method, gradient elution with 10 mM ammonium bicarbonate (pH 9) and methanol was performed. A comparison of columns with different internal diameter and/or smaller particles showed optimal resolution and sensitivity when an Acquity C18 column (1.7 microm, 2.1 mm x 50 mm) was used. Deuterium labeled internal standards were used, but with careful evaluation of their stability since loss of deuteriums was seen. With limits of detection of 0.25 pg/ml for fentanyl and 2.5 pg/ml for norfentanyl in urine and 5 pg/ml for fentanyl and norfentanyl in whole blood the presented method is highly appropriate for the analysis of fentanyl and norfentanyl in forensic urine and blood samples. PMID- 20542479 TI - Mining ventricular cerebrospinal fluid from patients with traumatic brain injury using hexapeptide ligand libraries to search for trauma biomarkers. AB - Traumatic brain injury (TBI) is an acute event resulting from external force to the brain and is a major cause of death and disability associated with high health care costs in the western world. Additional injuries, originating from the secondary molecular events after the initial intensive care, may be limited by the use of objective biomarkers to provide the best treatment and patient prediction outcome. In this study, hexapeptide ligand libraries (HLL) have been used for the enrichment of suggested protein biomarkers for TBI in cerebrospinal fluid (CSF). HLL have the potential to enrich low abundant proteins and simultaneously reduce the high abundant proteins, rendering a sample with significantly reduced dynamic range. The CSF proteome from two TBI inflicted patients have been extensively mapped using a large initial sample volume obtained by extraventricular drainage. Shotgun proteomics, in combination with isoelectric focusing (IEF) and nano-LC-MS/MS, identified 339 unique proteins (MudPIT scoring p < or = 0.05) with a protein overlap of 130 between the patients. As much as 45% of the proteins reported in the literature to be associated with degenerative/regenerative processes occurring after a trauma to the head were identified. Out of the most prominent potential protein biomarkers, such as neuron specific enolase, glial fibrillary acidic protein, myelin basic protein, creatine kinase B-type and S-100beta, all except myelin basic protein were detected in the study. This study shows the possibility of using HLL as a tool for screening of low abundant protein biomarkers in human CSF. PMID- 20542481 TI - [Spontaneous chylous pericardial effusion: report of two cases]. AB - Most cases of chylopericardium in childhood are secondary to thoracic surgery, especially after cardiac surgery. However, it can also be present in children without this history, as we show in this report. First, a nine year-old boy in whom chylopericardium was the first manifestation of a lymphangiomatosis, and the second one, a fifteen months old girl with a history of Down's syndrome and autoimmune enteropathy, which was classified as primary congenital chylopericardium. Also, a review of literature over the last 13 years is made, and management of this rare entity is discussed. PMID- 20542482 TI - Tolerance of prefabricated skin flaps to ischaemia and reperfusion: experimental study. AB - Custom prefabrication of tissues allows the surgeon to build what is required for the reconstruction and has enabled the surgeon to reinforce new blood supply into selected blocks of tissue without vessel anastomosis. However, prefabricated flaps have several drawbacks and characteristics that differentiate them from conventional flaps. The objective of this study was to test the tolerance of prefabricated flaps to ischaemia/reperfusion injury in rats. In the first stage, the unilateral-inferior-epigastric pedicle was ligated and divided, and then a skin flap was fabricated by implantation of distally ligated femoral arteriovenous pedicle beneath the abdominal skin. The femoral vessels were implanted either in skeletonised or in muscle-cuffed fashion beneath the abdominal skin, a portion of which was raised as an island flap, based on these vessels. Prefabricated flaps (3*6 cm) were raised 6 weeks after, and were subjected to 10 h ischaemia and followed by 12 h reperfusion. Flap survival and histological changes at the pedicle-skin junction were evaluated at 7 days. Flap necrosis in the sham group was 0%, whereas the control group (conventional) had 47.27+/-13.50% necrosis. Flaps prefabricated with skeletonised femoral pedicle demonstrated an insignificant pattern with 63.74+/-10.62% necrosis when compared with prefabricated flaps with muscle-cuffed pedicle with the percentage of necrosis of 64.51+/-11.24. The area of necrosis was significantly increased when both the prefabricated flaps were compared with the control group or with the sham-prefabricated group (p<0.05). Skin flaps prefabricated with either pedicle alone or pedicles with muscle cuff are more susceptible to ischaemia and following reperfusion in comparison with the normal flaps. PMID- 20542480 TI - Genetic susceptibility to breast cancer. AB - Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours unselected for family history. The relationship between genetic variants and pathological subtypes of breast cancer, and the implication of discoveries of novel genetic variants to risk prediction in BRCA1/2 mutation carriers and in populations unselected for mutation carrier status, are discussed. PMID- 20542483 TI - A new approach to microneurovascular TRAM-flap breast reconstruction--a pilot study. AB - BACKGROUND: The aims of the present study were to investigate whether microneurovascular breast reconstruction with a free transverse rectus abdominis musculocutaneous (TRAM) flap and nerve repair with nerves other than ThIV and ThXI improve sensory recovery of the breast compared to traditional free TRAM flap without nerve repair, and which nerve is optimal for the neural anastomosis of the flap. METHODS: Twenty breast cancer patients underwent breast reconstruction with a free TRAM flap and nerve repair (neuro-TRAM) with the best available nerve from the axillary area and 20 control patients had traditional free TRAM flap without nerve repair (standard-TRAM). Neurorrhaphy was done by end to-end or end-to-side techniques. Sensory and quantitative sensory testings (QST) were performed. Patient satisfaction was evaluated by a clinical questionnaire. The results were analysed by Mann-Whitney tests. RESULTS: Mean follow-up was 32 months for the neuro-TRAM, and 54 months for the standard-TRAM group. Sensory outcome was better in the neuro-TRAM group (sensory score 45% of that of the contralateral breast) than in the standard-TRAM group (26% of the contralateral side). The median (quartiles) of total scores in the operated breasts was 12.9 (9.5-19.2) in neuro-TRAM group and 8.1 (3.5-10.7) in standard-TRAM group (Mann Whitney Test (p=0.006)). All nerves available in the thoracic and axillary areas and both of the anastomosis techniques were successful in the reinnervation procedure. Nerve repair did not influence overall patient satisfaction. CONCLUSIONS: This study indicates that any nerve repair results in improved sensory recovery after TRAM flap breast reconstruction. Any nerve available for anastomosis in the recipient site is potentially able to provide moderately good cutaneous sensibility to the TRAM-breast. PMID- 20542484 TI - Surgical technique: The intercostal space approach to the internal mammary vessels in 463 microvascular breast reconstructions. AB - The internal mammary vessels are one of the most frequently used recipient sites for microsurgical free-flap breast reconstruction, and an accepted technique to expose these vessels involves removal of a segment of costal cartilage of the rib. However, in some patients, cartilage removal may result in a visible medial chest-wall depression that requires corrective procedures. We, therefore, use an intercostal space approach to the internal mammary vessels, as there is minimal disturbance of the costal cartilage with this technique. We have developed and performed our technique over an 8-year period in 463 microvascular breast reconstructions, and present it here as it contains modifications not previously described that may be of interest to other surgeons. There was no serious morbidity associated with the intercostal space approach, the internal mammary vessels were reliably and safely exposed in all these cases and the flap success rate was 95.8%. PMID- 20542485 TI - Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. AB - PURPOSE: To examine the histopathologic effect of a single intravitreal injection of bevacizumab on newly formed vessels in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Interventional case series and laboratory investigation. METHODS: Two days after intravitreal injection of bevacizumab (1.25 mg/eye), pars plana vitrectomy or trabeculectomy was performed for the treatment of PDR or neovascular glaucoma (NVG) associated with PDR. Ten surgically removed preretinal proliferative tissues and 6 deep scleral flaps containing trabecular meshwork were fixed in 2% glutaraldehyde or 4% paraformaldehyde and were subjected to transmission electron microscopic analysis, immunohistochemical analysis, and terminal deoxyuridiine triphosphate (dUTP) nick-end labeling staining. Two surgically removed preretinal proliferative tissues and 2 deep scleral flaps from patients with PDR and NVG, but without preoperative intravitreal injection of bevacizumab (IVB), served as controls. RESULTS: In control tissues, vascular endothelial cells possessed many fenestrations and were accompanied by pericytes. Apoptotic vascular endothelial cells frequently were observed in tissue after intravitreal injection of bevacizumab, whereas they were not observed in control tissues. Additionally, no apparent fenestration was observed in newly formed vessels from either proliferative tissue or trabecular meshwork after intravitreal injection of bevacizumab. In both PDR and NVG tissues after intravitreal injection of bevacizumab, overexpression of smooth muscle actin was observed in newly formed vessels, suggesting that the treatment may have increased pericytes on the vasculature as compared with control tissue. CONCLUSIONS: Intravitreal injection of bevacizumab may induce changes in immature, newly formed vessels of PDR or NVG tissue, leading to endothelial apoptosis with vascular regression, while inducing normalization of premature vessels by increasing pericyte coverage and reducing vessel fenestration. PMID- 20542486 TI - The use of titanium T-plate as platform for globe alignment in severe paralytic and restrictive strabismus. AB - PURPOSE: To evaluate the long-term effectiveness of improved ocular alignment using a suture/T-plate anchoring platform system. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: setting: Institutional. study population: Seven consecutive patients with large angle deviations attributable to paralytic and/or restrictive strabismus managed jointly by orbital and strabismus surgeons. intervention procedure: The T-plate base is anchored to the orbital rim with the shaft projecting toward the orbital apex to simulate the origin of the affected muscle. A nonabsorbable suture serves as the coupling element linking the muscle insertion to the tip of the T-plate such that the suture coincides with the axis of the dysfunctional muscle and yields a pull vector to simulate the passive tensile force of the muscle. Information analyzed included patient demographics, etiology of strabismus and characteristics, prior muscle surgeries, secondary interventions, subjective appraisal of diplopia, and final ocular alignment measurements. main outcome measures: Subjective appraisal of diplopia, final ocular alignment in primary gaze, and late stability. RESULTS: All 7 patients showed marked reduction in ocular deviation with a median change of 33 prism diopters (PD) and a range of 7 to 72 PD. For the 6 patients with medial rectus dysfunction, the final ocular alignment ranged from 6 to 18 PD of residual exotropia in primary gaze. The patient with sixth nerve palsy had 5 PD of residual esotropia. There were no failures after an average of 59.4 months of follow-up. CONCLUSIONS: A globe tethering technique using a suture/titanium T plate anchoring platform system effectively treats refractory cases of paralytic and restrictive strabismus with large angles of deviation. PMID- 20542487 TI - Visual outcomes of LASIK-induced monovision in myopic patients with presbyopia. AB - PURPOSE: To evaluate binocular visual acuity (VA), contrast sensitivity, and stereopsis in myopic patients after laser in situ keratomileusis (LASIK)-induced monovision. DESIGN: Prospective, observational study. METHODS: We performed a prospective study of 37 consecutive patients older than 45 years who underwent bilateral myopic LASIK with planned monovision. At the 6-month postoperative visit, we evaluated distance and near binocular visual acuity, contrast sensitivity, and stereopsis. Binocular tests were done without spectacles (in monovision condition) and compared with the results obtained by repeating the same binocular tests with the same patients (serving as a control group) after spectacle correction of the residual myopic defect in the nondominant eye for distance tests (reverting monovision) and after spectacle correction of the presbyopia bilaterally for near tests (near best spectacle-corrected VA). RESULTS: By inducing a mean residual spherical equivalent defect of -0.97 diopter in the nondominant eye, the patients achieved a mean near binocular uncorrected visual acuity (UCVA) of 0.74, a mean reading test binocular UCVA of 0.88 using an acceptable spontaneous reading distance (48 cm), and a mean distance binocular UCVA of 1.08. A slight decrease in contrast sensitivity and stereopsis was observed in monovision compared to full distance correction. CONCLUSIONS: Monovision is a valid option for myopic patients with presbyopia who are considering LASIK. Good distance and near UCVAs can be obtained with this procedure. PMID- 20542489 TI - Categorization and cognitive deficits in compulsive hoarding. AB - According to the cognitive-behavioural model of compulsive hoarding, information processing deficits in the areas of attention, memory, decision-making, and categorization contribute to hoarding behaviour. The purpose of the current study was to examine whether individuals with compulsive hoarding exhibited impairment on executive functioning and categorization tasks. Three groups of participants were recruited (N = 60): individuals with compulsive hoarding syndrome, individuals with an Axis I mood or anxiety disorder, and non-clinical control participants. All participants completed self-report measures of cognitive difficulties, neuropsychological tests of executive functioning and decision making, and four categorization tasks. Results suggested that hoarding participants reported more cognitive failures and more problems with attention and decision-making than non-clinical control participants. In addition, hoarding participants performed worse than both control groups on the Stockings of Cambridge (SOC), a neuropsychological test of planning ability, and were slower and more anxious during a categorization task. These findings suggest that specific deficits in executive functioning may be associated with the difficulties hoarding patients have organizing their possessions. PMID- 20542490 TI - Between nitros(yl)ation and nitration: regulation of thioredoxin-1 in myocardial ischemia/reperfusion injury. PMID- 20542488 TI - Participation of the endocannabinoid system in lipopolysaccharide-induced inhibition of salivary secretion. AB - OBJECTIVE: The aim of the present paper was to assess whether lipopolysaccharide (LPS)-induced inhibition of salivary secretion involves the activation of the endocannabinoid system and the participation of tumor necrosis factor (TNF)alpha in the submandibular gland. DESIGN: Pharmacological approaches were performed by using CB1 and/or CB2 cannabinoid receptor antagonists, AM251 and AM630, respectively, injected into the submandibular gland, to study the participation of the endocannabinoid system in LPS inhibitory effects on metacholine-induced salivary secretion. To assess the participation of TNFalpha on LPS inhibitory effects, salivary secretion was studied in LPS treated rats after the intraglandular injection of etanercept, a soluble form of TNF receptor which blocks TNFalpha action. Finally, to evaluate the possible interplay between endocannabinoids and TNFalpha on the submandibular gland function reduced during LPS challenge, the salivary secretion was studied after the intraglandular injection of this cytokine alone or concomitantly with AM251 and AM630. RESULTS: AM251 and AM630, injected separately or concomitantly, partially prevented LPS induced inhibition of salivation. Also, anandamide synthase activity was increased in submandibular glands extracted from rats 3h after LPS injection, suggesting that the endocannabinoid system was activated in response to this challenge. On the other hand, etanercept, prevented the inhibitory effect of LPS on salivary secretion and moreover, TNFalpha injected intraglandularly inhibited salivary secretion, being this effect prevented by AM251 and AM630 injected concomitantly. CONCLUSION: The present results demonstrate the participation of the endocannabinoid system and TNFalpha on salivary responses during systemic inflammation induced by LPS. PMID- 20542491 TI - Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response. AB - Benfotiamine (BFT) is a transketolase activator that directs glucose to the pentose phosphate pathway. The present study investigated whether BFT improves the recovery after myocardial infarction (MI) and explored underlying mechanisms of protection. Non-diabetic and streptozotocin-induced type 1 diabetic mice were supplemented with BFT (70 mg/kg/day in drinking water) for 4 weeks and then subjected to MI or sham operation. Cardiac function was monitored by echocardiography. At two weeks post-MI, intra-ventricular pressure was measured by Millar tip-catheter and hearts were collected for biochemical, immunohistochemical and expressional analyses. No treatment effect was observed in sham-operated mice. Post-MI mortality was higher in diabetic mice and hemodynamic studies confirmed the worsening effect of diabetes on functional recovery. Furthermore, diabetic mice demonstrated increased cardiomyocyte apoptosis, reduced reparative angiogenesis, larger scars, enhanced oxidative stress, and blunted activation of the pro-survival VEGF receptor-2/Akt/Pim-1 signaling pathway. BFT improved post-MI survival, functional recovery and neovascularization and reduced cardiomyocyte apoptosis and neurohormonal activation in diabetic as well as in non-diabetic mice. In addition, BFT stimulated the activity of pentose phosphate pathway enzymes, leading to reduction of oxidative stress, phosphorylation/activation of VEGF receptor-2 and Akt and increased Pim-1, pBad and Bcl-2 levels. These effects were contrasted on silencing glucose-6-phosphate dehydrogenase, the key enzyme in pentose phosphate pathway, or inhibiting Akt. BFT benefits post-MI recovery through stimulation of pro-survival mechanisms and containment of neurohormonal response. These results may have implications for the treatment of myocardial ischemia. PMID- 20542492 TI - Excellent reproducibility of laser speckle contrast imaging to assess skin microvascular reactivity. AB - OBJECTIVE: We compared the inter-day reproducibility of post-occlusive reactive hyperemia (PORH) assessed by single-point laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LSCI), and the reproducibility of local thermal hyperemia (LTH) assessed by LDF, laser Doppler imaging (LDI) and LSCI. We also tested whether skin blood flow assessment by LDF and by LSCI are correlated. METHODS: Skin blood flow was evaluated during PORH and LTH using LDF, LDI (for LTH only) and LSCI on the forearms of healthy volunteers, at a 7day interval. Data are expressed as cutaneous vascular conductance (CVC), as a function of baseline and scaled to the thermal plateau. Reproducibility is expressed as within subject coefficients of variation (CV, in %) and intra-class correlation coefficients (ICC). RESULTS: Twenty-eight healthy participants were enrolled in this study. The reproducibility of the PORH peak CVC was better when assessed with LSCI compared to LDF (CV=8%; ICC=0.76 and CV=30%; ICC=0.54, respectively). Inter-day reproducibility of the LTH plateau was better when assessed with LSCI or LDI than LDF (CV=15%, ICC=0.66; CV=17%, ICC=0.51 and CV=42%, ICC=0.28 respectively). Finally, we observed significant correlation between simultaneous LDF and LSCI measurements of the PORH peak CVC (R=0.54; p=0.001). CONCLUSION: The recently developed LSCI technique showed very good inter-day reproducibility for assessing PORH and LTH. Moreover, we showed significant correlation between LSCI and single-point LDF for PORH. However, more data are needed to evaluate the linearity between the LSCI signal and skin blood flow. PMID- 20542493 TI - Greenspace and children's physical activity: a GPS/GIS analysis of the PEACH project. AB - OBJECTIVE: To quantify the volume and intensity of children's physical activity after school in greenspace and elsewhere. METHODS: Data were collected between 2006 and 2008 from 1,307 children aged 10-11 in Bristol, UK. Accelerometers and Global Positioning System receivers measured activity and location every 10 s (epoch) after school for four days. Data were mapped in a Geographic Information System with a greenspace dataset. Activity volume (accelerometer counts per minute), time in moderate-vigorous physical activity (MVPA), and the odds of an epoch being MVPA (using logistic regression) were compared for greenspace, non greenspace and indoors. RESULTS: 13% of monitored time was spent outdoors (2% in greenspace), during which time 30% of activity volume and 35% of MVPA was accumulated. 7% of boys' activity volume and 9% of MVPA were in greenspace with girls slightly lower (5% and 6% respectively). The odds of an epoch being MVPA in greenspace relative to outdoor non-greenspace was 1.37 (95% CI 1.22-1.53) for boys and 1.08 (95% CI 0.95-1.22) for girls. CONCLUSION: Most activity occurring outdoors is not in greenspace and non-green urban environments are therefore very important for children's activity. However, when boys are in greenspace, activity is more likely to be of higher intensity. PMID- 20542494 TI - Functional amygdala-hippocampus connectivity during anticipation of aversive events is associated with Gray's trait "sensitivity to punishment". AB - BACKGROUND: The reinforcement sensitivity theory postulates a behavioral inhibition system that modulates reaction to stimuli indicating aversive events. Gray's dimension of anxiety, reflecting human trait sensitivity to aversive events, determines the extent to which stimuli activate the behavioral inhibition system. Although structural brain imaging has previously identified the amygdala and the hippocampus as two major components related to the behavioral inhibition system, the functional dynamics of the responses in these structures remain unclear. METHODS: In this study, we examined the event-related functional magnetic resonance imaging blood oxygen level-dependent response in the hippocampus and amygdala as well as the functional connectivity of the two regions during anticipation of monetary loss in 45 healthy human subjects. RESULTS: Anticipation of loss elicited activation in the hippocampus as well as in the amygdala. Additionally, substantial functional connectivity between the two areas was observed. Furthermore, this functional connectivity was significantly correlated with individual differences in Gray's trait sensitivity to aversive events. Specifically, higher trait sensitivity to aversive events was associated with increased functional connectivity following cues indicating potential loss. CONCLUSIONS: In summary, we show that individual differences regarding Gray's trait sensitivity to aversive events as defined by the reinforcement sensitivity theory are associated with the neural dynamics of the amygdala-hippocampal circuit during anticipation of aversive events. In particular, evidence is provided for a relationship between functional brain imaging data and a psychometric approach specifically measuring Gray's trait sensitivity to aversive events, thereby potentially identifying the neural substrate of the behavioral inhibition system. PMID- 20542496 TI - Proinflammatory cytokines down-regulate intestinal selenoprotein P biosynthesis via NOS2 induction. AB - Selenoprotein P (SeP), serving as selenium transporter and extracellular antioxidant, is assumed to have a protective role in the gastrointestinal tract, which is particularly susceptible to oxidative damage. Decreased SeP mRNA levels have been found in colon cancer; however, information on the control of intestinal SeP biosynthesis is scarce. We analyzed SeP biosynthesis in human intestinal epithelial Caco-2 cells subject to differentiation from crypt- to villous-like enterocytes. In the course of Caco-2 cell differentiation, SeP mRNA expression and secretion increased concomitant with three regulators of SeP transcription: hepatocyte nuclear factor-4alpha, forkhead box class O1a, and peroxisomal proliferator-activated receptor-gamma coactivator 1alpha. Treatment of differentiated Caco-2 cells with the proinflammatory cytokines IL-1beta, TNF alpha, and IFN-gamma caused a down-regulation of SeP biosynthesis, resulting from induction of nitric oxide synthase 2. These observations were corroborated by decreased SeP mRNA levels in the colon of dextran sodium sulfate-treated mice, an animal model of experimental colitis. We conclude that inflammation of the intestinal mucosa causes a decline in locally produced selenoprotein P in the colon that eventually may contribute to the emergence of inflammatory bowel disease-related colorectal cancer. PMID- 20542495 TI - Mechanism for the protective effect of resveratrol against oxidative stress induced neuronal death. AB - Oxidative stress can induce cytotoxicity in neurons, which plays an important role in the etiology of neuronal damage and degeneration. This study sought to determine the cellular and biochemical mechanisms underlying resveratrol's protective effect against oxidative neuronal death. Cultured HT22 cells, an immortalized mouse hippocampal neuronal cell line, were used as an in vitro model, and oxidative stress and neurotoxicity were induced in these neuronal cells by exposure to high concentrations of glutamate. Resveratrol strongly protected HT22 cells from glutamate-induced oxidative cell death. Resveratrol's neuroprotective effect was independent of its direct radical scavenging property, but instead was dependent on its ability to selectively induce the expression of mitochondrial superoxide dismutase (SOD2) and, subsequently, reduce mitochondrial oxidative stress and damage. The induction of mitochondrial SOD2 by resveratrol was mediated through the activation of the PI3K/Akt and GSK-3beta/beta-catenin signaling pathways. Taken together, the results of this study show that up regulation of mitochondrial SOD2 by resveratrol represents an important mechanism for its protection of neuronal cells against oxidative cytotoxicity resulting from mitochondrial oxidative stress. PMID- 20542497 TI - Elevated extracellular calcium increases fibroblast growth factor-2 gene and protein expression levels via a cAMP/PKA dependent pathway in cementoblasts. AB - Cementoblasts, tooth root lining cells, are responsible for laying down cementum on the root surface, a process that is indispensable for establishing a functional periodontal ligament. Cementoblasts share phenotypical features with osteoblasts. Elevated levels of extracellular Ca(2+) have been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of extracellular Ca(2+) signaling in cementogenesis has not been examined. Using RT-PCR, we found that elevated levels of extracellular Ca(2+) increase fibroblast growth factor (FGF)-2 gene expression with a peak at 6h. Pretreatment with a protein kinase A (PKA) inhibitor, H89, or an adenylate cyclase inhibitor, MDL-12,330A, inhibited Ca(2+)-stimulated Fgf-2 expression. In contrast, pretreatment with the protein kinase C (PKC) inhibitor GF-109203X or the phospholipase C (PLC) inhibitor U73122 did not affect the expression of Fgf-2 transcripts, suggesting that the increase in Fgf-2 expression was dependent on the PKA but not the PLC/PKC signaling pathway. Treatment with an activator of adenylate cyclase, forskolin, or a cell-permeable analog of cAMP, 8-Br-cAMP, enhanced Ca(2+)-stimulated Fgf-2 expression, but a single treatment with forskolin or 8-Br-cAMP did not, suggesting that cAMP generation is indispensable but not sufficient for Ca(2+)-stimulated FGF2 expression. Next, we examined the cation specificity of the putative receptor and showed that treatment with trivalent/divalent inorganic ions, Ca(2+), Gd(3+), Sr(2+), or Al(3+), caused a dose-dependent increase in Fgf-2 mRNA levels in a cAMP-dependent fashion, whereas Mg(2+) and the organic ions neomycin and spermine had no effect on Fgf-2 gene expression levels. These findings suggest that an extracellular Ca(2+)-sensing mechanism is present in cementoblasts and its activation leads to FGF-2 stimulation in a cAMP/PKA dependent fashion. Understanding the pathway regulating key genes involved in modulating the regeneration of oral tissues will assist in designing regenerative therapies based on reliable biological principles. PMID- 20542498 TI - Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates. AB - There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of a Shigella vaccines is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates. This finding is now extended to the O-SPC of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1. The structures of O-SPC, containing core plus 1-4 O-SP repeat units (RUs), were analyzed by NMR and mass spectroscopy. The first RUs attached to the cores of S. flexneri 2a and 6 LPS were different from the following RUs in their O-acetylation and/or glucosylation. Conjugates of core plus more than 1 RU were necessary to induce LPS antibodies in mice. The resulting antibody levels were comparable to those induced by the full length O-SP conjugates. In S. dysenteriae type 1, the first RU was identical to the following RUs, with the exception that the GlcNAc was bound to the core in the beta-configuration, while in all other RUs the GlcNAc was present in the alpha-configuration. In spite of this difference, conjugates of S. dysenteriae type 1 core with 1, 2, or 3 RUs induced LPS antibodies in mice with levels statistically higher than those of the full size O-SP conjugates. O-SPC conjugates are easy to prepare, characterize, and standardize, and their clinical evaluation is planned. PMID- 20542499 TI - [Total obstruction after vertical laparoscopic gastrectomy]. PMID- 20542500 TI - [Incidence of iatrogenic perforation during colonoscopy and their treatment in a university hospital]. AB - INTRODUCTION: Colon perforation is a fairly uncommon, but serious, complication during endoscopy of the lower gastrointestinal tract. Treatment is controversial, although surgery is used in the majority of cases. The aims of this study were to determine the incidence of perforations due to colonoscopy in our hospital and to find out the results of the treatment options used. MATERIAL AND METHODS: Retrospective study of perforations caused by colonoscopy between January 2004 and October 2008. The variables analysed were: demographic characteristics, colonoscopy indication, clinical signs and symptoms, diagnostic tests used, time between perforation and the diagnosis, treatment type, hospital stay and complications. RESULTS: A total of 13,493 colonoscopies were performed during the study period. A perforation of the colon was found in 13 (0.1%) patients. Nine perforations occurred whilst performing a diagnostic colonoscopy (0.08%) and the remaining 4 after a therapeutic colonoscope (0.16%). In 10 of the cases the diagnosis was made within the first 12h, and in 5 of these the perforation was identified during the procedure itself. The most common location was the sigmoid, in 7 cases. Surgical treatment was carried out on 11 patients, and in the other two it was resolved by conservative treatment. The most used surgical technique was simple suture followed by resection with anastomosis. One patient died due to intra-abdominal sepsis. CONCLUSION: Perforations caused by colonoscopy are rare, but serious, complications. The majority of these patients required surgical treatment, with conservative treatment being reserved for selected patients. PMID- 20542501 TI - Immunolocalization of humanin in human sperm and testis. AB - We have discovered, by immunocytochemistry and immunoelectronmicroscopy, that humanin (HN) is expressed in human ejaculated sperm and testis. In sperm, the HN immunolabeling pattern depends on sperm morphology; in particular, HN is mainly localized in the midpiece of sperm in semen samples with normal morphology and in cytoplasmic residues and entire tail in those with abnormal morphology. We also found HN in the cytoplasm and nucleus of spermatocytes and spermatids and in experimentally uncoiled chromatin of mature ejaculated sperm. Because it has been established that HN has antiapoptotic properties, it is reasonably hypothesized that HN may play an important role in preventing apoptosis in human sperm and testis. Thus, the examination of the HN localization in normal and abnormal sperm could be proposed as an auxiliary test to better define sperm quality. PMID- 20542502 TI - Birth after 12 hours of oocyte refrigeration. AB - OBJECTIVE: To assess cycle outcome after oocyte refrigeration. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): One couple in a donor oocyte program. INTERVENTION(S): Intracytoplasmic sperm injection and blastocyst culture after refrigeration of oocytes for 12 hours. MAIN OUTCOME MEASURE(S): Birth. RESULT(S): Fourteen two-pronuclei zygotes from 17 metaphase II refrigerated oocytes resulted in transfer of two blastocysts at day 5 and cryopreservation of six excess embryos at day 6. The patient delivered one healthy male baby after 38 weeks' gestation. CONCLUSION(S): The successful outcome of oocyte refrigeration indicates that this protocol could be useful in circumstances in which a delay in obtaining spermatozoa arises. PMID- 20542503 TI - Live birth after anonymous donation of twice-cryopreserved embryos that had been stored in liquid nitrogen for a cumulative storage time of approximately 13.5 years. AB - OBJECTIVE: To report a live birth after transfer of anonymously donated, twice cryopreserved embryos that had been stored in liquid nitrogen for approximately 13.5 years. DESIGN: Case report. SETTING: A private assisted reproduction center. PATIENT(S): A 44-year-old recipient of donated cryopreserved embryos. INTERVENTION(S): Anonymous donation of cryopreserved blastocysts for procreation. MAIN OUTCOME MEASURE(S): Live birth after thawing and replacement of re cryopreserved blastocysts. RESULT(S): Fourteen pronuclear-stage embryos and four cleavage-stage embryos were cryopreserved during a primary IVF cycle. In two separate cycles, one cycle for the primary patient and a subsequent cycle for the first embryo donor recipient, the 18 embryos were thawed and grown to the blastocyst stage for transfer. Supernumerary blastocysts (n = 5) not replaced at either of these two thaw cycles were re-cryopreserved and subsequently donated to another embryo donor recipient. Five blastocysts survived the thaw and three were transferred, resulting in a live birth. The embryos were cryopreserved for a cumulative storage time of approximately 4,909 days (13.4 years). CONCLUSION(S): The longevity (viability) of cryopreserved embryos maintained in liquid nitrogen remains to be determined; cryopreserved embryo donation for procreation should not be overlooked, regardless of the length of time that embryos remain in cryostorage. PMID- 20542504 TI - Molecular profiling of human oocytes after vitrification strongly suggests that they are biologically comparable with freshly isolated gametes. AB - To assess the effects of vitrification on the biomolecular profile of oocytes, we analyzed through real-time reverse transcriptase-polymerase chain reaction eight genes encoding critically important proteins for embryo development and compared this partial transcriptome with that of freshly collected gametes isolated from the same women. The comparison of the molecular profiles demonstrated that our vitrification protocol does not alter the biomolecular quality of oocytes: in fact, between the two groups we found the absence of statistically significant variations. Accordingly, this cryopreservation technique might be helpful in preserving women's fertility. PMID- 20542505 TI - Effects of semen storage and separation techniques on sperm DNA fragmentation. AB - OBJECTIVE: To determine the effect of semen storage and separation techniques on sperm DNA fragmentation. DESIGN: Controlled clinical study. SETTING: An assisted reproductive technology laboratory. PATIENT(S): Thirty normoozospermic semen samples obtained from patients undergoing infertility evaluation. INTERVENTION(S): One aliquot from each sample was immediately prepared (control) for the sperm chromatin dispersion assay (SCD). Aliquots used to assess storage techniques were treated in the following ways: snap frozen by liquid nitrogen immersion, slow frozen with Tris-yolk buffer and glycerol, kept on ice for 24 hours or maintained at room temperature for 4 and 24 hours. Aliquots used to assess separation techniques were processed by the following methods: washed and centrifuged in media, swim-up from washed sperm pellet, density gradient separation, density gradient followed by swim-up. DNA integrity was then measured by SCD. MAIN OUTCOME MEASURE(S): DNA fragmentation as measured by SCD. RESULT(S): There was no significant difference in fragmentation among the snap frozen, slow frozen, and wet-ice groups. Compared to other storage methods short-term storage at room temperature did not impact DNA fragmentation yet 24 hours storage significantly increased fragmentation. Swim-up, density gradient and density gradient/swim-up had significantly reduced DNA fragmentation levels compared with washed semen. Postincubation, density gradient/swim-up showed the lowest fragmentation levels. CONCLUSION(S): The effect of sperm processing methods on DNA fragmentation should be considered when selecting storage or separation techniques for clinical use. PMID- 20542506 TI - Intrauterine balloon tamponade as a treatment for immune thrombocytopenic purpura induced severe uterine bleeding. AB - OBJECTIVE: To report our experience of applying balloon tamponade in the treatment of intrauterine bleeding in two patients with immune thrombocytopenic purpura (ITP). Immune thrombocytopenic purpura is a well-known hematologic autoimmune disease. The uterus may be a major site of bleeding in patients with ITP. Halting bleeding is imperative to reduce blood loss and platelet consumption and to allow medical treatment to increase platelet count. Balloon tamponade has been described as an effective method to control bleeding in a variety of clinical situations; it is an effective and accessible modality, requiring no analgesia or anesthesia, and helps facilitate continuous monitoring of uterine bleeding. DESIGN: Report of two cases. SETTING: Obstetrics and gynecology department in a tertiary care center in Jerusalem, Israel. PATIENT(S): Two patients with ITP with severe uterine bleeding refractory to treatment with estrogen and IV IgG. INTERVENTION(S): Intrauterine balloon tamponade. MAIN OUTCOME MEASURE(S): Cessation of uterine bleeding, appearance of complications. RESULT(S): Insertion of balloon tamponade successfully controlled bleeding in both cases. The patient in case 1 subsequently had persistent hypomenorrhea. The patient in case 2 had abdominal pain and suspected pelvic inflammation. CONCLUSION(S): Our presented cases demonstrate that uterine bleeding can be controlled successfully in patients with ITP with an intrauterine balloon. This novel application raises many technical issues, such as the appropriate filling pressures and duration of treatment. Possible risks, such as endometrial injury, still remain to be resolved and mandate future clinical research. PMID- 20542507 TI - Pressure changes during embryo transfer. AB - OBJECTIVE: To investigate the pressure changes in the transferred load during mock ET. DESIGN: Experimental setup. SETTING: Academic Research Institute of Mechanical Engineering and private centers of reproductive medicine. PATIENTS(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Laboratory simulations of ET into a rigid transparent uterine model equipped with a pressure sensor. RESULT(S): Injection of a transferring load during mock ET could increase pressure locally up to 155 mm Hg in <0.1 seconds. The recorded pressure increase slope reached values as high as 72,000 mmHg/s, and the pressure decrease slope reached 144,000 mmHg/s. The pressure buildup in the transferred liquid was proportional to the ejection speed of the transferred load. CONCLUSION(S): ET can cause rapid pressure fluctuations in the transferred liquid. Therefore, it is advisable to transfer the embryo gently with minimum ejection speed, to avoid exposing the embryo to the steep pressure gradient. PMID- 20542508 TI - Embryo yield after in vitro fertilization in women undergoing embryo banking for fertility preservation before chemotherapy. AB - OBJECTIVE: To evaluate embryo yield after IVF in patients undergoing embryo banking before chemotherapy. DESIGN: A retrospective cohort study. SETTING: Hospital-based academic medical center. PATIENT(S): Thirty-eight women diagnosed with cancer or autoimmune disease presenting for IVF cycles, with or without intracytoplasmic sperm injection (ICSI), for embryo cryopreservation before any therapy were compared with 921 presumably fertile women undergoing IVF for male factor infertility from January 2001 through October 2007. INTERVENTION(S): Standard IVF or ICSI protocol, embryo freezing, and ET. MAIN OUTCOME MEASURE(S): The number of 2 pronuclear (2PN) embryos created and suitable for cryopreservation or transfer. RESULT(S): No statistically significant differences were observed between preservation and male factor groups for number of embryos, number of oocytes, or amount of gonadotropin needed to stimulate follicular development. Peak serum E(2) levels were significantly lower for women with disease-seeking fertility preservation. CONCLUSION(S): Women facing chemotherapy as treatment for cancer or systemic autoimmune disease infrequently undergo fertility preservation. If offered this potentially fertility-preserving option, these data suggest equivalent embryo yield compared with women with infertile male partners. Our data report no significant complications in subsequent births in those who sought fertility preservation, which is informative and encouraging for these women and their providers. PMID- 20542509 TI - Transmissible microdeletion of the Y-chromosome encompassing two DAZ copies, four RBMY1 copies, and both PRY copies. AB - OBJECTIVE: To study a transmissible partial AZFb and -c microdeletion. DESIGN: Case report. SETTING: Service of Reproductive Medicine, Molecular Biology, CHU Lyon, France. PATIENT(S): A case of oligoasthenospermia with partial spermatogenic failure. Screening for Yq microdeletions revealed the absence of sY143, suggesting an AZFb microdeletion. INTERVENTION(S): Sequence-tagged site mapping indicated that the deletion encompassed a portion of the AZFb and -c region. Genomic DNA from the patient's father gave the same pattern. During the course of these investigations, a pregnancy occurred. On the 46,XY amniocyte and cord blood DNA, the same microdeletion was found. MAIN OUTCOME MEASURE(S): Study of the fine structure of the Y-chromosome and the gene copy number. RESULT(S): The three males of this family have a rearrangement including a deletion encompassing r3 and r4, the palindrome P3, and its boundary regions: u3 and u1 in its distal part. This induced a reduction in DAZ and RBMY1 copy number and complete loss of PRY. CONCLUSION(S): PRY is not indispensable to complete spermatogenesis; and with two RBMY1 and two DAZ copies, complete spermatogenesis can be conserved. PMID- 20542510 TI - Risk of axillary nerve injury during percutaneous proximal humerus locking plate insertion using an external aiming guide. AB - OBJECTIVES: The purpose of this study was to determine which screws could be safely inserted percutaneously into a proximal humerus locking plate using a new external aiming guide without injuring the axillary nerve. We also sought to evaluate that all the screws could be accurately inserted ina locked position with the external guide. METHODS: Eight cadaveric specimens were implanted with a proximal humerus locking plate using a minimally invasive direct-lateral deltoid splitting approach using an attached external aiming guide for screw insertion. The anatomic proximity of the axillary nerve to the guidewires and screws was measured following soft tissue dissection and inspection of the nerve. RESULTS: The two superior holes (C1 and C2) were proximal to the axillary nerve with an average distance of 15.1 mm. Screw F was on average 6.6 mm distal to the axillary nerve but within 2 mm of the nerve in two specimens. In all specimens, the locking screws were appropriately seated in a locked position using the external aiming guide. CONCLUSIONS: This study suggests that percutaneous fixation of a proximal humerus locking plate with an external aiming guide can be safely used for proximal humerus fractures. The limited number of screws that can be inserted into the proximal fragment using the current external guide arm may compromise fixation of more unstable fractures. Therefore, the indications for percutaneous locking plate fixation of the proximal humerus using an external aiming guide should be limited to stable fracture patterns that can be anatomically reduced. PMID- 20542511 TI - Carotid distension and distensibility impairment in individuals affected by familial combined hyperlipidemia. AB - OBJECTIVE: To investigate whether individuals affected by familial combined hyperlipidemia, a common lipid disorder increasing the cardiovascular risk, had different carotid ultrasound parameters compared to control subjects without this family disorders. METHODS: 127 cases and 127 controls matched for age and gender were enrolled. Serum glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, ApoB, insulinemia were measured by standard laboratory techniques. All the subjects underwent B-mode ultrasonography to measure the end-diastolic and end-systolic diameter of the common carotid artery and, successively, to calculate distensibility, compliance, Young's elastic modulus and distension. RESULTS: Carotid diameter and Young's elastic modulus were significantly greater among FCH subjects than among controls, and carotid distensibility, compliance, distension and score distension were significantly lower than control, also after analysis of covariance in order to adjust all the carotid indexes for confounding variables. A multiple regression analysis confirmed that familial combined hyperlipidemia status was correlated to carotid indexes. In a model including the lipid parameters, triglycerides was the only lipid variable correlated with distensibility but not with distension. CONCLUSION: This hyperlipidemia, particularly hypertriglyceridemia, could be the direct responsibility of carotid modification leading to the impairment of the distension/distensibility that, in turn, makes the patients prone to atherosclerosis. PMID- 20542512 TI - Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. AB - OBJECTIVE: To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. METHODS AND RESULTS: Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142). CONCLUSIONS: Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability. PMID- 20542513 TI - Control of center of mass motion state through cuing and decoupling of spontaneous gait parameters in level walking. AB - Can the center of mass (COM) motion state, i.e., its position and velocity relative to the base of support (BOS), which dictate gait stability, be predictably controlled by the global gait parameters of step length and gait speed, or by extension, cadence? The precise relationships among step length and gait speed, and the COM motion state are unknown, partially due to the interdependence between step length and gait speed and the difficulty in independent control of both parameters during spontaneous level walking. The purposes of this study were to utilize simultaneous audio-visual cuing to independently manipulate step length and gait speed, and to determine the extent to which the COM position and velocity can be subsequently controlled. Fifty-six young adults were trained at one of the three gait patterns in which both the step length and gait speed were targeted simultaneously. The results showed that the cuing could successfully "decouple" gait speed from step length. Although this approach did yield reliable control of the COM velocity through manipulation of gait speed (R(2)=0.97), the manipulation of step length yielded less precise control of COM position (R(2)=0.60). This latter control appears to require manipulation of an additional degree-of-freedom at the local segment level, such that the inclusion of trunk inclination with step length improved the prediction of COM position (R(2)=0.80). PMID- 20542514 TI - Stabilizing to disruptive transition of focal adhesion response to mechanical forces. AB - Strong mechanical forces can, obviously, disrupt cell-cell and cell-matrix adhesions, e.g., cyclic uniaxial stretch induces instability of cell adhesion, which then causes the reorientation of cells away from the stretching direction. However, recent experiments also demonstrated the existence of force dependent adhesion growth (rather than dissociation). To provide a quantitative explanation for the two seemingly contradictory phenomena, a microscopic model that includes both integrin-integrin interaction and integrin-ligand interaction is developed at molecular level by treating the focal adhesion as an adhesion cluster. The integrin clustering dynamics and integrin-ligand binding dynamics are then simulated within one unified theoretical frame with Monte Carlo simulation. We find that the focal adhesion will grow when the traction force is higher than a relative small threshold value, and the growth is dominated by the reduction of local chemical potential energy by the traction force. In contrast, the focal adhesion will rupture when the traction force exceeds a second threshold value, and the rupture is dominated by the breaking of integrin-ligand bonds. Consistent with the experiments, these results suggest a force map for various responses of cell adhesion to different scales of mechanical force. PMID- 20542515 TI - Probing the kinetic performance limits for ion chromatography. II. Gradient conditions for small ions. AB - A gradient kinetic plot method is used for theoretical characterisation of the performance of polymeric particulate anion exchange columns for gradient separations of small inorganic anions. The method employed requires only information obtained from a series of isocratic column performance measurements and in silico predictions of retention time and peak width under gradient conditions. Results obtained under practically constrained conditions provide parameters for the generation of high peak capacities and rapid peak production for fast analysis to be determined. Using this prediction method, a maximum theoretical peak capacity of 84 could be used to achieve separation of 26 components using a 120min gradient (R(s)>1). This approach provides a highly convenient tool for development of both mono- and multidimensional ion chromatography (IC) methodologies as it yields comprehensive understanding of the influence of gradient slope, analysis time, column length and temperature upon kinetically optimised gradient performance. PMID- 20542516 TI - Pressurized planar electrochromatography, high-performance thin-layer chromatography and high-performance liquid chromatography--comparison of performance. AB - Kinetic performance, measured by plate height, of High-Performance Thin-Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Pressurized Planar Electrochromatography (PPEC) was compared for the systems with adsorbent of the HPTLC RP18W plate from Merck as the stationary phase and the mobile phase composed of acetonitrile and buffer solution. The HPLC column was packed with the adsorbent, which was scrapped from the chromatographic plate mentioned. An additional HPLC column was also packed with adsorbent of 5 microm particle diameter, C18 type silica based (LiChrosorb RP-18 from Merck). The dependence of plate height of both HPLC and PPEC separating systems on flow velocity of the mobile phase and on migration distance of the mobile phase in TLC system was presented applying test solute (prednisolone succinate). The highest performance, amongst systems investigated, was obtained for the PPEC system. The separation efficiency of the systems investigated in the paper was additionally confirmed by the separation of test component mixture composed of six hormones. PMID- 20542517 TI - Preparation of Eu(3+) doped (Y,Gd)(2)O(3) flowers from (Y,Gd)(2)(CO(3))(3).nH(2)O flowerlike precursors: Microwave hydrothermal synthesis, growth mechanism and luminescence property. AB - In this study, (Y,Gd)(2)O(3) and (Y,Gd)(2)O(3):Eu flowerlike microstructures were prepared through two steps: well-organized 3-dimensional (3D) flowerlike precursors were first synthesized by a facile urea-based microwave hydrothermal method, then followed by heat treatment. The morphology of the 3D flowerlike precursors could be modulated by adjusting the synthetic conditions including concentration of the starting material, reaction time and temperature. Higher the concentration of Y/Gd ions or reaction temperature, earlier the 3D flowerlike precursors were obtained. The samples were characterized by various means. The flowers were found to derive from colloidal spheres, which experienced a dissolution/crystalline, attachment and self-assembly process. Room temperature photoluminescence spectrum of 3D flowerlike (Y,Gd)(2)O(3):Eu showed enhanced emission property than the spheres. PMID- 20542518 TI - Children with specific language impairment show rapid, implicit learning of stress assignment rules. AB - An implicit learning paradigm was used to assess children's sensitivity to syllable stress information in an artificial language. Study 1 demonstrated that preschool children, with and without specific language impairment (SLI), can generalize patterns of stress heard during a brief period of familiarization, and can also abstract underlying ordered rules by which stress patterns were assigned to syllables. In Study 2, the salience of stressed elements was acoustically enhanced. Counter to expectations, there was no evidence of learning with this manipulation for either the typically developing children or children with SLI. The results suggest that children with SLI and their typically developing peers are sensitive to syllable stress cues to language structure. However, attempts to draw attention to these patterns by making them more salient may prompt children to use alternate learning strategies that do not lead to an implicit understanding of how stress contributes to the structure of language. LEARNING OUTCOMES: The reader will be able to understand: (1) that children with SLI can learn and generalize the rules for assigning word-level stress patterns within minutes of hearing examples, but (2) strategies to enhance learning may actually have the opposite effect for these children. PMID- 20542519 TI - Morphological factors as indicators of malignancy of squamous cell carcinomas in cattle exposed naturally to bracken fern (Pteridium aquilinum). AB - Squamous cell carcinomas (SCCs) of the upper digestive tract (UDT) of cattle have been associated with chronic bracken fern (Pteridium aquilinum) toxicity and infection with bovine papillomavirus type-4. These tumours share some morphological similarities with human head and neck SCCs. In this study, morphological changes were correlated with the biological behaviour of 40 alimentary SCCs in cattle grazing on pastures with high bracken content. The majority of SCCs were localized to the cranial and caudal regions of the UDT (almost 45% each). More than 60% of the tumours were well differentiated and were found mostly in the cranial region. Metastasis occurred in 58% of the cases, mostly to regional lymph nodes. All poorly differentiated SCCs had evidence of metastasis. Morphological patterns characterized by islands and ribbons of neoplastic keratinocytes were more prominent in well differentiated SCCs. These patterns varied greatly in moderately differentiated SCCs. Poorly differentiated tumours were characterized by the presence of cellular aggregates and individual cells and these tumours had more marked desmoplasia. A significant positive association was established between lymphoplasmacytic inflammatory infiltration and tumour-associated tissue eosinophilia. Evaluation of argyrophylic nucleolar organizer regions (AgNORs) revealed higher proliferation indices in poorly differentiated tumours than in moderately or well differentiated lesions. There was significant correlation between the AgNOR index and histological grading. The morphological factors analyzed were all related to histological grading, which is the major factor predicting the biological behaviour of SCCs in cattle naturally exposed to bracken fern. PMID- 20542520 TI - Validity of depression rating scales during pregnancy and the postpartum period: impact of trimester and parity. AB - The objective of the current study was to delineate the optimal cutpoints for depression rating scales during pregnancy and the postpartum period and to assess the perinatal factors influencing these scores. Women participating in prospective investigations of maternal mental illness were enrolled prior to 28 weeks gestation and followed through 6 months postpartum. At each visit, subjects completed self-rated depression scales--Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI) and clinician-rated scales--Hamilton Rating Scale for Depression (HRSD(17) and HRSD(21)). These scores were compared to the SCID Mood Module for the presence of fulfilling diagnostic criteria for a major depressive episode (MDE) during 6 perinatal windows: preconception; first trimester; 2nd trimester; 3rd trimester; early postpartum; and later postpartum. Optimal cutpoints were determined by maximizing the sum of each scale's sensitivity and specificity. Stratified ROC analyses determined the impact of previous pregnancy and comparison of initial to follow-up visits. A total of 534 women encompassing 640 pregnancies and 4025 follow-up visits were included. ROC analysis demonstrated that all 4 scales were highly predictive of MDE. The AUCs ranged from 0.857 to 0.971 and were all highly significant (p < .0001). Optimal cutpoints were higher at initial visits and for multigravidas and demonstrated more variability for the self-rated scales. These data indicate that both clinician-rated and self-rated scales can be effective tools in identifying perinatal episodes of major depression. However, the results also suggest that prior childbirth experiences and the use of scales longitudinally across the perinatal period influence optimal cutpoints. PMID- 20542521 TI - Glyoxalase-I mRNA expression and CCK-4 induced panic attacks. AB - RATIONALE: There is evidence that the anti-glycation enzyme glyoxalase-1 (GLO1) may play a role in anxiety-related behaviour. However, discordant findings between GLO1 expression and anxiety-related behaviour have been observed in animal models. Because no data are available on the relation between GLO1 mRNA expression and human anxiety so far, we investigated the expression of GLO1 mRNA in peripheral blood cells in relation to cholecystokinin-tetrapeptide (CCK-4) induced panic anxiety in healthy subjects as an established model of human anxiety in healthy volunteers. METHODS: Twenty-three healthy subjects underwent challenge with CCK-4. GLO1 mRNA expression was assessed by quantitative real-time polymerase chain reaction prior to CCK-4 injection. Baseline anxiety was assessed with the State-Trait-Anxiety-Inventory (STAI) and panic response was measured with the Panic Symptom Scale (PSS). RESULTS: CCK-4 elicited a marked anxiety response accompanied by a significant increase in heart rate. GLO1 mRNA expression did not correlate with state or trait anxiety nor with severity of CCK 4 induced anxiety. CONCLUSIONS: The lack of correlation between GLO1 mRNA expression and CCK-4 induced panic severity suggests that GLO1 is not involved into the acute panic response to CCK-4 in healthy volunteers. Therefore, further studies are needed to clarify the involvement of GLO1 in anxiety disorders at baseline and in anxiety challenge paradigms to resolve the apparent contradictions of preclinical studies concerning the relationship between GLO1 expression and anxiety. PMID- 20542522 TI - Ipsilateral visual illusion after unilateral posterior cerebral artery infarction: a report of two cases. AB - In cases of unilateral posterior cerebral artery (PCA) infarction, abnormal visual perception in the ipsilateral visual field, which is usually believed to be intact, is not met frequently and may confuse doctors during evaluation. Recently, we observed two patients who presented with contralateral hemianopsia accompanied by ipsilateral visual illusions after acute unilateral PCA infarctions. Their visual illusion was characterized by zooming in, macropsia or micropsia. These symptoms appeared to be related to deficits in size constancy. Lesions of both patients commonly involved the ipsilateral forceps major. The consistent presentation observed in these two patients suggests that dominance of size constancy can be located in the left hemisphere in some individuals. PMID- 20542523 TI - Do we need a specialization in Environmental Medicine? AB - Promoting Environmental Medicine and Environmental Neurology needs in the first place a building up knowledge and research. Education for young students and training during the entire curriculum are a second step. These common goals are necessary to emphasize the main effects of Environment in diseases and so to lead to better care. PMID- 20542524 TI - [Left ventricular hypertrophy and prognosis of systemic arterial hypertension]. PMID- 20542525 TI - [Neonatal repercussions of immigration in Spain: comparison of periods 2003-2004 and 2007-2008]. AB - BACKGROUND AND OBJECTIVES: To describe the characteristics of immigrant women's newborns in our environment, and to compare them with those of native women. PATIENTS AND METHODS: All newborns attended in the Neonatology Unit of Hospital del Mar in Barcelona, Spain, between January 2007-December 2008 were included (n=3,177). Pregnant immigrant women were classified in six regions. Twelve diagnoses were defined and their relative risks were calculated. The results were compared with the results obtained in a previous study of the period 2003-2004. RESULTS: There were 1,373 native newborns and 1,743 of immigrant origin. Immigrant women showed a higher rate of HBsAg carrier status (RR 4.33), neonatal infection risk (RR 1.24) and also macrosomia (RR 1.4). There were 6 HIV positive pregnant immigrant women compared with 8 Spanish women, and drug abuse was lower in the immigrant group (RR 0.15). There were no significant differences in the rate of other diagnoses. In the comparative rates between both periods there was an increased rate of immigrant women's newborn. We did not find any differences in the mean birth weight among newborns of immigrant women during both periods of time. HIV and hepatitis C infection remained higher in native pregnant women and hepatitis B infection in immigrant women and gypsy native women. CONCLUSIONS: The study shows similar results between the two periods with persistence of complications secondary to an inadequate prenatal care, lower drug abuse and moderate increase in HIV and VHC infection in immigrant women and hepatitis B infection in immigrant women and gypsy native women. PMID- 20542526 TI - Cryopreservation of Trypanosoma evansi after DEAE-cellulose purification: Evaluation of infective parameters. AB - Cryopreservation is a method of keeping parasites alive in a laboratory. However, this technique may also damage the parasite. Alternatively, parasites may be maintained by in vitro culture. Unfortunately, for Trypanosoma evansi no effective medium that is able to maintain the parasite for more than 4 months has been described. In this study, we examined the effect of purifying trypomastigote through DEAE-cellulose chromatography before and after cryopreservation, by analyzing the pre-patent period, longevity, parasitemia, and count of viable parasites. Our results showed a three-times increase in the concentration of viable trypomastigote in DEAE-purified cryopreserved parasites as compared to non DEAE-purified cryopreserved parasites. This indicates that DEAE-cellulose chromatography followed by cryopreservation is an effective method for the storage and preservation of T. evansi, with the advantage that the stocked parasites will be ready to use in molecular biology procedures. PMID- 20542527 TI - Plasma melatonin in domestic female Mediterranean sheep (Comisana breed) and goats (Maltese and Red Syrian). AB - The plasma melatonin nychtemeral profiles in Mediterranean ewes and goats were evaluated six times throughout the year. Melatonin levels were high throughout the night and generally below the assay detection limit during daytime. However, during long days, 30% of the last daytime samples had high melatonin concentrations. Plasma melatonin levels were higher in Comisana sheep than in goats, and higher in Maltese than in Red Syrian goats, with highly significant effect of the individual animal and high repeatability. Plasma melatonin was higher in April than in August. When there was a large difference between the duration of day and night, the plasma melatonin pattern and the light/dark cycle did not always match exactly, suggesting some form of superimposition and/or the prevalence of an endogenous rhythm. The difference found at similar scotoperiods with increasing or decreasing day length may be involved in the perception of the photoperiodic changes. PMID- 20542528 TI - Self-reported attitudes and behaviors of general surgery residents about ethical academic practices in test taking. AB - BACKGROUND: A correlation exists between people who engage in academic dishonesty as students and unethical behaviors later as professionals. Academic dishonesty has been assessed among medical students, but not among general surgery residents. We sought to describe the attitudes of general surgery residents with regard to ethical practices in test taking. METHODS: A survey with 4 scenarios describing activities related to examination taking that may or may not be considered unethical was administered. Participants were asked about participation in the activities-either personally or any knowledge of others-and whether the activities were unethical. RESULTS: Fifty-seven of 62 residents (92%) participated. For each scenario, >70% indicated that neither they nor anyone else they knew had participated in the activities. Behaviors deemed unethical included memorizing or using memorized questions to prepare for future tests (52%), selling questions for financial gain (90%), and purchasing previously used questions (57%). No difference in attitudes was seen among incoming interns, junior-level (postgraduate year [PGY]1-3), or senior-level (PGY4-6) residents. CONCLUSION: Overall, general surgery residents indicated that they had not participated in activities they felt to be unethical. Defining what is unethical was less clear. This represents an area for further education. PMID- 20542529 TI - Anaplastic pancreatic cancer: Presentation, surgical management, and outcome. AB - BACKGROUND: Anaplastic pancreatic cancers are rare neoplasms. The available data are focused on pathologic and molecular features, and little is known about the clinical presentation and management. The outcome of operative exploration and resection is unknown. METHODS: From a prospective database, all consecutive operations for anaplastic pancreatic cancer performed at our institution were identified. The clinicopathologic details were analyzed and the outcome was compared with a matched group of typical pancreatic ductal adenocarcinomas (nested case-control study). RESULTS: Eighteen patients with anaplastic pancreatic cancer were identified. The patients had a median age of 64 years. The tumors were large (median diameter, 4 cm) and showed peripheral contrast enhancement in radiologic imaging. Fifteen (83%) patients underwent resection, a palliative bypass procedure was performed in 1 (6%) patient, and 2 patients underwent exploration with biopsy only. Perioperative morbidity was 39% and mortality was 6%. The median survival rate in patients with anaplastic pancreatic cancer was 5.7 months and was less than in the control group of patients with pancreatic ductal adenocarcinoma (15.7 months). In anaplastic pancreatic cancer, the median duration of survival was significantly greater after R0/R1 resection, as compared with palliative surgery (7.1 vs 2.3 months). The duration of survival was significantly greater in neoplasms with osteoclast-like giant cells. In 3 (17%) patients, long-term survival of 33, 49, and 161 months was observed. CONCLUSION: Anaplastic pancreatic cancer is an aggressive type of pancreatic cancer with a short median survival; however, because of the observation of prolonged survival after resection, resection should be performed whenever possible. The presence of osteoclast-like giant cells is associated with a favorable prognosis. PMID- 20542530 TI - The spermatogenesis and the sperm structure of Terebrantia (Thysanoptera, Insecta). AB - Spermatogenesis and the sperm structure of the terebrantian Aeolothrips intermedius Bagnall are described. Spermatogenesis consists of two mitotic divisions; the second is characterized by the loss of half of the spermatids, which have pyknotic nuclei. Early spermatids have two centrioles, but when spermiogenesis starts, a third centriole is produced. The three basal bodies give rise to three flagella; later these fuse into a single flagellum which contains three 9+0 axonemes. The basal bodies are surrounded by a large amount of centriole adjunct material. During spermiogenesis this material contributes to the shifting of the three axonemes towards the anterior sperm region parallel to the elongating nucleus, and it is transformed into a dense cylinder. In the mature spermatids the three axonemes amalgamate to create a bundle of 27 doublet microtubules. Near the end of spermiogenesis the dense cylinder of the centriole adjunct lies parallel to the nucleus and the axonemes. It ends where the mitochondrion appears at half-sperm length. We confirm that Terebrantia testes have a single sperm cyst; their sperm are characterized by a cylindrical nucleus, three axonemes fused into one, a small mitochondrion and a short cylindrical centriole adjunct which corresponds to the dense body described in a previous work. The acrosome is lacking. At the midpoint of the anterior half of the sperm the outline of the cross-section is bilobed, with the nucleus contained in a pocket evagination of the plasma membrane. These characters are discussed in light of a comparison between Tubulifera and Terebrantia. PMID- 20542531 TI - Lycopersicon esculentum lectin is a marker of transient amplifying cells in in vitro cultures of isolated limbal stem cells. AB - The maintenance of a healthy corneal epithelium under both normal and wound healing conditions is achieved by a population of stem cells (SCs) located in the basal epithelium at the corneoscleral limbus. In the light of the development of strategies for reconstruction of the ocular surface in patients with limbal stem cell deficiency, a major challenge in corneal SCs biology remains the ability to identify stem cells in situ and in vitro. To date, not so much markers exist for the identification of different phenotypes. CESCs (corneal epithelial stem cells) isolated from limbal biopsies were maintained in primary culture for 14 days and stained with Hoechst and a panel of FITC-conjugated lectins. All lectins, with the exception of Lycopersicon esculentum, labelled CESCs irrespective of the degree of differentiation. Lycopersicon esculentum, that binds N acetylglucosamine oligomers, labelled intensely only the surface of TACs (single corneal epithelial stem cells better than colonial cells). These results suggest that Lycopersicon esculentum lectin is a useful and easy-to-use marker for the in vitro identification of TACs (transient amplifying cells) in cultures of isolated CESCs. PMID- 20542532 TI - Computational analysis of human adenovirus serotype 18. AB - The genome of the sole remaining unsequenced member of species A, human adenovirus type 18 (HAdV-A18), has been sequenced and analyzed. Members of species A are implicated as gastrointestinal pathogens and were shown to be tumorigenic in rodents. These whole genome and in silico proteome data are important as references for reexamining and integrating earlier work and observations based on lower resolution techniques, such as restriction enzyme digestion patterns, particularly for hypotheses based on pre-genomics data. Additionally, the genome of HAdV-A18 will also serve as reference for current studies examining the molecular evolution and origins of human and simian adenoviruses, particularly genome recombination studies. Applications of this virus as a potential vector for gene delivery protocols may be practical as data accumulate on this and other adenovirus genomes. PMID- 20542533 TI - Genetic bottlenecks during systemic movement of Cucumber mosaic virus vary in different host plants. AB - Genetic bottlenecks are stochastic events that narrow variation in a population. We compared bottlenecks during the systemic infection of Cucumber mosaic virus (CMV) in four host plants. We mechanically inoculated an artificial population of twelve CMV mutants to young leaves of tomato, pepper, Nicotiana benthamiana, and squash. The inoculated leaves and primary and secondary systemically infected leaves were sampled at 2, 10, and 15 days post-inoculation. All twelve mutants were detected in all of the inoculated leaves. The number of mutants recovered from the systemically infected leaves of all host species was reduced significantly, indicating bottlenecks in systemic movement. The recovery frequencies of a few of the mutants were significantly different in each host probably due to host-specific selective forces. These results have implications for the differences in virus population variation that is seen in different host plants. PMID- 20542534 TI - Results of an international ring test with the dung fly Musca autumnalis in support of a new OECD test guideline. AB - A standardized bioassay using the face fly, Musca autumnalis L. (Diptera: Muscidae), was developed to test the lethal and sublethal toxicity of parasiticide residues in livestock dung. The repeatability of this test was assessed for the parasiticide ivermectin in seven tests performed in four laboratories in Germany and France. Additional results of limit tests were provided by two laboratories from the UK. Test results had an acceptable range of heterogeneity. The calculated effect concentration at which 50% emergence was observed (EC50) averaged 4.65+/-2.17 (Standard Deviation (SD) microg ivermectin/kg fresh dung (range: 1.20-7.7)). Effects on emergence were, with one exception, not observed below the No Observed Effect Concentration (NOEC) ranging between 1.11 and 3.33microg ivermectin/kg. No effect on development time was observed. We conclude that the face fly is suitably sensitive, and the methods sufficiently repeatable, to support use of this standardized bioassay by the international community in the registration of new veterinary pharmaceuticals. Following these considerations, this species was accepted as a possible test organism in a recently published OECD Guideline (No. 228). PMID- 20542535 TI - Effects of pollution on land snail abundance, size and diversity as resources for pied flycatcher, Ficedula hypoleuca. AB - Passerine birds need extra calcium during their breeding for developing egg shells and proper growth of nestling skeleton. Land snails are an important calcium source for many passerines and human-induced changes in snail populations may pose a severe problem for breeding birds. We studied from the bird's viewpoint how air pollution affects the shell mass, abundance and diversity of land snail communities along a pollution gradient of a copper smelter. We sampled remnant snail shells from the nests of an insectivorous passerine, the pied flycatcher, Ficedula hypoleuca, to find out how the availability of land snails varies along the pollution gradient. The total snail shell mass increased towards the pollution source but declined abruptly in the vicinity of the smelter. This spatial variation in shell mass was evident also within a single snail species and could not be wholly explained by spatially varying snail numbers or species composition. Instead, the total shell mass was related to their shell size, individuals being largest at the moderately polluted areas. Smaller shell size suggests inferior growth of snails in the most heavily polluted area. Our study shows that pollution affects the diversity, abundance (available shell mass) and individual quality of land snails, posing reproductive problems for birds that rely on snails as calcium sources during breeding. There are probably both direct pollution-related (heavy metal and calcium levels) and indirect (habitat change) effects behind the observed changes in snail populations. PMID- 20542536 TI - Lagged temperature effect with mosquito transmission potential explains dengue variability in southern Taiwan: insights from a statistical analysis. AB - The purpose of this study was to link meteorological factors and mosquito (Aedes aegypti) abundance to examine the potential effects of climate variations on patterns of dengue epidemiology in Taiwan during 2001-2008. Spearman's rank correlation tests with and without time-lag were performed to investigate the overall correlation between dengue incidence rates and meteorological variables (i.e., minimum, mean, and maximum temperatures, relative humidity (RH), and rainfall) and percentage Breteau index (BI) level >2 in Taipei and Kaohsiung of northern and southern Taiwan, respectively. A Poisson regression analysis was performed by using a generalized estimating equations (GEE) approach. The most parsimonious model was selected based on the quasi-likelihood based information criterion (QICu). Spearman's rank correlation tests revealed marginally positive trends in the weekly mean (rho=0.28, p<0.0001), maximum (rho=0.26, p<0.0001), and minimum (rho=0.30, p<0.0001) temperatures in Taipei. However, in Kaohsiung, all negative trends were found in the weekly mean (rho=-0.32, p<0.0001), maximum (rho=-0.30, p<0.0001), and minimum (rho=-0.32, p<0.0001) temperatures. This study concluded that based on the GEE approach, rainfall, minimum temperature, and RH, all with 3-month lag, and 1-month lag of percentage BI level >2 are the significant predictors of dengue incidence in Kaohsiung (QICu=-277.77). This study suggested that warmer temperature with 3-month lag, elevated humidity with high mosquito density increased the transmission rate of human dengue fever infection in southern Taiwan. PMID- 20542537 TI - An evaluation of resident exposure to respirable particulate matter and health economic loss in Beijing during Beijing 2008 Olympic Games. AB - Previous epidemiological studies showed that air pollutants, especially respirable particulate matter, including PM(10), could impose harmful effects on human health. The assessment of the effects of PM(10) on mortality and morbidity makes an important basis for enhancing pollution control efforts, and for protecting public health. In this study, we measured the levels of Beijing residents' exposure to PM(10) during three different time periods around the Beijing Olympic Games held in 2008, and calculated the economic cost associated with human health. A comparative analysis of human exposure to PM(10) and associated health economics was also made to see the difference between 2005 and 2008. GIS technology was employed to interpolate the distribution of population and PM(10) data collected by 27 stations at a scale of 1kmx1km. Study results show that Beijing's population is distributed in a highly inhomogeneous manner, with the majority of people dwelling in the city proper. During the Olympic Games, population-weighted PM(10) exposure came down by 46% and 19% respectively, compared with the pre-OG and the post-OG periods. Consequently, the economic cost associated with human health during the Games came down by 38% and 16% respectively, compared with the pre-OG and the post-OG periods. Comparative analysis shows that during the Olympic Games, both PM(10) and the economic cost associated with health as a proportion of GDP sat at the bottom of the 4-year statistics, indicating that in addition to favorable weather conditions, enhanced traffic and emission control policies and measures have produced a noticeable effect on PM(10) reduction. PMID- 20542538 TI - The bivariate statistical analysis of environmental (compositional) data. AB - Environmental sciences usually deal with compositional (closed) data. Whenever the concentration of chemical elements is measured, the data will be closed, i.e. the relevant information is contained in the ratios between the variables rather than in the data values reported for the variables. Data closure has severe consequences for statistical data analysis. Most classical statistical methods are based on the usual Euclidean geometry - compositional data, however, do not plot into Euclidean space because they have their own geometry which is not linear but curved in the Euclidean sense. This has severe consequences for bivariate statistical analysis: correlation coefficients computed in the traditional way are likely to be misleading, and the information contained in scatterplots must be used and interpreted differently from sets of non compositional data. As a solution, the ilr transformation applied to a variable pair can be used to display the relationship and to compute a measure of stability. This paper discusses how this measure is related to the usual correlation coefficient and how it can be used and interpreted. Moreover, recommendations are provided for how the scatterplot can still be used, and which alternatives exist for displaying the relationship between two variables. PMID- 20542539 TI - Lead (Pb) legacy from vehicle traffic in eight California urbanized areas: continuing influence of lead dust on children's health. AB - This article describes the magnitude of U.S. lead (Pb) additives in gasoline from 1927 to 1994 and estimated quantities of Pb dispersed by vehicle traffic in eight urbanized areas (UAs) of California from 1950 to 1982. The findings are the basis for predicting the health impact of Pb on children living in UA of California. Quantitative U.S. national data for 1927-1994 were from the U.S. Senate hearing of the 1984 Airborne Lead Reduction Act. Vehicle traffic data, fuel efficiency, percentage leaded gasoline, and quantities of Pb in gasoline were obtained for 1982 from public and corporate records to estimate vehicle Pb emissions for small to very large UAs of California. California fuel consumption records and yearly quantities of Pb additives per gallon were the basis for estimating the 1950-1982 dispersion of Pb in each UA. Lead additives were calculated by multiplying annual vehicle fuel used by average Pb per gallon. The proportion of Pb additive for each UA was calculated from vehicle miles traveled (VMT) driven in 1982 divided by miles per gallon fuel consumption times the ratio of leaded to unleaded fuel times Pb additive per gallon. U.S. Environmental Protection Agency calculations of the fates of Pb were used to estimate Pb aerosol dispersal in each UA. About 108 billion miles of travel in 1982 within 8 UAs accounts for 3200metric tons of Pb additives or approximately 60% total Pb additives in California. Between the 1950-1982 peak of Pb additives, about 258,000metric tons are accounted for out of the state 412,000metric tons total during the same time period. The estimates of the quantities of Pb dust that accumulated within various UAs in California assists with predicting the continuing influences of Pb on children's exposure. Mapping the soil Pb reservoir assists with establishing the priority for enhancing environments of children. PMID- 20542540 TI - Environmental impact of mining activities on the surface water quality in Tibet: Gyama valley. AB - Nearly 20years of industrial scale metal mining operations in Tibet have caused an impact on the region's surface water quality. However, no information with respect to the pollution has been provided to the public. The aim of this work was to evaluate the chemical quality of the stream water and to assess the present and future potential risks of acid mine drainage to the regional and downstream environments. This study, based on data collected in 2006, 2007 and 2008 in the Gyama valley, using the Environmental Risk Index (I(ER)) documents that elevated concentrations of Cu, Pb, Zn, Mn, Fe and Al in the surface water and streambed at the upper/middle part of the valley pose a considerably high risk to the local environment. In contrast, the risk level at the stream source area is zero and only minor risk at the lower reaches. The iron and copper contamination of the upper/middle part of the river appears to be both natural and accelerated by the mining activities. The level of dissolved contaminants in the water decreases within short distance downstream due to precipitation and sorption to the streambed and strong dilution by a tributary stream and eventually by the Lhasa River. A high content of heavy metals in the stream sediments as well as in a number of tailings with gangue and material from the ore processing, poses a great potential threat to the downstream water users. Environmental changes such as global warming or increased mining activity may increase the mobility of these pools of heavy metals. PMID- 20542541 TI - The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behcet disease and their association with thrombosis. AB - OBJECTIVE: To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behcet disease (BD) and their relationship with thrombosis. METHODS: Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls. RESULTS: Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49+/-8.88 microg/ml vs. 26.76+/-11.57 microg/ml, p<0.0001) and significantly higher levels of TM (3.26+/-1.85 ng/ml vs. 2.6+/-0.69 ng/ml, p=0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p>0.05). Despite a tendency to positive correlation (r=0.37, p=0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r=-0.51, p<0.0001) between these two parameters in BD patients. CONCLUSION: The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction. PMID- 20542542 TI - Optimizing thrombelastography (TEG) assay conditions to monitor rFVIIa (NovoSeven) therapy in haemophilia A patients. AB - INTRODUCTION: There is no established laboratory method that can predict the most optimal dose of bypassing agents for treatment of haemophilia A. The objectives of the study was to develop an assay that can a) differentiate between the haemostatic capacity in blood from healthy individuals and severe and moderate haemophilia patients; b) show a dose-response correlation to rFVIIa addition; and c) show dose response differences of rFVIIa addition to plasma samples from non inhibitor patients of different severity. MATERIALS AND METHODS: Citrated whole blood from 25 haemophilia A patients was used in four thrombelastography (TEG) assays initiated with: 1) kaolin, 2) Tissue Factor (TF, Innovin 1:42,500), 3) TF 1:42,500+1.2 nM tPA (tissue plasminogen activator) or 4) TF 1:200,000. rFVIIa was added to give a final concentration in the range of 0.02-4.8 microg/ml. RESULTS: The TEG assays showed large differences in clot formation demonstrated by prolonged clotting time (R-time), decreased maximum thrombus generation (MTG) between severe and moderate haemophilia A patients and between haemophilia patients and healthy males. The maximal amplitudes (MA) of the clot and resistance against fibrinolysis were only compromised when TF with tPA was added. CONCLUSION: In vitro addition of rFVIIa improved all TEG profiles significantly in a dose-dependent manner; but only the TEG assay containing kaolin could differentiate between the rFVIIa doses, showing that blood from severe patients need higher doses of rFVIIa to normalize the clot formation profile compared to blood from moderate patients. Kaolin seems to be the most useful TEG assay for monitoring rFVIIa treatment. PMID- 20542543 TI - Haemostatic profile of healthy premature small for gestational age neonates. AB - BACKGROUND: The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. OBJECTIVE: To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. STUDY DESIGN: We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, von Willebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. RESULTS: Premature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. CONCLUSIONS: Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms. PMID- 20542544 TI - Prevalence and significance of anti-prothrombin (aPT) antibodies in patients with Lupus Anticoagulant (LA). AB - OBJECTIVE: Anti-prothrombin (aPT) antibodies have been found in Lupus Anticoagulant (LA) positive patients. Their prevalence and relative contribution to thromboembolic risk in LA-positive patients is not well defined. The aim of this study was to determine their presence and association with thromboembolic events in a large series of patients with confirmed LA. METHODS: Plasma from LA positive patients was collected at Thrombosis Centers and sent to a reference central laboratory for confirmation. Positive plasma was tested using home-made ELISA for the presence of aPT and anti-beta(2)GPI antibodies. RESULTS: LA was confirmed in 231 patients. Sixty-one of 231 (26%, 95%CI 22-33) LA positive subjects were positive for IgG aPT and 62 (27%, 95% CI 21-33) were positive for IgM aPT antibodies. Clinical features of Antiphospholipid Syndrome (APS) were not associated with the presence of IgG aPT [43 APS in 61 (70%) positive and 109 APS in 170 (64%) negative IgG aPT subjects, p=ns] or IgM aPT. Rate of positivity of IgG and IgM a beta(2)GPI was significantly higher than that of IgG and IgM aPT. Clinical events accounting for APS occurred in 97 of 130 (75%) IgG a beta(2)GPI positive and in 55 of 101 (54%) IgG a beta(2)GPI negative patients (OR 2.4, 95% CI 1.4 to 4.3, p=0.002). No significant association with clinical events in patients positive for both IgG aPT and IgG a beta(2)GPI as compared to those positive for one or another test was found. When patients negative for both IgG aPT and IgG a beta(2)GPI (LA positive only) were compared with remaining patients, a significantly lower association with clinical events was found (OR=0.4, 95% CI: 0.2 to 0.7, p=0.004). CONCLUSIONS: As compared to IgG a beta(2)GPI, the prevalence of IgG aPT in patients with LA is significantly lower and not associated with the clinical features of APS. PMID- 20542545 TI - Pooled analysis of trials may, in the presence of heterogeneity inadvertently lead to fragile conclusions due to the importance of clinically relevant variables being either hidden or lost when the findings are pooled. PMID- 20542546 TI - MicroRNA signatures differentiate uterine cancer tumor subtypes. AB - OBJECTIVE: Endometrial cancer (EC) is the most common gynecologic malignancy. Type I EC has a favorable prognosis, while type II ECs account for half of all treatment failures. Little knowledge of the biological differences is available to predict EC outcomes besides their pathological distinctions. MicroRNAs (miRNA) are a family of non-translated RNAs important in regulating oncogenic pathways. Mis-expression patterns of miRNAs in EC, as well as differences in miRNA expression patterns between the subtypes of EC, has not been previously evaluated. Our purpose was to identify miRNA profiles of EC subtypes, and to identify miRNAs associated with these subtypes to ultimately understand the different biological behavior between these subtypes. METHODS: Ninety-five fresh/frozen and paraffin-embedded samples of endometrial type I and II cancer, carcinosarcomas and benign endometrial samples were collected. MiRNA expression profiles were evaluated by microarray analysis. Statistical analysis was performed. RESULTS: Distinct miRNA signatures in tumor versus normal samples and in endometrioid vs. uterine papillary serous carcinomas exist. Additionally, carcinosarcomas have a unique miRNA signature from either the type I or II epithelial tumors. CONCLUSIONS: We hypothesize that further understanding the miRNAs that separate these subtypes of EC will lead to biological insights into the different behavior of these tumors. PMID- 20542547 TI - Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats. AB - Oocytes secrete soluble paracrine factors called Oocyte Secreted Factors (OSFs) which regulate the cumulus cell phenotype. Follicle populations in ovaries from prepubertal females have smaller diameters than their adult counterparts. Oocytes from small follicles are less competent than those from large follicles. The aim of this study was to investigate, in prepubertal goats, the effect of OSFs secreted by denuded oocytes (DOs) from small (<3 mm) or large (>or=3 mm) follicles during IVM on embryo development and the blastocyst quality of cumulus oocyte complexes (COCs) from small follicles and to determine if GDF9 participates in this process. Treatment groups were: (A) COCs non selected by their follicle size (control group); (B) cumulus oocytes complexes from small follicles (SFCOCs), (C) cumulus oocytes complexes from small follicles co cultured with denuded oocytes from small follicles (SFCOCs + SFDOs), and (D) cumulus oocytes complexes from small follicles co-cultured with denuded oocytes from large follicles (SFCOCs + LFDOs). The effect of the addition of kinase inhibitor SB-431542, which antagonizes GDF9, was tested in A, C, and D treatment groups. Co-cultured SFCOCs with SFDOs or LFDOs significantly augmented the blastocyst rate in comparison to SFCOCs alone (15.77%, 17.39% vs. 10.31%, respectively). Blastocysts from SFCOCs + LFDOs group showed higher rates of tetraploid nuclei than blastocysts from SFCOCs and the control group (14.43% vs. 5.45% and 5.24%, respectively; P < 0.05). However, we did not observe differences in the hatching rate, mean cell number or embryo cryotolerance (P > 0.05) between the four treatment groups. The addition of SB-431542 during IVM did not have any effect on blastocyst rate (P > 0.05). In conclusion, in prepubertal goats, COCs with a low embryo developmental competence as a consequence of follicle size can be improved by coculturing them with denuded oocytes from both small and large follicles. GDF9 does not seem play a role in this improvement. PMID- 20542548 TI - The neural correlates of highly iconic structures and topographic discourse in French Sign Language as observed in six hearing native signers. AB - "Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and spatial-classifier signs. We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of topographic discourse and highly iconic structures in French Sign Language (LSF) in six hearing native signers, children of deaf adults (CODAs), and six LSF-naive monolinguals. LSF materials consisted of videos of a lecture excerpt signed without spatially organized discourse or highly iconic structures (Lect LSF), a tale signed using highly iconic structures (Tale LSF), and a topographical description using a diagrammatic format and spatial-classifier signs (Topo LSF). We also presented texts in spoken French (Lect French, Tale French, Topo French) to all participants. With both languages, the Topo texts activated several different regions that are involved in mental navigation and spatial working memory. No specific correlate of LSF spatial discourse was evidenced. The same regions were more activated during Tale LSF than Lect LSF in CODAs, but not in monolinguals, in line with the presence of signing-space structure in both conditions. Motion processing areas and parts of the fusiform gyrus and precuneus were more active during Tale LSF in CODAs; no such effect was observed with French or in LSF-naive monolinguals. These effects may be associated with perspective-taking and acting during personal transfers. PMID- 20542549 TI - ERP evidence of hemispheric independence in visual word recognition. AB - This study examined the capability of the left hemisphere (LH) and the right hemisphere (RH) to perform a visual recognition task independently as formulated by the Direct Access Model (Fernandino, Iacoboni, & Zaidel, 2007). Healthy native Hebrew speakers were asked to categorize nouns and non-words (created from nouns by transposing two middle letters) into man-made and natural categories while their performance and ERPs were recorded. The stimuli were presented parafoveally to the right and left visual fields. As predicted by the Direct Access Model, ERP data showed that both the left hemisphere and right hemisphere were able to differentiate between words and non-words as early as 170 ms post-stimulus; these results were significant only for the contralaterally presented stimuli. The N1 component, which is considered to reflect orthographic processing, was larger in both hemispheres in response to the contralateral than the ipsilateral presented stimuli. This finding provides evidence for the RH capability to access higher level lexical information at the early stages of visual word recognition, thus lending weight to arguments for the relatively independent nature of this process. PMID- 20542550 TI - Influence of surface pretreatment of fiber posts on cement delamination. AB - OBJECTIVES: To evaluate the influence of post surface pretreatment on the delamination strength of different cements from a prefabricated FRC post tested in a three-point bending test. METHODS: Three cements were tested; RelyX Unicem, DC Core Automix, and Panavia F2.0. Per cement, 40 posts (D.T. Light Post Illusion size 3) were divided into four groups; no pretreatment (control), sandblasting, silanization, and sandblasting followed by silanization. A cement layer was applied to the posts using a standardized poly-oxy-methacrylate mold. The specimens were subjected to a three-point bending test recording the initial and catastrophic failure loads. Two-way ANOVA and Tukey post-hoc tests were used to analyze the differences between the variables. RESULTS: At the initial failure load, all specimens demonstrated delamination of the cement layer, therefore initial failure load was defined as delamination strength. With RelyX Unicem, none of the pretreatments showed significant differences. When using Panavia F2.0, silanization (735+/-51 MPa) resulted in higher initial failure values than sandblasting (600+/-118 MPa). When DC Core Automix was used, silanization (732+/ 144 MPa) produced significantly higher initial failure values than the no pretreatment group (518+/-115 MPa) and the combined sandblasting and silanization group (560+/-223 MPa). Two failure types were observed; cohesive and adhesive failure. In the silanization groups, more cohesive failures were observed for all cements tested. SIGNIFICANCE: Especially when non self-adhesive cements are used, silanization of fiber posts has a beneficial effect on cement delamination strength and failure type. PMID- 20542551 TI - A quantum mechanical quantitative structure-activity relationship study of the flexural modulus of C, H, O, N-containing polymers. AB - OBJECTIVE: The result of this research was to develop a quantum mechanically based QSAR model for polymer flexural modulus from structural features of small oligomers of the polymers. The final model was to have both explanatory power and be a reasonably accurate screening tool for new materials. METHODS: A quantitative structure-activity relationship (QSAR) was developed using the CODESSA program from quantum mechanical information provided by the AM1 semiempirical method, as implemented in AMPAC. RESULTS: A four-descriptor correlation equation with R(2)=0.91, also satisfying our other statistical criteria. A tetramer was determined to be a sufficient simulator for the polymer chain. The descriptors in the model show that rigidity of the monomer, electrostatic interactions and branching are the most important contributors to the flexural modulus value for a particular system. SIGNIFICANCE: The QSAR model we have developed here is conceptually satisfying for flexural, and provides an easily usable tool for rational biomaterials design. PMID- 20542552 TI - 3D FEA of high-performance polyethylene fiber reinforced maxillary dentures. AB - OBJECTIVE: This project studies the effect of high-performance polyethylene (HPPE) fibers on stress distributions in a maxillary denture and the influence of fiber position on improving denture performance. METHODS: A denture was scanned with a 3D Advanced Topometric Sensor digitizing system. The measuring system converted the images into a 3D digital model. A 3D reverse engineering technology then produced a numerical model which was then refined with Rapidform software. The underlying mucosa and bone were constructed using a freeform system integrated with a PHANTOM haptic device. A fiber lamella reinforcement was incorporated into the denture at different positions (fitting side, mid-palatal plane, polished side) with SolidWorks software. Boundary conditions were constrained at the top of the basal bone while bite force of 230 N was applied to the posterior teeth on both sides. The denture models were analyzed with ABAQUS software. RESULTS: Stress concentrations were found at the incisal notch and at the anterior and posterior palatal surfaces of the unreinforced denture. The incorporated reinforcement effectively reduced the stress concentrations at these surfaces. Placement of the fibers at polished side was the best position in reducing stress concentrations. SIGNIFICANCE: 3D FEM usefully provides a non laboratory means to reveal the weak areas in the maxillary complete denture, and exhibit the effectiveness of HPPE reinforcement together with fiber positions on enhancement of denture strength. PMID- 20542553 TI - The pedestrian behaviour of Spanish adolescents. AB - Adolescent pedestrians are a particularly vulnerable group of road users. This research tested the applicability of the recently developed Adolescent Road user Behaviour Questionnaire (ARBQ) amongst a sample of 2006 Spanish adolescents. Confirmatory Factor Analysis of the full scale found that the original three factors did not adequately fit the data, but an acceptable fit was obtained for the shortened 21-item version of the scale. In line with research from the UK, the present study found that males reported more unsafe road crossing behaviour and playing on the roads, but there was no gender difference for engaging in planned protective behaviour. This research also confirmed that unsafe road crossing behaviour increased with age, while dangerous playing on the road and planned protective behaviours both decreased with age. The present study also confirmed that the ARBQ is a useful tool for investigating the safety-related behaviour of adolescents on the road. PMID- 20542554 TI - Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. AB - BACKGROUND: Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris. We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina. METHODS: 65 patients (aged 18-85 years) with angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. We used computer-generated randomisation to assign patients to allopurinol (600 mg per day) or placebo for 6 weeks before crossover. Our primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain. We did a completed case analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 82040078. FINDINGS: In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s (IQR 211-408) from a baseline of 232 s (182-380), and placebo increased it to 249 s (200-375; p=0.0002). The point estimate (absolute difference between allopurinol and placebo) was 43 s (95% CI 31-58). Allopurinol increased median total exercise time to 393 s (IQR 280-519) from a baseline of 301 s (251-447), and placebo increased it to 307 s (232-430; p=0.0003); the point estimate was 58 s (95% CI 45-77). Allopurinol increased the time to chest pain from a baseline of 234 s (IQR 189-382) to 304 s (222-421), and placebo increased it to 272 s (200-380; p=0.001); the point estimate was 38 s (95% CI 17-55). No adverse effects of treatment were reported. INTERPRETATION: Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina. FUNDING: British Heart Foundation. PMID- 20542555 TI - Allopurinol for chronic stable angina: old drug, new tricks? PMID- 20542556 TI - Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use. AB - Antibiotic-loaded biomaterials are currently part of standard medical procedures for both local treatment and prevention of implant infections. The achievement of local delivery of significant quantities of active drugs directly at the site of infection, bypassing or reducing the risks of systemic effects, represents a strong point in favor of this approach. When the aim is to resolve an existing infection, controlled local release of antibiotics can be properly targeted based on the characteristics of the bacterial isolate obtained from the infection site. Under these circumstances the choice of the antibiotic is rational and this local administration route offers new unprecedented possibilities for an efficacious in situ treatment, avoiding the adverse effects of conventional systemic chemotherapies. Although the idea of self sterilizing implants is appealing, controversial is the use of antibiotic-loaded biomaterials in uninfected tissues to prevent implant infections. Systems designed for prolonged release of prophylactic inhibitory or subinhibitory amounts of antibiotics, in absence of strict harmonized guidelines, raise concerns for their still weakly proved efficacy but, even more, for their possible contribution to enhancing biofilm formation and selecting resistant mutants. This consideration holds especially true if the antibiotic-loaded represents the first-line treatment against multiresistant strains. PMID- 20542557 TI - The use of thermal printing to control the properties of calcium phosphate deposits. AB - The objective of this work was to characterize the deposits of calcium phosphate produced by thermal printing in terms of structure, topography and mechanical properties. Hydroxyapatite was molten and directed to (a) a titanium target in relative motion and (b) stationary titanium substrates preheated to 100 degrees C and 350 degrees C. Scanning electron microscopy showed round-like deposits, but high resolution profilometry measured the profile. Micro-Raman spectroscopy and X ray diffraction characterized the surface for structure, while nanoindentation revealed the hardness and elastic modulus. A symmetrical hemispherical deposit was formed on a surface in slow relative motion, but an off-centre shape formed at a higher relative speed. Deposits on preheated surfaces (100 degrees C and 350 degrees C) were identified as amorphous calcium phosphate. Nanoindentation revealed no significant difference in hardness between the amorphous deposits (4.0-4.4+/-0.3 GPa), but the elastic modulus increased from 65+/-4 GPa (annealed calcium phosphate reference) to 88+/-3 GPa (100 degrees C surface) and then to 98+/-3 GPa (350 degrees C substrate). The large change in elastic modulus is thought to arise from the dehydroxylation during thermal printing. Production of functional materials through crystallization is discussed to extend the range of possible microstructures. The characterization and testing approach is useful for hemispherical deposits produced by printing, coatings (laser ablation, thermal spraying, simulated body fluid) and melt extrusion elements in scaffolds. PMID- 20542558 TI - Epoxy-amine synthesised hydrogel scaffolds for soft-tissue engineering. AB - Highly porous and biodegradable hydrogels based on poly(ethylene glycol) (PEG) and cystamine (Cys) were fabricated using epoxy-amine chemistry and investigated as scaffolds for soft-tissue engineering. Whereas the application of fused-salt templates provided a comprehensive interconnecting pore morphology, the incorporation of a specially designed poly(epsilon-caprolactone) (PCL) cross linker provided enhanced mechanical function without adversely effecting the scaffolds positive biological interactions. The addition of only 1.2 wt% of the PCL cross-linker was sufficient to provide improvements in the ultimate stress of 30-40%. In vitro studies not only confirmed the non-cytotoxic nature of the scaffolds, but also their degradation products, which were isolated and characterised by nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionisation time-of-flight mass spectroscopy (MALDI ToF MS). In vivo trials were conducted over a period of 8 weeks through implantation of the scaffolds into the dorsal region of rats. At both 2 and 8 week time points the explants revealed complete infiltration by the surrounding tissue and the development of a vascular network to support the newly generated tissue, without an excessive foreign-body response. PMID- 20542559 TI - A near-infrared fluorescent heptamethine indocyanine dye with preferential tumor accumulation for in vivo imaging. AB - Near-infrared (NIR) fluorescence imaging holds great promise for tumor imaging due to low tissue autofluorescence and deep tissue penetration. However, most tumor-targeting fluorescent probes require combination of targeting agents and fluorescent reporters. In this study, we described a NIR heptamethine cyanine dye, IR-780 iodide, with preferential accumulation in multiple tumor cells without the necessity of chemical conjugation. The IR-780 iodide was found to retain in tumors but not normal cells in multiple tumor xenografts in nude mice and chemically-induced lung tumors in C57BL/6 mice. The fluorescent signal of tumors could persist at least 20 days with a significant signal-to-background ratio. As a lipophilic cation, a predominant accumulation of IR-780 iodide was shown in the mitochondria of tumor cells owing to the high magnitude of mitochondrial membrane potential in tumor cells than normal cells. We further showed that the transportation of IR-780 iodide into tumor cells was mediated by the organic anion transporter peptides (OATPs) because the dye accumulation was significantly inhibited by sulfobromophthalein (BSP), a competitive inhibitor of OATPs. Our study shows that IR-780 iodide that preferentially accumulates in tumor cells and is natively NIR fluorescent would be useful in tumor detection. PMID- 20542560 TI - Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. AB - Besides toxicity tests, biokinetic studies are a fundamental part of investigations to evaluate a safe and sustainable use of nanoparticles. Today, gold nanoparticles (Au NPs) are known to be a versatile tool in different areas such as science, engineering or medicine. In this study, we investigated the biokinetics after intravenous and intratracheal applications of poly(ethylene glycol) (PEG) modified Au NPs compared to plain Au NPs. Radioactive-labeled Au NPs of 5 nm inorganic core diameter were applied to rats and the NP content in tissues, organs and excretion were quantified after 1-hour and 24-hours. After intravenous injection, a prolonged blood circulation time was determined for Au NPs with 10 kDa PEG chains. Non-PEGylated Au NPs and 750 Da PEG Au NPs accumulated mostly in liver and spleen. After intratracheal application the majority of all three types of applied NPs stayed in the lungs: the total translocation towards the circulation did not differ considerably after PEGylation of the Au NPs. However, a prolonged retention time in the circulation was detected for the small fraction of translocated 10 kDa PEG Au NPs, too. PMID- 20542561 TI - Effect of functionalized polycaprolactone on the behaviour of murine preosteoblasts. AB - The efficiency of biomaterials used in bone repair depends greatly on their ability to interact with bone cells. Hence, we have functionalized polycaprolactone (PCL) films by peptides derived from the bone sialoprotein containing RGD sequence (pRGD), to increase their ability to interact with murine MC3T3-E1 preosteoblasts, and favour cell response to recombinant human bone morphogenetic protein-2 (rhBMP-2). RGE peptides (pRGE) were used as negative controls. The PCL films were hydrolyzed with NaOH and then carboxylic acid groups were activated to allow chemisorption of the peptides. Alkaline treatment increased the hydrophilicity of PCL films without significantly change their roughness. Peptide immobilization on PCL was checked by X-ray photoelectron spectroscopy. Hydrolyzed PCL films (Hydro PCL), which adsorbed fibronectin and vitronectin from serum after 1 h incubation, prevented the spreading of MC3T3-E1 preosteoblasts, while films bearing pRGD or pRGE did not. In contrast, MC3T3-E1 preosteoblasts attached to pRGD and incubated for 1 h in serum-free medium spread better than cells on Hydro PCL or pRGE. Only cells on pRGD had organized cytoskeleton, phosphorylated focal adhesion kinase on Y(397) and responded to rhBMP-2 by activating Smad pathway. Thus, pRGD PCL may be used to favour bone cell cytoskeletal organization and response to rhBMP-2. PMID- 20542562 TI - Different roles of inositol 1,4,5-trisphosphate receptor subtypes in prostaglandin F(2alpha)-induced calcium oscillations and pacemaking activity of NRK fibroblasts. AB - We investigated the role of inositol 1,4,5-trisphosphate (IP(3))-receptor isoforms in the prostaglandin F(2alpha) (PGF(2alpha))-induced calcium oscillations and pacemaking activity of normal rat kidney (NRK) fibroblasts. Reverse transcription polymerase chain reaction (RT-PCR) studies revealed that NRK fibroblasts express only the IP(3)-receptor subtypes IP(3)R1 and IP(3)R3. Quantitative RT-PCR analysis demonstrated that their expression levels varied as a function of the growth status of NRK cells; NRK cells made quiescent (Q) by serum deprivation expressed significantly higher levels of subtypes 1 and 3 than cells grown to density-arrest (DA). Using Ca(2+)-imaging techniques, we show that the frequency of PGF(2alpha)-induced calcium oscillations in DA-cells is lower than in Q-cells. To study whether these differences in the frequency of calcium oscillations relate to the relative amounts of IP(3)-receptor subtypes expressed by the cells, we knocked down the genes for either IP(3)-receptor subtype by using an shRNA approach. Knockdown of the IP(3)R1 gene significantly decreased the frequency of the PGF(2alpha)-induced calcium oscillations in both Q- and DA cells. It also reduced the frequency of the repetitive firing of calcium action potentials by DA-cells. In contrast, knockdown of the IP(3)R3 gene caused an increase in the frequency of both processes, suggesting a role for this receptor subtype as an anti-Ca(2+)-oscillatory unit in NRK fibroblasts. Our findings indicate that the reduction in the frequency of PGF(2alpha)-induced calcium oscillations in DA-cells compared with Q-cells results from the reduced expression ratio of IP(3)R1 versus IP(3)R3 receptors in DA-cells. Moreover, these data provide direct evidence that the frequency of IP(3)-dependent calcium oscillations determines the periodicity of action potential firing by density arrested NRK fibroblasts. PMID- 20542563 TI - Constitutional inv(3) in myelodysplastic syndromes. AB - The constitutional pericentric inversion on chromosome 3, inv(3), is rarely found in a normal population. The aim of our study was to investigate its possible link to hematologic malignancy. Chromosomes from bone marrow cells in 890 patients with hematologic disorders were analyzed with the Q-banding technique. Thirty four patients had inv(3) (3.8%). In 241 patients with myelodysplastic syndromes the frequency was 6.2% as opposed to 2.9% in the remaining 649 patients (p=0.02). The increased frequency of inv(3) in patients with myelodysplastic syndromes indicates that inv(3) could be a risk factor for the development of the disease. PMID- 20542564 TI - Intravascular large B-cell lymphoma, an exclusively small vessel disease? A case report and review of literature. PMID- 20542565 TI - Is there still a role for G-banding in CLL? PMID- 20542567 TI - Immunogenicity of multiple-epitope antigen gene of HCV carried by novel biodegradable polymers. AB - In order to develop a promising vaccine candidate utilizing a combined approach to induce both antibody production and T-cell activity, the DNA fragment containing MA of HCV with five conserved epitopes was synthesized. Two types of HCV vaccine candidates (the DNA type and DNA/polymers) were constructed using MA. PLA-PEG-PLA and PLGA-PEG-PLGA were synthesized and used as micelles with encapsulated plasmid pcDNA3.1(+)-MA. The preparation of copolymers, the cloning and analysis of recombinant plasmid DNA, in vitro expression, and immunogenicity in transgenic mice were evaluated in detail. The results indicated that even single immunization and oral immunization with DNA/polymers achieved satisfying immune responses in vivo tests. As biodegradable and nontoxic triblock copolymers, the novel copolymers demonstrated a great advantage, as they made long-term and single-immunizing vaccines possible; in addition, the copolymers showed a better adjuvant effect and scarcely any side effects. PMID- 20542566 TI - Immunophenotype of acute myeloid leukemia with NPM mutations: prognostic impact of the leukemic compartment size. AB - NPM mutations are the most common genetic abnormalities found in non promyelocytic AML. NPM-positive patients usually show a normal karyotype, a peculiar morphologic appearance with frequent monocytic traits and good prognosis in the absence of an associated FLT3 mutation. This report describes the immunophenotypic and genetic characteristics of a consecutive series of NPM mutated de novo AML patients enroled in the CETLAM trial. Eighty-three patients were included in the study. Complete immunophenotype was obtained using multiparametric flow cytometry. Associated genetic lesions (FLT3, MLL, CEBPA and WT1 mutations) were studied by standardized methods. Real-time PCR was employed to assess the minimal residual status. The most common pattern was CD34-CD15+ and HLA-DR+. Small CD34 populations with immunophenotypic aberrations (CD15 and CD19 coexpression, abnormal SSC) were detected even in CD34 negative samples. Nearly all cases expressed CD33 (strong positivity), CD13 and CD117, and all were CD123+. The stem cell marker CD110 was also positive in most cases. Biologic parameters such as a high percentage of intermediate CD45+ (blast gate) (>75% nucleated cells), CD123+ and FLT3-ITD mutations were associated with a poor outcome. Quantitative PCR positivity had no prognostic impact either after induction or at the end of chemotherapy. Only PCR positivity (greater than 10 copies) detected in patients in haematological remission was associated with an increased relapse rate. Further studies are required to determine whether the degree of leukemic stem cell expansion (CD45+CD123+cells) increases the risk of acquisition of FLT3-ITD and/or provides selective advantages. PMID- 20542568 TI - Interest of diffusion-weighted and gadolinium-enhanced dynamic MR sequences for the diagnosis of parotid gland tumors. AB - PURPOSE: This study aimed to evaluate the value of diffusion-weighted imaging (DWI) and gadolinium-enhanced dynamic magnetic resonance imaging (MRI) for differentiating benign and malignant parotid gland tumors, and for characterizing the various histological types (pleomorphic adenoma, and Warthin's and malignant tumors). PATIENTS AND METHODS: This retrospective study involved 60 patients with suspected parotid gland tumors (mean age: 59.4 years), and was carried out from April 2005 to February 2008. All had undergone pathological examination. All MRI examinations were performed using the Siemens Magnetom Avanto 1.5T MRI system. Non-enhanced T1-weighted (T1W), gadolinium-enhanced fat-suppressed T1W and T2 weighted (T2W) images were obtained for all 60 patients, with diffusion-weighted echoplanar imaging (DW-EPI) and apparent diffusion coefficient (ADC) evaluation in 59 patients, and gadolinium-enhanced dynamic MRI sequences in 51 patients. Interpretation was carried out by two experienced radiologists (the first evaluation used T1W, gadolinium-enhanced fat-suppressed T1W and T2W images; the second evaluation used T1W, T2W, DWI and dynamic MRI) and, for each case, the benign/malignant nature of the tumor and its histological type were determined. RESULTS: After the second reading, increases were noted in sensitivity, specificity, malignant positive predictive value (PPV) and negative predictive value (NPV), as well as in accuracy (90-100% for the first observer, and 90-97% for the second observer). Interobserver reliability also showed a significant increase from the first to the second reading (kappa=0.63 to 0.87, respectively). CONCLUSION: Gadolinium-enhanced dynamic MRI and DW-EPI with ADC evaluation improved the performance of MRI in distinguishing between benign and malignant parotid gland tumors, and characterizing the different histological types of benign tumors (pleomorphic adenoma and Warthin's), thus leading to greater consensus in interpretation of the images. PMID- 20542569 TI - Impact of non-occupational exposure to polybrominated diphenyl ethers on menstruation characteristics of reproductive-age females. AB - Polybrominated diphenyl ethers (PBDEs) have documented effects on thyroid functions and rodent behavior in vivo. Epidemiological studies, however, have revealed only limited information about associations between PBDE exposure and menstruation characteristics. Our goal was to examine whether high breast milk PBDE levels in reproductive-age females lead to interference with menstruation characteristics. We analyzed 15 PBDE congeners in 46 breast milk samples. Fifteen PBDE congeners (BDE-15, 28, 47, 49, 99, 100, 153, 154, 183, 196, 197, 203, 207, 208, and 209) were analyzed using a gas chromatograph equipped with a high resolution mass spectrometer. The mean sum of PBDEs (SigmaPBDEs) in breast milk was 3.42 ng/g lipid. Women's age at menarche was not correlated with breast milk PBDE levels. Increased BDE-208 and 209 levels were significantly associated with the prolonged length of average and the longest menstrual cycle independent of age, pre-pregnant BMI, and parity. Higher concentrations of SigmaPBDEs and the higher brominated PBDEs from BDE-183 to 209, except 197, were significantly linked to women whose menstruation periods were still coming irregularly at the sampling time. Age-adjusted odds ratios (ORs) of BDE-153, 183, 207, 208, and SigmaPBDEs were significantly higher in women with length of average menstrual cycle >32 days, compared to the control. Women whose menstruation periods still came irregularly when they were 18 years old had higher age-adjusted ORs of BDE 207, 208, 209, and SigmaPBDEs than those whose periods came regularly at the same age. Although SigmaPBDEs and certain higher brominated PBDEs appear to have potential to prolong length of average menstrual cycle and delay the age when menstruation periods begin coming regularly, these findings are not conclusive because our sample size is small and more scientific evidence is needed. PMID- 20542570 TI - ERICA: A multiparametric toxicological risk index for the assessment of environmental healthiness. AB - A risk assessment strategy considering the impact of chemicals on the whole ecosystem has been developed in order to create a sound and useful method for quantifying and comparing the global risk posed by the main different hazardous chemicals found in the environment. This index, called Environmental Risk Index for Chemical Assessment (ERICA), merges in a single number the environmental assessment, the human health risk assessment and the uncertainty due to missing or uncertain data. ERICA uses a dedicated scoring system with parameters for the main characteristics of the pollutants. The main advantage is that it preserves a simple approach by condensing in this single value an analysis of the risk for the area under observation. ERICA quantifies and compares the global risk posed by hazardous chemicals found in the environment and can be considered a diagnostic and prognostic method for environmental contaminants in critical and potentially dangerous sites, such as incinerators, landfills and industrial areas or in broader geographical areas. The application of the proposed integrated index provides a preliminary quantitative analysis of possible environmental alert due to the presence of one or some pollutants in the investigated site. This paper presents the method and the equations behind the index and a first case study based on the Italian legislation and a pilot study located on the Italian seacoast. PMID- 20542571 TI - New insights into the molecular mechanisms of classical complement activation. AB - C1q, the initiator of the classical complement cascade, is a versatile molecule with numerous ligands and variety of functions. Recent mutagenesis, epitope mapping and structural data brought novel understanding of the molecular mechanisms of C1q binding to target molecules, and subsequent C1 activation. Evidence has emerged suggesting that residues located within the C1q apical surface, and the exposed side surface of the B chain, facilitate the interaction of C1q with the majority of C1q ligands. The binding of C1q to IgG, IgM, CRP, and PTX3 is most likely a contiguous process, developing in different phases. During the initial phase, residues located within the gC1q apex, and shared between the three chains, are involved in the interaction with the ligands. After this initial recognition event, the Ca(2+) ion is attracted by the negatively charged C1q ligand. This loss of the Ca(2+) ion induces a rotation of the globular C1q head, facilitating further ligand binding, and transmitting an activation signal to C1r-C1s. This review summarizes these data, and offers a unifying model for C1 activation by negatively charged gC1q targets. PMID- 20542572 TI - The proteasome inhibitor bortezomib disrupts tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and natural killer (NK) cell killing of TRAIL receptor-positive multiple myeloma cells. AB - Bortezomib, a potent 26S proteasome inhibitor, is approved for the treatment of multiple myeloma (MM) and clinical trials are under way to evaluate its efficacy in other malignant diseases. However, cytotoxic effects of bortezomib on immune competent cells have also been observed. In this study, we show that bortezomib downregulates cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on primary human interleukin (IL)-2-activated natural killer (NK) cells. Pharmacological inhibition of the transcription factor, NF kappaB also profoundly decreased TRAIL expression, suggesting that NF-kappaB is involved in the regulation of TRAIL expression in activated human NK cells. Furthermore, perforin-independent killing of the human MM cell lines RPMI8226 and U266 by NK cells was markedly suppressed following bortezomib treatment. In addition, blocking cell surface-bound TRAIL with a TRAIL antibody impaired NK cell-mediated lysis of the TRAIL-sensitive MM cell line, RPMI8226. In conclusion, the proteasome is likely to be involved in the regulation of TRAIL expression in primary human IL-2-activated NK cells. Proteasome inhibition by bortezomib disrupts TRAIL expression and TRAIL dependent and/or independent pathway-mediated killing of myeloma cells, suggesting that bortezomib may potentially hamper NK dependent immunosurveillance against tumors in patients treated with this drug. PMID- 20542574 TI - Progress monitoring and feedback in psychiatric care reduces depressive symptoms. AB - BACKGROUND: To date, the monitoring of patient progress using standardized assessments has been neglected in hospital-based psychiatric care. Findings in outpatient psychotherapy have demonstrated clinically significant benefits for providing feedback to the sizeable minority of patients who were otherwise unlikely to experience positive outcome (Lambert, 2007). However, a similar system for presenting feedback on patient progress has not yet been assessed for group therapy within psychiatric inpatient settings. The current study aimed to develop and evaluate the effectiveness of a feedback system suitable for use in psychiatric services. METHODS: In a nonrandomized trial, 1308 consecutive inpatients and day patients, whose diagnoses were primarily depressive and anxiety disorders, completed the World Health Organization's Wellbeing Index (WHO 5) routinely during a ten-day cognitive behavioral therapy group. The first cohort (n=461) received treatment as usual. The second cohort (n=439) completed monitoring measures without feedback, and for patients in the third cohort (n=408), feedback on progress was provided to both clinicians and patients midway through the treatment period. RESULTS: Feedback was effective in reducing depressive symptoms (F(1,649)=6.29, p<.05) for those patients at risk of poor outcome, but not effective in improving wellbeing (F(1,569)=1.14, p>.05). LIMITATIONS: The current findings may be generalized to patient samples that exhibit largely depressive disorders, however rigorous follow-up is warranted. CONCLUSIONS: Similar to outpatient settings, feedback appears to be beneficial for improving symptom outcomes but further time may be required for wellbeing to be affected. PMID- 20542575 TI - The Chinese version of the Personal and Social Performance Scale (PSP): validity and reliability. AB - The Personal and Social Performance Scale (PSP) is a 100-point single-item rating scale that assesses four important domains of patients with mental disorders. This study was designed to examine the validity and reliability of a Chinese version of the PSP. The study was conducted in a sample of 157 patients with schizophrenia (confirmed by DSM-IV-TR criteria, SCID-P interview). The internal consistency (Cronbach's alpha=0.84) and the inter-rater reliability (kappa value=0.82, ICC=0.94 for PSP total score) was good. The test-retest reliability was high (intraclass correlation coefficient (ICC) of 0.95). The scale showed good construct validity with statistically significant correlations with the Global Assessment of Functioning Scale (GAF) (ICC of 0.95). The PSP score had a good negative correlation with the Positive and Negative Syndrome Scale (PANSS) total score. The improvement in PSP after 8 weeks of treatment was significantly correlated with the reduction in PANSS: after 8 weeks of treatment, the responders (defined as those with a reduction in PANSS total score >=50%) experienced a greater improvement in PSP than the non-responders. The Chinese version of the PSP is a convenient and valid instrument to assess the personal and social functions of stabilized and acute patients with schizophrenia. PMID- 20542576 TI - The emerging role for chemokines in epilepsy. AB - Epilepsy has been considered mainly a neuronal disease, without much attention to non-neuronal cells. In recent years growing evidence suggest that astrocytes, microglia, blood leukocytes and blood-brain barrier breakdown are involved in the pathogenesis of epilepsy. In particular, leukocyte-endothelium interactions and eventually subsequent leukocyte recruitment in the brain parenchyma seem to represent key players in the epileptogenic cascade. Chemokines are chemotactic factors controlling leukocyte migration under physiological and pathological conditions. In the light of recent advances in our understanding of the role of inflammation mechanisms in the pathogenesis of epilepsy, pro-inflammatory chemokines may play a critical role in epileptogenesis. PMID- 20542578 TI - Use of clearance concepts and modeling techniques in the prediction of metabolic drug-drug interactions. AB - Quantitative prediction of the in vivo drug-drug interactions (DDIs) caused by metabolic inhibition, one of the most common DDI mechanisms in clinical practice, has long been challenged. The DDI-induced increase in the area under the plasma concentration-time curve of a substrate drug can now be predicted with a certain degree of accuracy based on the inhibition parameters obtained in in vitro studies together with information on the pharmacokinetic properties of both the substrate and inhibitor. Here we argue that physiologically based pharmacokinetic modeling facilitates more precise prediction of the DDI-induced change in substrate exposure and is also expected to assist in prediction of recently recognized DDIs involving drug transporters. Quantitative prediction of DDIs involving both metabolism and transport would provide valuable information for increased efficiency in drug development and avoidance of toxic interactions in clinical practice. PMID- 20542577 TI - Mutational analysis of HOXA2 and SIX2 in a Bronx population with isolated microtia. AB - OBJECTIVE: Microtia is a developmental malformation of the external ear with genetic and environmental causes. The prevalence of microtia varies but several studies suggest increased incidence in Hispanic and African American populations. No causal genetic mutations have been identified in these populations. Mutations in the homeobox gene HOXA2 caused microtia in a single Iranian family. Another homeobox gene, SIX2, acts downstream of HOXA2 during development and provides another possible candidate for mutational analysis. METHODS: To determine whether mutations in HOXA2 or SIX2 cause sporadic microtia, DNA sequencing analysis was performed on exons in both genes in 8 patients of Hispanic and African descent in the Bronx. Identified variants were assayed in an additional 4 patients and 100 Hispanic control samples using Sequenom MassArray to rule out causality in heterozygous patients. RESULTS: No mutations were identified in the coding sequence of HOXA2 or SIX2. Four novel single nucleotide variants were identified among the patient samples. These variants lie in the intron and 3' UTR of HOXA2 and the 5' and 3' UTRs of SIX2. One variant in the intron of HOXA2 lies in a conserved predicted transcription factor binding site for SMARCA3. All four variants are also present at >5% frequency in Hispanic control samples, ruling out these novel variations as causal. CONCLUSIONS: Lack of mutations in the coding regions of HOXA2 or SIX2 among the sporadic microtia patients studied indicate different etiologies. Identification of four novel single nucleotide polymorphisms in patients and controls of Hispanic descent, but not of Caucasian populations, points to genetic diversity in an understudied population. PMID- 20542579 TI - 'Too much good news' - are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer's disease? AB - Scores of compounds ameliorate cognitive deficits or neuropathology in transgenic mouse models of Alzheimer's disease (AD), yet these triumphs in mice have not translated into successful therapies for people. Why have studies in mice failed to predict results of human trials? We argue that most transgenic mouse 'models of AD' actually simulate the asymptomatic phase of the disease, and the results of interventional studies in these mice should be considered in the context of disease prevention. In addition, recent advances in imaging technology and biomarker discovery should aid in comparisons of mouse and human neurological status and, importantly, might allow us to predict better the response of people to drugs tested in mice. PMID- 20542580 TI - Neurochemical alterations in lemon shark (Negaprion brevirostris) brains in association with brevetoxin exposure. AB - Brevetoxins are persistent, bioaccumulative, lipophilic polyether neurotoxins synthesized by Karenia brevis, a harmful algal bloom (HAB) dinoflagellate. Although some marine organisms accumulate potentially harmful levels of brevetoxins, little is known about neurotoxic effects in wild populations. Here, tissue (i.e., liver, kidney, muscle, intestine, gill, brain) brevetoxin levels (as ng PbTx-3 eq/g) and four neurochemical biomarkers (monoamine oxidase, MAO; cholinesterase, ChE; muscarinic cholinergic receptor, mAChR; N-methyl-d-aspartic acid receptor, NMDAR) were compared between eleven lemon sharks collected during a K. brevis bloom and eighteen lemon sharks not exposed to a bloom (controls) in a case-control manner. Brevetoxin levels in tissues were significantly higher in HAB-exposed sharks when compared to controls, and tissue levels (e.g., 277-3112 ng/g in livers, 429-2833 ng/g in gills) in HAB-exposed sharks were comparable to levels detected in a shark (e.g., 1223 ng/g in liver, 930 ng/g in gill) that died presumably of toxin exposure. Further, there were significant correlations between brain brevetoxin levels and ChE activity (r=-0.41; p<0.05), MAO activity (r=-0.37; p<0.05), mAChR levels (r=0.55; p<0.01), and NMDAR levels (r=-0.49; p<0.01). There were no relationships between neurochemical biomarkers and metals (total mercury, methylmercury, selenium). Overall, these results in tissues from free-ranging lemon sharks indicate that ecologically relevant exposures to brevetoxins may cause significant changes in brain neurochemistry. As disruptions to neurochemistry precede structural and functional damage to the nervous system, these results suggest that relevant exposures to HABs may be causing sub-clinical effects in lemon sharks and raise further questions about the ecological and physiological impacts of HABs on marine biota. PMID- 20542581 TI - Effects of statin therapy on non-calcified coronary plaque assessed by 64-slice computed tomography. AB - Computed tomography angiography (CTA) enables characterization of non-calcified coronary atherosclerotic lesions (NCALs) and assessment of plaque vulnerability. We investigated whether the characteristics of NCALs detected by 64-slice CTA were influenced by preceding statin therapy and serum lipid profiles. METHODS: Among 493 consecutive patients who underwent coronary CTA, we enrolled 114 patients with NCALs. We divided the patients into three groups according to preceding statin therapy: intensive statins (IS, n=24), moderate statins (MS, n = 26), and no statin (NS, n = 64). The vulnerability of each NCAL was evaluated by density (low-density plaque defined as CT density <= 38 HU), positive remodeling (remodeling index > 1.05), and the presence of adjacent spotty calcification. RESULTS: Percentages of patients in the IS, MS, and NS groups with low-density NCALs were 46%, 58%, and 80%, respectively (p = 0.009) and positive remodeling NCALs were 54%, 58%, and 75%, respectively (p = 0.10). We also found an inverse correlation between serum LDL-C level and the minimum plaque CT density. According to the regression equation, a CT density of 38 HU corresponded with LDL C of 100 mg/dl. The number of low-density plaques was positively correlated with low-density to high-density lipoprotein cholesterol ratio (LDL-C/HDL-C). An LDL C/HDL-C > 2.5 independently predicted multiple low-density plaques (OR 2.39 [95%CI: 1.28-4.86], p < 0.001). CONCLUSIONS: Our CTA findings demonstrate that low-density NCALs occur less frequently in patients with intensive statin pre treatment. A high LDL-C/HDL-C ratio is also associated with larger numbers of low density NCALs. PMID- 20542582 TI - A new classification of Kounis syndrome. PMID- 20542583 TI - Energy-intake and activity risk factors for owner-perceived obesity in a defined population of Swedish dogs. AB - Our main objective was to obtain baseline data on daily metabolisable energy (ME) intake, activity, and risk factors for obesity in a population of 460 privately owned Swedish dogs in 1999. A previously validated mail-and-telephone questionnaire was used (Sallander et al., 2001a). The dogs were of 124 breeds, 1 3 years old, and had body weights (BW) between 1 and 75kg. The ME intakes of this population could be described with the equation ME(intake) (kilojoules, kJ/d)=554BW(0.66) (r(sp)=0.73, P=0.0001). The energy intake originating from commercial foods was 79% (median, range 45-97). Table foods generally had a higher fat content (median 13g/megajoule, MJ, range 1-122) than commercial foods (median 8g/MJ, range 2-18; P=0.0001). The median energy density was 1603kJ/100g (median; range 1106-2105). Almost all (97%) dogs were taken for walks, and there was a significant difference between the duration of the walks during weekdays and weekends (medians 60 and 90min/d, respectively, P=0.006). Sixty percent of all dogs were trained in activities such as obedience (31%), hunting (27%) or tracking (18%) for a median of 35min/d (range 1-146). The final regression model for obesity included the factors sex, appetite and feeding a home-made diet/table foods. Dogs that were perceived to have good or very good appetite had 3.42-fold greater odds for obesity than individuals with bad or very bad appetite (95% CI 1.19-9.80; P=0.022). Females had 2.17-fold greater odds of being obese than males did (95% CI 1.30-3.70; P=0.003). Also, dogs fed table foods or home-made diets had 2.06-fold greater odds of obesity than those that were not given these food items (95% CI 0.97-4.35; P=0.050). PMID- 20542585 TI - Titanium-coating of stainless steel as an aid to improved cleanability. AB - In the food industry, wear of surfaces provides numerous topographical features in which microorganisms may be retained. We hypothesise that by modifying the surface chemistry, this effect may be decreased. Cellulose acetate sheets softened with acetone were pressed onto both new fine polished and used stainless steel surfaces in order to take impressions of surface features for subsequent visualisation and characterisation in the laboratory, using scanning electron microscopy, atomic force microscopy (R(a)) and white light profilometry (S(a)). The method gives high resolution negative replicas of the surface, can be used quickly, safely and efficiently, and enables investigations into surface wear over time, and the effect of defined topographic features on surface hygiene and cleanability. Subsequently, the retention of microorganisms on fine polished stainless steel and titanium coated fine polished stainless steel was assessed in the presence and absence of a meat conditioning film. The titanium coating discouraged the retention and enhanced the removal of both Escherichia coli and the meat conditioning film. PMID- 20542584 TI - Lighting up multiprotein complexes: lessons from GPCR oligomerization. AB - Spatiotemporal characterization of protein-protein interactions (PPIs) is essential in determining the molecular mechanisms of intracellular signaling processes. In this review, we discuss how new methodological strategies derived from non-invasive fluorescence- and luminescence-based approaches (FRET, BRET, BiFC and BiLC), when applied to the study of G protein-coupled receptor (GPCR) oligomerization, can be used to detect specific PPIs in live cells. These technologies alone or in concert with complementary methods (SRET, BRET or BiFC, and SNAP-tag or TR-FRET) can be extremely powerful approaches for PPI visualization, even between more than two proteins. Here we provide a comprehensive update on all the biotechnological aspects, including the strengths and weaknesses, of new fluorescence- and luminescence-based methodologies, with a specific focus on their application for studying PPIs. PMID- 20542586 TI - Urinary type IV collagen excretion predicts subsequent declining renal function in type 2 diabetic patients with proteinuria. AB - Baseline urinary type IV collagen excretion was negatively correlated with the subsequent GFR change (r(s)=-0.39, p=0.04) in our cohort of 30 type 2 diabetic patients with proteinuria. Therefore, it could be used to predict subsequent declining renal function in type 2 diabetic patients with proteinuria. PMID- 20542587 TI - High concentrations of anti-caspase-8 antibodies in Chilean patients with type 1 diabetes. AB - INTRODUCTION: Deregulation of apoptosis across the Fas-FasL pathway is an increasingly relevant phenomenon in the pathogenic mechanisms associated with autoimmune diseases. Caspase-8 initiates the activation of the apoptotic process and interacts directly with Fas in the membrane of the T lymphocyte. OBJECTIVES: To standardize an Elisa essay to measure the concentration of anti-caspase-8 antibodies in plasma of Type 1 Diabetes (T1D) patients and analyze their possible distribution and association with characteristics of the disease. METHODS AND SUBJECTS: 124 patients newly diagnosed with T1D and 132 controls: children and youngsters. ELISA test was standardized to detect anti-caspase-8 antibodies in plasma. It correlated the concentration of this antibody with classical markers of autoimmunity as anti-IA-2 and anti-GAD65, and the clinical characteristics at onset of diabetes mellitus. The statistical analysis was performed using logistic regression. RESULTS: Patients with T1D showed a higher concentration of anti caspase-8 antibodies regarding the controls (87.5 ng/ml versus 24.3 ng/ml, p < 0.0001, values expressed as median). The proportion of patients with T1D and high concentrations of anti-caspase-8 (percentile 50-75) was significantly different from the control group (p < 0.0001). Anti-caspase-8 showed a strong association with positive anti-GAD65 (OR = 3.48, p < 0.035) and ketoacidosis (OR = 10.74, p < 0.0001) events, with glycemia and age at diagnosis as contributing variables. CONCLUSION: This is the first report in the literature of levels of anti-caspase 8 antibodies in T1D through ELISA. The high concentration in patients with T1D, and its strong correlation with anti-GAD65 auto-antibodies, suggests a potential role of anti-caspase-8 auto-antibodies as surrogate marker autoimmunity in T1D patients. PMID- 20542589 TI - Community and nosocomial transmission of Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus: implications for healthcare. AB - In the UK, infections due to Panton-Valentine leucocidin-positive community associated meticillin-resistant Staphylococcus aureus (PVL-MRSA) have been reported sporadically. In September 2006, a fatal PVL-MRSA infection occurred in a Filipino healthcare worker (HCW) after she underwent caesarean section. Throat and nasal swabs were obtained from contacts of cases in community and hospital. MRSA with an antibiogram similar to the PVL-MRSA strain were characterised including toxin gene profiling, polymerase chain reaction- and sequence-based typing. Carriers underwent decolonisation treatment, and HCWs were restricted from patient care until they and their household members were considered negative for PVL-MRSA. The PVL-MRSA belonged to ST30, was protein A gene (spa) type t019, SCCmec IVc, agr 3, and resistant only to beta-lactam antibiotics. Representatives of the same lineage were identified among a further 16 individuals in community and hospital. Infections likely to be caused by PVL-MRSA had occurred in 12 cases, and were likely to be hospital-acquired in two patients (one fatal) and occupationally acquired in one HCW. Nine cases worked as nursing staff in the hospital. Eight of these had emigrated from the Philippines in the previous five years and were linked socially. Thus, PVL-MRSA-ST30 was detected in a HCW community in the UK. This is the first report of nosocomial transmission of this pandemic clone in the UK associated with a fatality. Increased vigilance in healthcare and community is needed in response to this emerging threat. PMID- 20542590 TI - Point-of-use filtration method for the prevention of fungal contamination of hospital water. AB - Published data implicate hospital water as a potential source of opportunistic fungi that may cause life-threatening infections in immunocompromised patients. Point-of-care filters are known to retain bacteria, but little is known about their efficacy in reducing exposure to moulds. We investigated the effect of point-of-use filters (Pall-Aquasafe) on the level of contamination of Aspergillus fumigatus and other filamentous fungi. The point-of-use filters were applied to several outlets (taps and showers) on the paediatric bone marrow transplantation (BMT) unit of the National Hospital in Oslo, Norway. In addition the efficacy was investigated using a test rig. The laboratory experiments showed that the filters were highly effective in reducing the number of colony-forming units for a period of at least 15 days. In the BMT unit the filters eliminated the fungi from the water on day 1 but due to particles present in the water the filters occluded, which prevented further evaluations. Our results show that point-of-use filtration might be an effective preventive measure to eliminate filamentous fungi at individual points of water use, thereby reducing patients' exposure. PMID- 20542591 TI - Do disposable pulse oximeter sensors impact infection rates? A review of the literature. PMID- 20542592 TI - Low measles, mumps and rubella (MMR) vaccine uptake in hospital healthcare worker contacts following suspected mumps infection. PMID- 20542588 TI - Positive T cell co-stimulation by TLR7/8 ligands is dependent on the cellular environment. AB - Toll-like receptors (TLRs) are mediators of innate immune responses detecting conserved pathogen-associated molecules. Whereas most TLRs are expressed on the cell surface, TLR3, 7, 8 and 9 are predominantly localized in endosomal compartments. Recent studies reported that TLRs are also expressed by T lymphocytes, resulting in direct co-stimulation of isolated CD4(+) T cells for example by Pam3CSK4 (TLR2 ligand) or flagellin (TLR5 ligand). We here describe enhanced IFN-gamma production and T cell proliferation by anti-CD3 T cell receptor (TCR) or antigenic stimulation of purified human CD4(+) T cells upon co culture with TLR7/8 specific single-stranded oligoribonucleotides or small molecule ligands. Surprisingly, TLR7/8 stimulation of CD4(+) T cells within a whole peripheral mononuclear cell (PBMC) environment did not result in enhanced T cell proliferation, but in a lack of proliferation that was cell-cell contact dependent. Immune cell depletion assays pointed towards a monocyte-mediated effect. Different TLR ligands influenced T cell proliferation differently. The effect of inhibition of T cell proliferation was most prominently seen for TLR7 ligands whereas the effects were minimal for TLR8 and TLR9 ligands indicating that the suppressive phenotype is unique only for certain TLRs. Our results strongly suggest that co-stimulation of T cell proliferation by TLR7/8 agonists is dependent on the specific cellular context. PMID- 20542593 TI - Diagnosis and management of necrotising fasciitis: a multiparametric approach. AB - Necrotising fasciitis (NF) is situated with myositis and myonecrosis at the severe end of a spectrum of skin and soft tissue infections but is far removed from erisepelas, impetigo and cellulitis. Inexperienced clinicians are easily misled by the protean manifestations of infection, especially exotoxin or superantigen mediated consequences from streptococcal NF. Early clinical suspicion and surgery are key to improving survival, and patients with NF need integrated multidisciplinary management, adjusted to the infecting organism(s), the site of infection, and the effects from any toxins produced. A multiparametric approach, incorporating various clinical and laboratory parameters, can aid aggressive management. This review describes the diagnosis and management of the major types of NF, emphasising important aetiological clues from the history and the appropriate usage of diagnostic investigations. The potential benefits of controversial therapeutic approaches, including hyperbaric oxygen and intravenous immunoglobulin, are discussed. PMID- 20542594 TI - Dissemination of Bacillus cereus in the burn unit due to contaminated non-sterile gloves. PMID- 20542595 TI - Active warming systems to maintain perioperative normothermia in hip replacement surgery. PMID- 20542596 TI - Clostridium difficile infections in a tertiary hospital: value of surveillance. PMID- 20542597 TI - Brain iron deposits are associated with general cognitive ability and cognitive aging. AB - A novel analysis of magnetic resonance imaging (MRI) scans based on multispectral image fusion was used to quantify iron deposits in basal ganglia and microbleeds in 143 nondemented subjects of the generally healthy Lothian Birth Cohort, who were tested for general cognitive ability (intelligence) at mean ages of 11, 70, and 72 years. Possessing more iron deposits at age 72 was significantly associated with lower general cognitive ability at age 11, 70, and 72, explaining 4% to 9% of the variance. The relationships with old age general cognitive ability remained significant after controlling for childhood cognition, suggesting that iron deposits are related to lifetime cognitive decline. Most iron deposits were in the basal ganglia, with few microbleeds. While iron deposits in the general population have so far been dismissed in the literature, our results show substantial associations with cognitive functioning. The pattern of results suggests that iron deposits are not only a biomarker of general cognitive ability in old age and age-related cognitive decline, but that they are also related to the lifelong-stable trait of intelligence. PMID- 20542599 TI - [Ethics of the cardiopulmonary resuscitation decisions]. AB - Cardiopulmonary Resuscitation (CPR) must be attempted if indicated, not done if it is not indicated or if the patient does not accept or has previously rejected it and withdrawn it if it is ineffective. If CPR is considered futile, a Do-Not Resuscitate Order (DNR) will be recorded. This should be made known to all physicians and nurses involved in patient care. It may be appropriate to limit life-sustaining-treatments for patients with severe anoxic encephalopathy, if the possibility of clinical evolution to brain death is ruled out. After CPR it is necessary to inform and support families and then review the process in order to make future improvements. After limitation of vital support, certain type of non heart-beating-organ donation can be proposed. In order to acquire CPR skills, it is necessary to practice with simulators and, sometimes, with recently deceased, always with the consent of the family. Research on CPR is essential and must be conducted according to ethical rules and legal frameworks. PMID- 20542598 TI - Subtypes based on cerebrospinal fluid and magnetic resonance imaging markers in normal elderly predict cognitive decline. AB - Cerebrospinal fluid (CSF) and structural magnetic resonance imaging (MRI) show patterns of change in Alzheimer's disease (AD) that precede dementia. The Alzheimer's Disease Neuroimaging Initiative (ADNI) studied normal controls (NC), subjects with mild cognitive impairment (MCI), and subjects with AD to identify patterns of biomarkers to aid in early diagnosis and effective treatment of AD. Two hundred twenty-two NC underwent baseline MRI and clinical examination at baseline and at least one follow-up. One hundred twelve also provided CSF at baseline. Unsupervised clustering based on initial CSF and MRI measures was used to identify clusters of participants with similar profiles. Repeated measures regression modeling assessed the relationship of individual measures, and of cluster membership, to cognitive change over 3 years. Most individuals showed little cognitive change. Individual biomarkers had limited predictive value for cognitive decline, but membership in the cluster with the most extreme profile was associated with more rapid decline in ADAS-cog. Subtypes among NC based on multiple biomarkers may represent the earliest stages of subclinical cognitive decline and AD. PMID- 20542600 TI - [Assessment of health outcomes in the type 2 diabetes process]. AB - OBJECTIVE: To analyse association between the development of type 2 diabetes and the health-related quality of life (HRQL). DESIGN: Descriptive cross-sectional study. SETTING: Primary care centre in Ayamonte (Huelva). PARTICIPANTS: Selection by simple random sampling between the patients registered with type 2 diabetes: n=143. The type 2 diabetes process is a tool that uses indicators of good clinical practice for the follow-up of the patients. Collection of data from records and personal interview for the questionnaire HRQL SF-36. RESULTS: A total of 101 patients were analysed, of which 51.5% were women. the average age was 66.8 years (SD 11.3). Performing physical activity 52.5%. Time of evolution of diabetes: 9.6 years (SD 7.7). Quality Index of the process: 64.5%. Worst score in physical component HRQL, mean of 41.9 (SD 9.6). Men had a better score, and it improves if there is regular physical exercise (mean difference 19.5% IC95%CI: 10.2-28.8). Age was inversely associated with physical function (r -0.354 P<0,005); and the time of evolution of diabetes with physical component (r -0.278 P<0.005). Retinopathy (t=2.03 P<0.04) and heart disease (t=2.6 P<0.008) were associated with lowest score in physical component. The association of HRQL with metabolic control, self control of glucose and diabetes education was not significant. Physical activity and comorbid diseases predict HRQL. CONCLUSIONS: The HRQL is poor in type 2 diabetics despite having good indicators in the process. The HRQL should be included as standard in the type 2 diabetes process. PMID- 20542601 TI - [Ankle-arm index and cardiovascular prevention]. PMID- 20542602 TI - [Gender inequalities in the Spanish Public Health and Health Administration Society (2000-2009)]. AB - OBJECTIVE: To describe gender inequalities in positions of leadership and scientific recognition in activities carried out by the Spanish Public Health and Health Administration Society (SESPAS), the Spanish Epidemiology Society (SEE) and the Health Economics Association (AES) for 2000-2009. METHODS: We performed a descriptive study of the gender distribution of the boards of directors, scientific and conference organization committees and chairpersons of the SESPAS, SEE and AES. The gender distribution of the editorial board of Gaceta Sanitaria, and of the authors of editorials published in the journal, as well as that of the editors of SESPAS Reports, was also analyzed. RESULTS: Between 2000 and 2009, there was a slight increase in women's participation in the SESPAS and there was greater gender parity in the SEE. However, representation of women in the AES was low. CONCLUSIONS: The causes of gender inequalities in public health professional societies should continue to be analyzed and actions should be taken to change the present situation. PMID- 20542603 TI - Synthesis and anticonvulsant activity of new 6-methyl-1-substituted-4,6 diazaspiro[2.4]heptane-5,7-diones. AB - In the present study on the development of new anticonvulsants, twenty new 6 methyl-1-substituted-4,6-diazaspiro[2.4]heptane-5,7-diones were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Their neurotoxicity was determined by the rotorod test. In this series, all of the alkyl- and aryl substituted 5,5-cyclopropanespirohydantoins showed more or less protection against MES and/or scPTZ models. The most active of the series was 6-methyl-1-(4 (methylsulfonyl)phenyl)-4,6-diazaspiro[2.4]heptane-5,7-dione (6 t), which showed a MES ED(50) value of 12.5 mg/kg in mice. The median toxic dose (TD(50)) was 310 mg/kg, providing compound 6 t with a protection index (PI = TD(50)/ED(50)) of 24.8 in the MES test which is better than phenytoin. PMID- 20542604 TI - Design, synthesis and antimicrobial activities of some new quinoline derivatives carrying 1,2,3-triazole moiety. AB - A new series of [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3-triazol-4-yl] methanamine derivatives were synthesized starting from 4-methoxyaniline through multi-step reactions. The title compounds 5a-y were prepared by treating the azide intermediate 4 with propargyl bromide and different alkyl/heterocyclic amines in a sequential three component synthesis. All the new compounds were characterized by spectral and elemental analyses. The newly synthesized final compounds were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains. The preliminary screening results indicated that most of the compounds demonstrated moderate to very good antibacterial and antifungal activities, comparable to the first-line drugs. PMID- 20542605 TI - Synthesis, structure and DNA cleavage studies of coumarin analogues of tetrahydroisoquinoline and protoberberine alkaloids. AB - Novel molecular matrices have been derived from coumarin-4-acetic acids and beta phenylethylamines using the Bischler-Napieralski protocol which has led to the synthesis of analogues of tetrahydropapaverine in which the dimethoxybenzene moiety has been replaced by substituted coumarins. One carbon homologation has led to cyclization at the C3 position of coumarin generating the protoberberine skeleton. Structures have been confirmed by diffraction studies. The results showed that compounds 6e, 6f, 7e and 7f were found to be very effective against DNA samples of Gram positive bacterium Staphylococcus aureus and fungus Aspergillus niger. PMID- 20542606 TI - [A violaceous infiltration of the pinna]. PMID- 20542607 TI - Impact of the Bologna process in Bachelor nursing programmes: The Swedish case. AB - The higher education reform in Europe known as the "Bologna Process" implies further harmonisation and integration of nursing programmes into the higher education system. This study explores this process in Sweden, where the development of nursing education into an undergraduate programme started in 1977. The aim of this study was to analyse characteristics of the major subject and its relationship to other subject areas, such as medical sciences and social sciences, in Bachelor level nursing programmes in Sweden following initial implementation of the Bologna process. A constructivist approach and descriptive content analysis were employed to analyse the 2008 nursing curricula and syllabi of 27 undergraduate programmes at 26 Swedish universities and university colleges. The results revealed variation in terms and concepts used for the major subject as well as its scientific foundation, demarcation between the major subject and other subjects included in the study programmes and its relationship to the profession. These variations are linked to the variety of research orientations under debate in the Scandinavian countries: Nursing Science and Caring Science; representing different knowledge domains, focus, challenges and visions for the discipline. Potential implications of basing curricula on a major subject other than Nursing Science in a Bachelor level nursing programme are highlighted. PMID- 20542608 TI - Gait asymmetry following an anterior and anterolateral approach to total hip arthroplasty. AB - BACKGROUND: Patients with osteoarthritis of the hip demonstrate a limp while ambulating, and persistent asymmetric limb loading following unilateral total hip arthroplasty might induce further complications in the affected and contralateral limbs. The purpose of this study was to investigate pre- to postsurgical changes in gait symmetry in patients receiving either an anterior or anterolateral hip replacement. METHODS: Three-dimensional kinematic and kinetic gait analyses were performed on 12 patients undergoing anterior surgery, 11 patients undergoing anterolateral surgery and 10 age-matched controls while level walking. A two-way mixed model analysis of variance with repeated measures was utilized to determine differences in symmetry indices and pelvic obliquity between groups and across time. FINDINGS: At presurgery, greater single limb support time and step length asymmetry was demonstrated by both patient groups when compared to controls. While the anterior hip replacement patients demonstrated greater improvement in gait symmetry by 6 weeks postsurgery, both patient groups approached control levels by 16 weeks postsurgery. No significant differences were seen between patient groups for pelvic obliquity, limb loading or temporal-distance symmetry at any time point. INTERPRETATION: Patients undergoing either anterior or anterolateral hip replacement enhanced their gait symmetry by 16 weeks following surgery. Improvement in gait symmetry at 6 weeks postsurgery, as compared to presurgery, was detected in patients undergoing anterior hip replacement. However, no such improvement was observed in patients receiving the anterolateral approach. Findings of this study highlight the potential impact of surgical approach on short-term changes in gait asymmetry. PMID- 20542609 TI - Biomechanics of short hip endoprostheses--the risk of bone failure increases with decreasing implant size. AB - BACKGROUND: Short uncemented metaphyseally anchored femoral endoprostheses are becoming popular and are proposed to be less invasive than longer conventional implants. However, it is proposed here that shortening femoral endoprostheses can increase the risk of periprosthestic fracture. METHODS: A simple analytical model of a femoral hip implant was developed to estimate the risk of bone overload for varying implant size, implantation geometry, implantation force and bone quality. The load capacity of a particular short implant design in poor quality cadaveric bone specimens was also measured experimentally, to validate the model. FINDINGS: The model demonstrated a high risk of bone overload for a short endoprosthesis in poor quality bone. The experimental results and a clinical example of failure, to which the model was applied, supported this finding. Bone stresses increased with decreasing implant length and diameter, varus implantation, incomplete seating and high implantation forces, approaching the strength of good quality bone in extreme cases. INTERPRETATION: Correct implantation and patient selection is essential for short femoral endoprostheses. PMID- 20542610 TI - Ammonia emissions from livestock industries in Canada: feasibility of abatement strategies. AB - An updated national ammonia (NH(3)) emissions inventory was employed to study the relationship between NH(3) emissions and livestock industries in Canada. Emissions from animal agriculture accounted for 322kilotonnes (kt) or 64% of Canadian NH(3) emissions in 2002. Cattle and swine accounted for the bulk of livestock emissions. The provinces of Alberta, Ontario, Quebec, and Saskatchewan accounted for 28.1%, 22.0%, 18.7%, and 13.1% of total livestock emissions, respectively. Emissions from Ontario and Quebec were attributed to the intensive production of dairy, hogs and poultry. Dairy cattle emissions per hectolitre of milk were higher in Ontario and Quebec than in other provinces, while swine emissions per livestock unit were higher than either beef or dairy cattle. A review of the abatement literature indicated diet manipulation to improve N efficiency and land spreading methods are very effective techniques to lower NH(3) emissions. Future research is required to evaluate the feasibility of biofilters and feces/urine separation methods. PMID- 20542611 TI - Mortality consequences of the 1959-1961 Great Leap Forward famine in China: Debilitation, selection, and mortality crossovers. AB - Using retrospective mortality records for three cohorts of newborns (1956-1958, 1959-1961, and 1962-1964) drawn from a large Chinese national fertility survey conducted in 1988, this article examines cohort mortality differences up to age 22, with the aim of identifying debilitating and selection effects of the 1959 1961 Great Leap Forward Famine. The results showed that the mortality level of the non-famine cohort caught up to and exceeded the level of the famine cohort between ages 11 and 12, suggesting both debilitating and selection effects. Multilevel multiprocess models further established a more direct connection between frailties in infancy and frailties at subsequent ages, revealing the underlying dynamics of mortality convergence between the famine and the non famine cohorts caused by differential excess infant mortality. These results provide important new insights into the human mortality process. PMID- 20542612 TI - The epidemiology of spirit possession in the aftermath of mass political violence in Mozambique. AB - In this article we assess the prevalence rates of harmful spirit possession, different features of the spirits and of their hosts, the correlates of the spirit possession experience, health patterns and the sources of health care consulted by possessed individuals in a population sample of 941 adults (255 men, 686 women) in post-civil war Mozambique in 2003-2004. A combined quantitative qualitative research design was used for data collection. A major study outcome is that the prevalence rates vary according to the severity of the possession as measured by the number of harmful spirits involved in the affliction. The prevalence rate of participants suffering from at least one spirit was 18.6 percent; among those individuals, 5.6 percent were suffering from possession by two or more spirits. A comparison between possessed and non-possessed individuals shows that certain types of spirit possession are a major cause of health impairment. We propose that knowledge of both local understandings of harmful spirit possession and the community prevalence of this kind of possession is a precondition for designing public health interventions that sensitively respond to the health needs of people afflicted by spirits. PMID- 20542613 TI - Do mental health and behavioural problems of early menarche persist into late adolescence? A three year follow-up study among adolescent girls in Oslo, Norway. AB - Early menarche has been linked to mental health and behavioural problems in several studies. Most of these studies are cross-sectional, the data gathered during puberty. Thus, there is a lack of research on the long-term effect of early menarche on mental health. The main aim of this study was to explore whether the differences in mental health problems between girls with early and late menarche persist into late adolescence. The data consisted of responses from a large school-based survey of all 10th grade girls (15 years of age) in Oslo, Norway. Of the 1860 participating girls in the 2001 survey, 1377 were included in the three year follow-up study in 2004, giving a response rate of 74%. Mental distress was measured with the Hopkins Symptom Check list 10-version. Additional items assessed were number of sexual partners, weight and body satisfaction. All information was self-reported, including age of menarche. We found a clear gradient in the cross sectional analyses at baseline of higher odds for mental distress at lower age of menarche even after adjustment for socio demographic and other factors. In the analysis of the follow-up data there was no statistically significant difference in mental distress across age of menarche, even though the differences in body and weight satisfaction and average body mass index remained at the same level between baseline and follow-up. We therefore conclude that the effects of age of menarche on mental health problems are a transitory problem during puberty. PMID- 20542614 TI - Proceedings of the American Association of Oral and Maxillofacial Surgeons 2009 Research Summit. PMID- 20542615 TI - Management of facial dermatofibrosarcoma protuberans: case report, justification of aggressive surgical treatment, and reconstruction with an anterolateral thigh flap. PMID- 20542616 TI - Replacement of the condyle and ascending ramus by a modular endoprosthesis in Macaca fascicularis--part 4: evaluation of the temporomandibular joints. AB - PURPOSE: To assess, using cone-beam computed tomography and histologic examination, whether the fixation of a condyle-ascending ramus mandibular modular endoprosthesis results in a physiologic condylar replacement in Macaca fascicularis. MATERIALS AND METHODS: The right condyle and ascending ramus were resected in 8 adult monkeys and replaced with a modular endoprosthesis, fixed with polymethyl methacrylate bone cement (Palacos). Four monkeys were sacrificed at 3 months and another 4 at 6 months postoperatively. The reconstructed and contralateral temporomandibular joints were harvested en bloc and studied using cone-beam computed tomography and descriptive histologic examination. Heterotopic bone formation was quantified using a modified grading scale. The condyle cartilage thickness in the contralateral temporomandibular joint was measured using histomorphometric methods. The results were compared with those of the unoperated control monkeys. RESULTS: Bone resorption in the glenoid fossa and pathologic changes in the articular disc were noted on the reconstructed side in most specimens. Nevertheless, cone-beam computed tomography findings, histologic findings, and condyle cartilage thickness measurements of the contralateral temporomandibular joint were not significantly different from those of the control specimens. CONCLUSION: Replacement of the condyle and ascending ramus using a modular endoprosthesis in Macaca fascicularis resulted in adaptive remodeling of the glenoid fossa at up to 6 months postoperatively. Long-term studies are required to further assess the potential of this mode of reconstruction. PMID- 20542617 TI - Informed consent: what do patients really want to know? AB - PURPOSE: Although it is generally advised to provide patients with as much information as possible during the informed consent process, little is known about the amount and type of information that patients actually desire. The purpose of this study was to address this question. PATIENTS AND METHODS: We gave 212 patients (93 men and 119 women) presenting to an emergency clinic for oral surgery, ranging in age from 18 years to more than 50 years, a questionnaire containing 12 questions at their initial visit that asked them how much information they would like about the general and specific risks associated with the procedure. They were also asked when they would like to receive that information and whether they would like it in written form. RESULTS: Of the patients, 57% wanted to know about all complications, 33% wanted to know only about the most common complications, and 10% did not want to know anything about possible complications. The desire to know about complications increased along with their suggested frequency. Seventy-eight percent said they would like written as well as verbal information, and most wanted it provided before scheduling their operation and again just before undergoing it. The only difference between the responses from men and women was that significantly more men wanted to know about the risk of surgery not improving their symptoms and the risk of nerve damage. There was no relationship between the age of the patient and the responses given. CONCLUSION: A thorough informed consent process generally provides more information than most patients desire. PMID- 20542618 TI - Application of unilateral pedicled buccal fat pad for nasal membrane closure in the bilateral complete cleft palate. PMID- 20542619 TI - Phleboliths and the vascular maxillofacial lesion. PMID- 20542621 TI - [The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the new law on smoking in Spain]. PMID- 20542620 TI - Malignant transformation of calcifying epithelial odontogenic tumor is associated with the loss of p53 transcriptional activity: a case report with review of the literature. PMID- 20542622 TI - [Non-invasive mechanical ventilation and the prognosis in chronic obstructive pulmonary disease]. PMID- 20542623 TI - Are chronic urticaria, analgesic intolerance and seasonal rhinitis markers of different severities and phenotypes of the asthma they accompany? AB - BACKGROUND: Asthma is a heterogeneous disease that presents with different clinical phenotypes. We aimed to compare the patients with asthma diagnosis alone with the patients, who, in addition to their asthma had accompanying analgesic intolerance (AI), chronic urticaria (CU) or seasonal rhinitis (SR) if there are any distinctions and specific characteristics of these defined patient groups. METHODS: Eighty-four asthma patients diagnosed with SR, 46 with CU, 75 with AI and 71 patients with asthma alone were enrolled to the study retrospectively. The reference group for the comparisons was the group with asthma diagnosis alone. RESULTS: The mean age of all patients was 37.2+/-13 (15-80) and 70.7% of them were females. Asthma patients with SR had a significantly earlier onset of asthma (age: 27.4+/-10.8 and 34.5+/-15.9; respectively, p<0.01), significantly better pulmonary function tests and were significantly more atopic (92.9% and 28.8%; p<0.001). Moderate-to-severe asthma significantly correlated with older age at the time of diagnosis, older age of asthma onset, higher body mass index, less atopy and fewer pollen sensitivity. Asthma severity of patients with SR was significantly milder than the reference group (OR: 0.6, 95% CI 0.5-0.8). Asthma with AI tended to be more severe although the relation was insignificant (OR:1.6 95% CI:0.8-3.5). CONCLUSIONS: Asthma patients with SR have significantly milder and earlier onset of asthma, better pulmonary function tests and are significantly more atopic while asthma with AI tends to be more severe. Asthma with CU does not show a specific phenotypic characteristic. PMID- 20542624 TI - Nerve-preserving sacrocolpopexy: anatomical study and surgical approach. AB - OBJECTIVE: The aim of our study is to describe the course of the autonomic nerves in the presacral space and to find the best nerve-preserving approach for sacrocolpopexy. STUDY DESIGN: The autonomic nerves of the presacral space were dissected on six specially preserved female cadavers. RESULTS: The superior hypogastric plexus is located in front of the abdominal aorta and its bifurcation and deviates to the left of the midsagittal plane. At the level of the promontory, or just below, the superior hypogastric plexus branches into two hypogastric nerves that run in front of the sacrum. In the presacral space the parasympathetic pelvic splanchnic nerves from the ventral rami of the sacral spinal nerves (S2-S3) join the hypogastric nerves, forming the inferior hypogastric plexus on both sides. From the inferior hypogastric plexus, nerve fibres spread out bilaterally to the pelvic organs. In two of the six cadavers sacral splanchnic nerves could be identified leading from the sacral sympathetic ganglion S1 of the sympathetic trunk to the inferior hypogastric plexus. CONCLUSION: Longitudinal incision of the peritoneum along the right common iliac artery and above the promontory allows for a safe approach for sacrocolpopexy. After exposing the vascular structure (e.g. medial sacral vessels) above the promontory, the anterior longitudinal ligament becomes visible and can be prepared for the fixation of the mesh for vaginal suspension. By protecting the superior hypogastric plexus and the part of the presacral area below the promontory we can preserve the hypogastric nerves, the sacral and pelvic splanchnic nerves and thus the autonomic innervation of the pelvic organs. Awareness of the course of the autonomic nerves in the presacral space will significantly improve the functional outcome of sacrocolpopexy and reduce bowel, urinary and sexual dysfunctions. PMID- 20542625 TI - Effects of hydrosalpinx on pinopodes, leukaemia inhibitory factor, integrin beta3 and MUC1 expression in the peri-implantation endometrium. AB - OBJECTIVES: To compare the expression of pinopodes, LIF, integrin beta(3) and MUC1 in the peri-implantation endometrium of women with and without hydrosalpinx. STUDY DESIGN: A prospective observational study in an assisted reproductive unit in a university teaching hospital, including 20 women with hydrosalpinx and 21 women without hydrosalpinx. Endometrial biopsies were performed on day LH+7 or +8. The proportion and density of pinopodes were assessed by scanning electron microscopy. LIF, integrin beta3 and MUC1 were evaluated with immunohistochemical staining. RESULTS: The proportion and the density of pinopodes were not significantly different between the hydrosalpinx and control groups. The LIF, integrin beta(3), and MUC1 expression were significantly reduced in both glandular epithelial cells and endometrial lumen of the hydrosalpinx group when compared with those of the control group. The expression of integrin beta(3) in stromal cells was also significantly lower in the hydrosalpinx group. CONCLUSIONS: The proportion and the density of pinopodes in the peri-implantation endometrium were not affected by the presence of hydrosalpinx while LIF, integrin beta(3) and MUC1 were significantly reduced in patients with hydrosalpinx. PMID- 20542626 TI - Lactate concentration in amniotic fluid: a good predictor of labor outcome. AB - OBJECTIVE: Previous publications have suggested that high levels of lactate in amniotic fluid (AF) correlate with dysfunctional labor. The aim of this study was to investigate whether lactate concentration in AF together with the partogram is a better predictor of operative intervention in dysfunctional labor than the partogram alone. STUDY DESIGN: A prospective observational study was carried out of 825 laboring women. Samples of AF were collected and the lactate concentration was analyzed at the bedside during labor. The main outcome of the study was the method of delivery (operative/spontaneous vaginal) in relation to the concentration of lactate in AF. Logistic regression was used to estimate the association between lactate concentration in AF and labor outcome and to adjust for well-known risk factors for dysfunctional labor. RESULTS: 385/825 women had an arrested labor according to the partogram, and 193 of them were delivered operatively. High lactate in AF (>10.1 mmol/l) when labor arrested was associated with an increased risk of operative intervention due to dysfunctional labor (adjusted OR, 5.4, 95% CI, 3.2-9.1). Low levels of lactate in AF (<10.1 mmol/l) were associated with an increased probability of spontaneous vaginal delivery (adjusted OR, 2.7, 95% CI, 1.7-4.8). CONCLUSION: The partogram together with the concentration of lactate in AF is a better predictor of operative intervention in dysfunctional labor than the partogram alone. PMID- 20542627 TI - Practical biophysics: Sensors for rapid detection of biological targets utilizing target-induced oligonucleotide annealing. AB - Detection and quantitation of biomolecules is one of the most commonly performed measurements in biomedical research and clinical diagnostics. There is high demand for convenient, rapid and sensitive biomolecule detection methodologies. In this review we discuss a family of sensors that have been developed in our laboratory that share a common simple biophysical mechanism of action and that are capable of rapid detection of a diverse range of biological targets. The sensors generate fluorescence signal in the presence of the target molecule through target-induced association of short fluorochrome-labeled complementary oligonucleotides that are attached to target recognition elements of the sensors (antibodies, aptamers, etc.) via nanometer scale flexible linkers. This sensor design can be used for detecting proteins, antibodies, nucleic acids and whole cells. The assays using these sensors require only adding a sample to the sensor mix followed by simple fluorescence intensity readout. The simplicity, the speed of detection and the potential for miniaturization are the main assets of these sensors. PMID- 20542628 TI - Sef is a negative regulator of fiber cell differentiation in the ocular lens. AB - Growth factor signaling, mediated via receptor tyrosine kinases (RTKs), needs to be tightly regulated in many developmental systems to ensure a physiologically appropriate biological outcome. At one level this regulation may involve spatially and temporally ordered patterns of expression of specific RTK signaling antagonists, such as Sef (similar expression to fgfs). Growth factors, notably FGFs, play important roles in development of the vertebrate ocular lens. FGF induces lens cell proliferation and differentiation at progressively higher concentrations and there is compelling evidence that a gradient of FGF signaling in the eye determines lens polarity and growth patterns. We have recently identified the presence of Sef in the lens, with strongest expression in the epithelial cells. Given the important role for FGFs in lens developmental biology, we employed transgenic mouse strategies to determine if Sef could be involved in regulating lens cell behaviour. Over-expressing Sef specifically in the lens of transgenic mice led to impaired lens and eye development that resulted in microphthalmia. Sef inhibited primary lens fiber cell elongation and differentiation, as well as increased apoptosis, consistent with a block in FGFR mediated signaling during lens morphogenesis. These results are consistent with growth factor antagonists, such as Sef, being important negative regulators of growth factor signaling. Moreover, the lens provides a useful paradigm as to how opposing gradients of a growth factor and its antagonist could work together to determine and stabilise tissue patterning during development and growth. PMID- 20542629 TI - Re: Per-Uno Malmstrom, Richard J. Sylvester, David E. Crawford, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 2009;56:247-56. PMID- 20542630 TI - The combination of neuronavigation with transcranial magnetic stimulation for treatment of opercular gliomas of the dominant brain hemisphere. AB - OBJECTIVE: The objective of this study is to investigate the application of transcranial magnetic stimulation combined with neuronavigation for preoperative mapping of the language area in neurosurgical interventions on the opercular area of the dominant hemisphere. METHODS: Five patients were operated upon gliomas in the opercular area. For localization of the speech area a transcranial magnetic stimulator MEDTRONIC-MagPro was used. BrainLAB-VectorVision Neuronavigation system was utilized for precise planning of the operative approach. RESULTS: Gross total resection was achieved in all patients. Three-month postoperative follow-up was done. Three of the patients had a transient postoperative motor aphasia which resolved within 1 month. CONCLUSION: This method is useful for preoperative localization of the speech area, as well as preoperative planning of the operative approach and intra-operative planning of the direction of brain retraction and operative corridor. PMID- 20542631 TI - Characterization and lead adsorption properties of activated carbons prepared from cotton stalk by one-step H3PO4 activation. AB - Activated carbons were prepared from cotton stalk by one-step H(3)PO(4) activation and used as adsorbent for the removal of lead(II). Taguchi experimental design method was used to optimize the preparation of the adsorbents. The results showed that the optimized conditions were: impregnation with a 50% (w/v) phosphoric acid solution with a mass ratio of 3:2 and activation temperature at 500 degrees C for 60 min with the rate of achieving the activation temperature equal to 10 degrees C min(-1). The cotton stalk activated carbon (CSAC) prepared at these conditions have 1.43 mmol g(-1) acidic surface groups and 1570 m(2) g(-1) BET surface area. Adsorption isotherms for lead(II) on the adsorbents were measured by conducting a series of batch adsorption experiments. The Langmuir maximum adsorption amount of lead(II) on CSAC was more than 119 mg g(-1), which was superior to the ordinary commercial activated carbon (CAC) on the market. Compared with the CAC, the CSAC had a wider applicable pH range from 3.5 to 6.5 for lead(II) uptake. The final pH values at equilibrium after adsorption were lower than the initial pH value, indicating that the ion-exchange process was involved in the adsorption. This is also confirmed by the result that the increase of acidic surface groups favored the adsorption process. Thermodynamic study indicated that the adsorption was a spontaneous and endothermic process. PMID- 20542632 TI - Laboratory and pilot plant scale study on the electrochemical oxidation of landfill leachate. AB - Kinetic data regarding COD oxidation were measured in a laboratory scale cell and used to scale-up an electro-oxidation process for landfill leachate treatment by means of boron-doped diamond anodes. A pilot-scale reactor with a total BDD anode area of 1.05 m(2) was designed. Different electrode gaps in the laboratory and pilot plant cells resulted in dissimilar reactor hydrodynamics. Consequently, generalised dimensionless correlations concerning mass transfer were developed in order to define the mass transfer conditions in both electrochemical systems. These correlations were then used in the design equations to validate the scale up procedure. A series of experiments with biologically pre-treated landfill leachate were done to accomplish this goal. The evolution of ammonia and COD concentration could be well predicted. PMID- 20542633 TI - Destruction of inorganic municipal solid waste incinerator fly ash in a DC arc plasma furnace. AB - Due to the toxicity of dioxins, furans and heavy metals, there is a growing environmental concern on municipal solid waste incinerator (MSWI) fly ash in China. The purpose of this study is directed towards the volume-reduction of fly ash without any additive by thermal plasma and recycling of vitrified slag. This process uses extremely high-temperature in an oxygen-starved environment to completely decompose complex waste into very simple molecules. For developing the proper plasma processes to treat MSWI fly ash, a new crucible-type plasma furnace was built. The melting process metamorphosed fly ash to granulated slag that was less than 1/3 of the volume of the fly ash, and about 64% of the weight of the fly ash. The safety of the vitrified slag was tested. The properties of the slag were affected by the differences in the cooling methods. Water-cooled and composite-cooled slag showed more excellent resistance against the leaching of heavy metals and can be utilized as building material without toxicity problems. PMID- 20542634 TI - Simultaneous speciation and preconcentration of ultra traces of inorganic tellurium and selenium in environmental samples by hollow fiber liquid phase microextraction prior to electrothermal atomic absorption spectroscopy determination. AB - A simple and effective speciation and preconcentration method based on hollow fiber liquid phase microextraction (HF-LPME) was developed for simultaneous separation of trace inorganic tellurium and selenium in environmental samples prior to electrothermal atomic absorption spectroscopy (ETAAS) determination. The method involves the selective extraction of the Te (IV) and Se (IV) species by HF LPME with the use of ammonium pyrrolidinecarbodithioate (APDC) as the chelating agent. The complex compounds were extracted into 10 microL of toluene and the solutions were injected into a graphite furnace for the determination of Te (IV) and Se (IV). To determine the total tellurium and selenium in the samples, first Te (VI) and Se (VI) were reduced to Te (IV) and Se (IV), and then the microextraction method was performed. The experimental parameters of HF-LPME were optimized using a central composite design after a 2(n-1) fractional factorial experimental design. Under optimum conditions, enrichment factors of up to 520 and 480 were achieved for Te (IV) and Se (IV), respectively. The detection limits were 4 ng L(-1) with 3.5% RSD (n=5, c=2.0 microg L(-1)) for Te (IV) and 5 ng L( 1) with 3.1% RSD for Se (IV). The applicability of the developed technique was evaluated by application to spiked, environmental water and soil samples. PMID- 20542636 TI - Risk assessment of trace elements in sediments: the case of the estuary of the Nerbioi-Ibaizabal River (Basque Country). AB - Long term (January 2005-January 2008) monitoring of sediments was used to investigate metal pollution in the estuary of the Nerbioi-Ibaizabal River (Bilbao, Basque Country). Sediments were collected from eight representative locations of the estuary approximately every three months. The concentration of fourteen elements was measured in sediment extracts. Different graphical representations of the data set, simple statistical methods and sediment quality guidelines were combined to investigate trends in space and time, identify pollution sources, and assess sediment quality from a toxicological point of view. In general terms, the main trend reveals a significant fall in metal concentration over the period investigated. There are still certain points of the estuary with relatively high concentration of toxic metals, but the toxicological approach suggests that the risk for living organisms is not important. PMID- 20542635 TI - Photocatalytic degradation of 1-naphthol by oxide ceramics with added bacterial disinfection. AB - 1-Naphthol photodegrades on the surfaces of TiO(2), ZnO, CeO(2), CdO, WO(3), Co(3)O(4), Sb(2)O(3), ZrO(2), La(2)O(3), Y(2)O(3), Pr(6)O(11), Sm(2)O(3) and Al(2)O(3), albeit at different efficiencies, and all the oxides show sustainable photocatalytic activity. The degradation conforms to the Langmuir-Hinshelwood kinetic model and enhances with the intensity of illumination. Dissolved oxygen is essential for the degradation. ZnO and TiO(2) anatase are the most efficient photocatalysts to degrade 1-naphthol. ZnO wurtzite, besides serving as an effective photocatalyt to degrade 1-naphthol, also acts as a bactericide; it inactivates E.coli even in absence of direct light. At a loading of 0.8 g L(-1), it kills about 44% of 2.5x10(12) CFU mL(-1) E. coli in (1/2) h under dark condition. PMID- 20542637 TI - Removal of rotenone insecticide by adsorption onto chemically modified activated carbons. AB - The removal of rotenone from synthetic and real wastewaters using modified activated carbons has been investigated. In order to enhance the removal capacity of rotenone, activated carbon was chemically modified through impregnation with NH(3) and (NH(4))(2)S(2)O(8) solutions. The resulting carbons were found to present different surface chemistries, while possessing similar textural properties. The adsorption data obtained at 298 K, on plain and modified carbons were well represented by the Langmuir isotherm model (R(2)>0.997). The highest adsorption capacity (Q(m)=270.3 mg g(-1)) was obtained with the ammonia-treated activated carbon. The relative effect of different surface groups on adsorption capacities were found to be in accordance with the pi-pi dispersive interaction model. The adsorption kinetic models have provided useful insights into rotenone adsorption mechanism. It was concluded that rotenone sorption process followed pseudo-second order model and was controlled by intra-particle diffusion mechanism with a significant contribution of film diffusion. The successful adsorptive removal of rotenone, from real wastewater samples on fixed bed columns, have demonstrated the suitability of this method as an effective alternative solution for the treatment of contaminated wastewaters. PMID- 20542638 TI - Thermal behaviors, nonisothermal decomposition reaction kinetics, thermal safety and burning rates of BTATz-CMDB propellant. AB - The composite modified double base (CMDB) propellants (nos. RB0601 and RB0602) containing 3,6-bis (1H-1,2,3,4-tetrazol-5-yl-amino)-1,2,4,5-tetrazine (BTATz) without and with the ballistic modifier were prepared and their thermal behaviors, nonisothermal decomposition reaction kinetics, thermal safety and burning rates were investigated. The results show that there are three mass-loss stages in TG curve and two exothermic peaks in DSC curve for the BTATz-CMDB propellant. The first two mass-loss stages occur in succession and the temperature ranges are near apart, and the decomposition peaks of the two stages overlap each other, inducing only one visible exothermic peak appear in DSC curve during 350-550 K. The reaction mechanisms of the main exothermal decomposition processes of RB0601 and RB0602 are all classified as chemical reaction, the mechanism functions are f(alpha)=(1-alpha)(2), and the kinetic equations are dalpha/dt = 10(19.24)(1-alpha)(2)e(-2.32x10(4)/T) and dalpha/dt = 10(20.32)(1 alpha)(2)e(-2.32x10(4)/T). The thermal safety evaluation on the BTATz-CMDB propellants was obtained. With the substitution of 26% RDX by BTATz and with the help of the ballistic modifier in the CMDB propellant formulation, the burning rate can be improved by 89.0% at 8 MPa and 47.1% at 22 MPa, the pressure exponent can be reduced to 0.353 at 14-20 MPa. PMID- 20542639 TI - Comparison of ELISA and PCR assays for the diagnosis of porcine cysticercosis. AB - Cysticercosis is a zoonotic disease due to Taenia solium, which involves porcines as intermediate host. It is endemic in Madagascar, however minimal data has been reported concerning porcine cysticercosis prevalence. Lack of ante-mortem diagnostic tools renders the evaluation of its prevalence difficult. Tongue palpation is specific but has poor sensitivity. Serological tests detecting antigens or antibodies are sensitive to human cysticercosis and apt for diagnosis but are not yet considered as a gold standard in porcine ante-mortem examination. PCR are widely used to detect pathogens but also poorly evaluated in regards to the diagnosis of cysticercosis. We compare the performance of PCR and ELISA assays on 67 pig serums: 22 from cysticercosis positive pigs (meat inspection) and 45 from cysticercosis negative animals (originating from a non-endemic country or grown in industrial and well isolated pigsties). Among the negative samples 19 were collected from pigs with trichinellosis and 4 from pigs with toxoplasmosis. Results indicate that ELISA assay showed high sensitivity and good specificity while the PCR assays showed high specificity but a low sensitivity. PMID- 20542640 TI - The role of an ingestible telemetric thermometer in preventing exertional heat stroke, for a patient with healed massive burns running the 2007 London marathon. PMID- 20542641 TI - Activity of topical antimicrobial agents against multidrug-resistant bacteria recovered from burn patients. AB - BACKGROUND: Topical antimicrobials are employed for prophylaxis and treatment of burn wound infections despite no established susceptibility breakpoints, which are becoming vital in an era of multidrug-resistant (MDR) bacteria. We compared two methods of determining topical antimicrobial susceptibilities. METHODS: Isolates of Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and Acinetobacter baumanii-calcoaceticus (ABC) from burn patients were tested using broth microdilution and agar well diffusion to determine minimum inhibitory concentrations (MICs) and zones of inhibition (ZI). Isolates had systemic antibiotic resistance and clonality determined. MDR included resistance to antibiotics in three or more classes. RESULTS: We assessed 22 ESBL-producing K. pneumoniae, 20 ABC (75% MDR), 20 P. aeruginosa (45% MDR), and 20 MRSA isolates. The most active agents were mupirocin for MRSA and mafenide acetate for the gram negatives with moderate MICs/ZI found with silver sulfadiazene, silver nitrate, and honey. MDR and non-MDR isolates had similar topical resistance. There was no clonality associated with resistance patterns. CONCLUSION: Despite several methods to test bacteria for topical susceptibility, no defined breakpoints exist and standards need to be established. We recommend continuing to use silver products for prophylaxis against gram-negatives and mafenide acetate for treatment, and mupirocin for MRSA. PMID- 20542642 TI - Acute kidney injury in critically ill burn patients. PMID- 20542643 TI - Long-term outcome and prognostic factors for adenocarcinoma/adenosquamous carcinoma of cervix after definitive radiotherapy. AB - PURPOSE: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. METHODS AND MATERIALS: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. RESULTS: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. CONCLUSION: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease. PMID- 20542644 TI - Clinical evaluation of soft tissue organ boundary visualization on cone-beam computed tomographic imaging. AB - PURPOSE: Cone-beam computed tomographic images (CBCTs) are increasingly used for setup correction, soft tissue targeting, and image-guided adaptive radiotherapy. However, CBCT image quality is limited by low contrast and imaging artifacts. This analysis investigates the detectability of soft tissue boundaries in CBCT by performing a multiple-observer segmentation study. METHODS AND MATERIALS: In four prostate cancer patients prostate, bladder and rectum were repeatedly delineated by five observers on CBCTs and fan-beam CTs (FBCTs). A volumetric analysis of contouring variations was performed by calculating coefficients of variation (COV: standard deviation/average volume). The topographical distribution of contouring variations was analyzed using an average surface mesh-based method. RESULTS: Observer- and patient-averaged COVs for FBCT/CBCT were 0.09/0.19 for prostate, 0.05/0.08 for bladder, and 0.09/0.08 for rectum. Contouring variations on FBCT were significantly smaller than on CBCT for prostate (p < 0.03) and bladder (p < 0.04), but not for rectum (p < 0.37; intermodality differences). Intraobserver variations from repeated contouring of the same image set were not significant for either FBCT or CBCT (p < 0.05). Average standard deviations of individual observers' contour differences from average surface meshes on FBCT vs. CBCT were 1.5 vs. 2.1 mm for prostate, 0.7 vs. 1.4 mm for bladder, and 1.3 vs. 1.5 mm for rectum. The topographical distribution of contouring variations was similar for FBCT and CBCT. CONCLUSION: Contouring variations were larger on CBCT than FBCT, except for rectum. Given the well-documented uncertainty in soft tissue contouring in the pelvis, improvement of CBCT image quality and establishment of well-defined soft tissue identification rules are desirable for image-guided radiotherapy. PMID- 20542645 TI - [Preterm births circumstances in babies born before 35 weeks in French Alpes: PREMALP study]. AB - OBJECTIVES: In a regional study of preterm infants born before 35weeks of gestation, the aim was to propose a new classification of preterm births into three groups, and to describe the pregnancy complications and fetal disorders in each group. PATIENTS AND METHODS: In two areas covered by a perinatal network, all preterm births, live births and stillbirths, which occurred between 22 and 34 completed weeks were recorded over a 21-month period. Each case was classified either in the medically-indicated preterm birth (I) group, or in the accepted spontaneous preterm birth (ASp) group or in the non-accepted spontaneous preterm birth (NASp) group. RESULTS: One thousand and sixty cases of preterm births were included; among them, 981 were live births or ended with per partum infant death. Forty-nine percent of these births were medically indicated, 32 % were ASp and 19 % were NASp. The distribution of pregnancy complications and fetal disorders differed between preterm birth groups: ischemic placental diseases were present in 38,2 % of medically-indicated births; preterm premature rupture of membranes occurred twice more often in I and ASp preterm births than in NASp preterm births. CONCLUSION: This classification is based on the medical decision; it allows to compare medical practices in given obstetrical situations. It appears to be reproducible and easy to use. PMID- 20542646 TI - [Endometrial cancer: survey of surgical practice in france in 2008]. AB - OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy. We aimed to assess the management of this disease among French surgeons as regards to the French guidelines. MATERIALS AND METHODS: Six hundred questionnaires were given to surgeons during two national French Meetings in 2008. They focused on the surgeon (age, gender, center of work, number of treated cancers individually and in the center) and on the disease (initial work-up, surgical management). Three case reports related to endometrial cancer were proposed to assess the conformity of the French guidelines (two case reports about endometrioid carcinomas stages IB and II and one about serous papillary adenocarcinoma). RESULTS: Nineteen percent of surgeons (n=114) answered the questionnaire. The French Guidelines were respected in less than 60 % in the answers of the three case reports (only 13.3 % of the answers were conformed in all the three cases). The surgeons who respected the recommendations took care of more than five treated patients per year (92.9 % versus 57.8 %, P=0.01), they were younger (41 year versus 49 years, P=0.01), and the post-graduation delay was shorter (9.1 versus 20.5 years, P=0.002). The center where the surgeon worked was not a determinant factor for treatment. The surgical procedures were mostly transverse laparotomy in 35.4 %. Peritoneal cytology and lymphadenectomy were provided in 69.9 % and 74.7 % of cases, respectively. CONCLUSION: Despite the limits of our study based on volunteer answers of surgeons to a questionnaire, our results highlight the efforts of learned societies and medical authorities should be used to standardize the treatment of cancer. A reflection should be conducted on the basis of initial training and throughout a professional career to provide patients optimal care of their pathology. PMID- 20542647 TI - Molecular diversity assessed by VNTR and IS1296 typing of historical Mycoplasma mycoides subsp. mycoides SC strains. AB - The last case of Contagious Bovine Pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides SC (MmmSC), in Europe was reported in Portugal in 1999. However, in view of its insidious nature, it is still possible that CBPP could re emerge. Despite differences in animal host and geographical origin, most of the European MmmSC field isolates were traditionally considered to be very homogeneous. In the present study we performed a retrospective variable-number tandem repeat (VNTR) and IS1296 genotyping analysis of 65 MmmSC field isolates associated to the last CBPP outbreaks that occurred in Portugal in order to elucidate their intra-specific genetic variability. A 8.8 kb region and two VNTR loci (VNTR4 and VNTR5) were analyzed for polymorphisms by PCR amplification. All but one strain presented the same IS1296 profile, in contrast with the VNTR genotyping that confirmed some diversity of Portuguese strains showing VNTR4, the most discriminatory one, four different patterns. VNTR4 type "9" (numbering according to the estimated number of repeats) was the most predominant one mainly in the Entre Douro-Minho region. All isolates from one geographic region (Beira Litoral) presented VNTR4 type "8" suggesting the existence of a region-specific VNTR. These facts raise the hypothesis that at least two CBPP re-emergence events could have occurred in Portugal since 1983 after 30 years of silence. This aspect represents a major concern and is a major reason for the maintenance of intensive research on this disease. PMID- 20542648 TI - Predictability of cerebral palsy in a high-risk NICU population. AB - AIM: This study aims to create a predictive model for the assessment of the individual risk of developing cerebral palsy in a large cohort of selected high risk infants. PATIENTS AND METHODS: 1099 NICU-admitted high-risk infants were assessed up to the corrected age of at least 12 months. CP was categorized relative to subtype, distribution and severity. Several perinatal characteristics (gender, gestational age, multiple gestation, small for gestational age, perinatal asphyxia and duration of mechanical ventilation), besides neonatal cerebral ultrasound data were used in the logistic regression model for the risk of CP. RESULTS: Perinatal asphyxia, mechanical ventilation>7 days, white matter disease except for transient echodensities<7 days, intraventricular haemorrhage grades III and IV, cerebral infarction and deep grey matter lesions were recognized as independent predictors for the development of CP. 95% of all children with CP were correctly identified at or above the cut-off value of 4.5% probability of CP development. Higher gestational age, perinatal asphyxia and deep grey matter lesion are independent predictors for non-spastic versus spastic CP (OR=1.1, 3.6, and 7.5, respectively). Independent risk factors for prediction of unilateral versus bilateral spastic CP are higher gestational age, cerebral infarction and parenchymal haemorrhagic infarction (OR=1.2, 31, and 17.6, respectively). Perinatal asphyxia is the only significant variable retained for the prediction of severe CP versus mild or moderate CP. CONCLUSION: The presented model based on perinatal characteristics and neonatal US-detected brain injuries is a useful tool in identifying specific infants at risk for developing CP. PMID- 20542649 TI - Measurement of glucose levels in the newborn. AB - Accurate measurement of blood glucose levels in the newborn is important as hypoglycaemia and hyperglycaemia are common treatable conditions and there is evidence linking both with detrimental clinical outcomes. Point of care (POC) glucose testing provides rapid results with small sample volumes and therefore clinical care can be modified quickly if needed. However the common thresholds for the diagnosis of hypoglycaemia in the newborn (blood glucose <2.0 mmol/l or <2.6 mmol/l) and hyperglycaemia (blood glucose >10 mmol/l) are at the limits of accuracy for many POC glucose analysers. Therefore although useful for screening, such devices cannot be relied upon for accurate diagnosis of hypoglycaemia. Stand alone local laboratory devices or glucose biosensors incorporated into blood gas analysers help to balance the benefits of POC testing with the accuracy of laboratory analyses. However these clinical methods all rely on intermittent blood sampling and there may be many hours between measurements, when both hypoglycaemia and hyperglycaemia may be undetected clinically. Less invasive and continuous methods of glucose monitoring are under development. Continuous glucose monitoring provides detailed information regarding glucose levels and has led to improvements in the care of patients with diabetes mellitus. These devices also have the potential to help provide improved glucose monitoring and management in the high risk neonate. PMID- 20542650 TI - Intrapulse changes in progesterone and LH concentrations and luteal blood flow during an estradiol-induced pulse of a metabolite of prostaglandin F2alpha in heifers. AB - Physiologic doses (0.1 mg followed by 0.05 mg 1h later) of estradiol-17beta in sesame-oil vehicle or vehicle alone (n=6/group) were given to heifers on day 14 after ovulation (preluteolysis) to study the effect of estradiol (E2) on circulating 13,14-dihydro-15-keto-PGF2alpha (PGFM) and on PGFM pulses. Blood samples were collected hourly for 10h after the 0.1-mg treatment. The E2 group had an increase (P<0.03) in PGFM concentration by 4h and greater (P<0.0001) prominence of the PGFM pulses. Changes in progesterone and LH concentrations and luteal blood flow within a PGFM pulse were characterized. Within a PGFM pulse in the E2 group, progesterone decreased (P<0.04) between Hours -2 and 0 (ascending portion; Hour 0=peak of pulse) and increased (P<0.04) between Hours 0 and 2 (descending portion). Intrapulse changes in progesterone were not detected in the vehicle group. Concentration of LH in the E2 group increased (P<0.05) between Hours -1 and 1 and in the vehicle group decreased (P<0.03) between Hours -1 and 0 and increased (P<0.06) between Hours 0 and 1. The percentage of luteal area with blood-flow signals increased (P<0.02) between Hours 0 and 1 in the E2 group, and there were no other differences between hours in either group. Results were consistent with reports of changes in progesterone concentration within a PGFM pulse in cattle and demonstrated intrapulse changes in LH concentration and luteal blood flow during an E2-induced PGFM pulse. PMID- 20542651 TI - Nodulation in black locust by the Gammaproteobacteria Pseudomonas sp. and the Betaproteobacteria Burkholderia sp. AB - Nodulation abilities of bacteria in the subclasses Gammaproteobacteria and Betaproteobacteria on black locust (Robinia pseudoacacia) were tested. Pseudomonas sp., Burkholderia sp., Klebsiella sp., and Paenibacillus sp. were isolated from surface-sterilized black locust nodules, but their nodulation ability is unknown. The aims of this study were to determine if these bacteria are symbiotic. The species and genera of the strains were determined by RFLP analysis and DNA sequencing of 16S rRNA gene. Inoculation tests and histological studies revealed that Pseudomonas sp. and Burkholderia sp. formed nodules on black locust and also developed differentiated nodule tissue. Furthermore, a phylogenetic analysis of nodA and a BLASTN analysis of the nodC, nifH, and nifHD genes revealed that these symbiotic genes of Pseudomonas sp. and Burkholderia sp. have high similarities with those of rhizobial species, indicating that the strains acquired the symbiotic genes from rhizobial species in the soil. Therefore, in an actual rhizosphere, bacterial diversity of nodulating legumes may be broader than expected in the Alpha-, Beta-, and Gammaproteobacteria subclasses. The results indicate the importance of horizontal gene transfer for establishing symbiotic interactions in the rhizosphere. PMID- 20542652 TI - Comparison and combination of spectroscopic techniques for the detection of counterfeit medicines. AB - During this study, Fourier transform infrared spectroscopy (FT-IR), near infrared spectroscopy (NIR) and Raman spectroscopy were applied to 55 samples of counterfeit and imitations of Viagra and 39 samples of counterfeit and imitations of Cialis. The aim of the study was to investigate which of these techniques and associations of them were the best for discriminating genuine from counterfeit and imitation samples. Only the regions between 1800-400 cm(-1) and 7000-4000 cm( 1) were used for FT-IR and NIR spectroscopy respectively. Partial least square analysis has been used to allow the detection of counterfeit and imitation tablets. It is shown that for the Viagra samples, the best results were provided by a combination of FT-IR and NIR spectroscopy. On the other hand, the best results for the Cialis samples were provided by the combination of NIR and Raman spectroscopy (1400-1190 cm(-1)). These techniques not only permitted a clear discrimination between genuine and counterfeit or imitation samples but also the distinction of clusters among illegal samples. This might be interesting for forensic investigations by authorities. PMID- 20542653 TI - Synthesis and characterization of liquid chromatographic columns containing the immobilized ligand binding domain of the estrogen related receptor alpha and estrogen related receptor gamma. AB - The ligand binding domains of the estrogen related receptors, ERRalpha and ERRgamma were covalently immobilized onto the surface of an aminopropyl silica liquid chromatography stationary phase to create the ERRalpha-silica and ERRgamma silica columns and onto the surface of open tubular capillaries to create the ERRalpha-OT and ERRgamma-OT columns. The ERR-silica and ERR-OT columns were characterized using frontal chromatographic techniques with diethylstibesterol and the binding affinities, K(d) values, to the immobilized receptors were consistent with the values obtained by a radioligand binding assay. The ERRgamma silica column was also characterized using non-linear chromatographic techniques using a series of tamoxifen derivatives. The relative K(d) values obtained for the derivatives were consistent with the relative ability of the compounds to inhibit the cellular proliferation of the human-derived T98G glioma cell line, expressed as IC(50) values. The results indicate that the columns containing immobilized ERRalpha and ERRgamma can be created and used to characterize the binding of compounds to the immobilized receptors and that the relative retention of compounds on these columns reflects the magnitude of their inhibitory activity. PMID- 20542654 TI - Rupture of a splenic artery aneurysm in the first trimester of pregnancy. AB - BACKGROUND: Rupture of a splenic artery aneurysm during pregnancy is a rare and serious event, occurring mainly during the third trimester. The risk of rupture for an existing splenic artery aneurysm is very high during pregnancy (from 20% to 50%). When it does rupture, the maternal mortality rate is around 75% and the fetal mortality rate 95%. Of 110 cases reported in the literature, only one ruptured during the first trimester. OBJECTIVES: The aim of this case report is to make emergency physicians aware of this diagnosis, because only if it is considered can it be managed rapidly and appropriately. CASE REPORT: We report the case of a 6-weeks pregnant patient referred to our institution in hemorrhagic shock who died of a ruptured splenic artery aneurysm shortly after surgery. The initial diagnosis considered was a ruptured ectopic pregnancy. CONCLUSION: We report this case to increase awareness of splenic artery rupture during pregnancy, even during the first trimester. PMID- 20542655 TI - Prognosis in patients presenting with non-traumatic coma. AB - BACKGROUND: Studies of patients presenting with coma are limited, and little is known about the prognosis of these cases. OBJECTIVE: The aim of this study was to investigate the acute and long-term prognosis after an episode of non-traumatic coma. METHODS: Adults admitted consecutively to an emergency department in Stockholm, Sweden between February 2003 and May 2005 with a Glasgow Coma Scale (GCS) score of 10 or below were enrolled prospectively. All available data were used to explore the cause of the impaired consciousness on admission. Patients surviving hospitalization were followed-up for 2 years regarding survival. RESULTS: The final study population of 865 patients had the following eight different coma etiologies: poisoning (n = 329), stroke (n = 213), epilepsy (n = 113), circulatory failure (n = 60), infection (n = 56), metabolic disorder (n = 44), respiratory insufficiency (n = 33), and intracranial malignancy (n = 17). The hospital mortality rate among the 865 patients was 26.5%, varying from 0.9% for epilepsy to 71.7% for circulatory failure. The accumulated total 2-year mortality rate was 43.0%, varying from 13.7% for poisoning to 88.2% for malignancy. The level of consciousness on admission also influenced the prognosis: a GCS score of 3-6 was associated with a significantly higher hospital mortality rate than a GCS score of 7-10. CONCLUSION: The prognosis in patients presenting with non-traumatic coma is serious and depends largely on both the level of consciousness on admission and the etiology of the coma. Adding the suspected coma etiology to the routine coma grading of these emergencies may more accurately predict their prognosis. PMID- 20542656 TI - Language barriers and the use of interpreters in the public health services. A questionnaire-based survey. AB - OBJECTIVE: This study aims to examine cross-cultural communication in health-care settings, which has implications for equal access to health services. We studied how often health-care workers experience a need for language assistance, what they do in such situations, what expectations they have of the interpreters and their evaluation of competency needs. METHODS: A quantitative cross-sectional design using a structured questionnaire was used. The participants were health care providers in Oslo, and the survey was conducted 2004-2005. RESULTS: The response rate was 35.1%. The largest category of participants (51.1%) consisted of nurses, followed by the second largest category (26.6%) of 120 physicians. Our results suggested an underutilization of interpreter services in the public health-care system. CONCLUSIONS: The use of interpreter services seems to be sporadic and dependent on the individual health-care practitioner's own initiative and knowledge. Many survey participants expressed dissatisfaction with both their own methods of working with interpreters and with the interpreter's qualifications. PRACTICE IMPLICATIONS: A key area for further improvement is the process of raising awareness among health-care providers and institutions regarding the legal responsibility they have to ensure the sufficient level of communication with their patients/clients. PMID- 20542657 TI - Gastric cancer in the elderly: an overview. AB - AIMS: Gastric cancer in the elderly represents a distinct entity with specific clinicopathological characteristics and the majority of affected patients belong to this age group. Subtotal or total gastrectomy with radical lymph node dissection, adjuvant chemoradiotherapy or perioperative chemotherapy represent the only potentially curative treatment options and seem to be performed with acceptable morbidity and mortality rates in selected elderly patients. Published research is very limited due to the strict selection and under-representation of elderly patients in clinical trials. A review of current recommendations and practice was performed. METHODS: A comprehensive literature review was performed searching Medline for articles published since 1974, using "gastric cancer", "elderly" and "treatment" as keywords. OBSERVATIONS: The data suggest that elderly patients that fulfill the inclusion criteria of clinical trials experience the same advantages and toxicities from chemotherapy as younger patients. Fit elderly patients with operable gastric cancer should be candidates for the standard surgical resection provided that preoperative comorbidities are taken into account. Perioperative chemotherapy or postoperative chemoradiotherapy should be added in case of locally advanced disease. Palliative systemic chemotherapy seems to prolong survival in recurrent and metastatic disease. CONCLUSIONS: Chronological age alone is not sufficient reason to withhold curative or palliative treatment from an elderly gastric cancer patient. Performance status does not suffice in order to estimate the general condition of elderly patients and cofactors regarding their functional, social and mental status have to be considered. PMID- 20542658 TI - K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. AB - OBJECTIVE: To determine the prognostic value of K-ras mutations in plasma DNA of unresectable pancreatic cancer patients. METHODS: Blood samples were collected from 91 patients with unresectable pancreatic cancer prior to treatment. K-ras gene was amplified from the circulating plasma DNA. Mutations were detected by direct sequencing. The relationship between the types of K-ras gene and prognosis of unresectable pancreatic cancer was evaluated. RESULTS: K-Ras codon 12 mutations were found in 30 of 91(33%) plasma DNA samples, 17mutations were c.35G>A (p.G12D), 11 were c.35G>T (p.G12V) and only 2 were c.34G>C (p.G12R)). K ras codon 12 mutations could significantly reflect the clinical parameters, including TNM tumor staging (P=0.033) and liver metastasis (P=0.014). The median survival time of patients with K-ras mutations was shorter than that of patients with wild-type K-ras gene (3.9 months vs. 10.2 months, P<0.001). K-ras codon 12 mutation from plasma DNA was an independent negative prognostic factor for survival (hazard ratio, 7.39; 95% confidence interval, 3.69-14.89). CONCLUSION: K ras mutation in plasma DNA is a predictive biomarker for a poor prognosis of unresectable pancreatic cancer patients. PMID- 20542659 TI - Separate cavity margins excision as a complement to conservative breast cancer surgery. AB - BACKGROUND: Positive lumpectomy margins (LM) usually mandate re-excision. However, approximately half of these patients have no residual tumour in the re excision specimen. The aim of this study was to investigate if separate cavity margin (CM) excision can safely reduce the need of re-operation. METHODS: Rate of re-operation for margin involvement and incidence of residual tumour in the re excision specimen were retrospectively evaluated in 237 patients (group A) who underwent lumpectomy alone, and in 271 patients (group B) treated by lumpectomy and CM excision. Patients with positive LM (group A) or CM (group B) underwent re excision. RESULTS: In the group A, 50/237 patients (21.1%) had LM+ and underwent re-excision. In the group B, 74/271 patients (27.3%) had LM+, but tumour was found within the CM specimen in 46 patients (17.0%), 24 LM+ and 22 LM-, and reached the CM cut edge in only 15 (5.5%), who finally underwent re-excision. Residual tumour was found in the re-excision specimen in 28/50 patients (56.0%) of the group A and in 7/15 patients (46.7%) of the group B. CONCLUSIONS: Separate CM excision strongly decreases the rate of re-operation for involved margin. However, the finding of various combinations of LM and CM status and the evidence that CM excision does not improve the positive predictive value of margin involvement suggest prudent conclusions. Only long term follow up of patients treated according to the CM status can exclude that the reduced rate of re operations allowed by this procedure would expose to an increased risk of local recurrence. PMID- 20542660 TI - An Examination of Psychotropic Medication Side Effects: does taking a greater number of psychotropic medications from different classes affect presentation of side effects in adults with ID? AB - This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the Matson Evaluation of Drug Side-effects (MEDS), which is an instrument used to assess side effects. There were three levels of the independent variable: Group 1--those taking zero psychotropic medications, Group 2--those taking one psychotropic medication, and Group 3--those taking two psychotropic medications across different medication classes. There was a significant main effect regarding number of psychotropic medication classes prescribed. Further analysis revealed that four of the nine MEDS domains had significantly different mean scores for number of psychotropic medication classes. For the majority of MEDS domains, such as Central Nervous System-General, Parkinsonism/Dyskinesia, and Behavioral/Akathesia domains, participants in the no psychotropic medication group had significantly lower mean scores than those in the one and two psychotropic medication groups. Only two MEDS domains, Cardiovascular and Hematologic Effects as well as Skin, Allergies, and Temperature, were significantly different between participants taking one psychotropic medication as compared with two psychotropic medications from different classes. Implications of these findings and recommendations for future research are discussed. PMID- 20542661 TI - Pediatric Evaluation of Disability Inventory: a cross-cultural comparison of daily function between Taiwanese and American children. AB - The study described the psychometric properties of the Pediatric Evaluation of Disability Inventory (PEDI) when used in Taiwanese normally developing children and illustrated the ethnic differences in determining capacity and independence in daily function between Taiwanese and American children. The Chinese version of the PEDI (PEDI-C) was administered to Taiwanese parents of 494 normally developing children and 110 children with developmental disabilities (DD). The scores of Taiwanese population were compared with the American counterparts using independent samples t-test. The PEDI-C had demonstrated good psychometric properties when used in Chinese-speaking population. The results revealed that internal consistency and inter-rater reliability was high. The unidimensionality of each domain was supported by Mokken analysis. The standardized factor scores of the PEDI-C differentiated children with DD from normally developing children. Group differences existed in various areas of daily function between Taiwanese and American children. Taiwanese children were less capable and needed more assistance in self-care and social function of daily living, especially after 4 years of age. Taiwanese and American children had similar capacity and performance in mobility. The identified discrepancy could serve as a guide of child-rearing for parents and for clinicians working with clients from different cultural backgrounds in a culturally diverse society. PMID- 20542662 TI - Simulating the shaping of the fastigial deep nuclear saccade command by cerebellar Purkinje cells. AB - Early lesion and physiological studies established the key contributions of the cerebellar cortex and fastigial deep nuclei in maintaining the accuracy of saccades. Recent evidence has demonstrated that fastigial oculomotor region cells (FORCs) provide commands that are critical both for driving and braking saccades. Modeling studies have largely ignored the mechanisms by which the FORC activity patterns, and those of the Purkinje cells (PCs) that inhibit them, are produced by the mossy fiber (MF) inputs common to both. We have created a hybrid network of integrate-and-fire and summation units to model the circuitry between PCs, FORCs, and MFs that can account for all observed PC and FORC activity patterns. The model demonstrates that a crucial component of FORC activity may be due to the rebound depolarization intrinsic to FORC neurons that, like the MF-driven activity of FORCs, is also shaped by PC inhibition and disinhibition. The model further demonstrates that the shaping of the FORC saccade command by PCs can be adaptively modified through plausible learning rules based on cerebellar long term depression (LTD) and long-term potentiation (LTP), which are guided by climbing fiber (CF) input to PCs that realistically indicates only the direction (but not the magnitude) of saccade error. These modeling results provide new insights into the adaptive control by the cerebellum of the deep nuclear saccade command. PMID- 20542664 TI - Seizure exacerbation and hormonal cycles in women with epilepsy. AB - PURPOSE: To investigate seizure frequency in relation to menstrual cycles and seizure exacerbations with respect to various clinical factors in women with epilepsy. METHODS: The authors prospectively evaluated premenopausal women with epilepsy aged 15-44. Catamenial epilepsy was defined as seizure frequency during the perimenstrual (C1), periovulatory (C2) or non-menstrual phase (C3) at least twice that during other phases. RESULTS: In total 255 menstrual cycles, 231 ovulatory and 24 anovulatory cycles were registered in 79 patients (29.7+/-7.8 years old). Average seizure frequency was 0.13+/-0.29/day during the menstrual phase, 0.14+/-0.24 during the follicular, 0.18+/-0.61 in the ovulatory, and 0.14+/-0.33 during the luteal phases. Catamenial seizure exacerbation was observed in 37/79 (46.8%) patients and 108/255 (42.4%) cycles, more frequently during anovulatory (17/24, 70.8%) than ovulatory (91/231, 39.4%) cycles (p=0.003). During ovulatory cycles, seizure exacerbation was primarily C1 (42.9%) or C2 (45.1%) pattern. Myoclonic seizures were more frequently associated with the C1 pattern. CONCLUSIONS: Overall, 46.8% of women had catamenial epilepsy. Seizure frequencies were greater during menstrual and ovulatory phases for ovulatory cycles, and during non-menstrual phases for anovulatory cycles. PMID- 20542665 TI - Orbitofrontal morphology in people at high risk of developing schizophrenia. AB - BACKGROUND: Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis. METHODS: Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects. RESULTS: We refined Chiavaras' classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor. CONCLUSIONS: Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia. PMID- 20542666 TI - Telepsychiatry and carer education for schizophrenia. AB - OBJECTIVE: Despite the scientific evidence, most families of people with schizophrenia in Europe never receive a carer education programme. We evaluated whether a carer education course delivered by telepsychiatry was as effective as a carer education course delivered in situ. METHOD: We delivered the carer education course for schizophrenia simultaneously to a carers group in rural north west Ireland (remote) via three ISDN lines and live to a carers group in a city (host). We compared knowledge gains using the Knowledge Questionnaire before and after each course. RESULTS: Fifty-six carers of people with schizophrenia participated in the trial. At baseline, participants at the remote and host centers did not differ in terms of knowledge about schizophrenia. After the course, carers at both centers improved significantly and the knowledge gains between groups were equivalent at 6 weeks. CONCLUSION: Telepsychiatry can deliver effective carer education programmes about schizophrenia and may provide one solution to bridging the chasm between scientific evidence and clinical reality. PMID- 20542667 TI - Second-generation antipsychotics and constipation: a review of the literature. AB - Antipsychotics are the cornerstone in the management of psychotic disorders and schizophrenia. They are effective agents but also have a wide range of side effects. In the recent literature constipation as possible side effect has received little attention. A review of the literature concerning constipation associated with antipsychotics was performed. Overall constipation is a rarely studied or reported side effect of antipsychotic medication. Nevertheless constipation is a common side effect. Antipsychotic agents differ in their liability to induce constipation. Constipation can be severe and can lead to serious consequences such as paralytic ileus, bowel occlusion and death. Active screening, monitoring and treatment are recommended. Further research on incidence, prevalence, underlying mechanisms and preventive measures is required. PMID- 20542669 TI - Corpus callosum size in adults with high-functioning autism and the relevance of gender. AB - The goal of the study was to investigate the size of the corpus callosum (CC) and its subsegments in relation to total brain volume (TBV) as an empirical indicator of impaired connectivity in autism with special respect to gender. In MRI data sets of 29 adults with high-functioning autism (HFA) and 29 age-, gender- and IQ matched control subjects, the TBV was measured and the CC was analyzed as a whole and in subsegments employing two different manual segmentation procedures. With respect to diagnosis, there were no significant differences in the dependent variables (CC, CC subsegments, and TBV). With respect to gender, only TBV was significantly increased in males compared with females, resulting in a significantly decreased CC/TBV ratio in males. This finding, however, was independent from gender and can be fully attributed to brain size. Our findings do not support the following hypotheses: (1) a hypothesis of impaired CC in HFA adults as a subgroup of patients with autism spectrum disorders, and (2) the sexual dimorphism hypothesis of the CC. PMID- 20542668 TI - Prepulse inhibition of the startle reflex in schizophrenia remains stable with short-term quetiapine. AB - PURPOSE: To study the short-term effect of treatment with quetiapine on prepulse inhibition (PPI) deficits of the startle reflex in schizophrenia patients. SUBJECTS AND METHODS: Using PPI, we studied a group of 21 schizophrenia patients and 16 controls. Seventeen of the patients were re-tested with PPI after 21 days of treatment with quetiapine. RESULTS: At baseline, an almost significant decrease in PPI was found in the patients as compared to the controls. PPI measurements did not change in the patients after 21 days of treatment with quetiapine, despite their clinical improvement. CONCLUSION: Our results suggest that short-term quetiapine treatment may not modify PPI measures in schizophrenia patients. PMID- 20542670 TI - Motor impulsivity and the ventrolateral prefrontal cortex. AB - Functional magnetic resonance imaging in a Go/Nogo task was employed to investigate the relationship between trait impulsivity and brain activation during motor response inhibition. We found a positive correlation between motor impulsivity and activation of bilateral ventrolateral prefrontal cortex during successful inhibitions, which suggests stronger recruitment to maintain task performance. PMID- 20542671 TI - [Multiple cerebral cavernomatosis in a 1-year-old child]. AB - Cavernous malformations are vascular lesions of the central nervous system. They are very rare in childhood. We report the case of sporadic cavernous cerebral angioma in a 1-year-old girl without pathologic antecedents revealed by a partial seizure. With this case and a review of the literature, we show the clinical and therapeutic characteristics of cerebral cavernomatosis in childhood. PMID- 20542672 TI - [Administration of a single Winter oral dose of 200,000 IU of vitamin D3 in adolescents in Normandy: evaluation of the safety and vitamin D status obtained]. AB - Adolescence, a period of growth and acquisition of bone mass, requires adequate calcium and vitamin D intake. This study was designed to assess the impact of a single loading dose of 200,000 IU of vitamin D(3) on the winter vitamin D status of healthy adolescents. Vitamin D status was assessed by 25-OH-D levels before, 3 weeks, and 3 months after this single dose, and safety was assessed by serum calcium and PTH and urinary calcium excretion in random samples from 27, 23, and 17 healthy adolescents derived from the same institution. The 25-OH-D peak value 2 weeks after the vitamin D supplement of 71-129 nmol/l (mean, 96 nmol/l), and a residual level at 3 months of 29-83 nmol/l (mean, 57 nmol/l) serum calcium and urinary calcium excretion expressed by the calcium/creatinine ratio were normal and stable at 2 weeks and 3 months, remaining less than 0.5 for the calcium/creatinine ratio. This simple measure, ensuring good compliance during adolescence, ensures optimal winter vitamin D status with no signs of overload. PMID- 20542673 TI - A segmentation framework for abdominal organs from CT scans. AB - OBJECTIVE: Computed tomography images are becoming an invaluable mean for abdominal organ investigation. In the field of medical image processing, some of the current interests are the automatic diagnosis of liver, spleen, and kidney pathologies, and the 3D volume rendering of these abdominal organs. Their automatic segmentation is the first and fundamental step in all these studies, but it is still an open problem. METHODS: In this paper we propose a fully automatic, gray-level based segmentation framework based on a multiplanar fast marching method. The proposed segmentation scheme is general, and employs only established and not critical anatomical knowledge. For this reason, it can be easily adapted to segment different abdominal organs, by overcoming problems due to the high inter- and intra-patient gray-level, and shape variabilities; the extracted volumes are then combined to produce the final results. RESULTS: The system has been evaluated by computing the symmetric volume overlap (SVO) between the automatically segmented (liver and spleen) volumes and the volumes manually traced by radiological experts. The test dataset is composed of 60 images, where 40 images belong to a private dataset, and 20 images to a public one. Liver segmentation has achieved an average SVO congruent with94, which is comparable to the mean intra- and inter-personal variation (96). Spleen segmentation achieves similar, promising results (SVO congruent with93). The comparison of these results with those achieved by active contour models (SVO congruent with90), and topology adaptive snakes (SVO congruent with92) proves the efficacy of our system. CONCLUSIONS: The described segmentation method is a general framework that can be adapted to segment different abdominal organs, achieving promising segmentation results. It has to be noted that its performance could be further improved by incorporating shape based rules. PMID- 20542674 TI - Ductal variant of adenocarcinoma prostate responding to docetaxel--a case report. PMID- 20542675 TI - Limited usefulness of QuantiFERON-TB Gold In-Tube for monitoring anti tuberculosis therapy. AB - The usefulness of IFN-gamma release assays to monitor the efficacy of anti tuberculosis (TB) treatment is controversial. Sixty patients affected by culture confirmed pulmonary TB (M = 36; mean age: 39.2 yr; Italians = 28) were serially tested in a low prevalence setting by means of QuantiFERON-TB GOLD In-Tube (QFT IT) at baseline and after a successful six-month therapy regimen (T6). A sub group of 40 cases was also tested at 1 and 3 months. Overall, 88.3% of patients scored a QFT-IT positive result at baseline, with the higher proportion of TB specific IFN-gamma responses in foreign-born patients (p = 0.04). TB-specific responses were highly variable over time, the within-person variability being correlated with baseline IFN-gamma levels (r = 0.731; p < 0.001). Overall, 61.6% of cases still tested QFT-IT positive at the completion of therapy. Average IFN gamma levels increased over time, being persistently significantly higher in Italian patients than in foreign-born cases both at baseline (p = 0.03) and at T6 (p = 0.02). Reversion mainly occurred in patients (26.6%) with baseline IFN-gamma levels close to the conventional cut-off value. No indeterminate results were recorded at any study time point. In conclusion, QFT-IT adds no significant information to clinicians for treatment monitoring when applied in routine clinical practice in a low prevalence setting. Kinetics of T cell responses upon TB treatment and reversion (and conversion) thresholds need to be addressed. Diversity of IFN-gamma responses among patients of different geographic origin is an issue to be investigated further. PMID- 20542676 TI - Epithelial apoptosis as a clinical marker in idiopathic interstitial pneumonia. AB - BACKGROUNDS: Epithelial cell apoptosis plays an important role in the pathogenesis of idiopathic interstitial pneumonia (IIP). METHODS: Serum levels of caspase-cleaved cytokeratin-18 (M30) were measured in 55 patients with IIP and 34 healthy controls using enzyme-linked immunosorbent assays. The IIP cases included usual interstitial pneumonia (UIP; n = 30), nonspecific interstitial pneumonia (NSIP; n = 15), and cryptogenic organizing pneumonia (COP; n = 10). The radiological scoring was performed based on high-resolution computed tomography (HRCT) findings. RESULTS: Patients with IIP had higher serum M30 levels than did the control group (178.6 +/- 91.5 vs. 113.7 +/- 46.8 U/L, p < 0.05). Among IIP patients, COP patients had higher serum M30 levels than did UIP or NSIP patients (264.9 +/- 132.7, 139.2 +/- 49.7, and 201.2 +/- 81.1 U/L, respectively; COP vs. UIP, p < 0.01). Serum M30 levels were negatively correlated with forced vital capacity (FVC; r(s) = -0.31), percent-predicted FVC (FVC%; r(s) = -0.38), and percent-predicted forced expiratory volume in 1 s (FEV(1)%; r(s) = -0.36). Serum M30 levels were correlated with radiological ground-glass opacity scores (r(s) = 0.61). CONCLUSION: The epithelial apoptosis marker serum level was correlated with IIP clinical status and is a potential marker to assess IIP. PMID- 20542677 TI - Allergic rhinitis alone or with asthma is associated with an increased risk of sickness absences. AB - The aim of the study is to examine the risk of sickness absence in public sector employees with allergic rhinitis or asthma or both conditions combined. This is a prospective cohort study of 48,296 Finnish public sector employees. Data from self-reported rhinitis and asthma were obtained from survey responses given during either the 2000-2002 or 2004 periods. Follow-up data on sickness absences for the public sector employees surveyed were acquired from records kept by the employers. During the follow-up, mean sick leave days per year for respondents were 17.6 days for rhinitis alone, 23.8 days for asthma alone and 24.2 days for both conditions combined. Respondents with neither condition were absent for a mean of 14.5 days annually. The impact of asthma and rhinitis combined on the risk of sick leave days was marginal compared to asthma alone (RR 1.1; 95% CI 1.0 1.3). In the subgroup analysis (those with current asthma or allergy medication), the risk ratio for medically certified sickness absence (>3 days) was 2.0 (95% CI 1.9-2.2) for those with asthma and rhinitis combined. Rhinitis, asthma and both these conditions combined increased the risk of days off work. PMID- 20542679 TI - Charge-based fractionation of oxyanion-forming metals and metalloids leached from recycled concrete aggregates of different degrees of carbonation: a comparison of laboratory and field leaching tests. AB - The release and charge-based fractionation of As, Cr, Mo, Sb, Se and V were evaluated in leachates generated from recycled concrete aggregates (RCA) in a laboratory and at a field site. The leachates, covering the pH range 8.4-12.6, were generated from non-carbonated, and artificially and naturally carbonated crushed concrete samples. Comparison between the release of the elements from the non-carbonated and carbonated samples indicated higher solubility of the elements from the latter. The laboratory leaching tests also revealed that the solubility of the elements is low at the "natural pH" of the non-carbonated materials and show enhancement when the pH is decreased. The charge-based fractionation of the elements was determined by ion-exchange solid phase extraction (SPE); it was found that all the target elements predominantly existed as anions in both the laboratory and field leachates. The high fraction of the anionic species of the elements in the leachates from the carbonated RCA materials verified the enhanced solubility of the oxyanionic species of the elements as a result of carbonation. The concentrations of the elements in the leachates and SPE effluents were determined by inductively coupled plasma mass spectrometry (ICP-MS). PMID- 20542678 TI - Manipulation of host membrane machinery by bacterial pathogens. AB - Subversion of host membrane machinery is important for the uptake, survival, and replication of bacterial pathogens. Understanding how pathogens manipulate host membrane transport pathways provides mechanistic insight into how infection occurs and is also revealing new information on biochemical processes involved in the functioning of eukaryotic cells. In this review we discuss several of the canonical host pathways targeted by bacterial pathogens and emerging areas of investigation in this exciting field. PMID- 20542680 TI - Patterning the cerebral cortex: traveling with morphogens. AB - The neocortex represents the brain structure that has been subjected to a major expansion in its relative size during the course of mammalian evolution. An exquisite coordination of appropriate growth of competent territories along multiple axes and their spatial patterning is required for regionalization of the cortical primordium and the formation of functional areas. The achievement of such a highly complex architecture relies on a precise orchestration of the proliferation of progenitors, onset of neurogenesis, spatio-temporal generation of distinct cell types and control of their migration. We will review recent work on alternative molecular mechanisms that, via the migration of signaling cells/structures, participate in coordinating growth and spatial patterning in the developing cerebral cortex. By integrating temporal and spatial parameters as well as absolute levels of signaling this novel strategy might represent a general mechanism for long-range patterning in large structures, in addition to the passive diffusion of morphogens. PMID- 20542681 TI - Structural and functional studies of gap junction channels. AB - X-ray analysis of the human connexin26 gap junction channel has provided structural details of its open state. The gap junction channel is formed by paired hemichannels on two adjacent cells; each hemichannel consists of six protomers, and exhibits a six-fold symmetry. The protomer folds in a typical four helix bundle. The amino-terminal region folds in a short helix and is inserted into the lumen to form a funnel structure. The structure of the amino-terminal region could explain the channel's gating mechanism. Extensive interactions between two hemichannels allow the gap junction channel to tightly connect two adjacent cells. The gap junction, which consists of hundreds of gap junction channels, could both serve as an intracellular channel and contribute to cellular adhesion. PMID- 20542682 TI - Unravelling the design principles for single protein mechanical strength. AB - In recent years single molecule manipulation techniques have improved to the extent that measurements of the mechanical strength of single proteins can now be undertaken routinely. This powerful new tool, coupled with theoretical frameworks to characterise the unfolding process, has enabled significant progress to be made in understanding the physical mechanisms that underlie protein mechanical strength. These design concepts have allowed the search for proteins with novel, mechanically strong folds to be automated and for previously mechanically characterised proteins to be engineered rationally. Methods to achieve the latter are diverse and include re-engineering of specific hydrophobic core residues, changing solvent conditions and the 'cross-linking' of side-chains that are separated in the rate-limiting unfolding transition. Predicting the mechanical behaviour of larger proteins and those with more complex structures remains a significant challenge while on-going instrument development is beginning to allow the examination of mechanical strength of protein across a wide range of force loading rates. The integral role of force in biology and the potential for exploitation of catalytic and structural proteins as functional bio-materials makes this a particularly important area of research. PMID- 20542683 TI - The loss of the CBX7 gene expression represents an adverse prognostic marker for survival of colon carcinoma patients. AB - We have previously shown that CBX7 expression is associated with a more malignant phenotype in thyroid cancer. On this basis, we decided to investigate its possible prognostic value in colorectal cancer (CRC). CBX7 expression has been analysed by immunohistochemistry in tissue microarray (TMA) specimens obtained from a large series of sporadic CRC resections (n=1420). The CBX7 expression data have been correlated with several clinico-pathological parameters. CBX7 expression is reduced or absent in a significant number of CRC samples in comparison to the normal colonic mucosa and the loss of CBX7 expression correlates with a poor outcome of CRC (p<0.001). The block of CBX7 expression seems to occur at a transcriptional level since quantitative RT-PCR analysis showed a reduced CBX7-specific mRNA levels in CRC samples versus normal counterpart tissue (up to more than 50-fold). Finally, the restoration of CBX7 expression in two CRC cell lines reduces their proliferation rate suggesting a role of the loss of CBX7 expression in the progression step of colon carcinogenesis. Therefore, the data reported here indicate that the evaluation of CBX7 expression may represent a valid tool in the prognosis of colon cancer since a reduced survival of CRC patients is associated with the loss of CBX7 expression. PMID- 20542684 TI - Potential use of filamentous fungi for wastewater sludge treatment. AB - Specific filamentous fungi (FF) have been recognized for sludge treatment and possibly these strains can be utilized for simultaneous bioflocculation, solids and pathogens reduction and, removal and degradation of toxic compounds. Based on current research work and findings, this review provides the state-of-art knowledge on the role of FF (or moulds) in sludge treatment. The proposed theories are presented, critically analyzed and future scope for specific research on utilization of FF for treatment of sludge is recommended. PMID- 20542685 TI - Optimization of microwave-assisted extraction of carbohydrates from industrial waste of corn starch production using response surface methodology. AB - Microwave-assisted extraction (MAE) was applied for production of carbohydrates mainly consisting of arabinoxylan from corn pericarp which is an industrial waste of corn starch production by using hot compressed water as a solvent. The solubilization rate increased with increase in heating temperature and reached 75.2% at 220 degrees C. The main extracted materials were carbohydrates consist of glucose, xylose and arabinose indicating solubilization of starch and hemicellulose, while residues were composed of cellulose. Four independent variables (heating temperature, come-up time, heating time and solid to liquid ratio) were optimized for maximizing the carbohydrates yield using the response surface methodology including fractional factorial design, the path of steepest ascent and central composite design. The optimized condition was as follows; heating temperature 176.5 degrees C, come-up time 2 min, heating time 16 min and solid to liquid ratio 1/20 (g/mL), respectively. The maximal yield attained 70.8% of carbohydrates with predominant production of xylo-oligosaccharides. PMID- 20542686 TI - Fractal kinetic analysis of the enzymatic saccharification of cellulose under different conditions. AB - Fractal kinetic analysis has been applied for the kinetics of enzymatic saccharification of cellulose. Based on the first order cellulose degradation kinetic, a fractal kinetic model with two parameters (rate coefficient and fractal exponent) has been developed. The model fits very well with the experimental data of enzymatic saccharification of cellulose under different conditions, including cellulase loading, nature of substrate, hydrolysis temperature, and addition of nonionic surfactant or polymer in the reaction medium. It indicates that the complex kinetics of enzymatic saccharification of cellulose can be described with the fractal kinetic model. The model exhibits that an addition of nonionic surfactant or polymer increases the rate coefficient and decreases the fractal exponent at the same time. A nonionic surfactant or polymer aqueous solution may be a potential medium engineering method for enzymatic saccharification of cellulose in biofuel industry. PMID- 20542687 TI - Optimization of the production of organic solvent-stable protease by Bacillus sphaericus DS11 with response surface methodology. AB - Response surface methodology (RSM) was employed to enhance the production of organic solvent-stable protease by Bacillus sphaericus DS11. A significant influence of glycerol, MgSO4.7H2O, and pH on organic solvent-stable protease production was noted with Plackett-Burman design. Then, a three-level Box-Behnken design was employed to optimize the medium composition and culture conditions for the production of the protease in shake-flask. Using this methodology, the quadratic regression model of producing organic solvent-stable protease was built and the optimal combinations of media constituents and culture conditions for maximum protease production were determined as glycerol 12.47 g/L, MgSO4.7H2O 0.73 g/L, and pH 8.25. Protease production obtained experimentally coincident with the predicted value and the model was proven to be adequate. The enhancement of protease from 465.06 U/mL to 1182.68 U/mL was achieved with the optimization procedure. PMID- 20542688 TI - Colour removal of dyes from synthetic and real textile wastewaters in one- and two-stage anaerobic systems. AB - Decolourisation of the azo dye model compound, Congo Red (CR), and real textile wastewater, was assessed in one- and two-stage anaerobic treatment systems (R1 and R2, respectively). High colour removals were achieved in both treatment systems even when a very high CR concentration (1.2 mM) was applied. However, R2 presented a slightly better stability, in which the acidogenic reactor (R(2,A)) played a major role on dye reduction, as compared to the methanogenic reactor (R(2,M)), evidencing the role of fermentative microorganisms. The minimum electron donor concentration required to sustain dye reduction was much higher than the stoichiometric amount. Additionally, a decrease on the hydraulic retention time (from 24 to 12 h) did not significantly affect decolourisation, indicating that electron transfer was not a concern. Finally, experiments with real textile wastewater showed low decolourisation efficiencies in both systems, most likely due to the presence of dyes not susceptible to reductive decolourisation under these experimental conditions. PMID- 20542689 TI - The fate of di-n-butyl phthalate in a laboratory-scale anaerobic/anoxic/oxic wastewater treatment process. AB - A laboratory-scale anaerobic/anoxic/oxic (AAO) wastewater treatment system was employed to investigate the effects of hydraulic retention time (HRT) and sludge retention time (SRT) on the removal and fate of di-n-butyl phthalate (DnBP). HRT had no significant effect on DNBP removal between 12 and 30 h. However, longer HRT increased DnBP accumulation in the system and DnBP retention in the waste sludge. When SRT was increased from 15 to 25 d, DnBP removal efficiency stayed above 95%. Compared to the removal of only 90% at SRT of 10d, longer SRT enhanced DnBP degradation efficiency. The optimal HRT and SRT for both nutrients and DnBP removal were 18 h and 15 d. At these retention times, about 72.66% of DnBP was degraded by the activated sludge process, 2.44% was released in the effluent, 24.44% was accumulated in the system, and 0.5% remained in the waste sludge. The anaerobic, anoxic and oxic reactors were responsible for 17.14%, 15.02% and 63.46% of the overall DnBP removal, respectively. Meanwhile a removal degradation model was formulated, and kinetic parameters were evaluated with batch experiments under anaerobic, anoxic, oxic conditions. The model can well forecast the effluent quality of anaerobic/anoxic/oxic reactors of the AAO process. PMID- 20542690 TI - An analysis of the 'legal high' mephedrone. AB - 'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunately there is little chemical or biological literature on these materials or certified standards. Here, we detail the analysis of the widely consumed synthetic N-methyl-cathinone analogue known as mephedrone ((1) 2 aminomethyl-1-tolyl-propan-1-one (4'-methylmethcathinone)) and report its spectral data and molecular properties. Material was purchased from an internet site and examined by extensive one- and two-dimensional NMR studies, high resolution mass spectrometry, elemental analysis and optical rotation, which demonstrated the sample to be of high purity and racemic in nature. Additionally, we report the molecular modelling properties of methyl-cathinones and compare them to their corresponding methyl-amphetamine series. This indicated that the methyl-cathinones are considerably more hydrophilic than the methyl-amphetamines which may account for the higher doses that are needed to demonstrate similar effects. The presence of a ketone in the side chain introduces a far more planar quality to the methyl-cathinones which is absent in the methyl-amphetamine series, and this planarity may contribute to toxicity. PMID- 20542691 TI - Novel coumarin derivatives as potential antidyslipidemic agents. AB - A series of novel benzocoumarin derivatives were synthesized and evaluated for their in vivo antidyslipidemic and in vitro antioxidant activities. Among 11 compounds tested, 2 compounds showed potent antidyslipidemic activity and 3 compounds showed potent antioxidant activity. PMID- 20542692 TI - In vitro antituberculosis activities of the constituents isolated from Haloxylon salicornicum. AB - In vitro antituberculosis activities of fractions and pure compounds (1-20) including seven triterpenes, two alkaloids, two cycloheximide derivatives, two coumarins six sterol derivatives and a long chain alcohol, respectively, isolated from Haloxylon salicornicum were determined against Mycobacterium tuberculosis H37Rv. Actively growing cultures were tested by rapid colorimetric method while the stationary phase cultures were tested by drug exposure methods for bactericidal activity. The MIC values were found to be 50 microg/ml for compounds 15, 19 and 20 where as rest of the compounds invariably showed MIC value of 100 microg/ml against the logarithmic phase culture. These were compare to Isoniazid as a control drug. The compounds exhibited no activity against the stationary phase culture of M. tuberculosis H37Rv up to 200 microg/ml. Further studies are required to investigate the in vivo efficacies and activities of the compounds in combination with antimicrobials that are already being used for TB therapy. PMID- 20542693 TI - Antioxidative activities of histidine containing caffeic acid-dipeptides. AB - Antioxidants have been utilized in both the food and cosmetics industries to neutralize the activities of reactive oxygen species (ROS) and free radicals. Histidine-containing peptides are powerful antioxidants that exist in nature. Additionally, hydroxycinnamic acid (HCA)-peptide conjugates exhibit a synergistically enhanced antioxidative activity. Thus, caffeic acid (CA), a natural antioxidant, was conjugated to histidine-containing dipeptides (His dipeptides) in order to develop better antioxidants. The antioxidative activities were measured using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test and lipid peroxidation test with ferric thiocyanate method. Some of the CA-His dipeptides exhibited better radical scavenging activities than CA, and all of the CA-His dipeptides showed enhanced lipid peroxidation inhibitory activities. His dipeptide enhanced the antioxidative activity of CA, and the position of histidine also affected the antioxidative activity of the compounds. CA-proline histidine amide (CA-Pro-His-NH(2)) exhibited the highest activity in both the free radical scavenging test and the lipid peroxidation inhibition test. PMID- 20542694 TI - Benzofuran-substituted urea derivatives as novel P2Y(1) receptor antagonists. AB - Benzofuran-substituted urea analogs have been identified as novel P2Y(1) receptor antagonists. Structure-activity relationship studies around the urea and the benzofuran moieties resulted in compounds having improved potency. Several analogs were shown to inhibit ADP-mediated platelet activation. PMID- 20542695 TI - Hormonal and metabolic modulation through nutrition: towards a primary prevention of breast cancer. AB - Breast cancer (BC) is a polygenic and multifactorial disease for which estrogens have been recognized as the main risk factor, and for which lifestyle plays a key role. Previous epidemiologic cancer research performed in Uruguayan population delimited its dietary and anthropometric profiles. Recognizing the difficulty for universalizing a nutritional basis for prevention due to different eating patterns among regions and countries, we summarize the existent knowledge linking nutrition, estrogens, metabolism and BC. As an attempt towards primary prevention of BC, we present recommendations mainly based on country-specific research findings and modifiable putative risk and protective factors, proposing to modify the intake of meats and other fatty foods--especially sources of Omega-6 and Omega-3 fatty acids--adding olive oil, selected vegetables, citrus fruits and working towards adequate body fat/muscle proportions. From a medical and ethical viewpoint, it is justified to recommend certain nutritional changes to women, because no adverse side effects are expected to occur. PMID- 20542696 TI - Non-pegylated liposomal doxorubicin in metastatic breast cancer patients: a valuable therapeutic option requiring caution. PMID- 20542697 TI - Management of radiation-induced sarcomas in a tertiary referral centre: a review of 25 cases. AB - INTRODUCTION: Radiation-induced sarcomas are a rare and late complication of radiotherapy for breast carcinoma which often have poor prognosis. METHODS: This study is a retrospective review of 25 patients referred to a regional sarcoma unit between 1978 and 2009. RESULTS: Radiation-induced sarcoma following the diagnosis and treatment of breast cancer occurred after a mean period of 156 months. Anatomical sites involved were the breast, chest wall, clavicle, scapula, humerus and axilla. Twenty one patients had wide local excision followed by chest wall reconstruction, latissimus dorsi flap cover or limb amputation. The estimated five years survival following the diagnosis of the radiation-induced sarcoma was 27% and the local recurrence rate 52%. CONCLUSION: Radiation-induced sarcoma following breast cancer has high local recurrence rate and poor prognosis. They should be managed in a multi-disciplinary setting. Long-term follow-up of patients treated with radiotherapy for breast cancer is therefore advisable. PMID- 20542698 TI - Diversification and focusing: strategies of microbial culture collections. AB - Implementation of quality measures, compliance with the Convention on Biological Diversity (CBD), and adoption of latest bioinformatics tools are among the main steps to be taken by microbial culture collections in order to provide resources for the emerging area of the knowledge-based bioeconomy. These measures have to be introduced side by side with the deposition of increasingly phylogenetically and physiologically diverse microbiological organisms. However, the necessary expansion of human resources and infrastructure is moving slowly, if at all. Furthermore, considering that the vast majority of microbial isolates do not find their way into public collections, a strategy should be devised to encourage researchers to deposit a higher fraction of strains. It appears obvious that in order to make available an even broader range of diversity to users and researchers, collections will have to decide whether to diversify on a broad taxon spectrum of the hierarchic system, holding a small number of representatives per species, or to follow the route of focusing on in-depth holdings of selected groups of organisms, depending on existing taxonomic expertise. These decisions require a worldwide coordinated activity with the outcome to be made transparent to users in an emerging global network. PMID- 20542699 TI - Idiopathic paroxysmal kinesigenic dyskinesia in Malaysia, a multi-racial Southeast Asian country. AB - Paroxysmal kinesigenic dyskinesia is a rare disorder, and there are few reports of Asian patients with this condition. We reviewed the clinical features of all patients with idiopathic paroxysmal kinesigenic dyskinesia (PKD) seen at a major neurological centre in Malaysia. The charts of 11 patients with idiopathic PKD seen between 1995 and 2008 were reviewed retrospectively. The male:female ratio was 9:2. Ten patients were of Chinese ethnicity, and one was Malay. Three patients (from two families) had a family history of PKD. The involuntary movement was dystonia in 73% of patients. In one patient, attacks were precipitated by vestibular stimulation. One patient had generalized epilepsy. Another patient who did not have epilepsy demonstrated epileptiform discharges. Only slightly over one-quarter of patients had a positive family history. Males, and people of Chinese ancestry, seem to be affected more frequently by PKD in certain Asian populations. PMID- 20542700 TI - An observational study on MR images of the effect of the discoid meniscus on articular cartilage thickness. AB - The discoid meniscus is known to affect the morphology and mechanics of the knee compartment in which it is housed. To determine whether it also is determinative of the articular cartilage thickness, measurements were made on MR images. There was no statistically significant difference in femoral or tibial articular cartilage thickness between compartments with normal meniscus and compartments with discoid meniscus. These findings suggest that mechanical disturbances wrought by the discoid shape do not have a 'Wolff law' effect. PMID- 20542701 TI - Cell-penetration by Co(III)cyclen-based peptide-cleaving catalysts selective for pathogenic proteins of amyloidoses. AB - Derivatives of the Co(III) complex of 1,4,7,10-tetraazacyclododecane (cyclen) with various organic pendants have been reported as target-selective peptide cleaving catalysts, which can be exploited as catalytic drugs. In order to provide a firm basis for the catalytic drugs based on Co(III)cyclen, the ability of the Co(III)cyclen-containing peptide-cleaving catalysts to penetrate animal cells such as mouse fibroblast NIH-3T 3 or human embryonic kidney (HEK) 293 cells is demonstrated in the present study. Since the catalysts destroy pathogenic proteins for amyloidoses, results of the present study are expected to initiate extensive efforts to obtain therapeutically safe catalytic drugs for amyloidoses such as Alzheimer's disease, type 2 diabetes mellitus, Parkinson's disease, Huntington's disease, mad cow disease, and so on. PMID- 20542702 TI - Development of a new radioligand for cholecystokinin receptor subtype 2 scintigraphy: from molecular modeling to in vivo evaluation. AB - To improve the targeting to tumors expressing the cholecystokinin receptor subtype 2 (CCK2R) with limited kidney uptake, we synthesized a novel cholecystokinin C-terminal tetrapeptide (CCK4)-based derivative conjugated to an original bipyridine-chelator (BPCA), 111In-BPCA-(Ahx)2-CCK4. To our knowledge this is the first CCK4-based radioligand that presents a high affinity for the CCK2R, a high and specific tumor uptake, a low renal accumulation and a very good visualization of tumors in vivo compared with an internal control, 111Indium trans-cyclohexyldiethylenetriaminepenta-acetic acid-cholecystokinin octapeptide (111In-CHX-A''-DTPA-CCK8). These properties make 111In-BPCA-(Ahx)2-CCK4, a promising candidate for imaging and peptide receptor radionuclide therapy of CCK2R positive tumors. PMID- 20542703 TI - Discovery of potent and orally active tricyclic-based FBPase inhibitors. AB - With the aim of exploring the effect of tricyclic-based FBPase inhibitors in cells and in vivo, a series of prodrugs of tricyclic phosphonates was designed and synthesized. Introducing prodrug moieties into tricyclic-based phosphonates led to the discovery of prodrug 15c, which strongly inhibited glucose production in monkey hepatocytes. Furthermore, prodrug 15c lowered blood glucose levels in fasted cynomolgus monkeys. PMID- 20542704 TI - Synthesis of 5-deoxy-beta-D-galactofuranosides as tools for the characterization of beta-D-galactofuranosidases. AB - Derivatives of 5-deoxy-beta-D-galactofuranose (5-deoxy-alpha-L-arabino hexofuranose) have been synthesized starting from D-galacturonic acid. The synthesis of methyl 5-deoxy-alpha-L-arabino-hexofuranoside (14alpha) was achieved by an efficient strategy previously optimized, involving a photoinduced electron transfer (PET) deoxygenation. Compound 14alpha was converted into per-O-acetyl-5 deoxy-alpha,beta-L-arabino-hexofuranoside (16), an activated precursor for glycosylation reactions. The SnCl4-promoted glycosylation of 16 led to 4 nitrophenyl (19alpha), and 4-methylthiophenyl 5-deoxy-alpha-L-arabino hexofuranosides (20alpha). The oxygenated analog 4-methylphenyl 1-thio-beta-D galactofuranoside (23beta) was also prepared. The 5-deoxy galactofuranosides were evaluated as inhibitors or substrates of the exo-beta-D-galactofuranosidase from Penicillium fellutanum, showing that the absence of HO-5 drastically diminishes the affinity for the protein. PMID- 20542705 TI - Cortical diversity in three species groups of Parmotrema sensu lato (Parmeliaceae, lichenized Ascomycota). AB - Conventional techniques for structural studies under light microscope were employed to describe and compare the upper cortex anatomy in three species groups of Parmotrema sensu lato. This study indicates that there is a pattern in the structure of the upper cortex in all the three groups of Parmotrema species studied here, and this pattern can be used to place each species group separately within the genus Parmotrema. Although the species of Parmotrema studied have palisade prosoplectenchymatous upper cortex, there are clear differences between the analyzed groups. The upper cortex of Parmotrema s. str. can be characterized by more elongated cells and very compressed hyphae with small interstices between them; the upper cortex of the species with reticular maculae is characterized by the presence of maculae produced by the organization of hyphae that rise towards to the upper cortex and that are not so compressed, while the upper cortex of the species with dimorphic rhizinae has less elongated almost-rounded cells without interstices or cracks but is generally accompanied by aeroplectenchyma. Besides, the first cell layer of the upper cortex presents differential staining by toluidine blue and the epicortex is tightly attached to it. PMID- 20542706 TI - Application of a stochastic TDCR model based on Geant4 for Cherenkov primary measurements. AB - Cherenkov measurements can be advantageously carried out using a counting instrumentation dedicated to liquid scintillation. In the case of radionuclide measurements, the interest of this technique is largely described in the literature. For instance, it is generally quoted that the possibility to measure directly the activity of aqueous solutions makes the sample preparation easier. Based on a three-photomultipliers apparatus, the Triple to Double Coincidence Ratio (TDCR) method is implemented in National Metrology Institutes for liquid scintillation measurements. Knowing the decay scheme associated with the radionuclide to be standardized, a free parameter model of light emission is constructed to determine the counter detection efficiency using the experimental TDCR value. Contrary to liquid scintillation, Cherenkov emission is characterized by a directional behavior. Instead of using an additional free parameter to take this effect into account, a stochastic modeling based on the Monte Carlo code Geant4 is proposed in order to extend the TDCR method to Cherenkov counting. The purpose of this model is to simulate the different optical processes of Cherenkov photons leading to the production of photoelectrons in the three-photomultipliers counter. The validation of this stochastic approach of the TDCR method for Cherenkov counting is carried out in the case of (90)Y activity measurements. PMID- 20542707 TI - Reduction of bone resorption by the application of platelet-rich plasma (PRP) in bone grafting of the alveolar cleft. AB - OBJECTIVE: We evaluated the effectiveness of platelet-rich plasma (PRP) on the regeneration of autogenous cancellous bone and marrow grafted in the alveolar cleft. DESIGN: Twenty patients with alveolar clefts were examined; 6 were the control group and received cancellous bone and marrow grafts without PRP, while the remaining 14 comprised the PRP group and received grafts with PRP. Prior to surgery, 50 ml of blood was withdrawn and 5 ml of PRP gel produced through centrifugal separation. The bone graft mixed with PRP was then packed into the alveolar cleft. Postoperative bone density was assessed as the aluminium equivalent value on occlusal X-ray films in a qualitative analysis. Quantitative evaluation of regenerated bone was made with computed tomography and panoramic radiographs at 1 month, 6 months and 1 year after surgery. RESULTS: Satisfactory bone bridging formation was observed in all patients without any complications. The bone density of the PRP group was lower than that of the control group at 1 week, but the same after 1 month. The added PRP reduced the resorption of regenerated bone postoperatively. CONCLUSION: Autogenous cancellous bone grafting with PRP, which significantly reduces postoperative bone resorption, is a reliable technique for alveolar bone grafting of cleft patients. PMID- 20542709 TI - Desorption ionization by charge exchange (DICE) for sample analysis under ambient conditions by mass spectrometry. AB - An ambient pressure ionization technique for mass spectrometric analysis of substances present on solid surfaces was developed. A nebulized spray containing molecular ions of a solvent such as toluene can be generated by passing the solvent through a stainless steel capillary held at a high voltage. When the stream of charged droplets produced in this way is directed onto a solid surface, the analytes present on the surface are desorbed and ionized by a charge exchange process. This technique was shown to desorb and generate positively charged molecular ions from compounds that are not readily ionized by some other ambient methods, under positive-ion generation mode. For example, intense signals representing radical cations of 1,4-hydroquinone, limonene, thymol, and several other compounds were observed when the analytes were deposited on a metal surface and exposed to a toluene spray nebulized from the metal capillary maintained at a potential of about +5 kV. In contrast, when the same samples were exposed to a spray of water/methanol/formic acid under customary DESI-like (positive-ion mode) conditions, no peaks representing the analytes were observed. PMID- 20542710 TI - Prediction of stroke rehabilitation outcome with xenon-enhanced computed tomography cerebral blood flow study. AB - BACKGROUND: Cerebral blood flow (CBF) of stroke patients in the chronic stage is supposed to reflect brain functions. We examined the relation between rehabilitation outcome and CBF values. METHODS: The study group comprised 101 consecutive patients (mean age, 69+/-12 years) including 61 patients with cerebral infarction, 32 patients with cerebral hemorrhage, and 8 patients with subarachnoid hemorrhage. Xenon-enhanced computed tomography was performed on 39 days on average after stroke onset. Regions of interest were in the cerebral cortices, putamen and thalamus, and CBF values were statistically compared with the functional independence measure (FIM). Furthermore, we performed a multivariate analysis for predictive factors. RESULTS: 1. The right mean CBF (mCBF) tended to be more closely correlated with the FIM total scores at discharge (r=0.495, P<.001) than the left mCBF (r=0.351, P<.001), in case of significance level 0.1 and statistical power 0.65. 2. The FIM total and motor scores at discharge showed the highest correlations to regional CBF (rCBF) in the right frontal cortex, and the FIM cognitive scores at discharge showed the highest correlation to rCBF in the left frontal cortex. 3. Right cerebral infarct subgroup (n=30) showed significant correlations between FIM total scores at discharge and mCBF values of the right (r=0.582, P<.001) and the left (r=0.563, P<.005) brain, respectively. 4. Rehabilitation outcome evaluated with the FIM total scores could be led by the formulae with the factors of age, gender, NIHSS, right/left hemispheric lesions and the right mCBF values (r=0.837, P<.001). CONCLUSION: The CBF of the right brain proved to be more influencing to rehabilitation results. PMID- 20542711 TI - Mind control? Creating illusory intentions through a phony brain-computer interface. AB - Can one be fooled into believing that one intended an action that one in fact did not intend? Past experimental paradigms have demonstrated that participants, when provided with false perceptual feedback about their actions, can be fooled into misperceiving the nature of their intended motor act. However, because veridical proprioceptive/perceptual feedback limits the extent to which participants can be fooled, few studies have been able to answer our question and induce the illusion to intend. In a novel paradigm addressing this question, participants were instructed to move a line on the computer screen by use of a phony brain-computer interface. Line movements were actually controlled by computer program. Demonstrating the illusion to intend, participants reported more intentions to move the line when it moved frequently than when it moved infrequently. Consistent with ideomotor theory, the finding illuminates the intimate liaisons among ideomotor processing, the sense of agency, and action production. PMID- 20542712 TI - Nonprecipitous changes upon withdrawal from imiglucerase for Gaucher disease because of a shortage in supply. AB - Because of an unpredicted and unavoidable shortage in global supplies of imiglucerase for Gaucher disease, we collected clinical and laboratory data from patients who were evaluated <= 6months before drug withdrawal and then retested before/during reinstatement of therapy. Hemoglobin, platelet counts, and liver and spleen index volumes by ultrasound as well as chitotriosidase were evaluated as percent change over time and relative to dose-years of exposure to enzyme therapy. Deterioration was seen in all four clinical parameters and in chitotriosidase activity in most patients and even among patients who stopped for only 3 months. No patient consistently showed nondeterioration in all five parameters. Platelet counts were most sensitive to therapy withdrawal. There was no overt correlation between percent change in these parameters and dose-years of therapy. Although we no longer think that drug vacations should be considered as a form of maintenance for patients requiring enzyme therapy for Gaucher disease, but if necessary-for compelling personal reasons-one may be reassured that a short-term drug interruption is not likely to lead to irreversible complications or return to baseline values of critical clinical parameters. PMID- 20542713 TI - Spectrum of gross motor and cognitive functions in children with cerebral palsy: gender differences. AB - BACKGROUND: Multiple differences between males and females are reported both in physiological and pathophysiological conditions. AIMS: To test the hypothesis that gender could influence the motor and cognitive development in children with cerebral palsy (CP). METHODS: Prospective, cross-sectional. One hundred seventy one children with CP (98 males and 73 females) were evaluated for motor (Gross Motor Function Measure, Gross Motor Function Classification System) and cognitive (Bayley II, Wechsler Scales) functions. Eighty-four of them were assessed before and other eighty-seven children after 4 years of age. RESULTS: No gender-related differences were observed in children with diplegia or quadriplegia, both for motor and cognitive functions. On the contrary, females with hemiplegia scored significantly better (P < 0.01) in cognitive functions and in the dimension D (standing) of the Gross Motor Function Measure, under the age of 4 years. These differences were not observed after this age. CONCLUSIONS: In this study we point out that gender might influence differently the psycho-motor development of children with hemiplegia and of those with a more severe clinical involvement as diplegia and quadriplegia. PMID- 20542714 TI - Does attrition bias longitudinal population-based studies on back pain? AB - BACKGROUND AND AIMS: Longitudinal population studies are a keystone in describing the course of back pain over time. Yet, potential bias because of repeated attrition has received little attention. This study aims to identify those back pain related indicators most susceptible to bias and to discuss practical consequences for back pain research. METHODS: Analyses were based on a population based longitudinal multi-centre postal back pain survey with two postal follow-up measurements within 2 years. The baseline sample comprised 9263 subjects. Different sets of measures at entry were used to predict subsequent attrition: Socio-demographic variables, indicators of back pain, health related measures, and response behaviour. Back pain related indicators comprised prevalence estimates, pain intensity, disability, and radiating pain. Weighted and unweighted back pain outcomes were compared at the first and second follow-up to assess bias. RESULTS: Only 52.3% of the eligible participants at baseline continued participation till the second follow-up. Age and prior response behaviour were the best predictors of attrition while health and back pain related variables were of less importance. Differences between weighted and unweighted estimates of back pain related indicators were small to negligible, thus indicating little bias in point estimates. Unexpectedly, the reported back pain burden slightly declined over time. CONCLUSION: The representativeness of the sample is consecutively reduced because of differential attrition over the different measurement points. Despite this, bias due to attrition has a marginal impact on the point estimates of virtually all back pain related outcomes. PMID- 20542715 TI - Xenon-based molecular sensors in lipid suspensions. AB - There have been many proposals to use xenon-based molecular sensors in biological settings. Fundamental to understanding the properties of these sensors in vivo is characterizing their behavior in lipid environments. We report the investigation of xenon-based molecular sensors in suspensions of lipid vesicles with a size comparable to cells. We detail spectroscopic properties of sensors associated with lipid vesicles as well as those in equilibrium in the surrounding solution. We characterize the dependence of the spectral parameters on temperature, relevant for studies at physiological temperatures. We also demonstrate the ability to perform selective saturation transfer (Hyper-CEST) between sensor, both lipid bound and unbound, and the bulk solution. Lastly, we demonstrate the applicability of saturation transfer in the heterogeneous medium as an imaging modality. PMID- 20542716 TI - Ventilator-associated pneumonia: role of colonizers and value of routine endotracheal aspirate cultures. AB - OBJECTIVES: To determine the role of colonizers in the causation of ventilator associated pneumonia (VAP) and the value of routine pre-VAP endotracheal aspirate (EA) cultures in appropriately treating VAP. METHODS: A prospective observational cohort study was conducted over a period of 15 months. Two hundred patients on mechanical ventilation for>48h were studied. RESULTS: Acinetobacter spp (33.7%) and Pseudomonas spp (29.8%) were the most common colonizers. Of the 200 patients, 36 developed VAP. In 20 VAP patients, the pre-VAP EA culture-based strategy was not useful. However, in the remaining 16 VAP patients, a pre-VAP EA culture-based strategy would have appropriately treated 13 (81%; 95% confidence interval (CI) 62-100%), in comparison to only nine (56%; 95% CI 32-80%) by the American Thoracic Society (ATS) strategy. The seven patients in whom the ATS guidelines were inappropriate had Acinetobacter spp and Pseudomonas spp resistant to the higher antibiotics recommended by the ATS for multidrug-resistant pathogens. The positive predictive values of Pseudomonas aeruginosa, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) isolated from pre-VAP EA cultures were 88%, 83%, and 100%, respectively. CONCLUSION: VAP patients should be treated based on ATS guidelines, but whenever P. aeruginosa, A. baumannii, and MRSA are isolated from pre-VAP EA cultures, the initial antibiotic therapy should be extended to treat these. PMID- 20542717 TI - [Neurocutaneous flaps applied on head and neck surgery: Anatomic study of feasibility using superficial cervical plexus branches]. AB - OBJECTIVE: To evaluate the feasibility of neurocutaneous flaps for head and neck surgery using the cervical superficial plexus branches. METHODS: Anatomic study on cervical superficial plexi (focusing on the great auricular and cervical transverse nerves) of five fresh specimens, which were injected with green colored latex. RESULTS: A constancy of anatomic landmarks has been observed with little inter-individual variability. The cervical superficial plexus branches were easily isolated, their length and course not varying much. Each cervical superficial plexus nerve is accompanied by a perinervous artery, essential condition to a neurocutaneous flap. We privileged the great auricular nerve for its superior length and diameter, in order to easy the raise of the flap. We took it at the low mastoidian level, pediculed on the great auricular nerve with a point on the posterior border of the sterno-cleido-mastoidian muscle. Pedicule size is 7 to 10cm allowing to reach ipsilateral alae of the nose, the chin or the pinna. Developing this technique for oropharyngeal reconstruction (internal side of the cheek, anterior floor of mouth...), whereas not realized in this study, must be considered. CONCLUSIONS: The anatomic study showed the cervical superficial plexus constancy with the systematic presence of a perinervous pedicle siding each branch. The great auricular nerve is a good candidate for the raise of a neurocutaneous flap. A standardized surgical procedure must be established before any clinical study. PMID- 20542718 TI - TNFalpha antagonist therapy does not increase the Epstein-Barr virus burden in patients with rheumatoid arthritis or ankylosing spondylitis. AB - OBJECTIVE: The risk of non-Hodgkin lymphoma is increased in rheumatoid arthritis (RA) but not in ankylosing spondylitis (AS). In RA, the degree of inflammation is closely associated with the lymphoma risk. Whether immunosuppressants such as methotrexate and TNFalpha antagonists affect the lymphoma risk in RA is unclear. The Epstein-Barr virus (EBV) may contribute to the pathogenesis of RA and may be involved in the development of lymphoma in patients taking methotrexate and/or TNFalpha antagonists, although these points remain debated. EBV load monitoring during immunosuppressive treatment may predict the occurrence of EBV-related lymphoma. Here, our objective was to prospectively measure the EBV load in patients receiving TNFalpha antagonists for RA or AS. METHODS: We prospectively studied patients with RA or AS before and after TNFalpha antagonist therapy initiation. The EBV load was measured in blood samples using the EBV R-gene Quantification Kit. Disease activity at the time of blood sampling was evaluated by determining the Disease Activity Score 28 (DAS28) in RA patients and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: We included 46 patients with RA (82.6% women; mean age, 52.7 +/- 11.3 years) and 27 with AS (men, 81.5%; mean age, 45.1 +/- 12.7 years). In the RA group, the EBV load was measured at baseline and 9.72 +/- 5.7 months later. The baseline EBV load was undetectable in 33 (70.2%) patients; mean EBV load in the 13 remaining patients was 9389 copies/ml (3.47 log10 +/- 0.45). Baseline EBV load did not correlate with disease activity (DAS28). At the follow-up assay, the EBV load became positive in five patients and increased significantly in one patient (four patients on etanercept, one on adalimumab, and one on infliximab); it became negative in six patients (five on adalimumab and one on etanercept) and showed non-significant changes in six patients. Mean EBV load in patients positive at follow-up was 3.63 +/- 0.52 log10 copies/ml. Mean DAS28 was 4.78 +/- 1.1 at baseline and 2.94 +/- 1.24 at follow-up. At follow-up, a good EULAR response was noted in 33 (71.7%) patients and a moderate EULAR response in seven (15.2%) patients. In the AS group, the baseline EBV load measurement occurred after 12.9 +/- 10.6 months. Baseline EBV load was undetectable in 25 (92.6%) patients; mean load in the remaining two patients was 4.15 +/- 0.46 log10 copies/ml. At follow up, the EBV load became positive in two patients (one on adalimumab and one on infliximab) and became negative in one patient (on adalimumab). Mean load in positive patients was 3.33 +/- 0.24 log10 copies/ml. Mean BASDAI was 55.1 +/- 16.2 at baseline and 17.88 +/- 18.62 at follow-up. A positive EBV load was significantly more common in the RA group than in the AS group (P = 0.039). EBV load changes did not differ significantly between the RA and AS groups or across TNFalpha antagonists. No cases of lymphoma were recorded. CONCLUSION: Introducing TNFalpha antagonist therapy does not affect the EBV load in patients with RA or AS. EBV load monitoring is probably unnecessary in patients given TNFalpha antagonists for RA or AS. PMID- 20542719 TI - Molecular basis of trait correlations. AB - Trait correlations are common phenomena in biology. Plant breeders need to consider trait correlations to either improve correlated traits simultaneously or to reduce undesirable side effects when improving only one of the correlated traits. Pleiotropy or close linkage are the two major reasons for genetic trait correlations and are often confounded at the level of quantitative trait loci or genes. With the progress of genetic and genomic approaches, discrimination of intragenic linkage from true pleiotropy is increasingly possible. This will substantially impact breeding strategies and will be helpful to understand the nature of trait correlations. PMID- 20542720 TI - Helping plants to deal with insects: the role of beneficial soil-borne microbes. AB - Several soil-borne microbes such as mycorrhizal fungi and plant growth-promoting rhizobacteria can help plants to deal with biotic and abiotic stresses via plant growth promotion and induced resistance. Such beneficial belowground microbes interact in a bidirectional way via the plant with aboveground insects such as herbivores, their natural enemies and pollinators. The role of these interactions in natural and agricultural ecosystems is receiving increased attention, and the molecular and physiological mechanisms involved in these interactions should be the focus of more attention. Here, we review the recent discoveries on plant mediated interactions between beneficial belowground microbes and aboveground insects. PMID- 20542721 TI - Plant structure visualization by high-resolution X-ray computed tomography. AB - New developments in high-resolution X-ray computed tomography (HRXCT) are promising for the broader application of this non-destructive imaging method in plant sciences. Here, we demonstrate how detailed three-dimensional morphological traits can be extracted rapidly from in vivoArabidopsis thaliana seedlings without sample manipulation. Furthermore, ex vivo scanning at sub-micron resolution allows the quantification and visualization of the cellular organization of plant tissue samples, making HRXCT a desired tool in developmental plant biology. PMID- 20542722 TI - AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. AB - Non-clinical studies, focusing on the pharmacodynamics (PD), pharmacokinetics (PK) and safety pharmacology of genetically modified Lactococcus lactis (L. lactis) bacteria, engineered to secrete human Trefoil Factor 1 (hTFF1), were performed to provide proof-of-concept for the treatment of oral mucositis (OM) patients. L. lactis strain sAGX0085 was constructed by stably inserting an htff1 expression cassette into the bacterial genome, and clinically formulated as a mouth rinse (coded AG013). PD studies, using different oral dosing regimens, were performed in a clinically relevant hamster model for radiation-induced OM. The PK profile was assessed in healthy hamsters and in hamsters with radiation-induced OM. In addition, in vitro and in vivo safety pharmacology studies were conducted, in pooled, complement-preserved human serum, and in neutropenic hamsters and rats respectively. Topical administration of L. lactis sAGX0085/AG013 to the oral mucosa significantly reduced the severity and course of radiation-induced OM. PK studies demonstrated that both living L. lactis bacteria, as well as the hTFF1 secreted, could be recovered from the administration site for maximum 24h post dosing, without systemic exposure. The in vitro and in vivo safety pharmacology studies confirmed that L. lactis sAGX0085 could not survive in systemic circulation, not even under neutropenic conditions. The results from the PD, PK and safety pharmacology studies reported here indicate that in situ secretion of hTFF1 by topically administered L. lactis bacteria provides a safe and efficacious therapeutic tool for the prevention and treatment of OM. PMID- 20542723 TI - Robotic surgery in head and neck cancer: a review. AB - The invasion of robotic technology in surgical fields cannot be ignored. Its success in various surgical disciplines especially in urology, cardiology, and gynaecology has set its own benchmarks. Extrapolation of similar results in head and neck is still in experimental stages and long term results are still eagerly awaited to truly establish its efficacy beyond awe and reality. Nonetheless, its future role in this area is inevitable given the encouraging results obtained so far. This article covers the inception to current application to speculation of robotic technology in complex area of head and neck surgery. PMID- 20542724 TI - Nematode effectors and plant responses to infection. AB - Genomic resources in Arabidopsis have made possible the discovery of plant genes that mediate the nematode infection process, particularly the complex process of root re-differentiation into either knots or cysts. The genomic DNA sequences of two root knot nematodes have been characterized and considerable sequence coverage of cDNA from several cyst nematodes is available. These resources have enabled the discovery of several nematode effectors that play roles in causing susceptibility. RNAi has been used to create Arabidopsis plants that are resistant to root knot or to cyst nematodes and this has been extended to make soybean resistant to the cyst nematode. PMID- 20542725 TI - Modulation of host nuclear ploidy: a common plant biotroph mechanism. AB - Plant biotrophs often establish highly specialized and localized interaction sites where sustained nutrient exchange occurs. Increased plant nuclear DNA ploidy at or adjacent to these sites has now been reported for a diverse set of interactions, including those with fungal and bacterial symbionts and parasitic fungi and nematodes. Also, novel regulators of induced endoreduplication have recently been identified. When localized host endoreduplication is reduced, so too is the growth and/or development of the biotroph, suggesting endoreduplication supports the enhanced metabolic demands imposed by these interactions. Transcriptome analyses support this function and further identify specific ploidy-impacted processes. Remarkably, notwithstanding differences in time scales, the ploidy-impacted processes are consistent with the Gene Balance Hypothesis, which can also be used to predict effector targets. As effector influence may diminish with enhanced ploidy, these interaction sites may be uniquely suited to identify effector-impacted processes as well as elucidate endocycle regulation and function. PMID- 20542726 TI - Microsporidia: a model for minimal parasite-host interactions. AB - Microsporidia are emerging fungi-like intracellular parasites of economic, veterinary and medical importance. The strategy they use to invade their host is related to the rapid extrusion of a unique and highly specialized organelle, the polar tube, which allows the injection of the infectious spore content within a target cell. This original process seems to be dependent on initial interactions between parasite and host cell components. The extreme reduction and compaction of most microsporidian genomes resulted in the loss of many metabolic pathways, which makes these parasites highly dependent on their host. Recent significant advances have been made in the understanding of mammal and insect immune responses against microsporidian infections with the involvement of both adaptive and innate immunity. PMID- 20542727 TI - Histidine kinases keep fungi safe and vigorous. AB - Signal transduction in human pathogenic fungi, like in other microorganisms, regulates a number of adaptive transcriptional responses to a variety of environmental cues. Among signal relay proteins, sensor, histidine kinase proteins (HK) are auto-phosphorylated upon perception of an environmental cue, and initiate a phosphorelay that results in transcriptional regulation of genes associated with specific stress signals or multiple stress cues. Human pathogenic fungi utilize HK proteins to adapt to stress, grow, sporulate, undergo morphogenesis, mate, sense anti-fungal drugs, and cause disease. While much is known about HK and RR proteins functionally, the MAPK pathways and downstream transcription factors and gene targets are largely unstudied in human pathogenic fungi. However, as HK proteins are broadly conserved and not apparently in humans, we suggest that they offer exploitation as new targets in anti-fungal drug discovery. PMID- 20542728 TI - Molecular structure and vibrational bands and chemical shift assignments of 4 allyl-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione by DFT and ab initio HF calculations. AB - The title molecule, 4-allyl-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3 thione (C(11)H(11)N(3)OS), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic space group is P2(1)/c, a=9.0907(5)A, b=9.1288(7)A, c=13.6222(7)A, alpha=90 degrees , beta=98.442 (4), gamma=90 degrees and V=2683.7(6)A(3), F(000)=488, D(x)=1.386 g/cm(3). In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional method (DFT/BLYP and DFT/B3LYP) with 6-31G(d) basis set. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) calculations with respect to selected degree of torsional freedom, which was varied from -180 degrees to +180 degrees in steps of 10 degrees . Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), and several thermodynamic properties were performed by the HF and DFT methods. PMID- 20542729 TI - Secondhand smoke exposures in indoor public places in seven Asian countries. AB - Exposure to secondhand smoke (SHS) is a major threat to public health. Asian countries having the highest smoking prevalence are seriously affected by SHS. The objective of the study was to measure SHS levels in hospitality venues in seven Asian countries and to compare the SHS exposure to the levels in Western countries. The study was carried out in four types of related hospitality venues (restaurant, cafe, bar/club and entertainment) in China, India, Japan, Korea, Malaysia, Pakistan and Sri Lanka. Real-time measurement of particulate matter of <2.5microm aerodynamic diameter (PM(2.5)) was made during business hour using a handheld laser operated monitor. A total of 168 venues were measured in seven countries. The average indoor PM(2.5) level was 137microg/m(3), ranging from 46microg/m(3) in Malaysia to 207microg/m(3) in India. Bar/club had the highest PM(2.5) level of 191microg/m(3) and restaurants had the lowest PM(2.5) level of 92microg/m(3). The average indoor PM(2.5) level in smoking venues was 156micro/m(3), which was 3.6 times higher than non-smoking venues (43microg/m(3)). Indoor PM(2.5) levels were significantly associated with country, type of venue, smoking density and air exchange rate (p<0.05). In the seven Asian countries, PM(2.5) levels were high due to SHS in public places. The current levels are comparable to the levels in Western countries before the adoption of smoke-free policy. Since Asian country has high prevalence of SHS in public places, there is an urgent need for comprehensive smoke-free regulation in Asian countries. PMID- 20542730 TI - The translatability of animal models for clinical development: biomarkers and disease models. AB - Translational science in medicine describes the transfer of basic in vitro and in vivo research into human applications. Animal models are important tools in translational science, and several different approaches such as genetically engineered animals, xenograft models, inbred strains and disease induction models are available for many diseases. Biomarkers are defined as any measurable parameters of biological processes. This includes disease pathophysiology and the impact of interventions thereon. Biomarkers represent the most important tool of translational science in medicine. Therefore, the development of biomarkers, which are useful and accessible both in animals and in humans, represents an important focus of translational activities. Imaging, for example, is translationally ideal as the readouts in disease models and patients are the same or at least very similar. Despite several approved animal models, the majority of compounds tested successfully in animals still fail to be successfully applied to human diseases. To reduce this rate of failure, animal models better resembling the human situation are needed. A new scoring system for the assessment of translatability is discussed; it facilitates the judgement on the predictivity of results from a given animal model regarding human translation by the weighed answers to important data features. These include robust animal data in more than one species, related human data and accessibility. PMID- 20542731 TI - At a crossroads in oncology. AB - We survey the current paradigm for cancer therapy and offer a perspective on the state of clinical oncology. Next, we address the key clinical and biological obstacles that have hampered progress to date. Recent insights into the true genetic complexity of cancer, the mixed clinical performance of targeted therapies, and the homogeneity of industry pipelines argue for new approaches to cancer therapy. PMID- 20542732 TI - LAT signaling pathology: an "autoimmune" condition without T cell self reactivity. AB - Partial loss-of-function mutations in several molecules involved in T-cell receptor (TCR) signaling result in inflammation and autoimmunity. How can mutations that reduce TCR signaling output, paradoxically lead to immune pathology? This review summarizes experiments demonstrating that mutations in the linker for activation of T cells (LAT) predispose toward aberrant T cell responses to antigen in the presence of normal thymic selection. In the absence of LAT, antigen-specific T cells give rise to self-perpetuating pro-inflammatory responses and induce the production of autoantibodies independently of TCR engagement. Therefore, some pathological conditions called "autoimmune" might not result from the presence of self-reactive T cells, but from defective mechanisms that normally keep T cell activation in check. PMID- 20542733 TI - Landmarks in the evolution of technologies for identifying trypanosomes in tsetse flies. AB - Understanding what the trypanosome pathogens are, their vectors and mode of transmission underpin efforts to control the disease they cause in both humans and livestock. The risk of transmission is estimated by determining what proportion of the vector population is carrying the infectious pathogens. This risk also depends on the infectivity of the trypanosomes to humans and livestock. Most livestock pathogens are not infective to humans, whereas the two sub-species that infect humans also infect livestock. As with other infectious diseases, we can therefore trace the foundation of many continuing disease control programs for trypanosomiasis to the discovery of the pathogens and their vectors more than a century ago. Over this period, methods for detecting and identifying trypanosomes have evolved through various landmark discoveries. This review describes the evolution of methods for identifying African trypanosomes in their tsetse fly vectors. PMID- 20542734 TI - Worm secretory molecules are causing alarm. PMID- 20542735 TI - Supporting and supervising district nurse students through patchwork text writing. AB - This article reports research and supervision practice experiences of teachers on a community nursing module, assessed by a patchwork text. The nature, relevance and characteristics of support and supervision involve judging use and relevance of story, personal memory and imagery as means of illustrating creativity and self-evaluative questioning interlinked with empirical evidence, research and policy discourses. All of these diverse elements require synthesis by practitioners if they are to demonstrate essential skills of community working, including responding to situational challenges, unpredictability and use of evidence in context. Supervision is characterised less by information provision and more by assisting students to understand connections and significance with the reflective diary assuming a crucial role in helping students appreciate personal and aesthetic dimensions. Challenges for supervisors include allowing students freedom to write in imaginative ways bounded by indexes of quality; and to act as role models, making explicit their own reflecting, open mindedness, connecting and synthesising. Use of an extended epistemology has helped supervisors appraise and value; balancing advice and direction with facilitation; diversity and homogeneity; parts and whole, expression, style and overall coherence. Finally, limitations and negative resource implications are identified and considered. PMID- 20542736 TI - Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. AB - BACKGROUND: Interferon beta is commonly used to treat patients with relapsing remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. INTERPRETATION: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. FUNDING: Biogen Idec. PMID- 20542737 TI - Improving combination trials for multiple sclerosis. PMID- 20542738 TI - Cerebral microemboli: smoking gun or innocent bystanders? PMID- 20542739 TI - A physiological role for inducible FOXP3(+) Treg cells. Lessons from women with reproductive failure. AB - We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 in activated PBMCs was already present above baseline before any cell division, indicating that it was induced in cells that were previously negative for this transcription factor. Because RSA women showed a more limited expansion of FOXP3-positive cells, we next assessed the role of IL-2 signaling through STAT5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-beta and IL-2 were diminished but also that the IL-2-STAT-5 signaling axis was down regulated in RSA women. Finally, in addition to a limited FOXP3(+) cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity. PMID- 20542740 TI - Moderating effect of optimism on emotional distress and seizure control in adults with temporal lobe epilepsy. AB - Stress is a commonly reported seizure precipitant among individuals with epilepsy. Yet, the relationship between stress and seizure susceptibility remains unclear. This study examined the relationship between emotional distress and lifetime seizure load in individuals with temporal lobe epilepsy (TLE), as well as the potential moderating effect of explanatory style on this relationship. Data were collected from 148 individuals with TLE. Scales 2 and 7 of the Minnesota Multiphasic Personality Inventory were used as a measure of emotional distress, and explanatory style was measured using the Revised Optimism-Pessimism Scale. Elevated Scale 2 scores were associated with an increase in seizure load only in subjects with Full Scale IQ scores> or =92. An interaction between emotional distress and explanatory style was not observed. Thus, for individuals with higher levels of intelligence, depression may be an important pathway in linking emotional distress to poor seizure control. PMID- 20542741 TI - Idiopathic mesial temporal lobe epilepsy: don't sow the tares with the wheat! PMID- 20542743 TI - An educational strategy for treating chronic, noncancer pain with opioids: a pilot test. AB - Chronic pain is common and can be devastating to the patient and challenging to the health care provider. Despite the importance of the topic, pain management curricula are incomplete in health professionals' training. We developed a longitudinal curriculum to teach therapy for chronic noncancer pain over four units and pilot-tested the teaching of one unit (opioids) to internal medicine residents. The educational strategies we used included didactic sessions, write up of a management plan following a model, case discussions, and role-play group activities. We pilot-tested one unit (opioid therapy) in March 2008. We performed learner evaluations, using a pretest and posttest, a write-up plan following a model, and a learner knowledge questionnaire. Results showed significant improvement in knowledge. Residents found the sessions and educational strategy to be excellent and reported higher confidence levels in managing patients with chronic noncancer pain. PERSPECTIVE: This article demonstrates that multiple teaching modalities-including didactic lectures, case discussions, write-up of a management plan following a model, and role-play group activities-are effective methods of teaching internal medicine residents how to use opioids to manage chronic noncancer pain. PMID- 20542742 TI - Relationship between fibromyalgia and obesity in pain, function, mood, and sleep. AB - Fibromyalgia syndrome (FMS) is a prevalent and disabling chronic pain disorder. Past research suggests that obesity is a common comorbidity and may be related to the severity of FMS. The main objective of the present study was to evaluate the relationships between FMS and obesity in the multiple FMS-related domains: hyperalgesia, symptoms, physical abilities, and sleep. A total of 215 FMS patients completed a set of self-report inventories to assess FMS-related symptoms and underwent the tender point (TP) examination, physical performance testing, and 7-day home sleep assessment. Forty-seven percent of our sample was obese and an additional 30% was overweight. Obesity was related significantly to greater pain sensitivity to TP palpation particularly in the lower body areas, reduced physical strength and lower-body flexibility, shorter sleep duration, and greater restlessness during sleep. The results confirmed that obesity is a prevalent comorbidity of FMS that may contribute to the severity of the problem. Potential mechanisms underlying the relationship are discussed. PERSPECTIVE: This report presents how obesity may be interrelated to fibromyalgia pain, disability, and sleep. We found that obesity is common in FMS. Approximately half of our patients were obese and an additional 30% were overweight. We also found that obesity in FMS was associated with greater pain sensitivity, poorer sleep quality, and reduced physical strength and flexibility. The results suggest that obesity may aggregate FMS and weight management may need to be incorporated into treatments. PMID- 20542744 TI - Effect of Th2 type cytokines on hCLCA1 and mucus expression in cystic fibrosis airways. AB - Correlations between expression of interleukin (IL)-9, the calcium-activated chloride channel hCLCA1 and mucus expression in cystic fibrosis (CF) airways have suggested a causal relationship. To verify this hypothesis mucosal tissue from upper airways of CF patients (N=5) was stimulated with the Th2 type cytokines IL 4, IL-9, or IL-13. Expression of hCLCA1 mRNA and protein as well as mucus and mucin (MUC5AC) gene expression was quantified using real time PCR, immunohistochemistry (hCLCA1) and PAS staining (mucus). Th2 type cytokines significantly increased hCLCA1 protein expression (P<0.05) whereas increase in hCLCA1 mRNA expression failed to reach statistical significance (P>0.05). Mucin protein and MUC5AC mRNA expression were not significantly changed (P>0.05). These data suggest that Th2 type cytokines may increase hCLCA1 expression in CF but may not have a significant effect on mucus expression. Therefore the role of hCLCA1 as a mediator of mucus overexpression in CF has to be questioned. PMID- 20542745 TI - Stable-isotope dilution GC-MS approach for nitrite quantification in human whole blood, erythrocytes, and plasma using pentafluorobenzyl bromide derivatization: nitrite distribution in human blood. AB - Previously, we reported on the usefulness of pentafluorobenzyl bromide (PFB-Br) for the simultaneous derivatization and quantitative determination of nitrite and nitrate in various biological fluids by GC-MS using their (15)N-labelled analogues as internal standards. As nitrite may be distributed unevenly in plasma and blood cells, its quantification in whole blood rather than in plasma or serum may be the most appropriate approach to determine nitrite concentration in the circulation. So far, GC-MS methods based on PFB-Br derivatization failed to measure nitrite in whole blood and erythrocytes because of rapid nitrite loss by oxidation and other unknown reactions during derivatization. The present article reports optimized and validated procedures for sample preparation and nitrite derivatization which allow for reliable quantification of nitrite in human whole blood and erythrocytes. Essential measures for stabilizing nitrite in these samples include sample cooling (0-4 degrees C), hemoglobin (Hb) removal by precipitation with acetone and short derivatization of the Hb-free supernatant (5 min, 50 degrees C). Potassium ferricyanide (K(3)Fe(CN)(6)) is useful in preventing Hb-caused nitrite loss, however, this chemical is not absolutely required in the present method. Our results show that accurate GC-MS quantification of nitrite as PFB derivative is feasible virtually in every biological matrix with similar accuracy and precision. In EDTA-anticoagulated venous blood of 10 healthy young volunteers, endogenous nitrite concentration was measured to be 486+/-280 nM in whole blood, 672+/-496 nM in plasma (C(P)), and 620+/-350 nM in erythrocytes (C(E)). The C(E)-to-C(P) ratio was 0.993+/-0.188 indicating almost even distribution of endogenous nitrite between plasma and erythrocytes. By contrast, the major fraction of nitrite added to whole blood remained in plasma. The present GC-MS method is useful to investigate distribution and metabolism of endogenous and exogenous nitrite in blood compartments under basal conditions and during hyperemia. PMID- 20542746 TI - [Use of a new protocol for prolactin extraction and reduction of false hyperprolactinemia]. AB - INTRODUCTION: Numerous authors have reported that prolactin measurement is influenced by several factors and consequently the values obtained may not faithfully reflect the physiological reality of the individual studied. Unless a series of measures is adopted, especially in the pre-analytic stage, values may be falsely elevated. The objective of the present study was to evaluate the extent to which optimization or non-optimization of the extraction procedure translates into higher results and how reports expressed in terms of monomeric (biologically active) prolactin could be crucial to adopt a diagnosis and therapeutic approach. MATERIAL AND METHODS: We performed two extractions in each woman (following the protocol universally used for this kind of analysis): one through direct puncture and another 60 min later without a new puncture (a catheter was inserted in the site of the first puncture and kept permeable by salinization). The monomeric fraction was then studied, if required. RESULTS: A statistically significant difference was observed between the 2 extractions. The monomeric fraction was three times lower in the second extraction than in the first. DISCUSSION: The results of this study justify systematic use of extraction techniques that avoid the stress of venous puncture, as well as the use of the term biologically active prolactin [monomeric (little) prolactin fraction] in reports. PMID- 20542747 TI - Subcutaneous wash-out procedure (SWOP) for the treatment of chemotherapeutic extravasations. AB - INTRODUCTION: Extravasations of chemotherapeutic drugs may lead to tissue necrosis and subsequent tissue defects, sometimes resulting in loss of function. In the absence of therapy, approximately one-third of vesicant extravasations will result in ulcerations, some of which necessitate plastic microsurgery to cover the soft tissue defects. The aim of this study was to describe the surgical technique itself and to present clinical results of the procedure in a clinical series of chemotherapeutic extravasation injuries that benefitted from a subcutaneous wash-out procedure (SWOP) by minimisation of serious complications. PATIENTS AND METHODS: Over a time period of 3 years, we treated 13 female patients following chemotherapeutic extravasation injury. Nine of the cases involved a high vesicant chemotherapy agent, and four patients involved chemotherapy with low vesicant potential. The therapeutic approach was performed using SWOP exclusively without the application of specific antidotes. RESULTS: The mean time interval between the extravasation injury and the SWOP was 345min (140-795min). In none of the cases was there a tissue breakdown, but there was a steady decrease in the inflammatory reaction of the cutaneous and subcutaneous soft tissues without additional complications over a 3-month follow-up period. CONCLUSION: The results of the study suggest that SWOP is a minimally invasive, safe and effective emergency treatment for chemotherapeutic extravasation injury. Based on the absence of comparative studies with regard to the efficacy of conservative therapy, SWOP should be offered as a therapeutic option for chemotherapeutic extravasations, especially in cases of medical malpractice and also as a defence in case of a legal conflict. PMID- 20542748 TI - MMP- and TIMP-secretion by human cutaneous keratinocytes and fibroblasts--impact of coculture and hydration. AB - Epithelial-mesenchymal interactions are important in wound healing and scarring, but are difficult to study in vitro. We have previously reported on an in vitro keratinocyte-fibroblast coculture system exploring these interactions and found that coculture modifies the levels of cytokines they secrete. The same coculture model was used to study changes in MMP- and TIMP-activity. We hypothesised that the previously shown decrease of collagen is partly due to increased MMPs. Adult human cutaneous keratinocytes and fibroblasts were cocultured under serum-free conditions. Keratinocytes were either kept at the air-liquid interface or hydrated. The conditioned medium was submitted to a multiplex sandwich enzyme linked immunosorbent assay including gelatinases, collagenases, stromelysins, and tissue inhibitors of metalloproteinases. Collagen content was determined by western blot. Zymography depicted the gelatinases in conditioned media. For confirmation of the coculture results fibroblasts were treated with conditioned media from keratinocyte monocultures as well. MMP-1, MMP-9, and MMP-10 were mainly secreted by keratinocytes, whereas MMP-2, TIMP-1 and -2 by fibroblasts. MMP-13 was secreted by both cell types at comparable levels. Collagenases, gelatinases, MMP-3, and TIMPs increased significantly in cocultures compared to monocultures. Hydration of keratinocytes revealed a significant increase of MMP-3 and MMP-2, and a decrease of TIMP-2. Paracrine interactions between keratinocytes and fibroblasts modify strongly MMPs and TIMPs, whereas hydration of keratinocytes had a smaller impact in this context. The observed changes may be in part responsible for reduced collagen in coculture-conditioned media. The present coculture experiments reemphasise the role of epidermis in controlling scarring. PMID- 20542749 TI - Ying-Yang flap technique for correction of male nipple hypertrophy: a case report and a review of the English-language literature. PMID- 20542750 TI - Novel regulators of stem cell fates identified by a multivariate phenotype screen of small compounds on human embryonic stem cell colonies. AB - Understanding the complex mechanisms that govern the fate decisions of human embryonic stem cells (hESCs) is fundamental to their use in cell replacement therapies. The progress of dissecting these mechanisms will be facilitated by the availability of robust high-throughput screening assays on hESCs. In this study, we report an image-based high-content assay for detecting compounds that affect hESC survival or pluripotency. Our assay was designed to detect changes in the phenotype of hESC colonies by quantifying multiple parameters, including the number of cells in a colony, colony area and shape, intensity of nuclear staining, and the percentage of cells in the colony that express a marker of pluripotency (TRA-1-60), as well as the number of colonies per well. We used this assay to screen 1040 compounds from two commercial compound libraries, and identified 17 that promoted differentiation, as well as 5 that promoted survival of hESCs. Among the novel small compounds we identified with activity on hESC are several steroids that promote hESC differentiation and the antihypertensive drug, pinacidil, which affects hESC survival. The analysis of overlapping targets of pinacidil and the other survival compounds revealed that activity of PRK2, ROCK, MNK1, RSK1, and MSK1 kinases may contribute to the survival of hESCs. PMID- 20542751 TI - Knowledge gaps and misconceptions about over-the-counter analgesics among adolescents attending a hospital-based clinic. AB - OBJECTIVES: Although many adolescents use over-the-counter (OTC) analgesics, their knowledge about these drugs is unclear. This study evaluates misconceptions and knowledge gaps about OTC side effects, risks, and interactions among adolescents attending a hospital-based clinic. METHODS: Adolescents aged 14 to 20 years presenting to an outpatient clinic were surveyed using a computer administered instrument. Participants answered questions regarding their use of specific OTC medications and knowledge of side effects, risks, and interactions of these drugs. A summary score of percent correct answers on knowledge questions was created, and univariate and multivariate statistical techniques examined differences between groups. RESULTS: Ninety-six adolescents completed the survey. Most (78%) adolescents had used OTC medications in the previous month. The most frequently reported OTC medications used were analgesics, including ibuprofen (46%), and Tylenol (45%); acetaminophen ingestion was reported by 15% of respondents. Although 35% reported knowing what acetaminophen is, 37% of these did not correctly identify acetaminophen and Tylenol as the same medication. The average overall knowledge score was 44%. In regression models including demographics, and OTC product use, older adolescents had higher overall average knowledge scores. Hispanic teens had less reported use and lower knowledge scores than adolescents of other race/ethnicities. CONCLUSIONS: Most adolescents use OTC analgesics, but many are confused about generic and brand name forms. There were also significant knowledge gaps about OTC use, side effects, and contraindications, especially for acetaminophen. Clinicians should be aware of the potential for OTC medication misuse by adolescent patients. PMID- 20542752 TI - Neuromuscular and muscle-tendon system adaptations to isotonic and isokinetic eccentric exercise. AB - OBJECTIVE: To present the properties of an eccentric contraction and compare neuromuscular and muscle-tendon system adaptations induced by isotonic and isokinetic eccentric trainings. SYNTHESIS: An eccentric muscle contraction is characterized by the production of muscle force associated to a lengthening of the muscle-tendon system. This muscle solicitation can cause micro lesions followed by a regeneration process of the muscle-tendon system. Eccentric exercise is commonly used in functional rehabilitation for its positive effect on collagen synthesis but also for resistance training to increase muscle strength and muscle mass in athletes. Indeed, eccentric training stimulates muscle hypertrophy, increases the fascicle pennation angle, fascicles length and neural activation, thus inducing greater strength gains than concentric or isometric training programs. Eccentric exercise is commonly performed either against a constant external load (isotonic) or at constant velocity (isokinetic), inducing different mechanical constraints. These different mechanical constraints could induce structural and neural adaptive strategies specific to each type of exercise. CONCLUSION: The literature tends to show that isotonic mode leads to a greater strength gain than isokinetic mode. This observation could be explained by a greater neuromuscular activation after IT training. However, the specific muscle adaptations induced by each mode remain difficult to determine due to the lack of standardized, comparative studies. PMID- 20542753 TI - FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population. AB - Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n=4; 10%), S249C (n=23; 59%), Y375C (n=7; 18%), G382R (n=4; 10%), and one novel mutation, G382E (n=1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patient's survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of overall survival in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors. PMID- 20542754 TI - Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: a meta-analysis. AB - Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR)=1.36, 95 percent confidence interval (95% CI): 1.09-1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and adenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene-gene and gene-environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population. PMID- 20542756 TI - Reversible projection technique for colon unfolding. AB - Colon unfolding provides an efficient way to navigate the colon in computed tomographic colonography (CTC). Most existing unfolding techniques only compute forward projections. When radiologists find abnormalities or conduct measurements on the unfolded view (which is often quicker and easier), it is difficult to locate the corresponding region on the 3-D view for further examination (which is more accurate and reliable). To address this, we propose a reversible projection technique for colon unfolding. The method makes use of advanced algorithms including rotation-minimizing frames, recursive ring sets, mesh skinning, and cylindrical projection. Both forward and reverse mapping can be computed for points on the colon surface. Therefore, it allows for detecting and measuring polyps on the unfolded view and mapping them back to the 3-D surface. We generated realistic colon simulation data incorporating most colon characteristics, such as curved centerline, variable distention, haustral folds, teniae coli, and colonic polyps. Our method was tested on both simulated data and data from 110 clinical CTC studies. The results showed submillimeter accuracy in simulated data and -0.23 +/- 1.67 mm in the polyp measurement using clinical CTC data. The major contributions of our technique are: 1) the use of a recursive ring set method to solve the centerline and surface correspondence problem; 2) reverse transformation from the unfolded view to the 3-D view; and 3) quantitative validation using a realistic colon simulation and clinical CTC polyp measurement. PMID- 20542757 TI - Basilar-membrane responses to broadband noise modeled using linear filters with rational transfer functions. AB - Basilar-membrane responses to white Gaussian noise were recorded using laser velocimetry at basal sites of the chinchilla cochlea with characteristic frequencies near 10 kHz and first-order Wiener kernels were computed by cross correlation of the stimuli and the responses. The presence or absence of minimum phase behavior was explored by fitting the kernels with discrete linear filters with rational transfer functions. Excellent fits to the kernels were obtained with filters with transfer functions including zeroes located outside the unit circle, implying nonminimum-phase behavior. These filters accurately predicted basilar-membrane responses to other noise stimuli presented at the same level as the stimulus for the kernel computation. Fits with all-pole and other minimum phase discrete filters were inferior to fits with nonminimum-phase filters. Minimum-phase functions predicted from the amplitude functions of the Wiener kernels by Hilbert transforms were different from the measured phase curves. These results, which suggest that basilar-membrane responses do not have the minimum-phase property, challenge the validity of models of cochlear processing, which incorporate minimum-phase behavior. PMID- 20542758 TI - Design and fabrication of a magnetic propulsion system for self-propelled capsule endoscope. AB - This paper investigates design, modeling, simulation, and control issues related to self-propelled endoscopic capsule navigated inside the human body through external magnetic fields. A novel magnetic propulsion system is proposed and fabricated, which has great potential of being used in the field of noninvasive gastrointestinal endoscopy. Magnetic-analysis model is established and finite element simulations as well as orthogonal design are performed for obtaining optimized mechanical and control parameters for generating appropriate external magnetic field. Simulated intestinal tract experiments are conducted, demonstrating controllable movement of the capsule under the developed magnetic propulsion system. PMID- 20542759 TI - Assessment of pulmonary flow using impedance pneumography. AB - There is a lack of noninvasive pulmonary function measurement techniques suitable for continuous long-term measurement of tidal breathing in mobile subjects, although tidal breathing analysis has been shown to contain information that relates to the level airway obstruction. This paper is the first to assess the suitability of impedance pneumography (IP) for measurement of continuous pulmonary flow and volume signals instead of only the respiration rate (RR) or tidal volume ( V(T)). We measured pneumotachograph (PNT) and IP signals simultaneously from 20 healthy male subjects in erect, dorsal supine, and lateral supine positions while voluntarily varying V(T). IP was measured using five different impedance lead configurations with electrodes integrated into a textile chest belt. The IP signals were compared with PNT signals to assess agreement of IP with a more well-established measurement method. The pulmonary flow signal waveform agreement was assessed with standard error of measurement (SEM) between the time-differentiated IP signal and the PNT signal as rho = 1-SEM. Additionally, we assessed the agreement of IP and PNT in V(T) estimation and the magnitude of the cardiogenic oscillation present in the impedance signal. The agreement in the pulmonary flow signal waveform shapes was found excellent at all tidal volumes and postures (mean rho > 0.90). The agreement between the PNT derived and the IP-derived V(T) estimates was very high when IP values were calibrated per subject and posture (mean difference < 3%). The main source of error in visual inspection of the IP signal was the cardiogenic distortion. From the five novel electrode configurations tested, the lateral ones were found clearly better than the anteroposterior ones. IP potentially enables the development of a noninvasive ambulatory measurement device for long-term studies of certain tidal breathing parameters in mobile subjects. PMID- 20542760 TI - Source separation from single-channel recordings by combining empirical-mode decomposition and independent component analysis. AB - In biomedical signal processing, it is often the case that many sources are mixed into the measured signal. The goal is usually to analyze one or several of them separately. In the case of multichannel measurements, several blind source separation techniques are available for decomposing the signal into its components [e.g., independent component analysis (ICA)]. However, only a few techniques have been reported for analyses of single-channel recordings. Examples are single-channel ICA (SCICA) and wavelet-ICA (WICA), which all have certain limitations. In this paper, we propose a new method for a single-channel signal decomposition. This method combines empirical-mode decomposition with ICA. We compare the separation performance of our algorithm with SCICA and WICA through simulations, and we show that our method outperforms the other two, especially for high noise-to-signal ratios. The performance of the new algorithm was also demonstrated in two real-life applications. PMID- 20542761 TI - An autoregressive model-based particle filtering algorithms for extraction of respiratory rates as high as 90 breaths per minute from pulse oximeter. AB - We present particle filtering (PF) algorithms for an accurate respiratory rate extraction from pulse oximeter recordings over a broad range: 12-90 breaths/min. These methods are based on an autoregressive (AR) model, where the aim is to find the pole angle with the highest magnitude as it corresponds to the respiratory rate. However, when SNR is low, the pole angle with the highest magnitude may not always lead to accurate estimation of the respiratory rate. To circumvent this limitation, we propose a probabilistic approach, using a sequential Monte Carlo method, named PF, which is combined with the optimal parameter search (OPS) criterion for an accurate AR model-based respiratory rate extraction. The PF technique has been widely adopted in many tracking applications, especially for nonlinear and/or non-Gaussian problems. We examine the performances of five different likelihood functions of the PF algorithm: the strongest neighbor, nearest neighbor (NN), weighted nearest neighbor (WNN), probability data association (PDA), and weighted probability data association (WPDA). The performance of these five combined OPS-PF algorithms was measured against a solely OPS-based AR algorithm for respiratory rate extraction from pulse oximeter recordings. The pulse oximeter data were collected from 33 healthy subjects with breathing rates ranging from 12 to 90 breaths/ min. It was found that significant improvement in accuracy can be achieved by employing particle filters, and that the combined OPS-PF employing either the NN or WNN likelihood function achieved the best results for all respiratory rates considered in this paper. The main advantage of the combined OPS-PF with either the NN or WNN likelihood function is that for the first time, respiratory rates as high as 90 breaths/min can be accurately extracted from pulse oximeter recordings. PMID- 20542762 TI - Modeling the role of the coronary vasculature during external field stimulation. AB - The exact mechanisms by which defibrillation shocks excite cardiac tissue far from both the electrodes and heart surfaces require elucidation. Bidomain theory explains this phenomena through the existence of intramural virtual electrodes (VEs), caused by discontinuities in myocardial tissue structure. In this study, we assess the modeling components essential in constructing a finite-element cardiac tissue model including blood vessels from high-resolution magnetic resonance data and investigate the specific role played by coronary vasculature in VE formation, which currently remains largely unknown. We use a novel method for assigning histologically based fiber architecture around intramural structures and include an experimentally derived vessel lumen wall conductance within the model. Shock-tissue interaction in the presence of vessels is assessed through comparison with a simplified model lacking intramural structures. Results indicate that VEs form around blood vessels for shocks > 8 V/cm. The magnitude of induced polarizations is attenuated by realistic representation of fiber negotiation around vessel cavities, as well as the insulating effects of the vessel lumen wall. Furthermore, VEs formed around large subepicardial vessels reduce epicardial polarization levels. In conclusion, we have found that coronary vasculature acts as an important substrate for VE formation, which may help interpretation of optical mapping data. PMID- 20542763 TI - Time-structure based reconstruction of physiological independent sources extracted from noisy abdominal phonograms. AB - The abdominal phonogram is a signal recorded by a sensitive acoustic sensor positioned on the maternal womb. The signal conveys information that is valuable for fetal surveillance (e.g., heart sounds), but hidden by maternal and environmental noises. To recover such information, earlier work successfully used single-channel independent component analysis (SCICA) to decompose the phonogram into independent components (ICs). After that, knowing that some ICs belong to the same process, similar ICs were grouped using K -means through similarities in their spectral content, a step that misclassified some fetal and maternal ICs, and consequently, distorted the recovered sources and made them virtually useless for studying fetal condition. Here, the rich time structure of the physiological components underlying the abdominal phonogram is exploited to automatically classify similar components and retrieve the independent sources corresponding to maternal activity (respiration and cardiovascular), fetal heart sounds, and noise. To do so, a periodicity-based analysis scheme is proposed and tested on a dataset composed of 750 ICs extracted by SCICA from segments of 25 single-channel phonograms recorded at fetal gestational ages between 29 and 40 weeks. Based on autocorrelation and power spectral density analysis, this scheme not only manages to quickly and automatically group similar ICs, but also correlates the recovered sources with specific physiological phenomena (either maternal or fetal), which is a further advantage. Further research will be conducted on more phonograms and explore alternatives for dimensional reduction and reconstruction of entire time series suitable for surveillance, not only for fetal well-being, but also for maternal condition. PMID- 20542764 TI - Separation of heart sound signal from noise in joint cycle frequency-time frequency domains based on fuzzy detection. AB - Noise is generally unavoidable during recordings of heart sound signal. Therefore, noise reduction is one of the important preprocesses in the analysis of heart sound signal. This was achieved in joint cycle frequency-time-frequency domains in this study. Heart sound signal was decomposed into components (called atoms) characterized by time delay, frequency, amplitude, time width, and phase. It was discovered that atoms of heart sound signal congregate in the joint domains. On the other hand, atoms of noise were dispersed. The atoms of heart sound signal could, therefore, be separated from the atoms of noise based on fuzzy detection. In a practical experiment, heart sound signal was successfully separated from lung sounds and disturbances due to chest motion. Computer simulations for various clinical heart sound signals were also used to evaluate the performance of the proposed noise reduction. It was shown that heart sound signal can be reconstructed from simulated complex noise (perhaps non-Gaussian, nonstationary, and colored). The proposed noise reduction can recover variations in the both waveform and time delay of heart sound signal during the reconstruction. Correlation coefficient and normalized residue were used to indicate the closeness of the reconstructed and noise-free heart sound signal. Correlation coefficient may exceed 0.90 and normalized residue may be around 0.10 in 0-dB noise environment, even if the phonocardiogram signal covers only ten cardiac cycles. PMID- 20542765 TI - Fast computation of Tchebichef moments for binary and grayscale images. AB - Discrete orthogonal moments have been recently introduced in the field of image analysis. It was shown that they have better image representation capability than the continuous orthogonal moments. One problem concerning the use of moments as feature descriptors is the high computational cost, which may limit their application to the problems where the online computation is required. In this paper, we present a new approach for fast computation of the 2-D Tchebichef moments. By deriving some properties of Tchebichef polynomials, and using the image block representation for binary images and intensity slice representation for grayscale images, a fast algorithm is proposed for computing the moments of binary and grayscale images. The theoretical analysis shows that the computational complexity of the proposed method depends upon the number of blocks of the image, thus, it can speed up the computational efficiency as far as the number of blocks is smaller than the image size. PMID- 20542766 TI - Fast nonconvex nonsmooth minimization methods for image restoration and reconstruction. AB - Nonconvex nonsmooth regularization has advantages over convex regularization for restoring images with neat edges. However, its practical interest used to be limited by the difficulty of the computational stage which requires a nonconvex nonsmooth minimization. In this paper, we deal with nonconvex nonsmooth minimization methods for image restoration and reconstruction. Our theoretical results show that the solution of the nonconvex nonsmooth minimization problem is composed of constant regions surrounded by closed contours and neat edges. The main goal of this paper is to develop fast minimization algorithms to solve the nonconvex nonsmooth minimization problem. Our experimental results show that the effectiveness and efficiency of the proposed algorithms. PMID- 20542767 TI - Passive polarimetric imagery-based material classification robust to illumination source position and viewpoint. AB - Polarization, a property of light that conveys information about the transverse electric field orientation, complements other attributes of electromagnetic radiation such as intensity and frequency. Using multiple passive polarimetric images, we develop an iterative, model-based approach to estimate the complex index of refraction and apply it to target classification. PMID- 20542768 TI - Fuzzy-rough supervised attribute clustering algorithm and classification of microarray data. AB - One of the major tasks with gene expression data is to find groups of coregulated genes whose collective expression is strongly associated with sample categories. In this regard, a new clustering algorithm, termed as fuzzy-rough supervised attribute clustering (FRSAC), is proposed to find such groups of genes. The proposed algorithm is based on the theory of fuzzy-rough sets, which directly incorporates the information of sample categories into the gene clustering process. A new quantitative measure is introduced based on fuzzy-rough sets that incorporates the information of sample categories to measure the similarity among genes. The proposed algorithm is based on measuring the similarity between genes using the new quantitative measure, whereby redundancy among the genes is removed. The clusters are refined incrementally based on sample categories. The effectiveness of the proposed FRSAC algorithm, along with a comparison with existing supervised and unsupervised gene selection and clustering algorithms, is demonstrated on six cancer and two arthritis data sets based on the class separability index and predictive accuracy of the naive Bayes' classifier, the K nearest neighbor rule, and the support vector machine. PMID- 20542770 TI - Diabetes mellitus: the scary killer haunting silently. PMID- 20542771 TI - Why so few women in interventional cardiology? PMID- 20542772 TI - Highlights and essentials from the first "Experts-live" course of the EuroCTO club. PMID- 20542773 TI - Long-term mortality after PCI in patients with diabetes mellitus: results from the Swedish Coronary Angiography and Angioplasty Registry. AB - AIMS: Patients with diabetes mellitus have poorer outcome following acute coronary syndromes and coronary revascularisation. Knowledge of long-term outcome after revascularisation in real-life situations is though limited was analysed. METHODS AND RESULTS: Patients included in the Swedish Coronary Angiography Angioplasty Registry (SCAAR) in 2002-2007 with no previous revascularisation were followed for mortality after a first PCI until the end of 2007 (mean follow-up time 1,059 days). Differences in background and procedural characteristics were adjusted for in a multivariable Cox regression model. Of 57,708 patients, 18.8% had diabetes. Absolute mortality rate after four years follow-up was after STEMI, non-ST-elevation ACS and stable CAD respectively 23.2%, 17.8% and 12.7% for persons with diabetes and 14.4%, 8.4% and 5.7% for persons without diabetes. Adjusted relative risk for long-term mortality after first PCI was higher in patients with diabetes compared with those without; RR (95% CI); 1.66 (1.33 1.72), and after all three different PCI indications; RR (95% CI) for CAD; 2.01 (1.69-2.40), non-ST-elevation ACS 1.73 (1.58-1.90) and STEMI 1.44(1.30-1.59). CONCLUSIONS: Long-term mortality is higher in diabetic patients compared with those without, after a first PCI and this mortality gap increases with follow-up time. Intensive secondary preventive measures are needed to improve this situation. PMID- 20542774 TI - Paclitaxel and sirolimus eluting stents versus bare metal stents: long-term risk of stent thrombosis and other outcomes. From the Western Denmark Heart Registry. AB - AIMS: Stent thrombosis is a serious complication of percutaneous coronary intervention (PCI). We examined the incidence of stent thrombosis and other outcomes in patients treated with PCI and paclitaxeleluting stents (PES), sirolimus-eluting stents (SES) or bare-metal stents (BMS). METHODS AND RESULTS: All patients who underwent PES, SES or BMS implantation from January 2002 to June 2005 were identified in the population-based Western Denmark Heart Registry. All were followed for 36 months. Cox regression analysis was used to estimate relative risk (RR), controlling for covariates. A total of 12,374 patients were treated with stents: 1,298 with PES, 2,202 with SES and 8,847 with BMS. The three year incidence of definite stent thrombosis was similar in the DES group (1.1%) and in the BMS group (0.7%) (adjusted relative risk [RR]: 1.24; 95% confidence interval [CI]: 0.85-1.81). Very late definite stent thrombosis occurred more frequently in DES-treated patients (adjusted RR: 2.89, 95% CI: 1.48- 5.65). The three-year mortality rate did not differ significantly between the two groups. Target lesion revascularisation (TLR) was lower in DES-treated patients than in BMS-treated patients (adjusted RR: 0.71, 95% CI: 0.63-0.81). CONCLUSIONS: An increased risk of very late definite stent thrombosis was observed in DES-treated patients compared with BMS-treated patients, but a similar mortality was detected. TLR continued to be lower among patients receiving DES. PMID- 20542775 TI - Long-term follow-up (four years) of unprotected left main coronary artery disease treated with paclitaxel-eluting stents (from the TRUE Registry). AB - AIMS: Limited data are available on the long-term outcome following PCI with paclitaxel-eluting stent (PES) implantation in patients with unprotected left main coronary artery (LMCA). The objective of this study was to evaluate "real world" long-term outcome following paclitaxel-eluting stent (PES) implantation for unprotected LMCA disease in patients enrolled in the TRUE registry. METHODS AND RESULTS: From March 2003 to October 2004, 93 consecutive patients (81.7% male) underwent PCI for unprotected LMCA disease. Surveillance angiography was performed at 6.8+/-3.3 months follow-up. The target lesion involved the distal LMCA in 68 (73.1%) patients. Double stenting techniques were performed in 46 (67.6%) distal LMCA, of these 50% were stented using the Crush technique. Clinical follow-up was complete in all patients with 85.8% angiographic follow-up rate. In-segment restenosis occurred in 16 (20.3%) patients and was focal in 72.4% of cases and significantly higher in patients with distal LMCA (36.8% vs. 13.6%, p<0.04). At a median follow-up of 1,450 days (IQR 1281-1595), the overall incidence of MACE was 35.5% and the TLR rate was 25.8% and significantly higher in patients with bifurcation stenting (32.3% vs. 8%, p<0.02). The estimated cardiac survival rate at one and four years was 96.7% and 93.3%, respectively. Total mortality rate was 14.1% and cardiac was 6.5%. There was one (1.1%) definite stent thrombosis (ST) and one (1.1%) probable ST. CONCLUSIONS: Treatment of unprotected LMCA disease with PES, after four years follow-up, appears to be safe and effective with a low rate of cardiac mortality and overall risk of ST. The need for target lesion revascularisation in 25.8% of patients highlights the need for more effective PCI especially in patients with distal LMCA disease. PMID- 20542776 TI - Carotid artery revascularisation in high-surgical-risk patients with the NexStent and the FilterWire EX/EZ: 3-year results from the CABERNET trial. AB - AIMS: To investigate long-term outcomes achieved in high-surgical-risk patients and other clinically-relevant subgroups after carotid stenting with the NexStent and Filterwire EX/EZ devices. METHODS AND RESULTS: CABERNET, a prospective, multicentre, single-arm trial, enrolled 454 patients with extracranial internal carotid artery stenosis (symptomatic > or =50%, n=110; asymptomatic > or =60%, n=344). Early outcomes at one year have been reported. The 3-year Kaplan-Meier estimated event rates were: 7.2%, all stroke; 2.8%, major stroke; 4.8%, ipsilateral stroke; 17.7%, all death; 7.1%, myocardial infarction; 4.4%, target vessel revascularisation. Asymptomatic patients had significantly fewer major strokes than symptomatic patients (1.9% vs. 5.7%, P=0.03) and patients <80 years had significantly fewer ipsilateral strokes than those > or =80 years (3.2% vs. 10.7%, P=0.002). Stroke outcomes did not differ significantly between patients with anatomical risk factors compared with those with comorbid medical risk factors. CONCLUSIONS: Long-term outcomes achieved in high-surgical-risk patients with the NexStent and Filterwire EX/EZ devices are favourable. Outcomes may be better in asymptomatic patients or those younger than 80 years of age. These data will be helpful in estimating short-term risks of carotid stenting and balancing these risks against the long-term benefit of stroke prevention. PMID- 20542777 TI - Between-centre reproducibility of volumetric intravascular ultrasound radiofrequency-based analyses in mild-to-moderate coronary atherosclerosis: an international multicentre study. AB - AIMS: To assess for the first time in a multicentre design the between-centre reproducibility of volumetric virtual histology intravascular ultrasound (VH IVUS) measurements with a semi-automated, computerassisted contour detection system in mild-to-moderately diseased coronary segments. METHODS AND RESULTS: Analysts of four European IVUS centres performed independent IVUS analyses (in total 7,188 cross-sectional analyses) and obtained volumetric data to evaluate the reproducibility of volumetric VH-IVUS measurements in 36 coronary segments (length 20.0+/-0.4 mm) from patients with stable angina. Geometric and compositional VH-IVUS measurements were highly correlated for the different comparisons. Overall intraclass correlation for vessel, lumen, plaque volume and plaque burden were 0.98, 0.92 0.95, and 0.86, respectively; for fibrous, fibro lipidic, necrotic core and calcified volumes overall intraclass correlations were 0.95, 0.93, 0.99, and 1.00, respectively. There were significant but small differences for vessel, lumen, fibrous and calcified volumes, and there was no significant difference for plaque volume. Of the plaque components necrotic core and calcified volume showed on average the highest reproducibility. CONCLUSIONS: These findings underline the necessity to centrally analyse IVUS data obtained in multicentre studies addressing mild-to-moderately diseased coronary arteries. In addition, pooling VH-IVUS data from different studies, analysed at different centres, may be problematical. PMID- 20542778 TI - In vivo evaluation of stent strut distribution patterns in the bioabsorbable everolimus-eluting device: an OCT ad hoc analysis of the revision 1.0 and revision 1.1 stent design in the ABSORB clinical trial. AB - AIMS: The ABSORB Cohort A clinical study has shown the feasibility and safety of the fully bioabsorbable everolimus-eluting structure (BVS, revision 1.0). However, the study also demonstrated somewhat higher acute and late recoil with the BVS structure compared to metallic drug eluting stents. Based on these clinical observations, modifications to the stent design (BVS, revision 1.1) were introduced for the ABSORB Cohort B study in order to decrease recoil. The aim was to compare in vivo the strut distribution between the BVS revision 1.0 (Cohort A), and BVS revision 1.1 (Cohort B) designs. METHODS AND RESULTS: OCT analysis was performed by two independent analysts in four patients from each cohort of the ABSORB study. Strut distribution was assessed in cross-section, and longitudinally in a frameby-frame analysis. Variables recorded included inter strut angle, maximum inter-strut angle and number of frames with < or =3 struts. The inter-observer correlation coefficient was also assessed. For both designs, on a patient level there was no significant difference in the number of analysed struts corrected for the length of the scaffold (p=0.78). Likewise, on a frame by frame analysis mean stent area, number of struts per frame, mean maximum inter strut angle, and mean inter-strut angle were similar for both groups. However, in both structures there was a cyclical variation in the maximum number of struts per frame. The frequency of this variation was significantly higher in Cohort B. The inter-observer correlation coefficient for strut counts, inter-strut angle and maximum inter-strut angle was 0.91, 0.87 and 0.74 respectively. CONCLUSIONS: This ad hoc analysis confirms that the revision 1.1 BVS design has a different longitudinal strut distribution to the revision 1.0 BVS design, indicating that the new design has a reduced maximum circular unsupported cross sectional area. PMID- 20542779 TI - Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis. AB - AIMS: The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR). METHODS AND RESULTS: IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR. CONCLUSIONS: Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis. PMID- 20542780 TI - Impact of time to therapy and presence of collaterals on the efficacy of FX06 in acute ST elevation myocardial infarction: a substudy of the F.I.R.E., the Efficacy of FX06 in the prevention of myocardial reperfusion injury trial. AB - AIMS: To determine whether the efficacy of FX06 was dependent upon the timing of reperfusion therapy or the presence of collaterals in the Efficacy of FX06 in the prevention of myocardial reperfusion injury (F.I.R.E.) trial. METHODS AND RESULTS: Two hundred and thirty-four (234) patients presenting with acute ST segment elevation myocardial infarction were randomised to FX06 or matching placebo given as an intravenous bolus at reperfusion. Infarct size was assessed at 5-7 days and four months after myocardial infarction by cardiac magnetic resonance imaging determined total late enhancement and necrotic core zone. Patients were stratified according to presentation status (time-to-therapy <3 hours, n=108; time-to-therapy=3-6 hours, n=115) and presence of collaterals (yes, 46; no, 177). There were no statistically significant differences between groups at day 5-7. At four months, we observed statistically significant reductions of both measures of infarct size (0.3% vs. 2.4%, p=0.038; 8.0% vs. 16.0%, p=0.032) in the group given FX06 and presenting early. There was also a statistically significant reduction of total late enhancement zone among patients given FX06 with collaterals (7.3% vs. 15.2%, p=0.043). No differences were evident among late presenters or those without collaterals. CONCLUSIONS: FX06 significantly reduced infarct size at four months in the early presenters and in those with collaterals. PMID- 20542781 TI - Long-term clinical outcomes and cost-effectiveness analysis in multivessel percutaneous coronary interventions: comparison of drug-eluting stents, bare metal stents and a mixed approach in patients at high and low risk of repeat revascularisation. AB - AIMS: To evaluate the long-term effectiveness and cost-efficacy of drug-eluting stents (DES) in a real world setting of multivessel percutaneous coronary intervention (PCI). METHODS AND RESULTS: We evaluated the 2-year outcome of all multivessel PCI in de novo lesions enrolled in a prospective web-based multicentre registry from July 2003 to December 2006. Among the 2,898 eligible patients, 1,315 were treated with bare-metal stent (BMS) alone, 657 with DES alone, and 926 with both. At 2-years, use of DES was associated with a lower propensity score adjusted incidence of major adverse cardiac events (MACE), death and myocardial infarction, and target vessel revascularisation (TVR) compared with BMS but only in patients at high risk of TVR. No difference was apparent between "pure" DES and the mixed approach. The matched cost-effectiveness analysis revealed DES to be more costly and more effective with a reasonable incremental cost-efficacy ratio for any MACE avoided only in patients with a high risk of TVR and only in comparison with "pure" BMS patients. CONCLUSIONS: In this real-world multivessel PCI registry, the use of DES and a mixed approach were associated with a 2-year reduction of adverse clinical outcomes in comparison with BMS especially in patients with a high risk of TVR. DES were cost-effective only in patients at high risk of TVR. PMID- 20542782 TI - Short- and long-term health related quality-of-life and anginal status of the Arterial Revascularisation Therapies Study part II, ARTS-II; sirolimus-eluting stents for the treatment of patients with multivessel coronary artery disease. AB - AIMS: Assessment of health related quality-of-life (HRQL) has become increasingly important as not only the clinician's view of the technical success, but also the patient's perception is being measured. We evaluated the HRQL following sirolimus eluting coronary stent (SES) (CYPHER(R); Cordis, Johnson & Johnson, Warren, NJ, USA) implantation in patients with multivessel disease, comparing the outcomes with the historical surgical and bare metal stent (BMS) arms of the ARTS-I study. METHODS AND RESULTS: The HRQL outcomes were compared to the outcome of the historical cohorts of the randomised ARTS-I trial using the same inclusion and exclusion criteria. HRQL was evaluated at baseline, at one month and at 6, 12 and 36 months after revascularisation using the SF-36 in patients treated with SES (n=585), BMS (n=483) or coronary artery bypass graft (CABG) (n=492). The HRQL compliance rates varied from 100% at baseline to 92% at 36 months. Both stenting and CABG resulted in significant improvement of HRQL and anginal status. There was a trend towards better HRQL after CABG than BMS beyond six months. Already from the first month up to three years, SES patients had, on average, 10% significantly better HRQL than BMS patients on the HRQL subscales physical functioning, role physical functioning, role emotional functioning and mental health (p<0.01) and a trend towards better HRQL in the other subscales. Up to 12 months, the HRQL was better after SES than CABG and was identical thereafter. At all time points, angina was more prevalent in the BMS group than in both the SES and CABG groups, in which the incidence of angina was similar. At three years, 10% of the SES patients suffered from angina, 13% of the CABG patients and 20% of the BMS patients. CONCLUSIONS: Both stenting and CABG resulted in a significant improvement in HRQL and angina. Along with a substantial reduction of restenosis, HRQL after SES was significantly improved as compared with BMS, and was similar to CABG. PMID- 20542783 TI - Non-culprit lesions detected during primary PCI: treat invasively or follow the guidelines? AB - AIMS: Evidence regarding the optimal treatment of non-culprit lesions detected during primary PCI is lacking. Our aim was to investigate whether early invasive treatment improves left ventricular ejection fraction (EF) and prevents major adverse cardiac events (MACE). METHODS AND RESULTS: Of 121 patients with at least one non-culprit lesion, 80 were randomised to early FFRguided PCI (invasive group), and 41 to medical treatment (conservative group). Primary endpoint was EF at six months, secondary endpoints included MACE. In the invasive group, early angiography was performed 7.5 days (5-20) after primary PCI. Forty percent of the non-culprit lesions did not show haemodynamic significance (FFR > 0.75). Subsequent PCI of at least one non-culprit lesion was performed in 52%, PCI without preceding FFR was performed in 8% and elective CABG was done in 4%. No in hospital events occurred in the conservative group. After six months, EF was comparable (59+/-9% vs. 57+/-9%, p=0.362), and there was no difference in MACE between invasively and conservatively treated patients (21 vs. 22%, p=0.929). CONCLUSIONS: An invasive strategy towards non-culprit lesions does not lead to an increase in EF or a reduction in MACE. The functional stenosis severity of non culprit lesions is frequently overestimated. PMID- 20542784 TI - A European multicentre, randomised study of the MAR-Tyn cobalt chromium tin coated stent in patients with de novo coronary artery lesions: study design and protocol. AB - AIMS: The aim of this randomised study is to evaluate the efficacy and safety of a new bare metal stents (BMS) with thin struts and a novel passive coating as compared to current standard BMS. METHODS AND RESULTS: We designed an international, multicentre, randomised trial planned to include 160 patients assigned to receive either the titanium-nitride coated MAR-tyn stent (International Biomedical Systems, Trieste, Italy) or the Vision stent (Abbott Vascular, Abbott Laboratories, Abbott Park, IL, USA). Patients with left main or bypass graft disease, complex coronary lesions, needing treatment of multiple lesions, with recent myocardial infarction, prior BMS in or within 5 mm of the target lesion, left ventricular ejection fraction < or =25% and at increased bleeding risk are excluded. All patients are treated with dual antiplatelet therapy for two months. The primary endpoint is in-stent late luminal loss (LL) at 6-month follow-up angiography. Secondary endpoints are the incidence of major adverse cardiovascular events (MACE) and stent thrombosis over 12 months after randomisation. Patients' enrolment is open in all centres. CONCLUSIONS: This study will address the important question of safety and efficacy of a novel, inert and highly compatible passive coating on a thin-strut BMS with a great potential to be superior to a non-coated widely used BMS. PMID- 20542785 TI - Impact of adventitial neovascularisation on atherosclerotic plaque composition and vascular remodelling in a porcine model of coronary atherosclerosis. AB - AIMS: There is little in vivo data in regards to the impact of adventitial neovascularisation on vascular remodelling and plaque composition. Using a porcine model of coronary atherosclerosis, we aimed to determine the impact of adventitial neovascularisation on plaque composition and vascular remodelling evaluated by IVUS. METHODS AND RESULTS: Coronary atherosclerosis was induced by adventitial delivery of lipids and a high cholesterol diet. At termination all vessels were analysed using IVUS to determine the degree of remodelling of each individual segment containing atherosclerotic lesions. Then, each segment was correlated with its correspondent histological frame for plaque composition and neovessel density. A total of 57 atherosclerotic lesions at different stages of development were analysed. The total neovessel count (TNC) correlated to the degree of plaque burden (15.6+/-7.2 TNC in <40% stenosis versus 35.7+/-14.0 TNC in >60% stenosis, p<0.01) and to the amount of intra-plaque collagen (32.4+/ 14.1%, lower TNC tertile versus 47.5+/-8.9% upper TNC tertile, p< 0.01). The amount of intra-plaque SMC content inversely correlated with the TNC (49.7+/ 18.9% versus 36.4+/-14.4%, lower versus upper tertiles, p<0.05). Plaques with the highest TNC showed higher remodelling indexes by IVUS (0.89+/-0.32 in lower TNC tertile versus 1.36+/-0.73 in upper TNC tertile, p<0.05) and higher macrophage cell content (161.42+/-157.6 in lower TNC tertile versus 340.6+/-127.2 in upper TNC tertile, p<0.05) compared to non-remodelled segments. CONCLUSIONS: Adventitial neovascularisation is more prominent in positively remodelled segments and appears to be associated to SMC loss, increase collagen deposition and localised macrophage infiltration. PMID- 20542786 TI - Renal artery intervention. PMID- 20542787 TI - Vessel diameter should be taken into account in saphenous stenting. PMID- 20542788 TI - Rheolytic versus aspiration thrombectomy in acute st-segment elevation myocardial infarction judged by OCT. PMID- 20542790 TI - EuroIntervention, a bright light. PMID- 20542789 TI - A right radial artery false aneurysm. PMID- 20542791 TI - The artery under the lens. PMID- 20542792 TI - The importance of preclinical research in contemporary interventional cardiology. PMID- 20542793 TI - The gap between vascular interventions and vascular medicine. PMID- 20542794 TI - To whom does cardiac MSCT belong? PMID- 20542795 TI - Consensus from the 5th European Bifurcation Club meeting. PMID- 20542796 TI - Rationale and use of antiplatelet and antithrombotic drugs during cardiovascular interventions: May 2010 update. PMID- 20542798 TI - Mitral annular reduction with subablative therapeutic ultrasound: pre-clinical evaluation of the ReCor device. AB - AIMS: To evaluate the potential for mitral annular (MA) size reduction using a novel device utilising therapeutic ultrasound (TU). METHODS AND RESULTS: The ReCor device (ReCor Medical, Inc., Ronkonkoma, NY, USA, Investigational device, not for use in human application) was studied in a closed chest canine animal model (35 dogs). Under fluoroscopy, a 12 Fr TU balloon catheter was advanced into the left atrium (transseptal approach). The TU balloon was inflated with contrast saline, positioned at the MA and energy delivered circumferentially, to heat the tissue locally. Five TU applications were delivered (at least 60W for at least 40 sec). Relative to baseline, mitral valve annular diameter reduction (measured by transthoracic echocardiography) was 8.4% immediately post procedure(p<0.001), 8.6% at one week (p<0.001), 8.8% at two weeks (p<0.001), 9.3% at three weeks (p<0.001), 10.8% at four weeks (p<0.001), 8.6% at three months (p<0.001) and 5.7% at six months (p<0.001). Histology showed an increase in elastin associated with tissue thickening at the annular level. Transmission electron microscopy demonstrated a decrease in diameter of individual collagen fibres in treated regions compared to controls. CONCLUSIONS: Therapeutic ultrasound (TU) energy application to the mitral annulus is feasible percutaneously. A reduction in annular dimensions occurs immediately and appears to be durable without peri annular damage. PMID- 20542797 TI - First human use of the TAXUS Petal paclitaxel-eluting bifurcation stent. AB - AIMS: This first human use (FHU) study in bifurcation lesions evaluated safety and feasibility of the TAXUS Petal paclitaxel-eluting dedicated bifurcation stent. METHODS AND RESULTS: This prospective, single-arm, multicentre study had a composite primary endpoint of 30-day death, myocardial infarction (MI), and target vessel revascularisation (TVR). Angiographic and intravascular ultrasound follow-up was at six months with clinical follow-up through five years. Mean age (N=28) was 60.9 + or - 9.3 years and 17.9% of patients had medically treated diabetes. Main branch (MB) lesion length was 13.8 + or - 5.9 mm with 4.4 + or - 2.5 mm in the side branch (SB). TAXUS Petal was successfully implanted in 89.3% of patients (25/28). On a per device basis, 73.5% (25/34) of Petal deployments were successful. The primary endpoint occurred in one patient (3.7%, in-hospital non-Q-wave MI). Through one year, TVR was 11.1%, target lesion revascularisation was 7.4%, and there were no deaths, Q-wave MIs, or stent thromboses. In-segment late loss (n=21) was 0.47 + or - 0.45 mm (proximal MB), 0.41 + or - 0.57 mm (distal MB), and 0.18 + or - 0.39 mm (SB). CONCLUSIONS: The requirement for rotational alignment made delivery of this first generation TAXUS Petal stent challenging and accounted for the relatively low device delivery success. Clinical and angiographic outcomes were satisfactory when successful delivery was achieved. PMID- 20542799 TI - Randomised comparison of titanium-nitride-oxide coated stents with bare metal stents: five year follow-up of the TiNOX trial. AB - AIMS: Revascularisation with Titanium-Nitride-Oxide (TiNOX) coated stents is safe and effective in patients with de novo native coronary artery lesions. In the TiNOX trial there was a reduction in restenosis and major adverse cardiac events as compared with stainless steel stents of otherwise identical design. The purpose of the present study was to evaluate the long-term outcome of these patients over five years. METHODS AND RESULTS: In 2003, 92 patients with de novo lesions were randomly assigned to treatment with TiNOX coated stents (n=45) or stainless steel stents (n=47; control). Baseline characteristics were similar in both groups. Follow-up at six months and five years was obtained in 87 patients. Five patients were lost to follow-up due to emigration or change in home address. At six months and five years, significantly less major adverse cardiac events (MACE) occurred in the TiNOX group (7% vs. 27%, [p=0.02] respectively and 16% vs. 39%, [p=0.03]), largely driven by a reduced need for target-lesion revascularisation. No stent thrombosis occurred in the TiNOX group vs. one in the control group. Patients in the TiNOX-group had lower all-cause mortality and less myocardial infarction, but the difference was not statistically significant. CONCLUSIONS: Five-year follow-up after implantation of titanium-nitride-oxide coated stents is favourable with a low rate of MACE and no stent thrombosis compared to bare metal stents of identical design. The need for revascularisation at five years was 9% in the TiNOX and 25% in the control group with little progression of native coronary disease. PMID- 20542800 TI - Optical coherence tomography (OCT) strut-level analysis of drug-eluting stents (DES) in human coronary bifurcations. AB - AIMS: We sought to evaluate the vascular response of stent struts deployed in bifurcation segments using optical coherence tomography (OCT). METHODS AND RESULTS: This study is a sub-analysis of ODESSA, a prospective randomised trial designed to evaluate healing of overlapped drug-eluting stents (DES) vs. bare metal stents (BMS) (sirolimus SES: paclitaxel PES: zotarolimus ZES: Liberte BMS in a 2: 2: 2: 1 ratio) for de novo coronary artery stenosis. OCT was performed at 6-month follow-up. Bifurcation segments with side branch diameters larger than 1.5mm by angiography were analysed. The cross-sectional image at the bifurcation segment was divided into three regions: opposite to the ostium (OO), adjacent to the ostium (AO), or side-branch ostium (SO). Struts were classified in three categories: uncovered (U), covered (C), or proliferative (P). The incidence of each strut category was compared between regions and stent types. There were 12,656 struts in 61 bifurcation segments (PES: 16, SES: 14, ZES: 23, Liberte BMS: 8) from 46 patients obtained at six months. PES had the highest rate of U in SO region (PES 60.1, SES 17.0, ZES 13.2, BMS 12.3 (%), P<0.0001), whereas SES demonstrated the highest rate of U in OO (PES 3.8, SES 14.0, ZES 1.5, BMS 0.0 (%), P=0.0025). CONCLUSIONS: This study demonstrates a variable pattern of strut coverage in the bifurcation among stent technologies, with a high percentage of PES floating struts remaining uncovered at 6-month follow-up. PMID- 20542801 TI - Optical coherence tomography for the assessment of pericardium covered stents for the treatment of degenerated saphenous vein grafts. AB - AIMS: Pre- and post-interventional optical coherence tomography (OCT) assessment of degenerated saphenous vein grafts (SVG) treated with implantation of pericardium covered stents. Percutaneous treatment of SVG represents one of the major challenges of current percutaneous coronary interventions (PCI). Artificial membrane-covered stents have failed to show additional benefit over conventional stents. METHODS AND RESULTS: Six cases of PCI of de novo lesions in degenerated SVGs were successfully treated with a novel pericardium covered stent (PCS). Successful deployment was achieved in all cases. Large emboli were retrieved in a distal filter in one case with a long degenerated lesion. Pre- and postinterventional OCT was performed to assess the lesion characteristics and vessel diameter before stenting and the pericardium layer integrity, strut apposition and presence of plaque prolapse after stenting. In order to better understand the OCT images, three PCS of different diameters were deployed in silicone tubes of 700 microm thickness wall with inner tube diameter matching the stent diameter. OCT was repeated after spreading a thin layer of gel inside the tube, mimicking the toothpaste-like plaque observed in SVG. In vivo and in vitro OCT images excluded the presence of plaque prolapse in all but one case and detected a characteristic pattern with bulging of the pericardium between struts, possibly due to trapping of soft intraluminal plaque (or gel) behind the pericardial layer. CONCLUSIONS: These cases offer insight into the mechanism of protection against distal embolisation, elucidated by the appearance of these stents after deployment in vivo and in vitro. PMID- 20542802 TI - Strut apposition after coronary stent implantation visualised with optical coherence tomography. AB - AIMS: To describe different patterns of stent strut apposition, as visualised with optical coherence tomography. METHODS AND RESULTS: Strut thicknesses were reconstructed according to the manufacturers' specifications. The stent area (SA) was measured by connecting the reconstructed abluminal surfaces of struts with a trace line, and the vessel wall area (VWA) was estimated from the abluminal strut surfaces, as well as from the lumen border, in cases of struts that were separated from the vessel wall by flush. Strut apposition was evaluated by comparing the SA- and VWA traces. We observed four patterns of strut apposition. Based on these, stent struts could be classified as: (I) apposed struts, (II) struts overlying the ostium of a side branch, (III) malapposed struts that were clearly separated from the vessel wall by flush, and (IV) pseudoapposed struts that were not separated from the vessel wall by visual estimate, but were malapposed in the sense that SA or = 2 on admission, anterior MI location and TIMI 0 flow before PCI. Killip class > or = 2 on admission was an independent predictor of major bleeding. Major bleeding (HR 3.5 [95% CI 2.3-5.4]) was associated with an increased risk of death at one year. CONCLUSIONS: After primary PCI, the incidence of major bleeding is less than 2%. Although relatively infrequent, major bleeding complications are strongly and independently related to short- and midterm mortality. PMID- 20542806 TI - A randomised comparison between everolimus-eluting stent and sirolimus-eluting stent in chronic coronary total occlusions. Rationale and design of the CIBELES (non-acute Coronary occlusion treated by EveroLimus-Eluting Stent) trial. AB - Chronic total coronary occlusions constitute a sub-group of lesions at very high risk of restenosis after successful percutaneous coronary intervention. The sirolimus-eluting coronary stent is the only drugeluting stent that has demonstrated to reduce angiographic restenosis and the need for new revascularisation procedures in comparison with bare-metal stents in randomised clinical trials focusing on these lesions. Everolimus-eluting stents have shown to offer optimal angiographic and clinical outcomes in comparison with bare-metal stents and paclitaxel-eluting stents, but no randomised trials have tested the device in chronic total occlusions. The CIBELES (non-acute Coronary occlusIon treated By EveroLimus- Eluting Stent) will randomise 208 patients with chronic total coronary occlusions in 13 centres from Portugal and Spain to receive everolimus- or sirolimus-eluting coronary stents. The primary endpoint will be angiographic in-stent late loss. PMID- 20542807 TI - Endothelial function rather than endothelial restoration is altered in paclitaxel as compared to bare metal-, sirolimusand tacrolimus-eluting stents. AB - AIMS: Drug eluting stents (DES) are under scrutiny for late stent thrombosis. Impaired re-endothelialisation is proposed as an explanation but coronary and peripheral-artery models disagree. We assessed physical and functional endothelial restoration within bare (BMS), paclitaxel, sirolimus and tacrolimus eluting stents and the distal microvasculature in porcine coronary arteries. METHODS AND RESULTS: Endothelium within and distal to DES and BMS was assessed for stent-strut endothelial-restoration (five days) and endothelial-function (five, 28 days, by eNOS and vWF expression) and by in vitro microvascular function. There were no significant differences (P=0.3) in stent strut endothelial-restoration at five days between DES (76-90%) and BMS (95%). However, the microvasculature distal to PES showed a decreased NO bioavailability at five days, which improved at 28 days. Within the stent, however, PES still showed a reduced eNOS expression at 28 days (P50%, which was completely reversed by a perlecan antibody. RUS3108 also inhibited SMC migration (Boyden chamber) and MMP-9 activity. In contrast, RUS3108 (100nM) modestly stimulated EC 3H-thymidine incorporation by 22% (p<0.02). In vivo, a total of 30 stents were deployed in rabbit iliac arteries as follows: 1) bare metal stents (n=10), 2) polymer onlycoated stents (n=10), and 3) polymer-coated stents containing RUS3108 (n=10). Rabbits were sacrificed at four weeks and stented segments were subjected to morphometric analysis. Intimal cross sectional area was significantly lower in the RUS3108-eluting stent group (0.31+ or -0.27 mm(2) versus 1.0 + or - 0.31 and 1.25 + or - 0.51 in the bare metal stents and polymer only coated stents groups, respectively, p<0.0001). CONCLUSIONS: RUS3108 is a novel perlecan-inducing compound, which is a potent inhibitor of SMC activity and a modest stimulator of EC proliferation. RUS3108-eluting stents may serve as an excellent modality for the prevention of ISR. PMID- 20542810 TI - Micro-computed tomographic assessment following extremely oversized partial postdilatation of drug-eluting stents. AB - AIMS: To assess the spatial geometry of drug-eluting stents (DES) following extremely oversized proximal postdilatation. Interventions of distal left main (LM) disease generally require stenting across the LM bifurcation with inherent vessel tapering along this segment and a high likelihood of stent malapposition, which can be avoided by such postdilations. METHODS AND RESULTS: Sixteen DES (four 3.5 mm-samples of Cypher Select Plus, Taxus Liberte, Endeavor Resolute, Xience V) were deployed in water; 12 samples were then proximally postdilated with noncompliant 5.0 mm balloons at 18 atm. All samples were examined by micro computed tomography. Taxus Liberte, Endeavor Resolute, and Xience V, showed increased cell areas in the transitional region (just distal to postdilated region), while Cypher Select showed its largest cells inside the postdilated region. Overall, the largest maximum cell area was observed in Endeavor Resolute, while Cypher Select showed the smallest (p<0.001, for both). In addition, the size of the very proximal postdilated cells was relatively small in most DES except Xience V. CONCLUSIONS: Extremely oversized partial stent postdilatation demonstrated significant between-DES differences in final spatial stent configuration and maximum cell size. These data could be of practical interest with regard to coronary interventions in LM stems with stenting across the LM bifurcation. PMID- 20542811 TI - Safety and efficacy of drug-eluting stents versus bare-metal stents in saphenous vein grafts lesions: a meta-analysis. AB - AIMS: Controversy exists about the safety and efficacy of drug-eluting stents (DES) in saphenous vein bypass grafts (SVGs). The aim of this study was to perform a meta-analysis of all published studies comparing DES and bare-metal stents (BMS) in patients with SVGs disease. METHODS AND RESULTS: We included 22 studies comparing DES versus BMS in 5,543 patients with SVGs disease. The primary efficacy endpoint was target vessel revascularisation (TVR). The primary safety endpoint was mortality. Other outcomes of interest were cardiac mortality, myocardial infarction, target lesion revascularisation (TLR), stent thrombosis and a combined of major adverse cardiac events (MACE). DES significantly reduced the risk of TVR, OR=0.56 (95% CI, 0.41-0.76, p=0.0003) and TLR, OR=0.58 (95% CI, 0.41-0.81; p=0.001). Total mortality and cardiac mortality were significantly lower in DES versus BMS, OR=0.69 (95% CI, 0.49-0.98, p=0.04) and OR=0.71 (95% CI, 0.51-0.99; p=0.04), respectively. The overall risk of stent thrombosis, and myocardial infarction were not significantly different for patients receiving DES vs. BMS. Total MACE were significantly lower in patients receiving DES, OR=0.55 (95% CI, 0.42-0.71; p<0.00001). CONCLUSIONS: This meta-analysis suggests that the use of DES in patients with SVG lesions is associated with a reduction of the need of reintervention and mortality compared with BMS. PMID- 20542812 TI - How should I treat a tortuous calcified right coronary artery? PMID- 20542813 TI - Coronary guidewires. PMID- 20542814 TI - Induction of mechanical and ST-T alternans following angioplasty in severe heart failure. PMID- 20542815 TI - Is functional assessment necessary in patients with stable angina? AB - Strategies during elective PCI procedures in patients with stable angina and multivessel disease are in the majority of catheterisation laboratories, more often than not based, solely on the angiographic analysis on the spur of the moment. This despite the knowledge that angiographic images are often lacking the discriminating power to predict accurately the exact physiologic impact of individual lesions. Evidence is however accumulating telling us that routine stenting of non significant lesion is at best of no additional benefit for the patient. the introduction of dedicated angioplasty guidewires equipped at the tip with a miniature pressure-sensor has greatly expanded the possibilities to accurately evaluate the functional importance of any lesion during diagnostic coronary angiogram by measuring the FFR index. Ths index, based on the measurements of the trans-stenotic coronary gradient during maximal vasodilatation, is accurate, and easy to implement. Results from several important trials (e.g.,DEFER) have brought to our attention the fact that non significant coronary lesion sas documented by FFR measurements, in patients with single vessel disease can safely be left untreated. Recently, the remarkable results from the FAME trial have made a strong case for integrating functional evaluation as a routine work up especially in the presence of angiographic ambiguous lesions referred for PCI in patients with multivessel disease. PMID- 20542816 TI - Magnetic resonance imaging for myocardial viability. AB - Detection of myocardial viability is an important issue that needs to be addressed when patients with dysfunctional myocardium are considered to be revascularised. The pathophysiological substrate may include myocardial hibernation, myocardial stunning, or both. The greatest benefit is in terms of myocardial function recovery and prognosis is obtained if the revascularised vascular territory contains viable myocardium. Viable myocardium can be detected with nuclear techniques (SPECT, PET), low dose dobutamine stress echocardiography and MRI. With MRI robust detection of viable myocardium can be performed with delayed enhancement (with gadolinium contrast agent), low dose dobutamine stress, and stress/rest perfusion imaging. For recovery of myocardial function there are relatively small differences between all available techniques, whereas for improvement of prognosis all techniques perform equally. Myocardial delayed enhancement imaging can also visualise micro-embolisation as a result of percutaneous coronary intervention. Furthermore, MRI delayed enhancement enables differentiation between ischaemic and non-ischaemic heart disease and can identify specific cardiomyopathies. PMID- 20542817 TI - Single-photon emission computed tomography for assessment of myocardial viability. AB - Left ventricular dysfunction in patients with chronic coronary artery disease may be a result of dysfunctional but viable myocardium due to myocardial hibernation. Coronary revascularisation may substantially improve regional and global left ventricular dysfunction and long-term survival if a substantial amount of dysfunctional but viable myocardium is present. Because coronary revascularisation, by percutaneous coronary intervention or coronary bypass surgery, is associated with an increased periprocedural risk in patients with severe left ventricular dysfunction, careful preprocedural selection is needed. Assessment of myocardial viability with SPECT may facilitate clinical decision making and should be considered in patients with ischaemic left ventricular dysfunction who are eligible for coronary revascularisation. The most frequently used SPECT protocols use thallium-201 (201Tl) rest-redistribution, technetium-99m (99mTc) labelled viability tracers, or 18F-fluorodeoxyglucose (FDG) for assessment of myocardial glucose metabolism. Approximately 50% of the patients with ischaemic left ventricular dysfunction have a substantial amount of dysfunctional but viable myocardium on SPECT and should be considered for coronary revascularisation. The absence of myocardial viability can help to identify patients who will not benefit from high-risk percutaneous coronary interventions or surgery. PMID- 20542818 TI - Computed tomography as a tool for percutaneous coronary intervention of chronic total occlusions. AB - Chronic total occlusions (CTO) constitute a major challenge in percutaneous coronary revascularisation (PCI). The development of new interventional strategies, the availability of purpose made tools including dedicated catheters and wires, as well as increasing expertise by the operators, have contributed to the modest success rates which today hover around 75%. Case selection is of utmost importance since failure of this high risk procedure with its typically high radiation doses, high contrast doses and increased complication rates is associated with long term adverse events. Imaging of the coronary arteries using the gold standard of invasive coronary angiography allows characterisation of the chronic total occlusion and is often able to predict the probability of successful recanalisation. Multislice computed tomography (MSCT) is increasingly being utilised as a non-invasive diagnostic imaging modality to detect coronary artery disease. Its ability to provide information on the soft tissue (including plaque) surrounding the lumen has been applied to better define the morphological features of CTOs. In fact, the amount of calcification, tortuosity and actual length of the occluded segment which are established predictors of success, are all better characterised by MSCT. Three dimensional reconstruction of the coronary anatomy and its integration with two dimensional fluoroscopy images during the actual CTO-PCI procedure may help to identify the best angiographic projection, offering a directional guide at the angiographically "missing segment". More technological advances are needed to optimise this multi-modality imaging integration. Whether this will result in better success rates for CTO-PCI is still the subject of ongoing research. It is then that we can evaluate the true benefit of the use of MSCT for CTO against the risk from excessive radiation associated with this strategy. PMID- 20542819 TI - Integrated anatomy and viability assessment PET-CT. AB - Myocardial viability testing can identify patients with ischaemic heart disease and left ventricular dysfunction who can potentially benefit from both improved cardiac function and prognosis after revascularisation. Evaluation of myocardial glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered the most sensitive tool to detect viability, and it predicts functional recovery as well as improved prognosis upon revascularisation. In parallel with the improved availability of PET, scanners have been changed into hybrid devices consisting of both multidetector computed tomography (CT) and PET (PET-CT). The immediate benefit for viability imaging is the ability to merge the coronary CT angiography images with FDG PET viability data. In addition, the possibility to utilise CT for myocardial viability imaging, such as delayed enhancement imaging of myocardial infarction with acceptable radiation dose has been intensely investigated. This review will describe the principles of viability assessment by PET, and discuss the possibilities provided by hybrid PET CT in this setting. PMID- 20542820 TI - Is there still a role for intravascular ultrasound in the current practice era? AB - Although coronary angiogram is considered the gold standard for coronary assessment, it consistently underestimates vessel size/lesion severity, and usually misses heavy calcified plaques. Intravascular ultrasound (IVUS) technology accurately determines vessel size/lesion severity and allows a detailed plaque composition evaluation. The role of IVUS guidance after bare metal stent implantation has been explored in various trials; however, no study has tested how the pre-procedural use of IVUS might impact intervention strategy and clinical outcome. Limited studies have specifically addressed the utility of IVUS after drug-eluting stent implantation. Based on the published evidence and on our clinical experience, we support a more liberal use of IVUS, especially when approaching complex coronary lesions, and resulting in an optimal interventional result that might impact clinical outcome. PMID- 20542821 TI - Echocardiography: guidance during valve implantation. AB - Transcatheter aortic valve implantation (TAVI) by percutaneous or transapical approach has emerged as an effective and less-invasive treatment for patients with severe symptomatic aortic valve stenosis and high surgical risk. Echocardiography is a fundamental tool in patients' selection for TAVI, for guiding the intervention as well as evaluating the position, deployment and function of the prosthesis. This review describes the role of echocardiography during the intervention, in procedure guidance and in the assessment of complications. PMID- 20542822 TI - Is refined OCT guidance of stent implantation needed? AB - The development of optical coherence tomography (OCT) provides new opportunities for the evaluation of coronary stents. Having a much higher spatial resolution than intravascular ultrasound (IVUS), OCT is currently used for long-term assessment of stent implantation. In the immediate future, however, it is quite likely that OCT will be used synergically with IVUS to optimise stent deployment; the criteria for optimising stent implantation using OCT will be clearly indebted to the evidence gathered with IVUS, with an added value in contexts like ambiguous images presenting after stenting, or in complex percutaneous coronary interventions (PCI) procedures like bifurcation stenting. However, since OCT is capable of identifying, during PCI, findings of potential relevance beyond the resolution IVUS, such as thrombus or tissue protrusion, intra-stent or edge dissections, or specific patterns of hyperplasia in restenotic lesions, it is foreseeable that new OCT-specific recommendations for optimal stent implantation will be made in the near future. PMID- 20542823 TI - Optical coherence tomography in patients with acute coronary syndrome. AB - Optical coherence tomography (OCT) is a novel invasive imaging technology that allows in vivo assessment of the coronary wall with high resolution (approximately 15 micron). OCT offers a number of specific diagnostic features to study culprit lesions in patients suffering from acute coronary syndrome (ACS). Clinical OCT studies in patients presenting with ACS were able to confirm post mortem histopathology findings and shed light on the dynamic nature of atherosclerotic plaque formation, modification and rupture. OCT confirmed in vivo that the incidence of target lesion and remote TCFA varies with the clinical syndrome of the patients, being most pronounced in patients with acute myocardial infarction as compared to patients with stable angina. In culprit lesions where rupture of a fibrous cap has been documented, the fibrous cap thickness was in the range of 50 micron and macrophage density was elevated. Encouraging small scale clinical studies evaluated treatment effects in this population. OCT was used to demonstrate statin effects on fibrous cap thickness or the effects of different stent designs. The markedly improved image quality and user friendliness of the second generation, Fourier-domain OCT, will allow large scale clinical application and thus, will increase our understanding of the pathophysiology and the prevention of ACS. PMID- 20542824 TI - Integrated non-invasive imaging techniques. AB - The development of imaging techniques for the non-invasive detection of atherosclerosis answered the specific need of identifying vulnerable plaque in asymptomatic patients, verify the presence of atherosclerosis in patients at intermediate risk of coronary artery disease and, lastly, evaluate the results of previous coronary interventions. Coronary computed tomography angiography is the non-invasive technique that has been most widely used for these purposes. The technique mainly focuses on the presence of calcium in the walls of the coronary arteries. Whether or not coronary arterial calcification is part of the development of atherosclerosis, it occurs in small amounts in the early lesions and is found more frequently in advanced lesions and at an older age. Plaques rich in collagen and calcium, which can be depicted by coronary calcium scoring, are widely considered firm and stable, whereas soft atheromas containing a core of lipids and necrotic debris that are biologically "unstable" and therefore prone to rupture, cannot be visualised by calcium scoring or correctly assessed by coronary computed tomography angiography. In fact, the relation of arterial calcification to the probability of plaque rupture is unknown. There is no definite relationship between vulnerable plaque and coronary artery calcification in comparative studies with intravascular ultrasound. On the other hand, radiographically detected coronary artery calcium can provide an estimate of total coronary plaque burden but, due to arterial remodelling, calcium does not concentrate exclusively at sites with severe coronary artery stenoses. In any event, this technique has great potential for identification of atherosclerosis. A more established use of coronary computed tomography angiography is in the evaluation of patients after coronary interventions. The future also holds promise for imaging coronary artery atherosclerotic plaques using magnetic resonance. At the present time, the differentiation of coronary plaque components with magnetic resonance is limited by inadequate spatial resolution; however, promising research is ongoing and the role of magnetic resonance in the evaluation of patients with coronary artery disease will continue to grow as its utility and prognostic importance will be further defined. PMID- 20542825 TI - Imaging decision-making for transfemoral or transapical approach of transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation has been shown to be a feasible alternative to surgical aortic valve replacement in selected high-risk patients. Although, being less invasive, catheter techniques remain associated with the potential of serious complications. Procedural success and avoidance of such complications critically depends on careful patient selection and comprehensive preprocedural evaluation of vascular access, cardiac and aortic root anatomy. This article reviews the role of currently available imaging modalities for appropriate patient selection and decision between transfemoral and transapical approach. PMID- 20542826 TI - Non-invasive imaging in percutaneous mitral valve procedures. AB - Novel percutaneous techniques for the treatment of mitral valve (MV) disease have recently been developed and provide an alternative to surgery in patients with high operative risk. However, the complexity of MV anatomy and the variety of mitral regurgitation mechanisms require sophisticated procedures and accurate patient selection. Non-invasive imaging (echocardiography, multislice computed tomography) provides crucial anatomical details and exact characterisation of the mechanism underlying mitral regurgitation, thereby facilitating selection of potential candidates for these procedures. Furthermore, imaging is needed for procedural guidance and assessment of long-term results; for these purposes echocardiographic techniques are mainly used. In this review, a detailed discussion on the use of non-invasive imaging in selection, procedural guiding and follow-up of patients undergoing percutaneous MV interventions is provided. PMID- 20542827 TI - Pre-operative aortic valve implantation evaluation: multimodality imaging. AB - Transcatheter aortic valve implantation procedures have been one of the main therapeutic breakthroughs of the last decade providing a feasible alternative therapy to patients with severe symptomatic aortic stenosis and high operative risk. To date, more than 10,000 patients have been treated with this novel therapy and promising results, using either a transarterial or transapical approach have been reported. Accurate preprocedural evaluation of candidates for TAVI is crucial to optimise the success rate and minimise the procedure-related complications. Multimodality imaging plays a central role in the preprocedural evaluation of these patients and provides valuable information on aortic stenosis severity, aortic valve anatomy, aortic valve annular dimensions and peripheral vascular anatomy, key issues to accurately select the prosthesis size and the procedural approach (transarterial vs. transapical). A combination of 2- and 3 dimensional echocardiography and multi-detector row computed tomography or magnetic resonance imaging may provide the most comprehensive approach to accurately evaluate these patients. The present article reviews the role of multimodality imaging before the TAVI procedure and provides a practical guide to evaluate patients who are candidates for TAVI. PMID- 20542828 TI - Evaluation of stents and grafts. AB - In the management of patients with obstructive coronary artery disease (CAD), percutaneous coronary intervention (PCI) with stent implantation is routinely performed. In patients with left main or three-vessel disease, however, coronary artery bypass grafting (CABG) may be the preferred therapeutic strategy. Importantly, both after PCI or CABG a small but non-negligible risk of restenosis remains. Early detection and treatment of in-stent restenosis or graft disease is of great clinical importance. Accordingly, accurate non-invasive methods to identify patients who would benefit from subsequent invasive coronary angiography (ICA) would be highly beneficial. Besides ICA, several non-invasive cardiac imaging techniques may be used to assess patients after revascularisation. In the present article, an overview of various anatomic and functional imaging techniques available to assess patients after revascularisation is provided. PMID- 20542829 TI - On cardiovascular imaging. PMID- 20542830 TI - Quantification of stenosis severity on multidetector row computed tomography. AB - A comprehensive evaluation of coronary anatomy and atherosclerosis can be provided by MDCT. Currently, several studies have used either manual or semi automated algorithms for quantification of different plaque characteristics, in particular the degree of luminal narrowing. Although the feasibility of these quantitative algorithms has been demonstrated, further refinement of quantitative CT algorithms is currently indicated to allow a comprehensive yet fully automated analysis of plaque characteristics. PMID- 20542831 TI - Cardiac CT: necessary for precise sizing for transcatheter aortic implantation. AB - Sizing for transcutaneous aortic valve replacement (TAVI) relies on non-invasive imaging. Incorrect sizing may result in adverse outcomes including paraprosthetic regurgitation, asymmetrical expansion which may impair prosthesis durability and, in the case of severe sizing errors, device embolisation or aortic root rupture. This review addresses the optimal approach for sizing. It is based on currently available data including the anatomical implications of using different imaging modalities, the steps of how to reproducibly measure the correct annulus diameter on MSCT, and current evidence for different sizing strategies. PMID- 20542832 TI - Can CT angiography replace catheter coronary angiography? AB - After a decade of rapid technological development cardiac CT has evolved into a valuable non-invasive coronary imaging technique, which raises the question whether this new diagnostic modality is ready to replace diagnostic catheter angiography. CT coronary angiography may not yet match the spatial and temporal resolution of selective X-ray angiography, it surpasses invasive angiography in terms of three-dimensional orientation, imaging of plaque and ostial abnormalities. For the moment invasive angiography combined with stress testing will remain the preferred approach in patients with a high probability of coronary disease and anticipated percutaneous intervention. However, for many patients with a low to intermediate likelihood of coronary artery disease, CT can be a reliably non-invasive alternative to catheter angiography. PMID- 20542833 TI - Detection of left main stem and three-vessel coronary artery disease by myocardial perfusion SPECT imaging. AB - Stress radionuclide myocardial perfusion single-photon emission computed tomography (SPECT) imaging (MPI) is a well-validated diagnostic procedure for the assessment of patients with suspected coronary artery disease (CAD). It has a high sensitivity for the detection of flow-limiting coronary stenosis and provides incremental prognostic information that contributes to risk stratification and guides clinical-decision making with regard to management and therapeutic interventions. The diagnostic accuracy and predictive value of MPI in patients with three-vessel and left main stem (LMS) disease is less well documented. There is evidence suggesting that assessment of myocardial perfusion on MPI is less effective at identifying significant three-vessel CAD as well as LMS disease. This limitation can be overcome, to a certain extent, by incorporating other imaging findings as well as clinical and stress testing parameters that help identify individuals at an increased risk of adverse cardiac events and hence those with severe and extensive coronary disease. Quantification of myocardial perfusion reserve using currently available radiotracers as well as simultaneous non-invasive assessment of coronary anatomy and atheromatous plaque may enhance the diagnostic performance of MPI in this subset of high-risk patients. PMID- 20542834 TI - Invasive functional testing. AB - The concept of "significant" coronary stenosis has been revisited since the introduction of physiological measurements in the cardiac catheterisation laboratory. Invasive functional testing evaluates coronary physiology by recording blood pressure, flow or velocity and yields important information about the epicardial arteries and the respective myocardial territory. Numerous clinical studies have demonstrated the value of physiological testing in the assessment of challenging angiographic subsets, such as multivessel disease, bifurcation lesions and diffuse coronary atherosclerosis. In selected cases, deferral of revascularisation on the basis of functional indices can actually decrease adverse cardiac events. Furthermore, physiological measurements after angioplasty and stent implantation can be used to optimise the angiographic results and improve patient outcome. This review will discuss the basic concepts of functional testing in the catheterisation laboratory and its main applications for the interventional cardiologist. PMID- 20542835 TI - Anatomy and function: PET-CT. AB - CT coronary angiography and perfusion PET form an attractive combination to study coronary artery lesions and their consequences in patients with coronary artery disease. Whereas CT provides non-invasive assessment of coronary lumen and wall, PET perfusion is a reliable method for the evaluation of myocardial flow. CT, although very capable of ruling out significant coronary artery disease, is less than satisfactory in assessing the actual significance of the detected lesions. PET imaging, despite its excellent sensitivity, fails to describe the exact anatomy of the epicardial vessels. By fusing image data from these two modalities, lesions can be accurately correlated with their physiological or anatomical counterparts. Hybrid PET-CT devices, now in wide clinical use, allow such fusion in a one-stop-shop study. Although still seeking its place in clinical scenarios, growing evidence suggests that hybrid PET-CT imaging of coronary anatomy and myocardial perfusion can accurately - and non-invasively - assess the existence and degree of coronary artery disease. PMID- 20542836 TI - Function and anatomy: SPECT-MPI and MSCT coronary angiography. AB - For the diagnosis of coronary artery disease (CAD), non-invasive cardiac imaging is indispensable. Myocardial perfusion imaging (MPI) by single photon emission computed tomography (SPECT) investigates the pathophysiological consequences of luminal obstructive CAD, while multislice computed tomography coronary angiography (CTA) indicates the presence, extent and location of coronary atherosclerosis. The integration of CTA and SPECT data may provide important information which may be useful for patient management. In this manuscript the value of both techniques will be described. In addition, the feasibility and potential value of combined anatomic and functional imaging will be discussed. PMID- 20542837 TI - Cellular neurothekoma of the nasal dorsum. PMID- 20542838 TI - A familial case of Nagashima-type palmoplantar keratosis. PMID- 20542839 TI - Pediatric primary cutaneous marginal zone B-cell lymphoma treated with intralesional rituximab. PMID- 20542840 TI - Medical dermocosmetology. How to invest in reliable claims. PMID- 20542841 TI - Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts. AB - Acute generalized exanthematous pustulosis (AGEP) is a significant adverse cutaneous reaction, most often provoked by drugs and acute infections. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. The clinical hallmark is the presence of multiple disseminated sterile pustules on an erythematous background, associated with fever and a massive neutrophilia and sometimes eosinophilia. The disease is characterised by an acute onset and a spontaneous resolution within 2 weeks. The involvement of drug-specific T cells in the pathomechanism can be confirmed by positive skin patch tests and lymphocyte transformation tests. In this review, we highlight the main clinical, pathophysiological and diagnostic aspects of this peculiar form of drug allergy. PMID- 20542845 TI - A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals. AB - PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost effective, especially among individuals with few remaining options for active antiretroviral therapy. PMID- 20542844 TI - Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and ritonavir-boosted atazanavir in HIV-infected patients. AB - PURPOSE: The ARIES study assessed safety and efficacy of an induction regimen with atazanavir/ritonavir (ATV/RTV) + abacavir/lamivudine (ABC/3TC) followed by simplification to ATV + ABC/3TC in antiretroviral-naive patients. METHODS: This report includes a noncomparative analysis of all patients in the induction phase of the ARIES study through 36 weeks (clinicaltrials.gov: NCT00440947). This open label study included 515 antiretroviral-naive,HLA-B*5701-negative patients receiving a regimen of ATV 300 mg, RTV 100 mg, and ABC/3TC 600 mg/300 mg once daily for 36 weeks; eligible patients were then randomized to continue the induction regimen or simplify to ATV 400 mg plus ABC/3TC 600 mg/300 mg once daily. RESULTS: Eighty-six percent (442/515) of patients completed 36 weeks on study; 80% (410/515) achieved HIV RNA <50 copies/mL (84% and 76% of patients with baseline HIV RNA of < and >or=100,000 copies/mL achieved this endpoint). Virologic failure (VF) was uncommon (3%); treatment-emergent major protease inhibitor and nucleoside reverse transcriptase inhibitor mutations were detected in 0/15 and 4/15 patients, respectively. Median CD4+ cell increase was 171 (range, -176 to 718) cells/mm(3). Hyperbilirubinemia (13%), diarrhea (4%), nausea (2%), and rash (2%) were the most frequent drug-related Grade 2-4 adverse events. Few adverse events (3%) led to study discontinuation. CONCLUSIONS: Induction with ATV/RTV + ABC/3TC once daily provides an efficacious and well-tolerated regimen for the initial treatment of HIV. PMID- 20542846 TI - Aging and HIV infection: a comparison between older HIV-infected persons and the general population. AB - BACKGROUND: As HIV-infected persons age, the relative contribution of HIV infection, combination antiretroviral therapy (cART), and the normal aging process to the frequent comorbidities is unknown. METHODS: We prospectively evaluated comorbidities, cardiovascular risk, cognitive function, and anthropomorphic and laboratory parameters of HIV-infected persons aged 50 years and over in two US urban clinics. Results were compared to controls from the National Health and Nutrition Examination Survey (NHANES) matched 1:1 by age, race, gender, smoking status, and body mass index (BMI). RESULTS: We enrolled 122 HIV-infected persons; median age 55 years, 83% male, 57% Caucasian, 39% current smokers, mean BMI 26 kg/m2, and 92% on cART. Compared to controls, HIV-infected persons had a higher prevalence of hypertension (54% vs 38%), hypertriglyceridemia (51% vs 33%), low bone mineral density (BMD) (39% vs 0%), and lipodystrophy and greater receipt of antihypertensive and lipid-lowering medications (all Ps < .05). Groups were similar in prevalence of coronary heart disease, diabetes mellitus, chronic viral hepatitis, non-AIDS-defining malignancies and Framingham Risk and cognitive function scores. CONCLUSIONS: Older HIV-infected persons have a higher prevalence of hypertension, hypertriglyceridemia, low BMD, and lipodystrophy than matched controls, suggesting that HIV and treatment-related factors exceed "normal" aging in the development of those problems. PMID- 20542847 TI - Twelve-year experience of nevirapine use: benefits and convenience for long-term management in a French cohort of HIV-1-infected patients. AB - OBJECTIVE: To describe safety and long-term efficacy of nevirapine (NVP) in a real-life setting. RESULTS: From 1996 to 2008, among the 745 patients who received NVP, 592 were still followed in our center; of these, 231 had stopped NVP because of failure (42%), side effects (28%), other causes (30%). Twenty seven percent of discontinuations occurred in the first 3 months; 68% were related to adverse events. In June 2008, 361/592 patients (61%) were still on NVP for a median duration of 176 weeks (range, 0.3-600), including 18% of naive patients, 15% of patients who initiated NVP in the context of virologic failure, and 66% of patients with an undetectable viral load (switch strategy). Median CD4 cell count increased from 377/microL (range, 8-1449) to 549/microL (range, 144 1621). Viral load was below 200 copies/mL at the latest visit in 97%, 96%, and 100% of the patients in the naive, failure, and switch groups, respectively. Over a 5-year period, the rate of antiretroviral drug persistence was 60.9% for NVP, 41.4% for efavirenz, and 23% for lopinavir/ritonavir (P < .0001). CONCLUSIONS: In a real-life setting, NVP demonstrates sustained efficacy and good safety and is very convenient to use as reflected by a high rate of persistency. PMID- 20542848 TI - Rapid improvement in fasting lipids and hepatic toxicity after switching from didanosine/lamivudine to tenofovir/emtricitabine in patients with toxicity attributable to didanosine. PMID- 20542850 TI - Stroke patients' and carers' perception of barriers to accessing stroke information. AB - PURPOSE: Education is a key component of post stroke care, but patients and carers often report dissatisfaction with information provided. A small number of studies have reported challenges surrounding the provision of information to this population, but patients' perspectives have not been explored in detail. The aim of this study was to identify patients' and carers' perceived barriers to accessing and understanding information about stroke. METHOD: Interviews were conducted with patients and their carers prior to and 3 months following discharge from an acute stroke unit. Transcripts were analysed using qualitative content analysis. RESULTS: The three categories of barriers were identified: (1) limited availability and suitability of information, (2) barriers in the hospital environment, and (3) patient and carer barriers. Three themes were also identified, namely, (1) who is responsible, (2) communication, and (3) not knowing. CONCLUSION: These results have clinical implications for the way in which health professionals coordinate and present stroke information to patients and carers. Addressing these barriers may enhance patients' and carers' access to, understanding of, and satisfaction with information about stroke. PMID- 20542851 TI - Do people with aphasia want written stroke and aphasia information? A verbal survey exploring preferences for when and how to provide stroke and aphasia information. AB - PURPOSE: Written health information can be better comprehended by people with aphasia if it is provided in an aphasia-friendly format. However, before pursuing research in the area of text-formatting for people with aphasia, it must be determined whether people with aphasia consider it helpful to receive health information in the written media. This study, therefore, aimed to determine the following: whether people with aphasia consider it important to receive written stroke and aphasia information; when people with aphasia prefer to receive this information; and what their preferences are for health information media. METHOD: Surveys were administered in a face-to-face interview with 40 adults with aphasia. Participants were purposefully selected using maximum variation sampling for a variety of variables including aphasia severity, reading ability, and time post stroke. RESULTS: Participants thought it important to receive written information about both stroke and aphasia. They considered it helpful to receive written information at several stages post stroke, particularly from 1 month onwards. The largest proportion (97%) of participants identified 6 months post stroke as the most helpful time to receive this information. Written information was the most preferred media at participants' present time post stroke (M = 39 months; range, 2-178 months). Videos/DVDs were the most preferred media during the 6 months immediately following the stroke. CONCLUSION: Despite reading and language difficulties, participants considered written information to be important, hence people with aphasia should receive written information about both stroke and aphasia. This information should be easily accessible throughout the continuum of care. PMID- 20542852 TI - A systematic review of cognitive interventions to improve functional ability in people who have cognitive impairment following stroke. AB - PURPOSE: Cognitive impairment is a frequent consequence of stroke and can impact the ability of people who have had a stroke to perform everyday activities. There are a number of intervention strategies that various health professionals may use when working with people who have cognitive impairment post stroke. The purpose of this systematic review was to determine whether interventions for people with cognitive impairment after a stroke improve their functional performance of basic and/or instrumental activities of daily living (ADL). METHOD: Searches were performed in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, PsycBITE, OTseeker, and Dissertation Abstracts. Studies were eligible for inclusion if they were a randomised controlled trial or quasi randomised controlled trial that evaluated an intervention that focused on providing cognitive retraining to adults with clinically defined stroke and confirmed cognitive impairment and measured functional ability, either basic or instrumental ADL, as either a primary or secondary outcome measure. RESULTS: Four studies, involving a total of 376 participants, were included in this review. There was no statistically significant difference between groups on basic ADL performance in any of the four studies or on instrumental ADL in the one study that measured this. CONCLUSION: There were not an adequate number of high quality trials to be able to make recommendations that support or refute the use of specific cognitive retraining interventions to improve functional outcomes following a stroke. More research is required before conclusions can be made about the effect of cognitive interventions on functional outcomes post stroke. PMID- 20542853 TI - Is there a role for meaningful activity in stroke rehabilitation? AB - PURPOSE: Stroke survivors report multiple psychosocial issues after discharge and difficulties returning to meaningful roles and activities. This study explored the impact of an occupation-based group program on activity levels, well-being, and self-efficacy after discharge from inpatient rehabilitation. METHODS: This pilot study recruited participants from two hospital rehabilitation units. Both units provided individual therapy programs. Unit A provided an additional occupation-based group program. Behavioural mapping recorded participants' activity levels in hospital for one weekday and one weekend day. Outcome measures collected at recruitment, discharge, and/or 1 month after discharge included Modified Barthel Index, use of community supports, length of stay, Stroke Impact Scale, and Self- Efficacy Gauge. RESULTS: Participants from Unit A (n = 8) had a significantly longer length of stay than Unit B (n = 11) and spent significantly more time in occupational therapy (P = .01). Both participant groups were more inactive on the weekday compared to the weekend (P = .03). Participants in Unit A were more likely to report low levels of social participation and stroke recovery (P <.05) on the Stroke Impact Scale. CONCLUSION: There was no indication from the results of this study that an occupation-based group program had a positive effect on the measured outcomes. PMID- 20542854 TI - Measuring outcomes in people who have had a stroke and their carers: can the telephone be used? AB - PURPOSE: Telephone interviews may be a cost-effective alternative to administering stroke outcome measures for people who are living in the community following a stroke, but there is a lack of research that has compared the different modes of administering outcome measures. The aim of this study was to determine whether telephone administration of selected stroke outcome measures resulted in significantly different results to face-to-face administration of the same outcome measures. METHOD: Nineteen participants who were taking part in a randomised controlled trial (RCT) evaluating the effectiveness of a postdischarge education and support package for stroke patients and their carers were recruited for this study. Participants had the RCT follow-up outcome measures, at 3 months post discharge, administered by both telephone and face-to-face. Participants were randomised to receive either the telephone or face-to-face administration first and a period of 2 weeks separated the two administrations. Outcome measures were the Knowledge of Stroke Questionnaire, a stroke self-efficacy questionnaire, Hospital Anxiety and Depression Scale, Stroke and Aphasia Quality of Life Scale, and the Caregiver Strain Index. RESULTS: There were no significant differences between scores obtained on any of the outcome measures that were administered by telephone and face-to-face (P > .05). CONCLUSION: The telephone can be used to administer the outcome measures that were evaluated in this study to stroke patients and carers. These findings may be of benefit to stroke researchers and clinicians who wish to incorporate the use of telephone measures into the follow up care of stroke patients and their carers. PMID- 20542856 TI - Tobacco use and cessation among veterans recovering from stroke or TIA: a qualitative assessment and implications for rehabilitation. AB - PURPOSE: To understand factors associated with tobacco use and related tobacco cessation among veterans recovering from stroke/transient ischemic attack (TIA) that will facilitate design of a tailored intervention for rehabilitation services. METHODS: Four focus groups were conducted with veterans who were smokers prior to an incident stroke or TIA along with their spouse or caregiver. Focus groups addressed tobacco use, cessation, and barriers to quitting during the recovery and maintenance periods. Focus group discussions were audiotaped, transcribed, and analyzed using an inductive qualitative method. RESULTS: Twenty eight veterans and spouses/caregivers participated. Five themes emerged from analysis: existing helpful resources for cessation, existing unhelpful resources, barriers and facilitators to cessation, desired resources for quitting, and association of stroke/TIA with tobacco use. Pharmacotherapy and support from medical providers were perceived as helpful whereas group programs and flyers were perceived as unhelpful. Barriers to quitting included boredom and lack of social support; facilitators included social support and the cost of tobacco products. Vocational and rehabilitation programs were highly desirable resources for quitting. Participants did not perceive their stroke/TIA to be associated with tobacco use. CONCLUSION: Results identified several issues concerning tobacco use and cessation relevant to patients recovering from stroke/TIA. These results can inform the development of a tailored cessation intervention for integration into rehabilitation and recovery treatment plans for patients with stroke/TIA. PMID- 20542855 TI - Single limb exercise: pilot study of physiological and functional responses to forced use of the hemiparetic lower extremity. AB - PURPOSE: Stroke-related deficits can impede both functional performance and walking tolerance. Individuals with hemiparesis rely on the stronger limb during exercise and functional tasks. The single limb exercise (SLE) intervention was a unique training protocol that focused only on the hemiparetic limb. Our objective was to determine the effect of the SLE intervention on cardiorespiratory fitness parameters. METHODS: Twelve participants (5 male) with a mean age of 60.6 +/- 14.5 years and 69.1 +/- 82.2 months post stroke participated in the training intervention. All participants performed SLE using the hemiparetic leg three times a week for 4 weeks. The nonhemiparetic limb served as the control limb and did not engage in SLE. Peak oxygen uptake (VO2 peak) and oxygen uptake (VO2) were measured at baseline and post intervention in all 12 participants. At pre and post intervention, gait velocity was assessed in a subset of participants (n = 7) using the 10-m fast-walk test. RESULTS: After the 4-week SLE training intervention, significant improvements were found for VO2 during submaximal work effort (P = .009) and gait velocity (n = 7) (P = .001). Peak oxygen uptake did not increase (P = .41) after the training intervention. CONCLUSION: These data suggest that SLE training was an effective method for improving oxygen uptake and reducing energy expenditure during submaximal effort. Unilateral exercise focused on the hemiparetic leg may be an effective intervention strategy to consider for stroke rehabilitation. PMID- 20542857 TI - Definition of Health 2.0 and Medicine 2.0: a systematic review. AB - BACKGROUND: During the last decade, the Internet has become increasingly popular and is now an important part of our daily life. When new "Web 2.0" technologies are used in health care, the terms "Health 2.0" or "Medicine 2.0" may be used. OBJECTIVE: The objective was to identify unique definitions of Health 2.0/Medicine 2.0 and recurrent topics within the definitions. METHODS: A systematic literature review of electronic databases (PubMed, Scopus, CINAHL) and gray literature on the Internet using the search engines Google, Bing, and Yahoo was performed to find unique definitions of Health 2.0/Medicine 2.0. We assessed all literature, extracted unique definitions, and selected recurrent topics by using the constant comparison method. RESULTS: We found a total of 1937 articles, 533 in scientific databases and 1404 in the gray literature. We selected 46 unique definitions for further analysis and identified 7 main topics. CONCLUSIONS: Health 2.0/Medicine 2.0 are still developing areas. Many articles concerning this subject were found, primarily on the Internet. However, there is still no general consensus regarding the definition of Health 2.0/Medicine 2.0. We hope that this study will contribute to building the concept of Health 2.0/Medicine 2.0 and facilitate discussion and further research. PMID- 20542858 TI - Sharing health data for better outcomes on PatientsLikeMe. AB - BACKGROUND: PatientsLikeMe is an online quantitative personal research platform for patients with life-changing illnesses to share their experience using patient reported outcomes, find other patients like them matched on demographic and clinical characteristics, and learn from the aggregated data reports of others to improve their outcomes. The goal of the website is to help patients answer the question: "Given my status, what is the best outcome I can hope to achieve, and how do I get there?" OBJECTIVE: Using a cross-sectional online survey, we sought to describe the potential benefits of PatientsLikeMe in terms of treatment decisions, symptom management, clinical management, and outcomes. METHODS: Almost 7,000 members from six PatientsLikeMe communities (amyotrophic lateral sclerosis [ALS], Multiple Sclerosis [MS], Parkinson's Disease, human immunodeficiency virus [HIV], fibromyalgia, and mood disorders) were sent a survey invitation using an internal survey tool (PatientsLikeMe Lens). RESULTS: Complete responses were received from 1323 participants (19% of invited members). Between-group demographics varied according to disease community. Users perceived the greatest benefit in learning about a symptom they had experienced; 72% (952 of 1323) rated the site "moderately" or "very helpful." Patients also found the site helpful for understanding the side effects of their treatments (n = 757, 57%). Nearly half of patients (n = 559, 42%) agreed that the site had helped them find another patient who had helped them understand what it was like to take a specific treatment for their condition. More patients found the site helpful with decisions to start a medication (n = 496, 37%) than to change a medication (n = 359, 27%), change a dosage (n = 336, 25%), or stop a medication (n = 290, 22%). Almost all participants (n = 1,249, 94%) were diagnosed when they joined the site. Most (n = 824, 62%) experienced no change in their confidence in that diagnosis or had an increased level of confidence (n = 456, 34%). Use of the site was associated with increasing levels of comfort in sharing personal health information among those who had initially been uncomfortable. Overall, 12% of patients (n = 151 of 1320) changed their physician as a result of using the site; this figure was doubled in patients with fibromyalgia (21%, n = 33 of 150). Patients reported community specific benefits: 41% of HIV patients (n = 72 of 177) agreed they had reduced risky behaviors and 22% of mood disorders patients (n = 31 of 141) agreed they needed less inpatient care as a result of using the site. Analysis of the Web access logs showed that participants who used more features of the site (eg, posted in the online forum) perceived greater benefit. CONCLUSIONS: We have established that members of the community reported a range of benefits, and that these may be related to the extent of site use. Third party validation and longitudinal evaluation is an important next step in continuing to evaluate the potential of online data-sharing platforms. PMID- 20542859 TI - Association of risk factors for cardiovascular disease and glomerular filtration rate: a community-based study of 4,925 adults in Beijing. AB - BACKGROUND: Several large prospective studies have reported that a low estimated glomerular filtration rate (eGFR) or chronic kidney disease (CKD) is independently associated with cardiovascular disease (CVD) events and all-cause mortality in high-risk populations. However, findings from community-based population studies are scarce and inconsistent. We investigated the level of eGFR and the relationship between CVD risk factors and eGFR or CKD in the population of Beijing, China. METHODS: This is a community-based observational survey in residents from three communities in Beijing for a routine health status checkup. Out of 5100 individuals who were eligible for inclusion, 4925 (96.57%) had complete data and were investigated the level of eGFR and the associated factors of reduced renal function. 2085 individuals with albuminuria values were included in the analyses on the associated factors of CKD. A questionnaire was used for risk factors of CVD. Anthropometry and blood pressure were measured. Serum creatinine, total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum glucose were detected. The urine albumin-creatinine ratio (ACR) was used as an expression for albumin excretion. The oral glucose tolerance test was performed for the participants with no history of diabetes to diagnose diabetes. eGFR was evaluated by the Chinese modified Modification of Diet in Renal Disease equation. Reduced renal function was defined as normal renal function: eGFR >=90 mL/min/1.73 m(2); mild reduced renal function: eGFR 89-60 mL/min/1.73 m(2); moderate to severe reduced renal function: eGFR <60 mL/min/1.73 m(2). CKD was diagnosed as eGFR <60 mL/min/1.73 m(2) or albuminuria was present. RESULTS: The prevalence of mild reduced renal function (eGFR 89-60 mL/min/1.73 m(2)), moderate to severe reduced renal function (eGFR <60 mL/min/1.73 m(2)) and CKD was 41.12% (2025/4925), 1.89% (93/4925) and 18.90% (394/2085) in the present study, respectively. The proportion of risk factors was higher in the low level of eGFR. Risk factors that exposed to reduced renal function were slightly different between male and female. The results of multivariate logistic regression analysis showed older age [increased by 10 years; odds ratios (OR) = 1.22], male gender (OR = 1.38), diabetes (OR = 1.67), hypertension (OR = 1.84) and hypertriglyceridaemia (>=1.7 mmol/L; OR = 1.68) were independently associated with CKD. CONCLUSIONS: In the general population in Beijing, China, multiple CVD risk factors increased with a decline in eGFR and older age, hypertension, diabetes and elevated TG were independently associated with CKD. PMID- 20542860 TI - Is indeterminate colitis really indeterminate? PMID- 20542861 TI - Progressive abdominal pain after acute pancreatitis. PMID- 20542862 TI - Pizza, beer, amylase, lipase and the acute abdomen. PMID- 20542864 TI - A Dutch patient presenting with a rare clinical syndrome. Cronkhite-Canada Syndrome. PMID- 20542863 TI - An unusual cause of anaemia. Anaplastic carcinoma. PMID- 20542865 TI - Rare cause of chronic abdominal pain. PMID- 20542866 TI - An unusual inflammation of the colon. Post-transplant lymphoproliferative disorder (PTLD) and diffuse large B cell lymphoma. PMID- 20542867 TI - Jaundice and rectal bleeding in a young man. PMID- 20542868 TI - When to leave a stone unturned ... PMID- 20542869 TI - Cryptogenic cirrhosis: or is it? An unusual case of portal hypertension. PMID- 20542870 TI - Food debris in trachestomic tube. PMID- 20542871 TI - Obscure gastrointestinal bleeding occurring 50 years after an appendectomy. PMID- 20542872 TI - Detection of allogeneic blood group A and B enzyme activities in patients with ABO incompatible kidney transplantation. AB - The phenomenon of accommodation in recipients of blood group ABO incompatible kidney transplantation (iKTx), in which grafts survive despite the presence of blood group A or B antigen in the graft and the presence of corresponding antibodies in the recipient's blood, is not uncommon. alpha1,3-N Acetylgalactosaminyltransferase and alpha1,3galactosyltransferase associated with the synthesis of blood group A and B antigen (A and B enzymes), respectively, were measured by a highly specific enzyme-linked immunosorbent assay in the sera and transplanted tissues of patients who underwent an ABO iKTx. Allogeneic A and B enzymes were present in the sera and tissues as well as A and B antigens in the tissues for a long period, which hitherto have never been seen in recipients prior to an iKTx. However, activities of these enzymes in the sera after an iKTx decreased in patients who experienced a serious acute antibody-mediated rejection and disappeared in patients who had an unrepairable rejection, leading to graft loss without establishment of accommodation. Our observations on the presence of allogeneic A and B enzymes in the recipients' sera should have implications in decision making for a successful iKTx. PMID- 20542873 TI - A membrane-bound trehalase from Chironomus riparius larvae: purification and sensitivity to inhibition. AB - A preparation of a membrane-bound trehalase from the larvae of the midge Chironomus riparius (Diptera: Chironomidae) was obtained by detergent solubilization, ion-exchange chromatography and concanavalin A affinity chromatography. Trehalase was purified 1080-fold to a specific activity of 75 U mg(-)(1). The initial rate of trehalase activity followed Henri-Michaelis-Menten kinetics with a K(m) of 0.48 +/- 0.04 mM. Catalytic efficiency was maximal at pH 6.5. The activity was highly inhibited by mono- and bicyclic iminosugar alkaloids such as (in order of potency) casuarine (IC(50) = 0.25 +/- 0.03 microM), deoxynojirimycin (IC(50) = 2.83 +/- 0.34 microM) and castanospermine (IC(50) = 12.7 +/- 1.4 microM). Increasing substrate concentration reduced the inhibition. However, in the presence of deoxynojirimycin, Lineweaver-Burk plots were curvilinear upward. Linear plots were obtained with porcine trehalase. Here, we propose that deoxynojirimycin inhibits the activity of trehalase from C. riparius according to a ligand exclusion model. Inhibition was further characterized by measuring enzyme activity in the presence of a series of casuarine and deoxynojirimycin derivatives. For comparison, inhibition studies were also performed with porcine trehalase. Results indicate substantial differences between midge trehalase and mammalian trehalase suggesting that, in principle, inhibitors against insect pests having trehalase as biochemical targets can be developed. PMID- 20542875 TI - Spotlight on microvascular permeability. PMID- 20542874 TI - Intracellular or extracellular heat shock protein 70 differentially regulates cardiac remodelling in pressure overload mice. AB - AIMS: Innate and adaptive immune responses are associated with the development of hypertension-induced myocardial hypertrophy and fibrosis. As a result, we investigated whether heat shock protein (HSP) 70, which is a molecule of damage associated molecular patterns, could induce inflammation in the myocardium and promote the development of hypertension-induced cardiac hypertrophy and fibrosis. METHODS AND RESULTS: We found that HSP70 serum levels, as well as the amount of HSP70 translocation to the cardiomyocyte membranes and the interstitial space, were elevated in the hypertensive mice caused by abdominal aortic constriction (AAC). Transcriptional inhibition of HSP70 expression by a specific heat shock transcript factor inhibitor, KNK437, reduced the serum level, and the re distribution of HSP70. It promoted myocardial hypertrophy and cardiac dysfunctions although it protected animals from AAC-induced cardiac fibrosis. On the other hand, the functional antagonism of HSP70 by an anti-HSP70 antibody attenuated AAC-induced cardiac hypertrophy and fibrosis without adverse haemodynamic effects. The cardioprotective effect of the anti-HSP70 antibody was largely attributed to its ability to block AAC-activated immune response in the heart, as was indicated by suppressing the hypertension-enhanced conjugation of HSP70 with toll-like receptor 4, reducing heart-infiltrating macrophages, decreasing the expression of pro-inflammatory factor monocyte chemoattractant protein-1 and profibrotic factor transforming growth factor beta 1, and attenuating pro-hypertrophy signal MAPK P38 and ERK. CONCLUSION: These results indicate that intracellular and extracellular HSP70 have different roles in the regulation of cardiac remodelling and function in response to hypertension. Extracellular HSP70 is a potential therapeutic target against cardiac hypertrophy and fibrosis. PMID- 20542876 TI - Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexin A5. AB - AIMS: Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. METHODS AND RESULTS: AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) >10% and an increase in LV ejection fraction (LVEF) >10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. CONCLUSION: CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease. PMID- 20542877 TI - Metabolic disorders in heart diseases with an inflammatory background. PMID- 20542878 TI - Sphingosine-1-phosphate modulation of basal permeability and acute inflammatory responses in rat venular microvessels. AB - AIMS: Although several cultured endothelial cell studies indicate that sphingosine-1-phosphate (S1P), via GTPase Rac1 activation, enhances endothelial barriers, very few in situ studies have been published. We aimed to further investigate the mechanisms whereby S1P modulates both baseline and increased permeability in intact microvessels. METHODS AND RESULTS: We measured attenuation by S1P of platelet-activating factor (PAF)- or bradykinin (Bk)-induced hydraulic conductivity (L(p)) increase in mesenteric microvessels of anaesthetized rats. S1P alone (1-5 uM) attenuated by 70% the acute L(p) increase due to PAF or Bk. Immunofluorescence methods in the same vessels under identical experimental conditions showed that Bk or PAF stimulated the loss of peripheral endothelial cortactin and rearrangement of VE-cadherin and occludin. Our results are the first to show in intact vessels that S1P pre-treatment inhibited rearrangement of VE-cadherin and occludin induced by PAF or Bk and preserved peripheral cortactin. S1P (1-5 uM, 30 min) did not increase baseline L(p). However, 10 uM S1P (60 min) increased L(p) two-fold. CONCLUSION: Our results conform to the hypothesis that S1P inhibits acute permeability increase in association with enhanced stabilization of peripheral endothelial adhesion proteins. These results support the idea that S1P can be useful to attenuate inflammation by enhancing endothelial adhesion through activation of Rac-dependent pathways. PMID- 20542879 TI - Plasma membrane Ca2+-ATPase equals no NO. PMID- 20542886 TI - 'And then there were three': highly efficient uptake of potassium by foliar trichomes of epiphytic bromeliads. AB - BACKGROUND AND AIMS: Vascular epiphytes have to acquire nutrients from atmospheric wash out, stem-flow, canopy soils and trapped litter. Physiological studies on the adaptations to nutrient acquisition and plant utilization of nutrients have focused on phosphorus and nitrogen; potassium, as a third highly abundant nutrient element, has received minor attention. In the present study, potassium uptake kinetics by leaves, within-plant distribution and nutrient accumulation were analysed to gain an improved understanding of physiological adaptations to non-terrestrial nutrient supply of plants. METHODS: Radioactively labelled (86)RbCl was used as an analogue to study uptake kinetics of potassium absorbed from tanks of epiphytes, its plant distribution and the correlation between uptake efficiency and abundance of trichomes, functioning as uptake organs of leaves. Potassium in leaves was additionally analysed by atomic absorption spectroscopy to assess plant responses to potassium deficiency. KEY RESULTS: Labelled rubidium was taken up from tanks over a wide range of concentrations, 0.01-90 mm, which was achieved by two uptake systems. In four tank epiphytes, the high-affinity transporters had average K(m) values of 41.2 microm, and the low-affinity transporters average K(m) values of 44.8 mm. Further analysis in Vriesea splenriet showed that high-affinity uptake of rubidium was an ATP-dependent process, while low-affinity uptake was mediated by a K(+)-channel. The kinetic properties of both types of transporters are comparable with those of potassium transporters in roots of terrestrial plants. Specific differences in uptake velocities of epiphytes are correlated with the abundance of trichomes on their leaf surfaces. The main sinks for potassium were fully grown leaves. These leaves thus function as internal potassium sources, which allow growth to be maintained during periods of low external potassium availability. CONCLUSIONS: Vascular epiphytes possess effective mechanisms to take up potassium from both highly diluted and highly concentrated solutions, enabling the plant to incorporate this nutrient element quickly and almost quantitatively from tank solutions. A surplus not needed for current metabolism is stored, i.e. plants show luxury consumption. PMID- 20542887 TI - Prospective audit on the use of the LMA-Supreme for airway management of adult patients undergoing elective orthopaedic surgery in prone position. AB - BACKGROUND: The LMA-Supreme (SLMA) is a single-use, latex-free, supraglottic airway device with a drain tube which allows immediate assessment of correct positioning of the device at insertion and throughout the procedure and provides access to gastric contents. The anatomically shaped airway tube facilitates easy insertion in anaesthetized patients in the supine, lateral, and prone positions. We present a prospective audit in 205 consecutive adult patients presenting for elective spine surgery in the prone position. Patients positioned themselves in the prone position, on a Montreal or Wilson mattress to optimize patient comfort in this position. Anaesthesia was then induced, and an appropriate-sized SLMA was inserted. METHODS: Prospective, descriptive audit of SLMA insertion in 205 consecutive adult patients, anaesthetized in the prone position for elective orthopaedic surgery with spontaneous (n=6) or positive pressure ventilation (PPV) (n=199). RESULTS: First-pass success was achieved in 184 insertions. Forty-two SLMA insertions were performed by anaesthesia trainees with first-pass success achieved in 38 insertions. All problems encountered during insertion were minor, and no patient had to be turned to the supine position for an airway problem. Problems during insertion were independent of patients' BMI. There were no failures of SLMA insertion or of maintenance of PPV during surgery. CONCLUSIONS: The results suggest that the SLMA is a useful device for airway management in patients anaesthetized in the prone position and for subsequent airway management with PPV, with or without neuromuscular block. PMID- 20542888 TI - Intraoperative high-dose remifentanil increases post-anaesthetic shivering. AB - BACKGROUND: Remifentanil is associated with increased incidence of post anaesthetic shivering (PAS). The aim of this study was to compare the effects of intraoperative high and low doses of remifentanil on PAS. METHODS: We investigated 50 consecutive patients, aged <60 yr, who underwent gynaecological laparotomy. Patients who underwent prolonged surgery (>4 h) were excluded from the study. Anaesthesia throughout surgery was maintained with i.v. propofol and remifentanil, and epidural ropivacaine, and no nitrous oxide was used. Fifty patients were randomly assigned to receive intraoperative remifentanil at 0.1 microg kg(-1) min(-1) (low-dose group, n=25) or 0.25 microg kg(-1) min(-1) (high dose group, n=25) until the end of surgery. Intraoperative analgesia was achieved by a fixed infusion rate of remifentanil and titrated epidural ropivacaine. PAS was evaluated by nursing stuff over the first hour after surgery. RESULTS: PAS occurred more frequently in the high-dose group than in the low-dose group (60% vs 20%, P=0.009). None of the patients complained of pain during the observation period due to epidural analgesia. There were no significant differences in rectal or palm skin temperature after extubation between the two dose groups. CONCLUSIONS: Remifentanil-induced PAS is not a phenomenon of intraoperative hypothermia. The higher incidence of PAS with higher doses of remifentanil probably reflects acute opioid tolerance and stimulation of N-methyl-d-aspartate receptors, similar to hyperalgesia. We conclude that patients administered high doses of remifentanil are sensitive to shivering after sudden drug withdrawal. PMID- 20542889 TI - Size of internal jugular vs subclavian vein in small infants: an observational, anatomical evaluation with ultrasound. AB - BACKGROUND: The primary goal of this study was to compare the size and depth of the internal jugular vein (IJV) and the subclavian vein (SCV) in infants under general anaesthesia. A secondary goal was to determine the correlation of weight, height, head circumference, and age to the size and depth of these veins. METHODS: Sixty small infants weighing from 1.4 to 4.5 kg were included. Using ultrasound, the diameters via short-axis (SAX) and long-axis (LAX) views, cross sectional area (CSA), and depth of the left and right IJV and SCV were measured. RESULTS: The diameter of the IJV was 7.9% larger on average than that of the SCV as measured via the SAX and LAX views (mean: 3.1 vs 2.9 mm; Wilcoxon's signed rank test: P<0.01). The CSA of the IJV was 27% larger on average than that of the SCV (mean: 10.2 vs 8.0 mm(2); Wilcoxon's signed-rank test: P<0.01). Seventy-five per cent of the neonates showed a larger CSA of the IJV. The SCV was 8.4% deeper on average from the skin surface than the IJV (mean: 6.4 vs 5.9 mm; Wilcoxon's signed-rank test: P<0.01). There was a significant positive correlation between weight, height, head circumference, and age to the size and depth of the veins (Spearman's rank correlation: P<0.01). CONCLUSIONS: Because of its most likely larger size, the IJV can be recommended as the better choice for cannulation in comparison with the SCV. However, other factors should also be considered. PMID- 20542890 TI - Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery. AB - MOTIVATION: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult. RESULTS: We present SignaLink, a database containing eight major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster and humans. Based on 170 review and approximately 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the eight pathways can cross talk. We quantified the possible tissue- and cancer-specific activity of cross talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery. CONCLUSIONS: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease, and underscore its importance in network-based drug target selection. AVAILABILITY: http://SignaLink.org. PMID- 20542891 TI - Contribution of strigolactones to the inhibition of tiller bud outgrowth under phosphate deficiency in rice. AB - Strigolactones (SLs) or SL-derived metabolite(s) have recently been shown to act as endogenous inhibitors of axillary bud outgrowth. SLs released from roots induce hyphal branching of arbuscular mycorrhizal (AM) fungi that facilitate the uptake of inorganic nutrients, such as phosphate (Pi) and nitrate, by the host plants. Previous studies have shown that SL levels in root exudates are highly elevated by Pi starvation, which might contribute to successful symbiosis with AM fungi in the rhizosphere. However, how endogenous SL levels elevated by Pi starvation contribute to its hormonal action has been unknown. Here, we show that tiller bud outgrowth in wild-type rice seedlings is inhibited, while root 2'-epi 5-deoxystrigol (epi-5DS) levels are elevated, in response to decreasing Pi concentrations in the media. However, the suppression of tiller bud outgrowth under Pi deficiency does not occur in the SL-deficient and -insensitive mutants. We also show that the responsiveness to exogenous SL is slightly increased by Pi deficiency. When Pi-starved seedlings are transferred to Pi-sufficient media, tiller bud outgrowth is induced following a decrease in root epi-5DS levels. Taken together, these results suggest that elevated SL levels by Pi starvation contribute to the inhibition of tiller bud outgrowth in rice seedlings. We speculate that SL plays a dual role in the adaptation to Pi deficiency; one as a rhizosphere signal to maximize AM fungi symbiosis for improved Pi acquisition and the other as an endogenous hormone or its biosynthetic precursor to optimize shoot branching for efficient Pi utilization. PMID- 20542892 TI - Distinction of the binding modes for human nuclear receptor ERRgamma between bisphenol A and 4-hydroxytamoxifen. AB - Bisphenol A (BPA) strongly binds to human estrogen-related receptor gamma (ERRgamma). BPA is an oestrogenic endocrine disruptor that influences various physiological functions at very low doses. BPA functions as an inverse-type antagonist of ERRgamma to retain its high basal constitutive activity by inhibiting the deactivating inverse agonist activity of 4-hydroxytamoxifen (4 OHT). We recently demonstrated that ERRgamma receptor residues Glu275 and Arg316 function as the intrinsic binding site of BPA's phenol-hydroxyl group. We also determined the chief importance of phenol-hydroxyl<-->Arg316 hydrogen bonding and the corroborative role of phenol-hydroxyl<-->Glu275 hydrogen bonding. However, there appeared to be a distinct difference between the receptor binding modes of BPA and 4-OHT. In the present study, using tritium-labelled or non-labelled BPA and 4-OHT, we evaluated in detail the receptor binding capabilities of wild-type ERRgamma and its mutants with amino acid alterations at positions 275 and 316. Both compounds exhibited a strong binding ability to wild-type ERRgamma due to the hydrogen bonding to Glu275 and Arg316. However, 4-OHT revealed significantly reduced occupancy for both wild-type and mutant receptors. The data obtained suggest that 4-OHT barely binds to ERRgamma due to the strong ability of Glu275 and Arg316 to recruit phenol compounds. PMID- 20542893 TI - Assessment of disease activity and progression in Takayasu's arteritis with Disease Extent Index-Takayasu. AB - OBJECTIVE: Disease Extent Index-Takayasu (DEI.Tak) is a new index developed for the follow-up of Takayasu's arteritis (TA), assessing only clinical findings without the requirement of imaging. We investigated the effectiveness of DEI.Tak in assessing disease activity and progression by comparing with physician's global assessment (PGA) and active disease criteria defined by Kerr et al. METHODS: The initial DEI.Tak forms were filled in for 145 TA patients cross sectionally to detect the baseline damage and after 29.8 (31) months (n = 105, 144 visits) only by including the new/worsening symptoms within the past 6 months. RESULTS: At baseline, all patients had a DEI.Tak >0 [mean (s.d.): 7.6 (4.2)]. At this evaluation, 62% of the patients had active, 16.2% had persistent and 21.8% had inactive disease according to the PGA. At follow-up, in 69% of the patients the DEI.Tak score was 0. However, 14% of them were accepted as having active and 17% persistent disease according to PGA. In contrast, 18% with a DEI.Tak >= 1 were inactive according to PGA. Patients with active or persistent disease with PGA had higher DEI.Tak compared with inactives [1.3 (1.9), 1 (1.3) vs 0.2 (0.6), respectively; P < 0.001]. According to Kerr's criteria 27% were active. The total agreement between DEI.Tak and Kerr's criteria was 94% (kappa = 0.85). Compared with PGA, Kerr's criteria had a total agreement of 74% and DEI.Tak 68%. CONCLUSION: During follow-up, most TA patients showed no clinical activity with DEI-Tak. Although the agreement between Kerr's criteria and DEI.Tak seemed very good, using Kerr's criteria instead of DEI.Tak increased the consistency with PGA, which could be explained by the influence of imaging data and acute-phase reactant levels on the physician's decisions. PMID- 20542895 TI - WHO reference values for human semen. PMID- 20542894 TI - Persistently moderate DAS-28 is not benign: loss of function occurs in early RA despite step-up DMARD therapy. AB - OBJECTIVES: Current UK management of RA initially employs conventional DMARDs, with biological therapy reserved for DMARD-resistant RA patients with persistently high 28-joint disease activity score (DAS-28). The aim of this study was to examine the effect on patient-reported function of persistently moderate DAS-28 despite modern step-up DMARD therapy in an early arthritis cohort. METHODS: Data were obtained from the Yorkshire Early Arthritis Register, a cohort of early (<12 months) RA patients treated with dose-escalated DMARDs. Change in HAQ exceeding the minimum clinically important difference (MCID) was determined for three values of MCID (0.22, 0.31 and 0.49). Changes in HAQ over Months 6-12 were compared between patients whose DAS-28(ESR) was persistently high (> 5.1 at 6- and/or 9-month visits and at the 12-month visit), persistently moderate (>3.2 and <= 5.1) or persistently low (<= 3.2). RESULTS: We selected 194 patients for this analysis. Deteriorating HAQ scores were observed in 10.9% of patients with persistently low DAS-28 compared with 21.4% (persistently moderate DAS-28) and 46.7% (persistently high DAS-28), respectively, for MCID = 0.22; 7.3, 14.3 and 20.0% for MCID = 0.31; 5.5, 10.7 and 11.1% for MCID = 0.49. CONCLUSIONS: A high DAS-28 was generally associated with a greater degree of functional decline, but persistent moderate elevation of DAS-28 was associated with important functional deterioration in 10-21% of early RA patients (depending on choice of MCID) following a modern DMARD protocol. A proportion of patients with persistently moderate DAS-28 may therefore benefit from more aggressive therapy than that allowed by current UK recommendations. PMID- 20542896 TI - The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis. AB - BACKGROUND: There are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers. METHODS: We conducted a systematic review and meta-analysis of controlled studies to compare pregnancy outcomes following transfer of thawed blastocysts that were frozen either on Day 5 or Day 6 following fertilization in vitro. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. Study selection and data extraction were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. RESULTS: We identified 15 controlled studies comprising 2502 frozen thawed transfers involving blastocysts that were either frozen on Day 5 or Day 6. Meta-analysis of these studies showed significantly higher clinical pregnancy rate [relative risk (RR) = 1.14, 95% confidence interval (CI): 1.03-1.26, P = 0.01] and ongoing pregnancy/live birth rate (RR = 1.15, 95% CI: 1.01-1.30, P = 0.03) with Day 5 compared with Day 6 frozen-thawed blastocyst transfers. Sensitivity analysis of those studies where blastocysts frozen on Day 5 or Day 6 were at the same stage of development showed no significant difference in the clinical pregnancy rate (RR = 1.07, 95% CI: 0.87-1.33, P = 0.51) and ongoing pregnancy/live birth rate (RR = 1.08, 95% CI: 0.92-1.27, P = 0.36). CONCLUSION: Slower developing blastocysts cryopreserved on Day 6 but at the same stage of development as those developing to the blastocyst stage on Day 5 have similar clinical pregnancy and ongoing pregnancy/live birth rates following frozen-thawed blastocyst transfers. PMID- 20542897 TI - Speriolin is a novel human and mouse sperm centrosome protein. AB - BACKGROUND: Oocytes in humans, mice and other mammals lack identifiable centrioles. The proximal centriole brought in by the fertilizing sperm in humans and most other mammals appears to gives rise to the centrioles at the spindle poles in the zygote, and is believed to indicate that centrioles are inherited through the paternal lineage. However, both the proximal and distal sperm centrioles degenerate in mice and other rodents. A bipolar mitotic spindle nucleates from multiple centrosome-like structures in the mouse zygote and centrioles are not seen until the blastocyst stage, suggesting that centrioles are inherited through the maternal lineage in mice. We previously identified speriolin as a spermatogenic cell-specific binding partner of Cdc20 that co localizes with pericentrin in mouse spermatocytes and is present in the centrosome in round spermatids. METHOD: The nature and localization of speriolin in mouse and human sperm and the fate of speriolin following fertilization in the mouse were determined using immunofluorescence microscopy, immunoelectron microscopy and western blotting. RESULTS: Speriolin surrounds the intact proximal centriole in human sperm, but is localized at the periphery of the disordered distal centriole in mouse sperm. Human speriolin contains an internal 163-amino acid region not present in mouse that may contribute to localization differences. Speriolin is carried into the mouse oocyte during fertilization and remains associated with the decondensing sperm head in zygotes. The speriolin spot appears to undergo duplication or splitting during the first interphase and is detectable in 2-cell embryos. CONCLUSIONS: Speriolin is a novel centrosomal protein present in the connecting piece region of mouse and human sperm that is transmitted to the mouse zygote and can be detected throughout the first mitotic division. PMID- 20542898 TI - The use of misoprostol before hysteroscopic surgery in non-pregnant premenopausal women: a randomized comparison of sublingual, oral and vaginal administrations. AB - BACKGROUND: The aim of the present study was to evaluate the efficacy of misoprostol administered orally, vaginally, or sublingually on cervical ripening before hysteroscopic surgery in premenopausal non-pregnant women. METHODS: Non pregnant premenopausal women scheduled for operative hysteroscopy (with a 10-mm hysteroscope) were assigned by computerized randomization to receive 400 mg of misoprostol, administered either orally or vaginally 6-8 h prior to surgery or 400 mg sublingually 2-4 h prior to surgery. The primary outcome in this study was the preoperative cervical width as measured by the largest number of Hegar dilators. The time to Hegar number 10 was also recorded along with side effects related to misoprostol and complications during surgery for each group. RESULTS: Patients were randomized to receive sublingual (n = 47), oral (n = 47) or vaginal (n = 47) misoprostol. The three groups were comparable in terms of age, BMI (body mass index), parity, gravidity, history of vaginal delivery, post-operative pathological findings and surgeon type. The preoperative cervical width [sublingual: 7.5 +/- 2.0 mm (8, 3-10); oral: 7.5 +/- 1.9 mm (7, 4-10); vaginal: 7.6 +/- 2.4 mm (8, 1-10)] was statistically similar among the groups. The time to Hegar number 10, side effects and complications during the hysteroscopy were comparable among the three groups. CONCLUSION: A limitation of this study was that the surgeons, but not the patients, were blinded to the test procedures. Nevertheless we found that sublingual, oral and vaginal misoprostol were equally effective for cervical priming before hysteroscopic surgery in premenopausal non pregnant women. PMID- 20542899 TI - Quantitative multiplex real-time PCR for detecting class 1, 2 and 3 integrons. AB - OBJECTIVES: Integrons are bacterial genetic elements that can capture and express genes contained in mobile cassettes. Integrons have been described worldwide in Gram-negative bacteria and are a marker of antibiotic resistance. We developed a specific and sensitive Taqman probe-based real-time PCR method with three different primer-probe pairs for simultaneous detection of the three main classes of integron. METHODS: Sensitivity was assessed by testing mixtures of the three targets (intI integrase genes of each integron class) ranging from 10 to 10(8) copies. Specificity was determined with a panel of integron-containing and integron-free control strains. The method was then applied to clinical samples. RESULTS: The PCR method was specific and had a sensitivity of 10(2) copies for all three genes, regardless of their respective quantities. The method was quantitative from 10(3) to 10(7) copies, and was able to detect integrons directly in biological samples. CONCLUSIONS: We have developed a rapid, quantitative, specific and sensitive method that could prove useful for initial screening of Gram-negative isolates, or clinical samples, for likely multidrug resistance. PMID- 20542900 TI - Novel genetic context of multiple bla OXA-58 genes in Acinetobacter genospecies 3. AB - OBJECTIVES: The detection in Acinetobacter genospecies 3 isolates of OXA-type carbapenemases, resulting in reduced susceptibility to carbapenem antibiotics, is increasingly reported. We identified an Acinetobacter genospecies 3 isolate carrying the gene for OXA-58 and aimed to resolve the genetic environment surrounding the bla(OXA-58) gene. METHODS: Species identification was confirmed by 16S-23S rRNA restriction analysis. MICs of imipenem, meropenem and ertapenem were determined, and the isolate was screened by PCR for bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like) and bla(OXA-58-like) genes. The sequence surrounding bla(OXA-58) was determined through amplification by inverse PCR and genome walking followed by sequencing. Genetic localization was investigated by Southern blotting. RESULTS: Isolate A164 was confirmed as belonging to Acinetobacter genospecies 3 and had reduced susceptibility to the carbapenems. The isolate was found to encode two bla(OXA-58) genes that may have been duplicated by the insertion sequence ISAba125, two copies of which were inserted into ISAba3 elements. The bla(OXA-58) genes appear to be plasmid borne. CONCLUSIONS: This is the first report of beta-lactamase duplication in Acinetobacter genospecies 3 and of gene duplication mediated by ISAba125. PMID- 20542902 TI - A simple phenotypic method for the differentiation of metallo-beta-lactamases and class A KPC carbapenemases in Enterobacteriaceae clinical isolates. AB - BACKGROUND: The increasing frequency of class A KPC enzymes and class B metallo beta-lactamases (MBLs) among Enterobacteriaceae as well as their possible co production makes their early differentiation urgent. METHODS: A simple phenotypic algorithm employing three combined-disc tests consisting of meropenem alone and with phenylboronic acid (PBA), EDTA, or both PBA and EDTA was designed for the differentiation of KPC and MBL enzymes. Augmentation of the zone of inhibition by >or=5 mm was considered a positive combined-disc test result. A total of 141 genotypically confirmed carbapenemase-positive Enterobacteriaceae clinical isolates (63 KPC producers, 47 MBL producers, and 31 KPC and MBL producers) with various carbapenem MICs were examined. For comparison, 84 genotypically confirmed carbapenemase-negative Enterobacteriaceae clinical isolates [39 extended-spectrum beta-lactamase (ESBL) producers, 22 AmpC producers, and 23 ESBL and AmpC producers] were also tested. RESULTS: The phenotypic algorithm was able to differentiate MBL from KPC producers as well as to detect the possible co production of both carbapenemases (positive result only with the combined-disc test using meropenem alone and with both PBA and EDTA). The method detected all KPC or MBL producers (sensitivity 100%) as well as 30 of the KPC and MBL producers (sensitivity 96.8%). All three combined-disc tests were negative for non-carbapenemase-producing isolates, except two ESBL and AmpC producers that gave positive combined-disc tests using meropenem alone and with PBA and both PBA and EDTA (specificity for KPC detection 98.8%). CONCLUSIONS: This phenotypic method is very helpful to detect carbapenemase production and provides a simple algorithm for the differentiation of KPC and MBL enzymes, especially in regions where KPC- and MBL-possessing Enterobacteriaceae are highly prevalent. PMID- 20542903 TI - Usefulness of PCR for monitoring benznidazole response in patients with chronic Chagas' disease: a prospective study in a non-disease-endemic country. AB - OBJECTIVES: This prospective study focused on the evaluation of antiparasitic therapy in chronic Chagas' disease, monitored by PCR. PATIENTS AND METHODS: One hundred and eighty-one patients, all seropositive for Trypanosoma cruzi infection, underwent specific chemotherapy with benznidazole. Twelve patients were classified as young (2-19 years), 122 patients were classified as adults (20 39 years) and 47 patients were classified as seniors (>or=40 years). In total, 116 (64%) were asymptomatic and 65 (36%) were symptomatic. Patients were monitored for 90, 150 and 420 days after treatment by PCR and serology. RESULTS: Before treatment, 68% had a positive PCR result. PCR positivity was significantly more frequent in patients aged 2-19 years (P = 0.0007) and in short-term immigrants (P = 0.0076). No differences in PCR sensitivity were observed between samples of patients with chronic symptomatic or indeterminate Chagas' disease. All patients presented an early conversion of PCR results 90 days post-treatment. However, at the end of the follow-up period PCR had become positive in four patients (4 out of 58 patients; 6.9%) who had strictly adhered to the treatment and in one who did not complete the treatment. Only one patient showed an alternating PCR during follow-up. CONCLUSIONS: We conclude that PCR is a useful tool for the early detection of parasite susceptibility to benznidazole and for the post-treatment parasitological follow-up of patients with chronic Chagas' disease. PMID- 20542901 TI - A novel approach to the antimicrobial activity of maggot debridement therapy. AB - OBJECTIVES: Commercially produced sterile green bottle fly Lucilia sericata maggots are successfully employed by practitioners worldwide to clean a multitude of chronic necrotic wounds and reduce wound bacterial burdens during maggot debridement therapy (MDT). Secretions from the maggots exhibit antimicrobial activity along with other activities beneficial for wound healing. With the rise of multidrug-resistant bacteria, new approaches to identifying the active compounds responsible for the antimicrobial activity within this treatment are imperative. Therefore, the aim of this study was to use a novel approach to investigate the output of secreted proteins from the maggots under conditions mimicking clinical treatments. METHODS: cDNA libraries constructed from microdissected salivary glands and whole maggots, respectively, were treated with transposon-assisted signal trapping (TAST), a technique selecting for the identification of secreted proteins. Several putative secreted components of insect immunity were identified, including a defensin named lucifensin, which was produced recombinantly as a Trx-fusion protein in Escherichia coli, purified using immobilized metal affinity chromatography and reverse-phase HPLC, and tested in vitro against Gram-positive and Gram-negative bacterial strains. RESULTS: Lucifensin was active against Staphylococcus carnosus, Streptococcus pyogenes and Streptococcus pneumoniae (MIC 2 mg/L), as well as Staphylococcus aureus (MIC 16 mg/L). The peptide did not show antimicrobial activity towards Gram-negative bacteria. The MIC of lucifensin for the methicillin-resistant S. aureus and glycopeptide-intermediate S. aureus isolates tested ranged from 8 to >128 mg/L. CONCLUSIONS: The TAST results did not reveal any highly secreted compounds with putative antimicrobial activity, implying an alternative antimicrobial activity of MDT. Lucifensin showed antimicrobial activities comparable to other defensins and could have potential as a future drug candidate scaffold, for redesign for other applications besides the topical treatment of infected wounds. PMID- 20542904 TI - Effect of storage conditions of dried plasma and blood spots on HIV-1 RNA quantification and PCR amplification for drug resistance genotyping. AB - OBJECTIVES: Dried blood spots (DBS) and dried plasma spots (DPS) are easy to collect and store, and have been successfully tested as an alternative to plasma for performing virological analyses. Adequate storage conditions still need to be established and cell-associated proviral DNA in DBS can contribute to the amplified products. We evaluated these two parameters. METHODS: Residual samples from 34 HIV-1-infected patients [mean viral load (VL) = 3.93 log(10) copies/mL] were used to prepare DPS and DBS, then stored at 20 degrees C and 37 degrees C. HIV-1 nucleic acids were extracted, with or without DNase treatments, to perform HIV-1 VL quantification and nested RT-PCR to amplify the reverse transcriptase gene (798 bp). RESULTS: For DBS stored for 3 months at 20 degrees C, VL could be measured for all samples and results were comparable to plasma VL. At 37 degrees C, a slight decrease was observed after 2 and 3 months (0.16 and 0.37 log(10) copies/mL mean difference, respectively). For DPS, a significant decrease in VL (0.70 and 1.07 log(10) copies/mL after 1 and 2 months, respectively) was seen at 37 degrees C, but not at 20 degrees C. PCR amplifications from DPS were only successful for 50% of samples with an initial VL >10 000 copies/mL after 1 month at 20 degrees C. From DBS, PCR amplifications are possible until 3 months for samples with plasma VL >5000 copies/mL. VL and PCR results for DBS treated with DNase are close to results obtained for DPS. CONCLUSIONS: Virological monitoring is still feasible for DBS after 3 months of storage at 37 degrees C when VL is >5000 copies/mL, but DNA contributes largely to the final results. PMID- 20542905 TI - Depletion of resuscitation-promoting factors has limited impact on the drug susceptibility of Mycobacterium tuberculosis. AB - OBJECTIVES: Mycobacterium tuberculosis has five homologues of the muralytic resuscitation-promoting factor (Rpf), which are collectively dispensable for growth in vitro, but are required for resuscitation from a non-culturable state and for virulence in a mouse infection model. Our study was aimed at assessing the drug susceptibility of mutants lacking all five rpf genes. METHODS: Drug susceptibility was determined in liquid medium using the broth microdilution method. RESULTS: Strains of M. tuberculosis that lack all five rpf-like genes display a 4-8-fold increase in susceptibility to vancomycin and erythromycin, but show no significant difference in susceptibility to other antibiotics tested, including first- and second-line antitubercular agents. CONCLUSIONS: These results suggest that the possible alterations in the peptidoglycan structure and/or turnover caused by Rpf deficiency have a limited impact on the drug susceptibility of M. tuberculosis. PMID- 20542906 TI - Comment on: Cerebrospinal fluid impairs antimicrobial activity of fosfomycin in vitro. PMID- 20542907 TI - Rapid assays for fluoroquinolone resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis. AB - OBJECTIVES: Multidrug-resistant tuberculosis has emerged as a global health threat. Given poor treatment outcomes of fluoroquinolone-resistant multidrug resistant tuberculosis, there is a pressing need for rapid drug susceptibility testing of multidrug-resistant Mycobacterium tuberculosis against fluoroquinolones. This review aims at evaluating these rapid assays. METHODS: PubMed and OvidSP were used to search MEDLINE and EMBASE for publications in English regarding rapid assays that tested ofloxacin, levofloxacin or moxifloxacin. Studies were included only in the concurrent presence of sensitivity and specificity data. Summary estimates of sensitivity and specificity were generated by the bivariate random effects model when there were at least three sets of data under the same assay category that tested the same fluoroquinolone with reference to a standard test. RESULTS: Of 108 articles identified, 24 articles were included in a meta-analysis of rapid assays that tested ofloxacin in culture isolates. Overall, rapid genotypic assays targeting gyrA only are significantly less specific (96% versus 99%) and non-significantly less sensitive (88% versus 94%) than rapid phenotypic assays. To test for the presence or absence of ofloxacin resistance to a certainty threshold of 90%, the required pre-test prevalence ranges of ofloxacin resistance for genotypic assays targeting gyrA only are 29%-47% overall, 36%-55% for PCR-DNA sequencing and 23% 44% for others. Corresponding ranges are 7%-65% for phenotypic assays overall and 3%-75% for Mycobacteria Growth Indicator Tube (MGIT). CONCLUSIONS: Assuming that the mean pre-test prevalence of fluoroquinolone resistance in culture isolates of multidrug-resistant M. tuberculosis is approximately 20%, rapid genotypic assays other than PCR-DNA sequencing, targeting gyrA only, can reliably screen for ofloxacin resistance. PMID- 20542908 TI - A rifampicin-containing antibiotic treatment improves outcome of staphylococcal deep sternal wound infections. AB - BACKGROUND: Deep sternal wound infection (DSWI) is a severe complication after cardiac surgery, mostly caused by staphylococci. Little is known about the optimal antibiotic management. METHODS: A 10 year retrospective analysis of 100 patients with staphylococcal DSWI after cardiac surgery in a tertiary hospital. Treatment failure was defined as sternal wound dehiscence or fistula at the end of the prescribed antibiotic therapy, 12 months later, or DSWI-related death. RESULTS: Most patients were male (83%) and the median age was 72 years [interquartile range (IQR) 63-76]. Coronary artery bypass was the most frequent preceding procedure (93%). The median time to diagnosis of DSWI was 13 days (IQR 10-18) after surgery. Clinical presentation consisted of wound discharge in 77% of patients. Coagulase-negative staphylococci were isolated in 54 and Staphylococcus aureus in 46 patients. All patients received antibiotics and 95% underwent surgical debridement. The median duration of antibiotic treatment was 47 days (IQR 41-78). During follow-up, 21 out of 100 patients experienced treatment failure. Of these, 8/21 patients (38%) died from DSWI after a median of 12 days (IQR 8-30). In the multivariate analysis, a rifampicin-containing antibiotic regimen was the only factor associated with lower risk of treatment failure (hazard ratio 0.26, 95% confidence interval 0.10-0.64, P = 0.004). Prolonged treatment (12 weeks instead of 6 weeks) did not alter outcome (P = 0.716) in patients without prosthetic valve endocarditis. CONCLUSIONS: Treatment of rifampicin-susceptible staphylococcal DSWI with a rifampicin-containing antibiotic regimen may improve the outcome. After surgical debridement an antibiotic treatment of 6 weeks may be adequate for staphylococcal DSWI. PMID- 20542909 TI - CPHmodels-3.0--remote homology modeling using structure-guided sequence profiles. AB - CPHmodels-3.0 is a web server predicting protein 3D structure by use of single template homology modeling. The server employs a hybrid of the scoring functions of CPHmodels-2.0 and a novel remote homology-modeling algorithm. A query sequence is first attempted modeled using the fast CPHmodels-2.0 profile-profile scoring function suitable for close homology modeling. The new computational costly remote homology-modeling algorithm is only engaged provided that no suitable PDB template is identified in the initial search. CPHmodels-3.0 was benchmarked in the CASP8 competition and produced models for 94% of the targets (117 out of 128), 74% were predicted as high reliability models (87 out of 117). These achieved an average RMSD of 4.6 A when superimposed to the 3D structure. The remaining 26% low reliably models (30 out of 117) could superimpose to the true 3D structure with an average RMSD of 9.3 A. These performance values place the CPHmodels-3.0 method in the group of high performing 3D prediction tools. Beside its accuracy, one of the important features of the method is its speed. For most queries, the response time of the server is <20 min. The web server is available at http://www.cbs.dtu.dk/services/CPHmodels/. PMID- 20542910 TI - RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach. AB - RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov. PMID- 20542911 TI - ParticleStats: open source software for the analysis of particle motility and cytoskeletal polarity. AB - The study of dynamic cellular processes in living cells is central to biology and is particularly powerful when the motility characteristics of individual objects within cells can be determined and analysed statistically. However, commercial programs only offer a limited range of inflexible analysis modules and there are currently no open source programs for extensive analysis of particle motility. Here, we describe ParticleStats (http://www.ParticleStats.com), a web server and open source programs, which input the X,Y coordinate positions of objects in time, and output novel analyses, graphical plots and statistics for motile objects. ParticleStats comprises three separate analysis programs. First, ParticleStats:Directionality for the global analysis of polarity, for example microtubule plus end growth in Drosophila oocytes. Second, ParticleStats:Compare for the analysis of saltatory movement in terms of runs and pauses. This can be applied to chromosome segregation and molecular motor-based movements. Thirdly ParticleStats:Kymographs for the analysis of kymograph images, for example as applied to separation of chromosomes in mitosis. These analyses have provided key insights into molecular mechanisms that are not possible from qualitative analysis alone and are widely applicable to many other cell biology problems. PMID- 20542912 TI - Are two better than one? Analysis of an FtsK/Xer recombination system that uses a single recombinase. AB - Bacteria harbouring circular chromosomes have a Xer site-specific recombination system that resolves chromosome dimers at division. In Escherichia coli, the activity of the XerCD/dif system is controlled and coupled with cell division by the FtsK DNA translocase. Most Xer systems, as XerCD/dif, include two different recombinases. However, some, as the Lactococcus lactis XerS/dif(SL) system, include only one recombinase. We investigated the functional effects of this difference by studying the XerS/dif(SL) system. XerS bound and recombined dif(SL) sites in vitro, both activities displaying asymmetric characteristics. Resolution of chromosome dimers by XerS/dif(SL) required translocation by division septum borne FtsK. The translocase domain of L. lactis FtsK supported recombination by XerCD/dif, just as E. coli FtsK supports recombination by XerS/dif(SL). Thus, the FtsK-dependent coupling of chromosome segregation with cell division extends to non-rod-shaped bacteria and outside the phylum Proteobacteria. Both the XerCD/dif and XerS/dif(SL) recombination systems require the control activities of the FtsKgamma subdomain. However, FtsKgamma activates recombination through different mechanisms in these two Xer systems. We show that FtsKgamma alone activates XerCD/dif recombination. In contrast, both FtsKgamma and the translocation motor are required to activate XerS/dif(SL) recombination. These findings have implications for the mechanisms by which FtsK activates recombination. PMID- 20542913 TI - MuD: an interactive web server for the prediction of non-neutral substitutions using protein structural data. AB - The discrimination between functionally neutral amino acid substitutions and non neutral mutations, affecting protein function, is very important for our understanding of diseases. The rapidly growing amounts of experimental data enable the development of computational tools to facilitate the annotation of these substitutions. Here, we describe a Random Forests-based classifier, named Mutation Detector (MuD) that utilizes structural and sequence-derived features to assess the impact of a given substitution on the protein function. In its automatic mode, MuD is comparable to alternative tools in performance. However, the uniqueness of MuD is that user-reported protein-specific structural and functional information can be added at run-time, thereby enhancing the prediction accuracy further. The MuD server, available at http://mud.tau.ac.il, assigns a reliability score to every prediction, thus offering a useful tool for the prioritization of substitutions in proteins with an available 3D structure. PMID- 20542914 TI - Providing web servers and training in Bioinformatics: 2010 update on the Bioinformatics Links Directory. AB - The Links Directory at Bioinformatics.ca continues its collaboration with Nucleic Acids Research to jointly publish and compile a freely accessible, online collection of tools, databases and resource materials for bioinformatics and molecular biology research. The July 2010 Web Server issue of Nucleic Acids Research adds an additional 115 web server tools and 7 updates to the directory at http://bioinformatics.ca/links_directory/, bringing the total number of servers listed close to an impressive 1500 links. The Bioinformatics Links Directory represents an excellent community resource for locating bioinformatic tools and databases to aid one's research, and in this context bioinformatic education needs and initiatives are discussed. A complete list of all links featured in this Nucleic Acids Research 2010 Web Server issue can be accessed online at http://bioinformatics.ca/links_directory/narweb2010/. The 2010 update of the Bioinformatics Links Directory, which includes the Web Server list and summaries, is also available online at the Nucleic Acids Research website, http://nar.oxfordjournals.org/. PMID- 20542915 TI - ICM Web: the interactive chromatin modeling web server. AB - The interactive chromatin modeling web server (ICM Web) is an interactive tool that allows users to rapidly assess nucleosome stability and fold sequences of DNA into putative chromatin templates. ICM Web takes a sequence composed of As, Cs, Gs, and Ts as input and generates (i) a nucleosome energy level diagram, (ii) coarse-grained representations of free DNA and chromatin and (iii) plots of the helical parameters (Tilt, Roll, Twist, Shift, Slide and Rise) as a function of position. The user can select from several different energy models, nucleosome structures and methods for placing nucleosomes in the energy landscape. Alternatively, if nucleosome footprints are known from experiment, ICM Web can use these positions to create a nucleosome array. The default energy model achieves a correlation coefficient of 0.7 with 100 experimentally determined values of stability and properly predicts the location of six positioned nucleosomes in the mouse mammary tumor virus (MMTV) promoter. ICM Web is suitable for interactively investigating nucleosome stability and chromatin folding for sequences up to tens of kilobases in length. No login is required to use ICM Web. PMID- 20542916 TI - Binding site number variation and high-affinity binding consensus of Myb-SANT like transcription factor Adf-1 in Drosophilidae. AB - There is a growing interest in the evolution of transcription factor binding sites and corresponding functional change of transcriptional regulation. In this context, we have examined the structural changes of the ADF-1 binding sites at the Adh promoters of Drosophila funebris and D. virilis. We detected an expanded footprinted region in D. funebris that contains various adjacent binding sites with different binding affinities. ADF-1 was described to direct sequence specific DNA binding to sites consisting of the multiple trinucleotide repeat . The ADF-1 recognition sites with high binding affinity differ from this trinucleotide repeat consensus sequence and a new consensus sequence is proposed for the high-affinity ADF-1 binding sites. In vitro transcription experiments with the D. funebris and D. virilis ADF-1 binding regions revealed that stronger ADF-1 binding to the expanded D. funebris ADF-1 binding region only moderately lead to increased transcriptional activity of the Adh gene. The potential of this regional expansion is discussed in the context of different ADF-1 cellular concentrations and maintenance of the ADF-1 stimulus. Altogether, evolutionary change of ADF-1 binding regions involves both, rearrangements of complex binding site cluster and also nucleotide substitutions within sites that lead to different binding affinities. PMID- 20542917 TI - Numbers of genes in the NBS and RLK families vary by more than four-fold within a plant species and are regulated by multiple factors. AB - Many genes exist in the form of families; however, little is known about their size variation, evolution and biology. Here, we present the size variation and evolution of the nucleotide-binding site (NBS)-encoding gene family and receptor like kinase (RLK) gene family in Oryza, Glycine and Gossypium. The sizes of both families vary by numeral fold, not only among species, surprisingly, also within a species. The size variations of the gene families are shown to correlate with each other, indicating their interactions, and driven by natural selection, artificial selection and genome size variation, but likely not by polyploidization. The numbers of genes in the families in a polyploid species are similar to those of one of its diploid donors, suggesting that polyploidization plays little roles in the expansion of the gene families and that organisms tend not to maintain their 'surplus' genes in the course of evolution. Furthermore, it is found that the size variations of both gene families are associated with organisms' phylogeny, suggesting their roles in speciation and evolution. Since both selection and speciation act on organism's morphological, physiological and biological variation, our results indicate that the variation of gene family size provides a source of genetic variation and evolution. PMID- 20542918 TI - Knocking down gene function with an RNA aptamer expressed as part of an intron. AB - We developed a powerful expression system to produce aptamers and other types of functional RNA in yeast to examine their effects. Utilizing the intron homing process, the aptamer-coding sequences were integrated into hundreds of rRNA genes, and the aptamers were transcribed at high levels by RNA polymerase I without any additional promoter being introduced into the cell. We used this system to express an aptamer against the heat shock factor 1 (HSF1), a conserved transcription factor responsible for mobilizing specific genomic expression programs in response to stressful conditions such as elevated temperature. We observed a temperature sensitive growth retardation phenotype and specific decrease of heat shock gene expression. As HSF1 enables and promotes malignant growth and metastasis in mammals, and this aptamer binds yeast HSF1 and its mammalian ortholog with equal affinity, the results presented here attest to the potential of this aptamer as a specific and effective inhibitor of HSF1 activity. PMID- 20542919 TI - Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26. AB - HDM2 is a p53-specific E3 ubiquitin ligase. Its overexpression leads to excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. HDM2 also affects the cell cycle, apoptosis and tumorigenesis through interacting with other molecules, including several ribosomal proteins. To identify novel HDM2 regulators, we performed a yeast two-hybrid screening using HDM2 as bait. Among the candidates, ribosomal protein L26 (RPL26) was characterized as a novel HDM2-interactor. The interaction between HDM2 and RPL26 was further validated by in vivo and in vitro assays. RPL26 modulates the HDM2-p53 interaction by forming a ternary complex among RPL26, HDM2 and p53, which stabilize p53 through inhibiting the ubiquitin ligase activity of HDM2. The ribosomal stress caused by a low dose of Act D enhances RPL26-HDM2 interaction and activates p53. Overexpression of RPL26 results in activating of p53, inhibits cell proliferation and induces a p53-dependent cell cycle arrest. These results provide a novel regulatory mechanism of RPL26 to activate p53 by inhibiting HDM2. PMID- 20542920 TI - Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells from patients with multiple sclerosis. AB - Recent studies have investigated the potential of autologous bone marrow-derived mesenchymal stem cells (MSCs) as a therapy for multiple sclerosis. Whether MSCs from individuals with multiple sclerosis are functionally and/or phenotypically abnormal has received less attention. Through our Phase I clinical trial, SIAMMS, we were able to isolate and characterize MSCs from individuals with multiple sclerosis. The objective of the study was to demonstrate that MSCs from individuals with multiple sclerosis show no significant differences from MSCs derived from individuals without multiple sclerosis. MSCs were isolated from bone marrow aspirates from four SIAMMS participants. We were also able to isolate MSCs from bone marrow obtained during a total hip replacement operation on an individual with multiple sclerosis. Control MSCs were isolated from bone marrow acquired during total hip replacement operations on five individuals without MS. MSCs were characterized using standard criteria: plastic adherence, differentiation along adipogenic/osteogenic/chondrogenic lineages, and expression of specific cell surface antigens. We also determined their proliferation potential. MSCs from individuals with multiple sclerosis and individuals without multiple sclerosis were similar in proliferation, differentiation potential and cell surface antigen expression. This has relevance to scientific studies investigating the therapeutic potential of autologous MSCs which primarily utilize MSCs from individuals without multiple sclerosis, and relevance to clinical studies extrapolating from these scientific findings. PMID- 20542921 TI - Pregnancy outcome in women with multiple sclerosis: results from a prospective nationwide study in Finland. AB - The majority of individuals obtaining the diagnosis of multiple sclerosis are women of childbearing age. They are naturally concerned as to how multiple sclerosis affects the course of pregnancy and the developing foetus. The objective of this study was to prospectively evaluate the incidence of pregnancy complications and delivery risks, and to follow the natural course of multiple sclerosis during and after pregnancy in a cohort of Finnish patients with multiple sclerosis. Sixty-one patients with multiple sclerosis who became pregnant during the years 2003-2005 were prospectively followed-up from early pregnancy until 6 months postpartum. Multiple sclerosis relapses, Expanded Disability Status Scale rates and obstetric details were recorded. The results were compared with the statistics obtained from Finnish Medical Birth Register from the year 2004. We found that patients with multiple sclerosis were no more likely to experience pregnancy complications than Finnish pregnant women generally, but they had a greater likelihood for a need of artificial insemination (4.9% vs. 0.9%; p = 0.0009). Subjects with multiple sclerosis were more likely to undergo assisted vaginal delivery than the at-large cohort (16.4% vs. 6.5%; p = 0.0017). We conclude that pregnancy does not seem to pose a woman with multiple sclerosis to a greater risk for pregnancy complications when compared with women in general. The potential need for instrumental delivery should, however, be taken into account when planning the delivery of a mother with multiple sclerosis. PMID- 20542922 TI - Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A. AB - We have reported recently that inhibition of protein phosphatase (PP)-2A and PP-1 by calyculin A, a specific inhibitor of PP-2A and PP-1, induced Alzheimer-like hyperphosphorylation of tau and spatial memory retention impairment. In this study, we tested the in vivo effects of melatonin on these Alzheimer-like changes. We found that administration of melatonin intraperitoneally for 9 consecutive days before injection of calyculin A could prevent calyculin A induced synaptophysin loss, memory retention deficits, as well as hyperphosphorylation of tau and neurofilaments. Furthermore, melatonin partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307 (Y307), a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde, a marker of oxidative stress, induced by calyculin A. These results suggest that melatonin could serve as a potential therapeutic agent for preventing Alzheimer-like pathological changes and behavioral abnormality via modulating the activity of PP-2A and oxidative stress. PMID- 20542923 TI - A randomized double-blind study comparing 25 and 50 mg TC-1734 (AZD3480) with placebo, in older subjects with age-associated memory impairment. AB - Cognitive decline is a feature of ageing and can be defined as normal (age associated memory impairment) or pathological (mild cognitive impairment/Alzheimer's disease). Stimulation of selective brain-specific neuronal nicotinic acetylcholine receptors might offer symptomatic treatment for normal ageing. The objective of this study was to assess the safety, tolerability and efficacy of TC-1734 (AZD3480), a selective alpha4beta2 nicotinic agonist, in the treatment of age-associated memory impairment. A randomized placebo-controlled trial was conducted in 16 community-based centers within the USA. Subjects who met objective criteria for age-associated memory impairment were recruited between November 2004 and December 2005. Subjects were randomly assigned to receive orally 25 mg (n = 59), 50 mg (n = 68) TC-1734 (AZD3480) or placebo (n = 66) in a double-blind fashion for 16 weeks. Main outcome measures included routine clinical safety measures, tolerability, cognitive assessment via the Cognitive Drug Research computerized test battery and a Subject Global Impression Scale of Cognition (SCI-Cog). Two outcomes from the computerized test battery - a factor assessing attention and one assessing episodic memory, along with the SGI Cog were defined as co-primary outcome variables. Baseline to Week 16 differences from placebo for 50 mg TC-1734 (AZD3480) were considered of primary importance. For 50 mg TC-1734 (AZD3480) attention factor the mean drug-placebo difference was 22.9 (95% confidence interval 4.8 to 41.4) p = 0.01 for episodic memory factor the difference was -7.6 (95% confidence interval -14.4 to -0.8), p = 0.029, and for the SGI-Cog the difference was 0.99 (95% confidence interval 0.2 to 1.8), p = 0.015. As all three co-primary outcomes were positive it can be concluded the compound likely had a beneficial effect on cognition. TC-1734 (AZD3480) appeared safe and well tolerated in this study. PMID- 20542924 TI - The genotoxic and oxidative damage potential of olanzapine in vitro. AB - Olanzapine (OLZ) is an atypical antipsychotic drug and is commonly used for the treatment of schizophrenia and bipolar disorder (BD). However, recent reports indicated that this drug could exhibit cytotoxic effects on nervous and immune systems. To our knowledge, there is scarce data considering the genotoxic or oxidative damage potentials of OLZ on human lymphocyte culture system. Therefore, in this study, the genotoxic potential of OLZ (0 to 160 uM) have been evaluated in human whole blood cultures (WBCs) related to oxidative status. Sister chromatid exchange (SCE) test was applied to estimate the DNA damage, and biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine oxidative stress. Our results indicated that the tested antipsychotic drug did not induce SCEs in lymphocytes of treated cultures. However, the application of the highest OLZ concentration caused oxidative stress. It is concluded that the OLZ can be used safely, but it is necessary to consider the tissue damages that are likely to appear depending on the oxidative stress. PMID- 20542925 TI - Dichlorvos-induced developmental toxicity in zebrafish. AB - The present study examined effects of the pesticide dichlorvos (O-(2,2 dichlorovinyl)-O,O dimethylphosphate [DDVP]) on embryonic development of zebrafish. In a first set of experiments, early life stages of zebrafish were exposed to five concentrations (5, 10, 25, 50, and 100 mg/L(-1)) of DDVP for 96 hours post fertilization (hpf). The 24-hpf LC(50) value of DDVP in the semistatic test was 39.75 mg/L(-1). Developmental abnormalities have been observed in embryos and larvae, such as no blood flow, cardiac edema, delayed hatching, and vertebra malformations. Most of the onserved effects were increased in a concentration-dependent manner. To investigate the behavior of the larvae, zebrafish exposed to 10 and 25 mg/L(-1) DDVP were observed on days 6 and 9 after fertilization. 25 mg L(-1) DDVP dose caused significant slowing of swimming activity on day 6 and 9 after fertilization. According to present study results, DDVP exposure during early development caused (i) clear behavioral impairments detectable during the posthatching period and (ii) mortality and developmental abnormalities in zebrafish. Dichlorvos is present in the environment with other similar organophosphate compounds. Additive responses to organophosphate compounds may induce lethal or sub-lethal effects in early life stages of fish chronically exposed to this class of chemicals. PMID- 20542926 TI - Evaluation of DNA damage in construction-site workers occupationally exposed to welding fumes and solvent-based paints in Turkey. AB - In this study, the comet assay was used to evaluate whether welding fume and solvent base paint exposure led to DNA damage in construction-site workers in Turkey. The workers (n = 52) were selected according to their exposure in the construction site and controls (n = 26) from the general population, with no history of occupational exposure. The alkaline comet assay, a standard method for assessing genotoxicity, has been applied in peripheral lymphocytes of all subjects. The mean percentages of DNA in tail (%DNA(T)) of each group were evaluated, including the comparisons between smokers in each different group and the duration of exposure. Significant increase in the mean %DNA(T) (p < 0.01) was observed in all exposed subjects (12.34 +/- 2.05) when compared with controls (6.64 +/- 1.43). Also %DNA(T) was significantly high (p < 0.01) in welders (13.59 +/- 1.89) compared with painters (11.10 +/- 1.35). There was a statistical meaningful difference in % DNA(T) between control and exposed smokers. Our findings indicate that exposure to welding fumes and paints induce genotoxic effect in peripheral lymphocytes, indicating a potential health risk for workers. Therefore, to ensure maximum occupational safety, biomonitoring is of great value for assessing the risk for construction workers. PMID- 20542927 TI - Importance of a balanced diet on the physical fitness level of schoolchildren aged 6-12. AB - Previous studies have focused on a single nutrient's relationship with disease and thus are unable to strongly support the health claims of a balanced diet. This article explores the integrated effect of nine nutrients on an individual's physical fitness level. Two-day dietary records and physical fitness assessments were collected in three primary schools. Cluster analysis allowed compliance with nutrient recommendations to be compared among groups of primary school students with different characteristics. Two clusters were identified statistically. Cluster B, which comprised more schoolchildren at the 'Good' and 'Pass' levels and fewer at the 'Excellent' level, had significantly more participants who met the guidelines for total fat, saturated fat, sodium and cholesterol, compared with Cluster A. This finding reveals the benefits of a balanced diet, with physical fitness level as the outcome measure. The results also have implications for approaching health problems from the diet-fitness perspective rather than the obesity-disease perspective. PMID- 20542928 TI - Involvement of hydrogenases in the formation of highly catalytic Pd(0) nanoparticles by bioreduction of Pd(II) using Escherichia coli mutant strains. AB - Escherichia coli produces at least three [NiFe] hydrogenases (Hyd-1, Hyd-2 and Hyd-3). Hyd-1 and Hyd-2 are membrane-bound respiratory isoenzymes with their catalytic subunits exposed to the periplasmic side of the membrane. Hyd-3 is part of the cytoplasmically oriented formate hydrogenlyase complex. In this work the involvement of each of these hydrogenases in Pd(II) reduction under acidic (pH 2.4) conditions was studied. While all three hydrogenases could contribute to Pd(II) reduction, the presence of either periplasmic hydrogenase (Hyd-1 or Hyd-2) was required to observe Pd(II) reduction rates comparable to the parent strain. An E. coli mutant strain genetically deprived of all hydrogenase activity showed negligible Pd(II) reduction. Electron microscopy suggested that the location of the resulting Pd(0) deposits was as expected from the subcellular localization of the particular hydrogenase involved in the reduction process. Membrane separation experiments established that Pd(II) reductase activity is membrane-bound and that hydrogenases are required to initiate Pd(II) reduction. The catalytic activity of the resulting Pd(0) nanoparticles in the reduction of Cr(VI) to Cr(III) varied according to the E. coli mutant strain used for the initial bioreduction of Pd(II). Optimum Cr(VI) reduction, comparable to that observed with a commercial Pd catalyst, was observed when the bio-Pd(0) catalytic particles were prepared from a strain containing an active Hyd-1. The results are discussed in the context of economic production of novel nanometallic catalysts. PMID- 20542929 TI - Differential PilA pilus assembly by a hospital-acquired and a community-derived Enterococcus faecium isolate. AB - Pili are hair-like structures protruding from the cell envelope of bacterial cells. Here, we describe the conditional and differential display of PilA-type pili, and PilE and PilF proteins, encoded from pilin gene cluster 1 at the surface of a hospital-acquired Enterococcus faecium bloodstream isolate (E1165) and a community-derived stool isolate (E1039), at two different temperatures. Both strains have virtually identical pilA gene clusters, as determined by sequencing. Western blotting and transmission immunoelectron microscopy revealed that PilA and PilF assembled into high-molecular-mass pilus-like structures at 37 degrees C in the E1165 strain, whereas PilE was not produced at either of the temperatures used; at 21 degrees C, PilA and PilF were cell-wall-anchored proteins. In contrast, in strain E1039, PilA, PilE and PilF pilin proteins were found to be displayed as cell-wall-anchored proteins at 37 degrees C only, and they were not associated with pilus-like structures. The discrepancy in pilus assembly between E1039 and E1165 cannot be explained by differences in expression of the genes encoding the predicted sortases in the pilA gene cluster, as these had similar expression levels in both strains at 21 and 37 degrees C. Double labelling electron microscopy revealed that PilA formed the pilus backbone in E1165, and PilF the minor subunit which was distributed along the PilA pilus shaft and positioned at the tip; however, it was deposited as a cell-wall anchored protein in a pilA isogenic mutant. The differential deposition of surface proteins from pilin gene cluster 1 and differences in pilus assembly in the two strains suggest a complex post-transcriptional regulatory mechanism of pilus biogenesis in E. faecium. PMID- 20542930 TI - Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor. AB - HpdR, an IclR-family regulator in Streptomyces coelicolor, is a substrate dependent repressor for the tyrosine catabolic gene hppD. In this study, S1 nuclease protection assays revealed that hpdR is subject to a negative autoregulation. Purified HpdR showed specific DNA-binding activity for the promoter region of hpdR, indicating that the autoregulation of hpdR is performed directly. The disruption of hpdR led to reduced production of CDA by S. coelicolor J1501, suggesting a positive effect of hpdR on CDA biosynthesis. Electrophoretic mobility shift assays showed that HpdR specifically bound to the promoter region of hmaS (SCO3229 in the CDA gene cluster), encoding 4 hydroxymandelic acid synthase. Disruption of hmaS in J1501 abolished CDA production. It is possible that hpdR regulates CDA biosynthesis by controlling the transcription of hmaS. PMID- 20542931 TI - A randomised controlled trial: outcomes of bladder rehabilitation in persons with multiple sclerosis. AB - OBJECTIVE: A stratified, randomised, waitlist controlled study over 12 months assessed the effectiveness of a 6 week bladder rehabilitation programme in persons with multiple sclerosis (pwMS) in an Australian community cohort. METHODS: Patients with definite MS and bladder issues (n=74) recruited from a tertiary hospital database were randomised to a treatment group (n=40) for an individualised bladder rehabilitation programme or to a control waitlist group (n=34). The Urogenital Distress Inventory (UDI6), Neurological Disability Scale (NDS) and the American Urological Association Symptom Index (AUA) assessed bladder impairment and 'activity limitation'; a single Quality of life (QoL) item in the AUA and the Incontinence Impact Questionnaire (IIQ7) measured restriction in 'participation'. Primary outcome measures were assessed at baseline and at 12 months. RESULTS: Analysis of per protocol data from 58 patients (treatment n=24, control n=34) showed reduced disability in the treatment group, with significant differences (p<0.001) and large effect sizes (>0.5) in post-treatment UDI6, NDS, AUA total, AUA QoL and IIQ7 scores for the two groups. The treatment group compared with the control group showed improvement: 78% versus 27% for UDI6 and 59% versus 17% improved for IIQ7. More patients in the control group deteriorated over the study period on the UDI6 (30% vs 0%; p<0.001) and IIQ7 (39 vs 0%; p=0.001). CONCLUSION: A multifaceted, individualised bladder rehabilitation programme reduces disability and improves QoL in pwMS compared with no intervention after 12 months of follow-up. Information on specific interventions in different bladder types in MS and the impact on QoL need further evaluation. Australian Clinical trials Registry ACTRNO12605000676617. PMID- 20542932 TI - Early detection of sporadic CJD by diffusion-weighted MRI before the onset of symptoms. PMID- 20542933 TI - Preserved motor axonal membrane potential in mitochondrial disease. AB - Mitochondrial disorders are characterised by protean neurological manifestations including peripheral neuropathy. The neuropathy is typically an axonal process, with a proposed mechanism being degradation of the membrane potential of the axon due to dysfunction of energy-dependent Na(+)/K(+) ATPase pump. To address this issue, we studied the excitability of motor axons in the median nerve in 16 individuals identified with gene testing or muscle biopsy. Twelve patients had clinical or nerve conduction abnormalities. Strength--duration time constant, threshold electrotonus, current--threshold relationship and recovery cycle were identical to control values. These findings imply that an alternative mechanism to a change in membrane potential is responsible for neuronal injury in these patients. PMID- 20542934 TI - Forensic psychiatry in Canada: a journey on the road to specialty. PMID- 20542935 TI - Veterans and the justice system: the next forensic frontier. PMID- 20542936 TI - False confessions, expert testimony, and admissibility. AB - The confession of a criminal defendant serves as a prosecutor's most compelling piece of evidence during trial. Courts must preserve a defendant's constitutional right to a fair trial while upholding the judicial interests of presenting competent and reliable evidence to the jury. When a defendant seeks to challenge the validity of that confession through expert testimony, the prosecution often contests the admissibility of the expert's opinion. Depending on the content and methodology of the expert's opinion, testimony addressing the phenomenon of false confessions may or may not be admissible. This article outlines the scientific and epistemological bases of expert testimony on false confession, notes the obstacles facing its admissibility, and provides guidance to the expert in formulating opinions that will reach the judge or jury. We review the 2006 New Jersey Superior Court decision in State of New Jersey v. George King to illustrate what is involved in the admissibility of false-confession testimony and use the case as a starting point in developing a best-practice approach to working in this area. PMID- 20542937 TI - Commentary: overcoming judicial preferences for person- versus situation-based analyses of interrogation-induced confessions. AB - The vast majority of false confessions occur in the context of interrogation, and in response to the sources of distress and persuasive tactics of the interrogation. However, there are widely held mistaken assumptions that a false confessor must suffer some personal defect such as a mental disorder. In this article, we explain that many normal people may give false confessions under certain social situations. We examine such situations and their effects on false confessions. We urge courts to recognize that suspect-enhanced vulnerabilities are not a necessary condition for the elicitation of false confessions, but rather that much lesser situational factors have just as much influence on the interrogated. We lay out a set of guidelines to assist expert testifiers in evaluating better an interrogation-induced confession. PMID- 20542938 TI - Humiliation: its nature and consequences. AB - In this article, we present a new analysis of what is involved when individuals undergo significant public humiliation. We describe the structure of humiliation that is, the factors that, taken collectively, render certain life events and circumstances humiliating; the most common destructive consequences of being subjected to them; and several personality factors that, when present, can serve to amplify the damaging effects of humiliating experiences. The analysis is intended to enable forensic clinicians, lawyers, judges, and other relevant parties to understand better what happens when individuals are humiliated and to identify more precisely the damage that such persons sustain. It is also intended to have heuristic value for the discussion, confrontation, and alleviation of humiliation in correctional, jurisprudential, clinical, and general societal contexts. PMID- 20542939 TI - Commentary: till we have faces--on humiliation. AB - My commentary takes up two points raised by Drs. Torres and Bergner: first, the social context in which humiliation takes place and the way such behavior is normalized; and second, the question of face, and in this context, the loss of face and its impact on identity. For me, the key concern in relation to humiliation is not so much loss of entitlement status, but a loss of identity. Humiliation is a fundamental attack on narrative identity, but I will make the (perhaps uncomfortable) suggestion that not everyone is humiliate-able and that, to some extent, one may be able to choose the extent of one's injuries through loss of face. PMID- 20542940 TI - Commentary: is the paradigm for humiliation sufficiently complex? AB - The authors Torres and Bergner present a simple, elegant paradigm for understanding the phenomenon of humiliation. They suggest it may have universal applicability and may be of heuristic value for clinicians and policy-makers involved in forensic and social arenas. They offer case examples to illustrate its utility. It is open to question, however, whether the paradigm is sufficiently complex to encompass all the variables in actual situations. In real life, the evolution of humiliation is a highly complicated, often messy process that takes place over time and often results in intense feelings of humiliation in more than one person, often affecting several persons. The authors' examples are reexamined from alternate assumptions about what may have happened in each case. An additional case example illustrates a high degree of interpersonal complexity, suggesting that actual situations may be too unwieldy to allow for simple analysis by the paradigm. PMID- 20542941 TI - Mortality rates of males who commit parricide or other violent offense against a parent. AB - Clinical information on parricidal offenders has accumulated in recent decades. The purpose of this study was to examine and compare the mortality of matricidal and patricidal offenders in detail by using a comprehensive national data set with follow-up ranging from 3 to 24 years. The sample included forensic psychiatric examination statements and mortality data of 99 matricidal, 113 patricidal, and 111 control male violent offenders evaluated in a forensic psychiatric examination from 1973 to 2004 in Finland. The Standardized Mortality Ratio among parricidal offenders 25 to 49 years of age was increased compared with that of the general population. One-third of deaths among parricidal offenders were attributable to suicide. The matricidal males who committed suicide had a significantly shorter survival time after the offense than did the patricidal and control offenders who died by suicide. The results of the present study are compared with the previous study findings on parricidal offenders and offenders in general. PMID- 20542942 TI - Commentary: addressing suicidality in the treatment of parricidal offenders. AB - The high rate of suicides among parricidal offenders has important treatment implications. It suggests that the assessment and management of the risks of suicide and of interpersonal violence need to be conducted in an integrative fashion. It highlights the role of hopelessness and despair in parricidal acts and the need to target these for treatment, ideally by combining group and individual psychotherapy. PMID- 20542943 TI - The effect of a forensic fellowship program on general psychiatry residents' in training examination outcomes. AB - This article describes how the establishment and existence of a forensic psychiatry fellowship program was associated with improvements in general psychiatry residents' scores on the Psychiatry Resident In-training Examination (PRITE). Four consecutive years of general psychiatry residents' PRITE scores spanning 2 years before and 2 years after implementation of the forensic fellowship program at our institution were compared. Mixed-model statistical analyses accounting for repeated measurements of individual residents across the periods indicated statistically significant improvement in forensic content scores and several other subspecialty areas in which our institution offers educational fellowship programs. External indicators of program outcomes such as standardized examination scores may provide a useful indication of the effects that an educational fellowship program can have on general psychiatry education. PMID- 20542944 TI - Maternal and paternal filicides: a retrospective review of filicides in Finland. AB - The purpose of this retrospective study was to illustrate the differences in maternal and paternal filicides in Finland during a 25-year period. In the sample of 200 filicides [neonaticides (n = 56), filicide-suicides (n = 75), other filicides (n = 69)], the incidence was 5.09 deaths per 100,000 live births: 59 percent of filicides were committed by mothers, 39 percent by fathers, and 2 percent by stepfathers. The mean age of the maternal victims (1.6 y) was significantly lower than that of the paternal victims (5.6 y), but no correlation between the sex of the victim and the sex of the perpetrator was found, and the number of female and male victims was equal. The sample of other filicides (n = 65) was studied more closely by forensic psychiatric examination and review of collateral files. Filicidal mothers showed mental distress and often had psychosocial stressors of marital discord and lack of support. They often killed for altruistic reasons and in association with suicide. Maternal perpetrators also dominated in filicide cases in which death was caused by a single episode or recurrent episodes of battering. Psychosis and psychotic depression were diagnosed in 51 percent of the maternal perpetrators, and 76 percent of the mothers were deemed not responsible for their actions by reason of insanity. Paternal perpetrators, on the other hand, were jealous of their mates, had a personality disorder (67%), abused alcohol (45%), or were violent toward their mates. In 18 percent of the cases, they were not held responsible for their actions by reason of insanity. During childhood, most of the perpetrators had endured emotional abuse from their parents or guardians, some of whom also engaged in alcohol abuse and domestic violence. The purpose of this study was to examine the differences between maternal and paternal filicides in a sample of 200 cases in Finland. This report also provides a psychosocial profile of the perpetrator and victim in 65 filicides and a discussion of the influence of diagnoses on decisions regarding criminal responsibility. PMID- 20542945 TI - Ritual and signature in serial sexual homicide. AB - Ritual and signature are fantasy-driven, repetitive crime scene behaviors that have been found to occur in serial sexual homicide. Notwithstanding numerous anecdotal case reports, ritual and signature have rarely been studied empirically. In a national sample of 38 offenders and their 162 victims, we examined behavioral and thematic consistency, as well as the evolution and uniqueness of these crime scene actions. The notion that serial sexual murderers engage in the same rituals and leave unique signatures at every scene was not supported by our data. In fact, the results suggest that the crime scene conduct of this group of offenders is fairly complex and varied. Implications of these findings for forensic assessments and criminal investigations are discussed. PMID- 20542946 TI - Whose DNA is it anyway? European court, junk DNA, and the problem with prediction. AB - In this article, we discuss the implications of a recent European Court of Human Rights (ECHR) decision about the use of retained DNA profiles in criminal cases. Met with polar but equal passion from both the privacy lobby and law enforcement, this case has opened concerns regarding ethics in the nascent science of DNA profiling. Although the technology is touted as the most exciting breakthrough since fingerprinting in crime solving, there are questions regarding its use. The case decided by the ECHR intensified the debate on privacy, state control of information, and the public's right to be safe. New proposals in response, however, raise more questions than they sought to answer, ranging from unfettered data mining to the pitfalls in risk prediction. PMID- 20542947 TI - Hoarding, hermitage, and the law: why we love the collyer brothers. AB - Interest in hoarding behavior has intensified, as it works its way through DSM-V deliberations and treatment models. Meanwhile, both documentarians and fiction writers have embraced accounts of individuals with disposophobia and romanticized versions of the Collyer brothers, the Hermits of Harlem. In this article, I examine the range of media and professional attention given to hoarders and their problems and then focus on a potential role for forensic mental health professionals. The psycholegal problems of hoarders include health and zoning code violations that evolve into criminal charges, civil commitment, questions of animal cruelty, landlord-tenant disputes, divorce and custody evaluations, testamentary capacity, and child-neglect charges. PMID- 20542948 TI - The slayer statute and insanity. AB - It is common law that persons cannot benefit from their crimes. For this reason, most states have enacted slayer rules that prevent a killer from sharing in the victim's estate. However, terms in the slayer rules, such as willful and unlawful, can be difficult to apply, as illustrated by the situation in which a slayer is found not guilty by reason of insanity. The Washington Supreme Court has recently addressed whether a man who killed his mother and was then found not guilty by reason of insanity in criminal court can inherit a portion of his mother's estate. PMID- 20542949 TI - The "Pseudocommando" mass murderer: part II, the language of revenge. AB - In Part I of this article, research on pseudocommandos was reviewed, and the important role that revenge fantasies play in motivating such persons to commit mass murder-suicide was discussed. Before carrying out their mass shootings, pseudocommandos may communicate some final message to the public or news media. These communications are rich sources of data about their motives and psychopathology. In Part II of this article, forensic psycholinguistic analysis is applied to clarify the primary motivations, detect the presence of mental illness, and discern important individual differences in the final communications of two recent pseudocommandos: Seung-Hui Cho (Virginia Tech) and Jiverly Wong (Binghamton, NY). Although both men committed offenses that qualify them as pseudocommandos, their final communications reveal striking differences in their psychopathology. PMID- 20542952 TI - Total intracorporeal anastomosis during single-port laparoscopic right hemicolectomy for carcinoma of colon: a new step forward. AB - BACKGROUND: Laparoscopic surgery is a feasible option for colonic carcinoma as short-and long-term results show. This technique is as safe and effective as the open approach. Single-port access surgery is considered a new minimally invasive approach in the search for better cosmetic results and less postoperative pain. One of the goals of single-port surgery is to preserve the satisfactory oncological results obtained by standard laparoscopy. This study presents the first single-port access right hemicolectomy for carcinoma of colon with intracorporeal anastomosis. METHODS: The authors report a single-port access right hemicolectomy in a 59-year-old male patient with a neoplasm of the cecum stage IIA (T3, N0) according to the TNM classification. RESULTS: A transumbilical single-port access right hemicolectomy was performed with no additional trocars and total intracorporeal anastomosis. Operative time was 140 minutes. No intraoperative or postoperative complications were reported. CONCLUSION: Single port access right hemicolectomy with intracorporeal anastomosis is a feasible and safe technique when performed by experienced laparoscopic surgeons. This approach must follow the basic principles of laparoscopic right hemicolectomy to achieve the same oncological results. The advantages of a total intracorporeal anastomosis include that there is no need to enlarge the umbilical incision and that avoid traction of the pedicle of the mesenterium of the transverse colon during the extracorporeal anastomosis. PMID- 20542953 TI - Three-dimensional color maps: a novel tool for assessing craniofacial changes. AB - INTRODUCTION: Three-dimensional (3D) color maps are useful for analyzing data acquired by laser scanning, stereophotography, or computed tomography (CT). The authors aim to illustrate the different applications of color maps in the craniomaxillofacial region. METHODS: The images obtained from the above techniques at 2 different time points are superimposed based on a common area unaffected by the surgical intervention or growth. Using specialized software, the distance differences between the 2 superimposed images are depicted in a graphical format as a 3D color map. A color-coded scale indicating the distances accompanies these maps. RESULTS: 3D color maps can be manipulated and viewed in a variety of angles to extract the maximum diagnostic information. They facilitate the critical evaluation of facial asymmetry, accuracy of fusing CT and 3D photo data sets, and postsurgical changes. CONCLUSION: 3D color maps aid the objective assessment of craniofacial structures while enhancing visual comprehension and communication with patients. PMID- 20542954 TI - 1.5:1 meshed AlloDerm bolsters for stapled rectal anastomoses does not provide any advantage in anastomotic strength in a porcine model. AB - INTRODUCTION: The most feared complication of colorectal anastomoses is leaks resulting in severe morbidity. The concept of staple-line reinforcement is a growing area of interest. In this study, the authors evaluated the feasibility and effect of using 1.5:1 meshed AlloDerm to bolster end-to-end stapled rectal anastomoses in a porcine model. METHODS: A total of 30 female 45-kg domestic pigs were studied, and each served as its own control by creating a bolstered and unbolstered anastomosis in each animal. All anastomoses were created with a 29-mm end-to-end stapling device. Bolstered anastomoses were randomized to proximal and distal positions along the rectum, and each rectorectal anastomosis was separated by an average of 10 cm. The animals were survived to 3, 5, and 30 days. Barium enemas were then performed and the 2 anastomotic sites harvested. Each anastomosis underwent burst testing. The internal diameter of each anastomosis was measured, and a biochemical analysis was performed for elastin and collagen content. RESULTS: Bolstered anastomoses offered no strength advantage as burst pressures were no different when compared with unbolstered anastomoses. There was also no difference in anastomotic internal diameter, biochemical analysis of elastin or collagen, or presence of adhesions when comparing bolstered with unbolstered anastomoses. There were 4 subclinical leaks-1 in the unbolstered group and 3 in the bolstered group. CONCLUSIONS: The routine use of 1.5:1 meshed AlloDerm sandwich bolsters in stapled rectal anastomosis does not confer any detectable advantage in anastomotic strength. Further studies are needed to determine equivalence to traditional stapled anastomoses. PMID- 20542955 TI - Signaling from membrane receptors to tumor suppressor WW domain-containing oxidoreductase. AB - The family of WW domain-containing proteins contains over 2000 members. The small WW domain module is responsible, in part, for protein/protein binding interactions and signaling. Many of these proteins are located at the membrane/cytoskeleton area, where they act as adaptors to receive signals from the cell surface. In this review, we provide molecular insights regarding recent novel findings on signaling from the cell surface toward WW domain-containing oxidoreductase, known as WWOX, FOR or WOX1. More specifically, transforming growth factor beta 1 utilizes cell surface hyaluronidase Hyal-2 (hyaluronoglucosaminidase 2) as a cognate receptor for signaling with WWOX and Smad4 to control gene transcription, growth and death. Complement C1q alone, bypassing the activation of classical pathway, signals a novel event of apoptosis by inducing microvillus formation and WWOX activation. Deficiency in these signaling events appears to favorably support cancer growth. PMID- 20542956 TI - Quiescence: a mechanism for escaping the effects of drug on cell populations. AB - We point out that a simple and generic strategy in order to lower the risk for extinction consists in developing a dormant stage in which the organism is unable to multiply but may die. The dormant organism is protected against the poisonous environment. The result is to increase the survival probability of the entire population by introducing a type of zero reproductive fitness. This is possible, because the reservoir of dormant individuals act as a buffer that can cushion fatal fluctuations in the number of births and deaths, which without the dormant population would have driven the entire population to extinction. PMID- 20542957 TI - Fifteen observations on the structure of energy-minimizing gaits in many simple biped models. AB - A popular hypothesis regarding legged locomotion is that humans and other large animals walk and run in a manner that minimizes the metabolic energy expenditure for locomotion. Here, using numerical optimization and supporting analytical arguments, I obtain the energy-minimizing gaits of many different simple biped models. I consider bipeds with point-mass bodies and massless legs, with or without a knee, with or without a springy tendon in series with the leg muscle and minimizing one of many different 'metabolic cost' models-correlated with muscle work, muscle force raised to some power, the Minetti-Alexander quasi steady approximation to empirical muscle metabolic rate (from heat and ATPase activity), a new cost function called the 'generalized work cost' C(g) having some positivity and convexity properties (and includes the Minetti-Alexander cost and the work cost as special cases), and generalizations thereof. For many of these models, walking-like gaits are optimal at low speeds and running-like gaits at higher speeds, so a gait transition is optimal. Minimizing the generalized work cost C(g) appears mostly indistinguishable from minimizing muscle work for all the models. Inverted pendulum walking and impulsive running gaits minimize the work cost, generalized work costs C(g) and a few other costs for the springless bipeds; in particular, a knee-torque-squared cost, appropriate as a simplified model for electric motor power for a kneed robot biped. Many optimal gaits had symmetry properties; for instance, the left stance phase was identical to the right stance phases. Muscle force-velocity relations and legs with masses have predictable qualitative effects, if any, on the optima. For bipeds with compliant tendons, the muscle work-minimizing strategies have close to zero muscle work (isometric muscles), with the springs performing all the leg work. These zero work gaits also minimize the generalized work costs C(g) with substantial additive force or force rate costs, indicating that a running animal's metabolic cost could be dominated by the cost of producing isometric force, even though performing muscle work is usually expensive. I also catalogue the many differences between the optimal gaits of the various models. These differences contain information that might help us develop models that better predict locomotion data. In particular, for some biologically plausible cost functions, the presence or absence of springs in series with muscles has a large effect on both the coordination strategy and the absolute cost; the absence of springs results in more impulsive (collisional) optimal gaits and the presence of springs leads to more compliant optimal gaits. Most results are obtained for specific speed and stride length combinations close to preferred human behaviour, but limited numerical experiments show that some qualitative results extend to other speed-stride length combinations as well. PMID- 20542958 TI - Bioenergy research: a new paradigm in multidisciplinary research. AB - The field of biology is becoming increasingly interdisciplinary and cross cutting. This changing research atmosphere is creating the way for a new kind of enquiry that while building upon the traditional research establishment is providing a new multidisciplinary framework to more effectively address scientific grand challenges. Using the US Department of Energy sponsored BioEnergy Science Center as an example, we highlight how impactful breakthroughs in biofuel science can be achieved within a large cross-disciplinary team environment. Such transformational insights are key to furthering our understanding and in generating models, theories and processes that can be used to overcome recalcitrance of biomass for sustainable biofuel production. Multidisciplinary approaches have an increasingly greater role to play in meeting rising demands for food, fibre, energy, clean environment and good health. Discoveries achieved by diverse minds and cross-applications of tools and analytical approaches have tremendous potential to fill existing knowledge gaps, clear roadblocks and facilitate translation of basic sciences discoveries as solutions towards addressing some of the most pressing global issues. PMID- 20542959 TI - Patient assessed health profile: a six-month quality of life questionnaire survey after day surgery. AB - AIM: Patient assessed quality of life is one of the principal end-points after day surgery. The aim of the present study was to describe the natural course, differences and timing of final evaluation for three common day surgical procedures; inguinal hernia repair (IHR), arthroscopic procedures (AS); and cosmetic breast augmentation (CBA). METHOD: A total of 355 patients prospectively completed an extended eight-item EQ-5D questionnaire (pain, mobility, mood, self care, activities, sleep, sex, need for analgesic), preoperatively and at one, three and six months postoperatively. RESULTS: Pain and mobility problems were frequently reported prior to surgery among IHR and AS patients, while CBA patients had less deviation from normal in the preoperative health profile. The proportions of patients reporting surgery-related deviations were 35%, 20% and 5% at one, three and six months respectively. After one month, 50% of AS patients still suffered subjective discomfort as compared to 13% and 20% of the IHR and CBA patients, respectively. Pain and ambulation problems were the most common symptoms in all groups. Six months after surgery, 94% of IHR, 89% of AS and 97% of CBA patients were fully recovered. CONCLUSIONS: No major morbidity or severe complications were observed and patients' satisfaction was high overall. We found procedure-specific changes in the postoperative health profile after day surgery. AS patients recovered more slowly compared with IHR and CBA patients. We conclude that time for final evaluation differs significantly between procedures. PMID- 20542960 TI - Diagnostic implications of 16S ribosomal assay for gonorrhoea. AB - OBJECTIVES: In the absence of a single nucleic acid amplification test (NAAT) that is both highly specific and sensitive for gonorrhoea, many have put forward the 16S-based assay as a confirmatory test for Neisseria gonorrhoeae. This study was undertaken to evaluate the performance of PCR based on 16S ribosomal gene in comparison with a porA pseudogene-based assay. METHODS: The specificity of both the porA pseudogene-based PCR and 16S ribosomal gene PCR was checked against a panel of strains comprising of non N gonorrhoeae Neisseria sp (NgNS) and other gram-negative and gram-positive bacteria. The sensitivity studies were performed using different dilutions of N gonorrhoeae DNA. PCRs were also done on endocervical and urethral swab samples collected from a total of 100 female and 50 male patients presenting to sexually transmitted disease clinics, Dermatology OPD of AIIMS and Safdarjang Hospital, New Delhi, India, recruited as per inclusion criteria. RESULTS: PCR assay based on 16S ribosomal gene showed cross reactivity with three of six strains of N sicca. The porA pseudogene-based PCR was highly specific. Analytical sensitivity of 16S-based ribosomal assay was more than that of porA pseudogene-based assay. In clinical samples, for female patients, sensitivity, specificity, positive predictive value and negative predictive value of 16S ribosomal assay was 100% (95% CI 51.7% to 100%), 91.5% (95% CI 83.4% to 96%), 42.9% (95% CI 18.8% to 70.4%) and 100% (95% CI 94.7% to 100%), respectively, while for the male patients it was 100% (95% CI 85% to 100%), 95.5% (95% CI 75.1% to 99.8%), 96.6% (95% CI 80.4% to 99.8%) and 100% (95% CI 80.8% to 100%), respectively. CONCLUSIONS: The data presented in this report supports use of 16S ribosomal assay as a screening assay only. The porA pseudogene target is highly specific for N gonorrhoeae and may be used as a supplemental assay. PMID- 20542961 TI - Rabeximod reduces arthritis severity in mice by decreasing activation of inflammatory cells. AB - OBJECTIVES: The novel small molecule 9-chloro-2,3-dimethyl-6-(N,N dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b] quinoxaline (Rabeximod) reduces severity of arthritis in rodent models of rheumatoid arthritis (RA) and multiple sclerosis (MS). This study aimed to investigate the cellular target in vivo. METHODS: Collagen antibody-induced arthritis (CAIA) is induced by monoclonal collagen type II antibodies and enhanced by lipopolysaccharide. It was investigated how and when Rabeximod operates on inflammatory cells after stimulation of either Toll-like receptor (TLR)4 (lipopolysaccharide) or TLR2 (lipomannan) in mice lacking functional signalling through TLR4 due to a spontaneous deletion of the Tlr4 gene. RESULTS: Rabeximod efficiently prevented arthritis during the time window when TLR2 or TLR4 ligands activate inflammatory macrophages. The effect operated downstream of TLR activation as Rabeximod was highly therapeutic in CAIA enhanced through TLR2 stimuli in TLR4 deficient mice. In addition, it was found that the arthritis ameliorating effect of Rabeximod was time dependent, since inhibition of tumour necrosis factor alpha production from macrophages in vitro was more pronounced if administered close to stimulation. CONCLUSIONS: Rabeximod suppresses arthritis by preventing activation of inflammatory cells, most likely macrophages, in a time dependent fashion, downstream of TLR2 and TLR4 stimulation. PMID- 20542962 TI - Serum HMGB1 levels are increased in active Wegener's granulomatosis and differentiate between active forms of ANCA-associated vasculitis. PMID- 20542963 TI - Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis. AB - OBJECTIVE: This 9-month open-label extension of the Circadian Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA 1) investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release (MR) prednisone for up to 12 months. METHODS: Of 288 patients with rheumatoid arthritis originally randomised to MR or immediate-release (IR) prednisone, 249 continued with prednisone chronotherapy (2-10 mg/day) in the 9-month open-label extension. Duration of morning stiffness of the joints (MS), disease activity scores (DAS28), American College of Rheumatology (ACR20) responses and plasma levels of interleukin 6 (IL-6) were assessed. Safety was analysed from adverse event reports and laboratory investigations. RESULTS: During the 3-month double blind phase, patients in the MR group achieved a reduction in MS of 33.1% while no change was observed in the IR group. After 6 months of treatment, MS was reduced in the IR/MR group by 54% and in the MR/MR group by 56%. MS reduction after 12 months was 45% (IR/MR group) and 55% (MR/MR group). Plasma levels of IL 6 declined on MR treatment. DAS28 was reduced from 5.8 to 4.8 (MR/MR group) and 4.9 (IR/MR group), respectively. 37% of the 219 patients who completed the 12 month study achieved improvement according to the ACR20 criteria. Adverse events did not differ from the known profile of low-dose prednisone. CONCLUSIONS: Prednisone chronotherapy with the MR tablet was safe and well tolerated and provided a sustained improvement which resulted in a better benefit to risk ratio of low-dose glucocorticoid treatment for at least 12 months. PMID- 20542964 TI - Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12Rbeta2 inhibition. AB - BACKGROUND: Patients with rheumatoid arthritis (RA) have a systemic Th1 defect associated with inflammation. OBJECTIVE: To examine the hypothesis that interleukin 17 (IL-17) contributes to this defect. METHODS: IL-17 effects on Th1 markers were examined on T-bet and interferon gamma (IFNgamma) expression in peripheral blood mononuclear cells (PBMCs) from patients with RA or healthy controls (HC). Receptor specificities were determined by analysis of the Th1 specific IL-12 receptor beta2 (IL-12Rbeta2), Th17-specific IL-23R and the common IL-12Rbeta1 chain expression. Effects of IL-17 or IFNgamma on IL-6, IL-1, IL-8, matrix metalloproteinase-8 (MMP-8) were measured by real-time RT-PCR in RA synovial cells. RESULTS: RA PBMCs were less responsive to IL-12-induced IFNgamma than HC PBMCs. IL-12 hyporesponsiveness was increased by IL-17 treatment associated with a selective reduction in IL-12Rbeta2, but not IL-23R, IL-12Rbeta1 or T-bet, which was reversed with IL-17R inhibition. IL-17 inhibited IL-12Rbeta2 expression in developing Th1 cells. In RA synovial cells, IL-17 induced IL-6, IL 1, IL-8 and MMP-8, whereas IFNgamma had minimal or inhibitory effects. CONCLUSION: In RA, IL-12 hyporesponsiveness is associated with IL-17R-mediated downregulation of IL-12Rbeta2 expression. IL-17 may reinforce Th17 lineage commitment and proinflammatory and destructive effects through Th1 inhibition and positive feedback effects in RA synovial cells. Anti-inflammatory effects of IL 17/IL-17R antagonism may include the restoration of protective Th1 responses. PMID- 20542965 TI - Care of patients with scleroderma in the intensive care setting. AB - Scleroderma or systemic sclerosis (SSc) is a connective tissue disease (CTD) associated with fibrosing and vascular complications involving multiple organs. The care of these patients in the critical care setting is frequently challenging due to multiple complications and refractory organ involvement. However, awareness of specific organ involvement associated with scleroderma can allow many complications to be anticipated and effectively treated. Cardiac involvement can lead to arrhythmias and heart failure, whereas pulmonary involvement can be associated with pulmonary arterial hypertension, fibrosis, or both. Renal vascular disease and scleroderma renal crisis (SRC), once a uniformly fatal complication, is particularly important to recognize early, as it can be treated successfully. Gastrointestinal involvement can lead to bleeding, aspiration, obstruction, and malabsorption. Severe Raynaud may lead to digital ischemia and gangrene. Therapies must target involved organ system or organ systems. Corticosteroids, a mainstay for related CTDs, do not typically provide any benefit and may cause harm. Vasodilators can effectively treat vascular complications but must target the appropriate vascular bed. Proactive utilization of proton pump inhibitors, recognition of bleeding from gastrointestinal vascular ectasia, and nutritional support can considerably ameliorate gastrointestinal morbidities. Effective treatment of fibrotic complications remains elusive and is the current frontier for scleroderma therapeutics. PMID- 20542966 TI - A long-distance runner with lateral knee pain. PMID- 20542967 TI - Trajectories of cardiorespiratory fitness in children with and without developmental coordination disorder: a longitudinal analysis. AB - OBJECTIVE: To compare the longitudinal trajectories of cardiorespiratory fitness (CRF) in children with probable developmental coordination disorder (DCD) with those of typically developing children. SETTING: School-based study, conducted in a large region of Ontario, Canada. 75 out of a possible 92 schools (83%) consented to participate. PARTICIPANTS: A cohort of children, enrolled in grade 4 (mean 9 years 11 months; SD 0.05) at baseline (n=2278) were followed twice-yearly over a 2-year period. MEASURES: The short form of the Bruininks-Oseretsky test of motor proficiency was used to identify children with probable DCD and the Leger shuttle run to measure maximal oxygen uptake (VO(2)max). RESULTS: Mixed-effects modelling was used to estimate the change over time in predicted VO(2)max for both children with probable DCD and typically developing children. For all children, VO(2)max declined over time. Children (boys and girls) with probable DCD not only had lower VO(2)max at baseline compared with typically developing children, VO(2)max declined among these children at a much steeper rate. CONCLUSION: Although previous research has found children with DCD to have poor CRF compared with typically developing children, most of this work has relied on cross-sectional designs to examine group differences. The results of this study confirm that differences in CRF between children with and without probable DCD persist over time, highlighting the concern that DCD is a risk factor for poor cardiovascular health in children. PMID- 20542968 TI - Doping is a threat to sporting excellence. AB - Savulescu et al have argued that the risk to athletes' welfare provides the only legitimate ground for restricting the use of performance enhancing drugs in sport. In this paper, it is argued that the idea of 'sport', properly understood, provides further reason to impose such restrictions. A 'balance of excellences' argument is proposed whereby doping is considered objectionable on account of its disrupting the relation between the excellences around which sporting competition is organised. We have reason to restrict the use of performance enhancing drugs in sport not only because of the threat they pose to athletes' health but also because of the threat they pose to athletes' displaying the relevant types of sporting excellence. PMID- 20542969 TI - Revalidation in sport and exercise medicine: a UK perspective. PMID- 20542970 TI - Motor responses to experimental Achilles tendon pain. AB - BACKGROUND: Achilles tendinopathies are characterised by pain and reduced function, and heavy-load exercises have been shown to be effective in the treatment of painful chronic Achilles tendinopathies. However, basic information is needed on how the biomechanics and neuromuscular control of the exercise are affected by Achilles tendon pain. OBJECTIVE: The authors aimed to determine the effects of experimental Achilles tendon pain on motor function during one-legged weight bearing ankle plantar and dorsal flexion exercises. METHODS: In a crossover study, with 16 healthy subjects tested on two different days separated by 1 week, three-dimensional ground reaction forces, ankle joint kinematics and surface electromyography (EMG) of the lower leg muscles were recorded during one legged full weight-bearing ankle plantar (concentric) and dorsal (eccentric) flexion exercises. Measurements were done before, during and after either experimental Achilles tendon pain or a non-painful control condition. Pain was induced by intratendinous injections of hypertonic saline with isotonic saline injections as control. Joint kinematics, ground reaction force frequency contents and average EMG amplitudes were calculated. RESULTS: Compared with the control condition experimental Achilles tendon pain reduced the EMG activity in agonistic, synergistic and antagonistic muscles, and increased the ground reaction force frequency content around 10 Hz, during both eccentric and concentric movement phases. CONCLUSIONS: These data show that experimental Achilles tendon pain causes widespread and reduced motor responses with functional effects on the ground reaction force. PMID- 20542971 TI - Comparison of sports medicine, public health and exercise promotion between bidding countries for the FIFA World Cup in 2018. AB - OBJECTIVE: To ascertain whether it is possible to assess countries bidding for international sporting events based on public health and sports medicine criteria. In particular, the authors undertook this exercise for countries bidding for the 2018 Federation Internationale de Football Association (FIFA) Football World Cup (2018 World Cup). DESIGN: A scorecard framework approach to pose and answer nine relevant questions. Questions were answered using Medline listed references (where possible) and internet research. RESULTS: England scored the highest overall, largely due to its sports medicine training programme and recognition, and funding of treatment for sports injuries. The Netherlands/Belgium scored highly in the questions relating to public health expenditure, Australia was very strong in sports medicine research, and Japan was the best of the bidding countries in terms of having a lower prevalence of overweight and obese people. CONCLUSIONS: It is possible to assess countries bidding for international sporting events based on their performance with respect to sports medicine, physical activity and health promotion criteria. Bodies organising major sporting events such as FIFA and the International Olympic Committee may wish to consider making public health measures part of the bidding criteria for hosting these events. PMID- 20542972 TI - Application of an online team physician survey to the consensus statement on sideline preparedness: the medical bag's highly desired items. PMID- 20542973 TI - Allez Hop, a nationwide programme for the promotion of physical activity in Switzerland: what is the evidence for a population impact after one decade of implementation? AB - OBJECTIVES: To present evidence for a population impact of a national physical activity promotion programme after a decade of implementation. METHODS: The programme Allez Hop offered local physical activity courses (mainly walking and Nordic walking) once a week over 12 weeks. Data from a pretest posttest survey in 2005 course participants (N=2157 at baseline (of 4130, 52.2%), 1587 at first follow-up (73.6%); smaller subsample with second follow-up) and from repeated cross-sectional national surveys have been analysed regarding changes in physical activity behaviour. RESULTS: The total number of Allez Hop courses was 18 684 between 1997 and 2008. 89.2% of participants were women, the mean age was 48.5 years. The proportion meeting the physical activity recommendations was 31.7% at baseline, in participants with first follow-up data it increased from 33.1% to 42.3% (p<0.001). On the population level in the main user group of Allez Hop (middle-aged women) the proportion not engaging in any sport decreased from 50.1% (1997) to 47.2% (2002) and to 43.1% (2007) (p<0.01). Walking/hiking was the second most frequently performed sport (33.7%) in 2007, with the most remarkable increase since 2000 (+11.1%). CONCLUSIONS: Allez Hop was successfully implemented for more than a decade, reached middle-aged women and a high proportion of insufficiently active individuals. Changes in participants' physical activity behaviour must be interpreted cautiously because of low response rates and short follow-up. However, indications for behavioural changes were observed at the population level, even though these data do not allow a causal link to Allez Hop. PMID- 20542974 TI - Gender influences: the role of leg dominance in ACL injury among soccer players. AB - OBJECTIVE: This study intends to look at the role of leg dominance in anterior cruciate ligament (ACL) injury risk among soccer (football) athletes. The purpose of this study was to test the hypothesis that soccer players rupture the ACL of their preferred support leg more frequently than the ACL in their preferred kicking leg, particularly in non-contact injuries, despite differences in gender. DESIGN: Retrospective observational study. SETTING: Outpatient orthopaedic practice. PATIENTS: Subjects who had sustained an ACL injury due to direct participation in soccer. N=93 (41 male, 52 female). INTERVENTIONS: These noncontact injuries were sustained while playing soccer. RESULTS: For non-contact injuries, roughly half of the injuries occurred in the preferred kicking leg (30) and the contralateral leg (28). However, by gender, there was a significant difference in the distribution of non-contact injury, as 74.1% of males (20/27) were injured on the dominant kicking leg compared with 32% (10/31) of females (p<0.002). CONCLUSIONS: When limited to a non-contact injury mechanism, females are more likely to injure the ACL in their supporting leg, whereas males tend to injure their kicking leg. This research suggests that limb dominance does serve as an aetiological factor with regard to ACL injuries sustained while playing soccer. If follow-up studies confirm that females are more likely to injure their preferred supporting leg, future research should investigate the cause for this discrepancy, which could result from underlying gender-based anatomical differences as well as differences in neuromuscular patterns during cutting manoeuvres or kicking. PMID- 20542975 TI - Coaches' perspectives on implementing an evidence-informed injury prevention programme in junior community netball. AB - OBJECTIVE: For effective sports injury prevention, information is needed about the implementation context for interventions. This study describes coaches' feedback on the implementation of an evidence-informed injury prevention programme in community junior netball using coaches' perceptions and the RE-AIM framework. METHODS: A lower-limb injury prevention programme (Down to Earth; D2E), for teaching safe-landing techniques, was delivered to 31 coaches from 31 junior community netball teams in a 1-h workshop. Coaches then delivered a 6-week programme at team training sessions starting in the week before the competition season commenced. 65% of coaches completed a feedback survey 17 weeks after they had delivered the programme. RESULTS: Most (88%) coaches believed that D2E improved their players' ability to perform correct landing techniques in games and that players had retained these improvements over the season. The majority (83%) indicated that an improvement in player athletic attributes was the greatest advantage of D2E, followed by a reduction in injury risk. Identified barriers to implementing D2E were running out of time and very young players finding the drills too difficult. Coaches reported that they needed more ideas for training drills that could be incorporated into their programmes and believed that their own coaching training did not adequately prepare them to implement an injury prevention programme. CONCLUSIONS: Although coaches believed that D2E was effective in developing correct landing techniques, some modifications are needed to make it more suitable for younger players and coach education by accreditation courses could be improved to support the implementation of injury prevention programmes. PMID- 20542976 TI - Does a 3-month multidisciplinary intervention improve pain, body composition and physical fitness in women with fibromyalgia? AB - OBJECTIVE: To determine the effects of a 3-month multidisciplinary intervention on pain (primary outcome), body composition and physical fitness (secondary outcomes) in women with fibromyalgia (FM). METHODS: 75 women with FM were allocated to a low-moderate intensity 3-month (three times/week) multidisciplinary (pool, land-based and psychological sessions) programme (n=33) or to a usual care group (n=32). The outcome variables were pain threshold, body composition (body mass index and estimated body fat percentage) and physical fitness (30 s chair stand, handgrip strength, chair sit and reach, back scratch, blind flamingo, 8 feet up and go and 6 min walk test). RESULTS: The authors observed a significant interaction effect (group*time) for the left (L) and right (R) side of the anterior cervical (p<0.001) and the lateral epicondyle R (p=0.001) tender point. Post hoc analysis revealed that pain threshold increased in the intervention group (positive) in the anterior cervical R (p<0.001) and L (p=0.012), and in the lateral epicondyle R (p=0.010), whereas it decreased (negative) in the anterior cervical R (p<0.001) and L (p=0.002) in the usual care group. There was also a significant interaction effect for chair sit and reach. Post hoc analysis revealed improvement in the intervention group (p=0.002). No significant improvement attributed to the training was observed in the rest of physical fitness or body composition variables. CONCLUSIONS: A 3-month multidisciplinary intervention three times/week had a positive effect on pain threshold in several tender points in women with FM. Though no overall improvements were observed in physical fitness or body composition, the intervention had positive effects on lower-body flexibility. PMID- 20542977 TI - Cognition and performance: anxiety, mood and perceived exertion among Ironman triathletes. AB - OBJECTIVE: The authors examined the changing patterns of mood before and after an Ironman triathlon, and the relationships between expected performance outcomes, perception of effort and pacing. DESIGN: Twelve participants in the 2008 Ironman Austria triathlon competition were studied before, during and after the event. Each participant completed measures of mood, anxiety and perceived exertion, while pacing was calculated from official race timings at various points on the course. RESULTS: Positive correlations were found between distance covered and rating of perceived exertion (RPE) during each of the individual disciplines, and also between RPE and the percentage of overall race time completed (r=0.826, p<0.001). A negative correlation was found between average speed and distance covered during the run segment (r=-0.911, p<0.005) with pace gradually declining. Differences occurred in the profile of mood states mood subscales of tension and fatigue between the baseline, prerace and postrace trials. Somatic anxiety was higher before the race compared with baseline measures. DISCUSSION: RPE followed a linear progression of RPE during each discipline followed by a re-setting of the perception of effort at the start of the next discipline. The increase in RPE for the entire event followed a linear increase. The linear decline in run pace is consistent with a recent model in which expected RPE is used to modulate pacing. Anxiety and mood responses of participants in this study indicate that the emotional response of athletes before and after ultra-endurance exercise is closely aligned with their conscious thoughts. PMID- 20542978 TI - Practice management of musculoskeletal injuries in active children. AB - BACKGROUND: Although increasing participation in physical activities has significant health benefits, there are no guidelines to help professionals decide when it is safe to return to activity after injury. OBJECTIVE: To examine the specific criteria (eg, strength, pain) that expert sport medicine clinicians use for return to activity decisions in children with musculoskeletal injuries. METHODS: The authors conducted an online cross-sectional survey of certified Canadian sport medicine doctors (MDs) and sport rehabilitation specialists (physiotherapists (PTs) or athletic therapists (ATs)). The authors asked how they would measure each of the following signs in the context of a knee injury: sport specific skills, pain, swelling, strength, range of motion (ROM) and balance. Clinicians also ranked the importance of each sign with respect to influencing their recommendations for each of five clinical vignettes. RESULTS: The overall response rate was 33.6% (464/1380) with similar rates for each profession. For each clinical sign, all three professions preferred the same measure to determine readiness to return to play: standardised testing for sport-specific skills, impact on function for pain, palpation for swelling, manual muscle testing for strength, visual inspection for ROM and standing on one leg with eyes closed for balance. Regarding importance of specific signs for return to activity, all professions had similar responses for one vignette, but MDs differed from PTs and ATs for the remaining four. Finally, pain was ranked as the no 1 or 2 most important sign in all five vignettes by 41.0% of MDs, 18.1% of ATs and 11.3% of PTs, whereas sport-specific skills was chosen by 9.6% MDs, 12.0% ATs and 16.1% PTs. CONCLUSION: Our results provide the foundation for future work leading towards the development of interdisciplinary consensus guidelines. PMID- 20542979 TI - Mitroaortic valve replacement after aortic transapical approach failure in a patient with essential thrombocytosis. AB - There is a lack of published information about intraoperative and postoperative course of cardiac surgery in patients with essential thrombocytosis using cardiopulmonary bypass. Both risks of intraoperative thrombosis of extracorporeal conduits or uncontrolled postoperative bleeding are present, but its incidence and treatment are not well known. Here, we present a rare case of a patient with essential thrombocytosis, moderate mitral regurgitation and severe aortic stenosis who had a transapical aortic valve implantation with short-term severe periprosthetic regurgitation, who needed a mitroaortic replacement on cardiopulmonary bypass with no complications. PMID- 20542980 TI - Active treatment rates for lung cancer in south Manchester: are we doing enough? AB - In an effort to improve the current lung cancer treatment outcomes in Britain, National guidelines were published followed by the introduction of National Lung Cancer Audit (LUCADA) project. LUCADA has defined active treatment as any therapeutic intervention with the aim of improving the quality or length of patients' survival irrespective of whether it is curative or palliative. From August 2003 to December 2006, all patients diagnosed to be new primary lung cancer referrals were enrolled into a prospective study. Out of the total of 433 patients the majority of patients were male (62%) and the mean age was 69 years. The histologies were small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and other cancers in 67 (15.5%), 306 (70.7%) and 11 (2.5%) patients, respectively, while 49 (11.3%) patients had no histological confirmation. Overall, the active treatment rate was 72% with 74 (18%), 158 (36%), 66 (15%) and 11 (3%) undergoing surgery, chemotherapy, radiotherapy and other methods, respectively. The active treatment rates for histologically proven SCLC, NSCLC and all lung cancers excluding SCLC were 83%, 77% and 71%, respectively, compared to the LUCADA national average of 73.5%, 66% and 56.5%, respectively. Among the NSCLC patients overall five-year survival was 27.4%. The stage specific survivals were 64.0%, 58.3%, 24.1% and 11.5%, respectively, for stages I, II, III and IV. These reassuring results show that south Manchester has good active treatment rates for lung cancer with survival outcomes comparable to other major series. PMID- 20542981 TI - Impact of obesity on outcome of patients undergoing off-pump coronary artery bypass grafting using aorta no-touch technique. AB - We prospectively examined 1359 adult patients undergoing isolated coronary revascularization with the Pi-circuit technique, consisting of beating heart, aorta no-touch, use of composite grafts, and off-pump arterial revascularization. Patients were divided into two groups based on body weight; Group A consisting of 295 (21.7%) obese patients [body mass index (BMI) > or =30 kg/m(2)] and Group B of 1064 (79.3%) non-obese patients (BMI <30 kg/m(2)). Advanced age and emergency surgery favored the non-obese group [63.0+/-10.4 vs. 65.3+/-9.6 years (P<0.0005) and 10.2% vs. 17.1% (P=0.004), with an increase in the number of octogenarians among them (1.7% Group A vs. 5.4% in Group B, P=0.11)]. The use of double internal mammary arteries (90.5% in Group A vs. 86.9% in Group B, P=0.109), the mean number of distal anastomoses (2.8+/-0.9 in Group A vs. 2.7+/-0.9 in Group B, P=0.5) and the number of sequential anastomoses performed (28.1% in Group A vs. 31% in Group B, P=0.3) were similar. No difference in morbidity rates was detected. All cause in-hospital mortality was comparable. Survival was similar in both groups also. Obesity is not a risk factor for morbidity and mortality in this group of patients. PMID- 20542982 TI - Connected speech production in three variants of primary progressive aphasia. AB - Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as 'fluent' or 'non-fluent', however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously. Secondly, we aimed to determine the neuroanatomical correlates of changes along these different dimensions. We recorded, transcribed and analysed speech samples for 50 patients with primary progressive aphasia, along with neurodegenerative and normal control groups. Patients were scanned with magnetic resonance imaging, and voxel-based morphometry was used to identify regions where atrophy correlated significantly with motor speech and linguistic features. Speech samples in patients with the non-fluent variant were characterized by slow rate, distortions, syntactic errors and reduced complexity. In contrast, patients with the semantic variant exhibited normal rate and very few speech or syntactic errors, but showed increased proportions of closed class words, pronouns and verbs, and higher frequency nouns, reflecting lexical retrieval deficits. In patients with the logopenic variant, speech rate (a common proxy for fluency) was intermediate between the other two variants, but distortions and syntactic errors were less common than in the non-fluent variant, while lexical access was less impaired than in the semantic variant. Reduced speech rate was linked with atrophy to a wide range of both anterior and posterior language regions, but specific deficits had more circumscribed anatomical correlates. Frontal regions were associated with motor speech and syntactic processes, anterior and inferior temporal regions with lexical retrieval, and posterior temporal regions with phonological errors and several other types of disruptions to fluency. These findings demonstrate that a multidimensional quantification of connected speech production is necessary to characterize the differences between the speech patterns of each primary progressive aphasic variant adequately, and to reveal associations between particular aspects of connected speech and specific components of the neural network for speech production. PMID- 20542983 TI - Insulin resistance and diabetic macular oedema in type 2 diabetes mellitus. AB - OBJECTIVE: To evaluate the association between insulin resistance and diabetic macular oedema in type 2 diabetes. METHODS: Patients with type 2 diabetes who agreed to undergo blood sampling were enrolled into this cross-sectional study. Patients who had received treatment for macular oedema within the past 3 months and those with other retinal diseases were excluded. The following data were recorded: age, sex, time of diabetes evolution, HbA1c, ophthalmologic and systemic treatment, and lens status. Optical coherence tomography (OCT) was performed to determine the morphological patterns of macular oedema. Insulin resistance was established by a McAuley index of <6.3 and fasting insulin levels of >16 mU/l. RESULTS: A total of 177 eyes from 90 patients were included; 27.1% of eyes were from insulin-resistant patients. There were no differences in age, time of evolution, sex, HbA1c level or lens status between insulin-resistant and non-resistant patients. Insulin-resistant patients were more likely to have exogenous insulin therapy (p<0.05; OR=3.8). An association was found between diabetic cystoid macular oedema and insulin resistance (Fisher exact test p=0.007; OR=2.53, 95% CI 1.52 to 4.2). There were no associations between insulin resistance and the other morphological patterns of oedema. Patients undergoing insulin therapy were found to have an association with a diffuse retinal thickening pattern on OCT (p=0.036; OR=1.4). However, no association was found between insulin therapy and the presence of cystoid macular oedema. CONCLUSIONS: The findings of this study indicate a relationship between insulin resistance and cystoid macular oedema that unrelated to the use of insulin. Insulin treatment was associated with diffuse macular oedema. PMID- 20542984 TI - Timing of recurrent uveitis in patients with Behcet's disease receiving infliximab treatment. AB - AIM: To investigate the relationship between recurrence of uveitis and timing of infliximab in patients with Behcet's disease. METHODS: Charts were retrospectively reviewed for 23 patients with refractory uveoretinitis associated with Behcet's disease treated using infliximab at our hospital. Infliximab was administered by intravenous infusion at weeks 0, 2 and 6, and every 8 weeks thereafter. The relationship between recurrence of uveitis and infliximab infusion was analysed. RESULTS: Mean duration of infliximab treatment for the 23 patients was 20 months, and the mean number of infliximab infusions was 12. Recurrent uveitis was seen during treatment in 13 of 23 patients, with no recurrences in the remaining 10 patients. Two patients developed recurrence soon after starting treatment-for example, first recurrence after starting infliximab was on day 19 or day 29, but the other 11 patients experienced recurrences after 5-6 months of infliximab treatment. As regards the timing of recurrences following infliximab infusion, 10 of the 13 patients developed recurrences ~5 weeks after infliximab infusion. Recurrent uveitis in these patients most often occurred during weeks 7-8 after infusion. However, three of the patients developed recurrent uveitis at various times, for example in weeks 1, 4, 7 and 8 after infliximab infusion. CONCLUSION: Infliximab is effective for suppressing recurrence of uveitis in Behcet's disease, but responses to infliximab differ among patients. Careful observation following infliximab infusion is necessary to manage the recurrence of uveitis during treatment. PMID- 20542985 TI - Cytotoxicity of activated natural killer cells against pediatric solid tumors. AB - PURPOSE: To develop new therapies for children with solid tumors, we tested the cytotoxicity of natural killer (NK) cells expanded by coculture with K562-mb15 41BBL cells. We sought to identify the most sensitive tumor subtypes, clarify the molecular interactions regulating cytotoxicity, and determine NK antitumor potential in vivo. EXPERIMENTAL DESIGN: We tested in vitro cytotoxicity of expanded NK cells against cell lines representative of Ewing sarcoma (EWS; n = 5), rhabdomyosarcoma (n = 4), neuroblastoma (n = 3), and osteosarcoma (n = 3), and correlated the results with expression of inhibitory and activating NK receptor ligands. We also compared expanded and primary NK cells, determined the effects of activating receptor ligation and of chemotherapeutic drugs, and assessed the therapeutic effect of NK cell infusions in xenografts. RESULTS: In 45 experiments, EWS and rhabdomyosarcoma cell lines were remarkably sensitive to expanded NK cells, with median cytotoxicities at 1:1 effector/target ratio of 87.2% and 79.1%, respectively. Cytotoxicity was not related to levels of expression of NK receptor ligands, nor was it affected by pretreatment of target cells with daunorubicin or vincristine, but was markedly inhibited by preincubation of NK cells with a combination of antibodies against the NK activating receptors NKGD2 and DNAM-1. Expanded NK cells were considerably more cytotoxic than unstimulated NK cells, and eradicated EWS cells engrafted in nonobese diabetic/severe combined immunodeficient Il2rgnull mice. CONCLUSIONS: Among pediatric solid tumors, EWS and rhabdomyosarcoma are exquisitely sensitive to expanded NK cells. The NK expansion method described here has been adapted to large-scale conditions and supports a phase I clinical study including patients with these malignancies. PMID- 20542986 TI - Phase II trial of short-course R-CHOP followed by 90Y-ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients. AB - PURPOSE: This study aimed to evaluate the efficacy and safety of the treatment with (90)Y-ibritumomab tiuxetan following a short-course of rituximab with cyclophosphamide-adriamycin-vincristine-prednisone (R-CHOP) in high-risk elderly patients with previously untreated diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL DESIGN: From December 2006 to October 2008, 55 high-risk elderly (age > or =60 years) untreated DLBCL patients were treated in seven Italian institutions with a short-course of chemotherapy consisting of four cycles of R CHOP21 followed by (90)Y-ibritumomab tiuxetan 6 to 10 weeks later. RESULTS: Of the 55 patients, 48 underwent radioimmunotherapy. The overall response rate to the entire treatment regimen was 80%, including 73% complete remissions and 7% partial remissions. Eight (50%) of the 16 patients who achieved less than a complete response with CHOP improved their remission status after (90)Y ibritumomab tiuxetan administration. With a median follow-up of 18 months, the 2 year progression-free survival was estimated to be 85%, with a 2-year overall survival of 86%. (90)Y-ibritumomab tiuxetan toxicity consisted of grade 3 to 4 hematologic toxicity in 28 of 48 patients, mainly neutropenia (23 patients) and thrombocytopenia (15 patients). Red cells and/or platelets transfusions were given to three patients. CONCLUSION: This study evaluated the feasibility, efficacy, and safety of a short-course R-CHOP21 regimen followed by (90)Y ibritumomab tiuxetan in high-risk elderly DLBCL patients. PMID- 20542987 TI - Contribution of human amniotic fluid stem cells to renal tissue formation depends on mTOR. AB - Human amniotic fluid stem cells (hAFSCs) can be grown in large quantities, have a low risk for tumour development and harbour a high differentiation potential. They are a very promising new fetal stem cell type for cell-based therapy approaches and for studying differentiation processes without raising the ethical concerns associated with embryonic stem cells. Recently, a protocol for studies on renal development has been established in which murine embryonic kidneys are dissociated into single-cell suspension and then reaggregated to form organotypic renal structures. Using this approach, we formed chimeric renal structures via mixing murine embryonic kidney cells with monoclonal hAFSCs. We demonstrate here that hAFSCs harbour the potential to contribute to renal tissue formation accompanied by induction of specific renal marker expression. As part of the two kinase complexes mTORC1 and mTORC2, mammalian target of rapamycin (mTOR) is the key component of an important signalling pathway, which is involved in the regulation of differentiation and in the development of a wide variety of human genetic diseases many with characteristic kidney symptoms. Modulating endogenous mTOR activity via specific siRNA approaches revealed that contribution of hAFSCs to renal tissue formation is regulated by mTORC1 and mTORC2. These findings (i) demonstrate renal differentiation potential of hAFSCs, (ii) prove chimeric cultures of mixtures of murine embryonic kidney cells and hAFSCs to be a powerful tool to study the effects of gene knockdowns for renal structure formation and (iii) provide new insights into the role of the mTOR pathway for renal development. PMID- 20542988 TI - Site-directed gene repair of the dystrophin gene mediated by PNA-ssODNs. AB - Permanent correction of gene defects is an appealing approach to the treatment of genetic disorders. The use of single-stranded oligodeoxynucleotides (ssODNs) has been demonstrated to induce single-point mutations in the dystrophin gene and to restore dystrophin expression in the skeletal muscle of models of Duchenne muscular dystrophy (DMD). Here we show that ssODNs made of peptide nucleic acids (PNA-ssODNs) can achieve gene repair frequencies more than 10-fold higher than those obtained using an older generation of targeting oligonucleotides. Correction was demonstrated in muscles cells isolated from mdx(5cv) mice and was stably inherited over time. Direct intramuscular injection of PNA-ssODNs targeting the mdx(5cv) mutation resulted in a significant increase in dystrophin positive fibers when compared with muscles that received the ssODNs designed to correct the dystrophin gene but made of unmodified bases. Correction was demonstrated at both the mRNA and the DNA levels using quantitative PCR and was confirmed by direct sequencing of amplification products. Analysis at the protein level demonstrated expression of full-length dystrophin in vitro as well as in vivo. These results demonstrate that oligonucleotides promoting strand invasion in the DNA double helix can significantly enhance gene repair frequencies of the dystrophin gene. The use of PNA-ssODNs has important implications in terms of both efficacy and duration of the repair process in muscles and may have a role in advancing the treatment of DMD. PMID- 20542989 TI - Imaging of atherosclerosis: carotid intima-media thickness. AB - Carotid ultrasound provides quantitative measurements of carotid intima-media thickness (CIMT) that can be used to assess cardiovascular disease (CVD) risk in individuals and monitor ongoing disease progression and regression in clinical trials. It is non-invasive, rapid, reproducible, and carries no risk. Numerous epidemiological studies have established that CIMT is a marker of subclinical atherosclerosis and is associated with established CVD risk factors and with both prevalent and incident CVD. The use of CIMT in outcome trials as a surrogate or predictor of CVD outcomes is widespread. Carotid ultrasound is being employed to test the efficacy of CVD treatment in order to identify potential useful drugs earlier and to possibly speed regulatory approval. Successive trials have generated lessons learned and applied, with slow but steady improvement in CIMT measurement reproducibility. PMID- 20542990 TI - Somatosensory comparison during haptic tracing. AB - Active sensing involves memory retrieval and updating as well as mechanisms that trigger corrections to the ongoing exploratory movement. The present study examined this process in a task where human subjects moved the index fingertip clockwise around the circumference of a virtual sphere created by a robotic device. The fingertip pressed into the sphere during the movement, and the subjects were to report slight differences in sphere size (or surface curvature), which occurred from trial to trial. During each 2- to 3-s trial, subjects gradually adjusted their speed and pressure according to the current surface curvature, achieving a consistent level of contact force in the last half of the exploration. The results demonstrate that subjects were gradually accumulating haptic information about curvature and, at the same time, gradually changing the motor commands for the movement. When subjects encountered an unexpected transition in curvature (from circular to flat), they reacted by abruptly decreasing contact force at a latency of about 50 ms. This short latency indicates that spinally mediated corrections are engaged during this task. The results support the hypothesis that during haptic exploration, the neural comparison between expected and actual somatosensory feedback takes places at multiple levels, including the spinal cord. PMID- 20542991 TI - A comprehensive study of whole-brain functional connectivity in children and young adults. AB - Over the past decade, examination of functional connectivity using functional magnetic resonance imaging has become an important tool to investigate functional changes in patient populations, healthy aging, and recently also child development. Most prior developmental studies focused on functional connectivity between brain regions important for cognitive or emotional control and the so called "default-mode network." In the present study, we investigated whole-brain functional connectivity in children (11-13 years; N = 19) and young adults (19-25 years; N = 29), without a priori restrictions to specific regions. We found similar patterns of functionally connected regions in children and young adults, but there were differences in the size of functionally connected regions (i.e., the number of voxels), as well as in the strength of functional connectivity (i.e., the correlation value) between brain regions. This indicates that functional connectivity continues to change during adolescence. Developmental differences were found across the whole brain, but the effects differed for functional connectivity patterns associated with higher cognitive or emotional functions and functional connectivity patterns associated with basic visual and sensorimotor functions. Finally, we showed that the majority of functional connectivity differences could not be explained on the basis of gray matter density alone. PMID- 20542992 TI - Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen. AB - Phenacetin was withdrawn from the market because it caused renal failure in some patients. Many reports indicated that the nephrotoxicity of phenacetin is associated with the hydrolyzed metabolite, p-phenetidine. Acetaminophen (APAP), the major metabolite of phenacetin, is also hydrolyzed to p-aminophenol, which is a nephrotoxicant. However, APAP is safely prescribed if used in normal therapeutic doses. This background prompted us to investigate the difference between phenacetin and APAP hydrolase activities in human liver. In this study, we found that phenacetin is efficiently hydrolyzed in human liver microsomes (HLM) [CL(int) 1.08 +/- 0.02 microl/(min . mg)], whereas APAP is hardly hydrolyzed [0.02 +/- 0.00 microl/(min . mg)]. To identify the esterase involved in their hydrolysis, the activities were measured using recombinant human carboxylesterase (CES) 1A1, CES2, and arylacetamide deacetylase (AADAC). Among these, AADAC showed a K(m) value (1.82 +/- 0.02 mM) similar to that of HLM (3.30 +/- 0.16 mM) and the highest activity [V(max) 6.03 +/- 0.14 nmol/(min . mg)]. In contrast, APAP was poorly hydrolyzed by the three esterases. The large contribution of AADAC to phenacetin hydrolysis was demonstrated by the prediction with a relative activity factor. In addition, the phenacetin hydrolase activity by AADAC was activated by flutamide (5-fold) as well as that in HLM (4-fold), and the activity in HLM was potently inhibited by eserine, a strong inhibitor of AADAC. In conclusion, we found that AADAC is the principal enzyme responsible for the phenacetin hydrolysis, and the difference of hydrolase activity between phenacetin and APAP is largely due to the substrate specificity of AADAC. PMID- 20542993 TI - Quality of life associated with perceived stigma and discrimination among the floating population in Shanghai, China: a qualitative study. AB - The floating population refers to the large and increasing number of migrants without local household registration status and has become a new demographic phenomenon in China. Most of these migrants move from the rural areas of the central and western parts of China to the eastern and coastal metropolitan areas in pursuit of a better life. The floating population of China was composed of 121 million people in 2000, and this number was expected to increase to 300 million by 2010. Quality of life (QOL) studies of the floating population could provide a critical starting point for recognizing the potential of regions, cities and local communities to improve QOL. This study explored the construct of QOL of the floating population in Shanghai, China. We conducted eight focus groups with 58 members of the floating population (24 males and 34 females) and then performed a qualitative thematic analysis of the interviews. The following five QOL domains were identified from the analysis: personal development, jobs and career, family life, social relationships and social security. The results indicated that stigma and discrimination permeate these life domains and influence the framing of life expectations. Proposals were made for reducing stigma and discrimination against the floating population to improve the QOL of this population. PMID- 20542994 TI - Health promoting schools and their impact on the oral health of mentally disabled people in Brazil. AB - Health promotion aims to ensure that the population has improved living and health conditions, and schools are appropriate environments in which to do this. The purpose of this study was to investigate the impact of health promotion in terms of oral health in special schools for mentally disable pupils in Brazil. The study was cross-sectional and adopted a qualitative and quantitative approach, using triangulation methods to observe the reality. An epidemiological survey was performed in order to analyse the oral health status; a semi structured questionnaire and participative observation were used for the qualitative analysis of the health promotion activities undertaken in the schools; case studies were carried out to evaluate the profile of oral health status in the context of the schools. The sample was comprised of 383 school children aged 2-19, stratified among 7 schools, Curitiba/Parana/Brazil. The analysis was performed by means of frequency distribution and associations between variables, using the SPSS 16.0 program. The oral health status prevalences in the population studied were dental caries, 49.3%; bleeding gums, 23.8%; dental trauma, 11% and toothache in the last 3 months, 17,8%. Dental caries and bleeding gums experience was associated with the level of the mother's education (p<0.00) and age group (p<0.00). Dental trauma and toothache in the last 3 months were associated with the level of the mother's education (p<0.00 and p<0.00, respectively). Analysis of the dimensions of health promotion demonstrated that health is being promoted in all the schools studied. However, the analysis of oral health indicators per school revealed a possible interference of socio-demographic aspects in the results. It was concluded that the analysed special schools for the mentally disabled promote health. However, the socio-demographic profile of this population appears to have greater influence on vulnerability than the school context in relation to oral health status. PMID- 20542995 TI - Utilizing audit and feedback to improve hospitalists' performance in tobacco dependence counseling. AB - INTRODUCTION: Hospitalized smokers benefit from smoking cessation counseling and nicotine replacement therapy (NRT). However, inpatient providers who care for hospitalized patients carry out these preventive measures inconsistently. METHODS: We designed a peer-led audit and feedback intervention to improve (a) the frequency of smoking cessation counseling and (b) the appropriateness of the prescribing of NRT by hospitalist practitioners in our hospital. Documentation of tobacco cessation counseling in progress notes and discharge summaries and the ordering and dosing of NRT were assessed for 30 hospitalists before and after an intervention. This intervention included specific feedback on their counseling and prescribing practices as well as education and was delivered as part of a one on-one academic detailing session. RESULTS: Five hundred and forty five and 1,119 patient-days were considered for this analysis in the pre- and postperiods, respectively. Documentation of tobacco dependence counseling in progress notes increased from 36% to 44% (p = .002) and from 7.5% to 46.8% in discharge summaries (p < .0001) following the intervention. The appropriateness of NRT dosing increased from 26% (before) to 64% (after) the intervention (p < .0001). DISCUSSION: A peer-led audit and feedback intervention for hospitalists significantly increases the frequency of smoking cessation counseling and the adequacy of NRT prescribing for hospitalized smokers. PMID- 20542996 TI - Management of ErbB2-positive breast cancer: insights from preclinical and clinical studies with lapatinib. AB - The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer. PMID- 20542997 TI - Lexical neighborhood density effects on spoken word recognition and production in healthy aging. AB - We examined the effects of lexical competition and word frequency on spoken word recognition and production in healthy aging. Older (n = 16) and younger adults (n = 21) heard and repeated meaningful English sentences presented in the presence of multitalker babble at two signal-to-noise ratios, +10 and -3 dB. Each sentence contained three keywords of high or low word frequency and phonological neighborhood density (ND). Both participant groups responded less accurately to high- than low-ND stimuli; response latencies (from stimulus offset to response onset) were longer for high- than low-ND sentences, whereas response durations time from response onset to response offset-were longer for low- than high-ND stimuli. ND effects were strongest for older adults in the most difficult conditions, and ND effects in accuracy were related to inhibitory function. The results suggest that the sentence repetition task described here taps the effects of lexical competition in both perception and production and that these effects are similar across the life span, but that accuracy in the lexical discrimination process is affected by declining inhibitory function in older adults. PMID- 20543003 TI - AP-1 overexpression impairs corticosteroid inhibition of collagen production by fibroblasts isolated from asthmatic subjects. AB - Asthma is characterized by airway remodeling associated with an increase in the deposition of ECM proteins such as type I collagen. These components are mainly produced by fibroblasts. Inhaled corticosteroids are considered the cornerstone of asthma therapy. Despite substantial evidence as to the anti-inflammatory action of corticosteroids, their effect on controlling ECM protein deposition in the airways is not completely understood. This study determined the effect of dexamethasone (Dex) on collagen production by bronchial fibroblasts derived from asthmatic and healthy subjects. Expression of procollagen mRNA in fibroblasts from asthmatics and normal controls was determined by quantitative PCR. Regulation of the procollagen-alpha(1)I promoter was evaluated by transient transfections. Transforming growth factor-beta (TGF-beta) protein expression was determined by ELISA. Protein expression of glucocorticoid receptor (GR) and interaction with activator protein-1 (AP-1), a collagen regulatory transcription factor, was assessed by Western blots, coimmunoprecipitations, and EMSA. AP-1 overexpression was performed by transient transfection using c-Fos/c-Jun expression plasmids. Dex significantly downregulated procollagen production and promoter activity in normal fibroblasts but had no effect on asthmatic fibroblasts. AP-1 and GR interaction increased after Dex stimulation in asthmatic fibroblasts. AP-1 overexpression in control fibroblasts abrogated collagen gene response to Dex. These results show that Dex failed to reduce collagen production in fibroblasts from asthmatic subjects. This impaired response may be related to AP-1 overexpression in these cells. PMID- 20543004 TI - Acute cigarette smoke inhalation blunts lung responsiveness to methacholine and allergen in rabbit: differentiation of central and peripheral effects. AB - Despite the prevalence of active smoking in asthmatics, data on the short-term effect of acute mainstream tobacco smoke exposure on airway responsiveness are very scarce. The aim of this study was to assess the immediate effect of acute exposure to mainstream cigarette smoke on airway reactivity to subsequent nonspecific and allergenic challenges in healthy control (n = 5) and ovalbumin sensitized rabbits (n = 6). We combined low-frequency forced oscillations and synchrotron radiation CT imaging to differentiate central airway and peripheral airway and lung parenchymal components of the response to airway provocation. Acute exposure to smoke generated by four successive cigarettes (CS) strongly inhibited the central airway response to subsequent IV methacholine (MCh) challenge. In the sensitized animals, although the response to ovalbumin was also inhibited in the central airways, mainstream CS did not blunt the peripheral airway response in this group. In additional groups of experiments, exposure to HEPA-filtered CS (n = 6) similarly inhibited the MCh response, whereas CO (10,000 ppm for 4 min, n = 6) or nitric oxide inhalation instead of CS (240 ppm, 4 x 7 min, n = 5) failed to blunt nonspecific airway responsiveness. Pretreatment with alpha-chymotrypsin to inhibit endogenous VIP before CS exposure had no effect (n = 4). Based on these observations, the gas phase of mainstream cigarette smoke may contain one or more short-term inhibitory components acting primarily on central airways and inhibiting the response to both specific and nonspecific airway provocation, but not on the lung periphery where both lung mechanical parameters, and synchrotron-imaging derived parameters, showed large changes in response to allergen challenge in sensitized animals. PMID- 20543002 TI - Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs. AB - Early-life respiratory infection with Pseudomonas aeruginosa is common in children with cystic fibrosis or immune deficits. Although many of its clinical manifestations involve neural reflexes, little information is available on the peripheral nervous system of infected airways. This study sought to determine whether early-life infection triggers a neurogenic-mediated immunoinflammatory response, the mechanisms of this response, and its relationship with other immunoinflammatory pathways. Weanling and adult rats were inoculated with suspensions containing P. aeruginosa (PAO1) coated on alginate microspheres suspended in Tris-CaCl(2) buffer. Five days after infection, rats were injected with capsaicin to stimulate nociceptive nerves in the airway mucosa, and microvascular permeability was measured using Evans blue as a tracer. PAO1 increased neurogenic inflammation in the extra- and intrapulmonary compartments of weanlings but not in adults. The mechanism involves selective overexpression of NGF, which is critical for the local increase in microvascular permeability and for the infiltration of polymorphonuclear leukocytes into infected lung parenchyma. These effects are mediated in part by induction of downstream inflammatory cytokines and chemokines, especially IL-1beta, IL-18, and leptin. Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life. PMID- 20543005 TI - Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells. AB - Type A human seasonal influenza (FluA) virus infection causes exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). l carbocisteine, a mucolytic agent, reduces the frequency of common colds and exacerbations in COPD. However, the inhibitory effects of l-carbocisteine on FluA virus infection are uncertain. We studied the effects of l-carbocisteine on FluA virus infection in airway epithelial cells. Human tracheal epithelial cells were pretreated with l-carbocisteine and infected with FluA virus (H(3)N(2)). Viral titers in supernatant fluids, RNA of FluA virus in the cells, and concentrations of proinflammatory cytokines in supernatant fluids, including IL-6, increased with time after infection. l-carbocisteine reduced viral titers in supernatant fluids, RNA of FluA virus in the cells, the susceptibility to FluA virus infection, and concentrations of cytokines induced by virus infection. The epithelial cells expressed sialic acid with an alpha2,6-linkage (SAalpha2,6Gal), a receptor for human influenza virus on the cells, and l-carbocisteine reduced the expression of SAalpha2,6Gal. l-carbocisteine reduced the number of acidic endosomes from which FluA viral RNA enters into the cytoplasm and reduced the fluorescence intensity from acidic endosomes. Furthermore, l-carbocisteine reduced NF-kappaB proteins including p50 and p65 in the nuclear extracts of the cells. These findings suggest that l-carbocisteine may inhibit FluA virus infection, partly through the reduced expression of the receptor for human influenza virus in the human airway epithelial cells via the inhibition of NF kappaB and through increasing pH in endosomes. l-carbocisteine may reduce airway inflammation in influenza virus infection. PMID- 20543007 TI - Structure-based engineering of a monoclonal antibody for improved solubility. AB - Protein aggregation is of great concern to pharmaceutical formulations and has been implicated in several diseases. We engineered an anti-IL-13 monoclonal antibody CNTO607 for improved solubility. Three structure-based engineering approaches were employed in this study: (i) modifying the isoelectric point (pI), (ii) decreasing the overall surface hydrophobicity and (iii) re-introducing an N linked carbohydrate moiety within a complementarity-determining region (CDR) sequence. A mutant was identified with a modified pI that had a 2-fold improvement in solubility while retaining the binding affinity to IL-13. Several mutants with decreased overall surface hydrophobicity also showed moderately improved solubility while maintaining a similar antigen affinity. Structural studies combined with mutagenesis data identified an aggregation 'hot spot' in heavy-chain CDR3 (H-CDR3) that contains three residues ((99)FHW(100a)). The same residues, however, were found to be essential for high affinity binding to IL-13. On the basis of the spatial proximity and germline sequence, we reintroduced the consensus N-glycosylation site in H-CDR2 which was found in the original antibody, anticipating that the carbohydrate moiety would shield the aggregation 'hot spot' in H-CDR3 while not interfering with antigen binding. Peptide mapping and mass spectrometric analysis revealed that the N-glycosylation site was generally occupied. This variant showed greatly improved solubility and bound to IL-13 with affinity similar to CNTO607 without the N-linked carbohydrate. All three engineering approaches led to improved solubility and adding an N-linked carbohydrate to the CDR was the most effective route for enhancing the solubility of CNTO607. PMID- 20543006 TI - MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac. AB - In a mouse model of neutrophil elastase-induced bronchitis that exhibits goblet cell metaplasia and inflammation, we investigated the effects of intratracheal instillation of the MANS peptide, a peptide identical to the NH(2) terminus of the myristoylated alanine-rich C kinase substrate (MARCKS) on mucin protein airway secretion, inflammation, and airway reactivity. To induce mucus cell metaplasia in the airways, male BALB/c mice were treated repetitively with the serine protease, neutrophil elastase, on days 1, 4, and 7. On day 11, when goblet cell metaplasia was fully developed and profiles of proinflammatory cytokines were maximal, the animals were exposed to aerosolized methacholine after intratracheal instillation of MANS or a missense control peptide (RNS). MANS, but not RNS, attenuated the methacholine-stimulated secretion of the major respiratory mucin protein, Muc5ac (50% reduction). Concurrently, elastase-induced proinflammatory cytokines typically recovered in bronchoalveolar lavage (BAL), including KC, IL-1beta, IL-6, MCP-1, and TNFalpha, were reduced by the MANS peptide (mean levels decreased 50-60%). Secondary to the effects of MANS on mucin secretion and inflammation, mechanical lung function by forced oscillation technique was characterized with respect to airway reactivity in response to cumulative aerosol stimulation with serotonin. The MANS peptide was also found to effectively attenuate airway hyperresponsiveness to serotonin in this airway hypersecretory model. Collectively, these findings support the concept that even in airway epithelia remodeled with goblet cell metaplasia and in a state of mucin hypersecretion, exogenous attenuation of function of MARCKS protein via the MANS peptide decreases airway mucin secretion, inflammation, and hyperreactivity. PMID- 20543008 TI - Radioactivity levels of limestone and gypsum used as building raw materials in Turkey and estimation of exposure doses. AB - The natural radionuclide contents of limestone and gypsum samples used as building raw materials in Turkey were measured by means of gamma spectrometer system with HPGe detector. The measured activity concentrations of (226)Ra, (232)Th and (40)K radionuclide were compared with the reported data from other countries. Radium equivalent activity and internal hazard index, absorbed gamma dose rate in indoor due to the external exposure and corresponding annual effective dose were determined to estimate the exposure risk arising due to the use of these raw materials. This study has shown that examined gypsum and limestone raw materials do not pose any excess radiological health problem and are safe for use in the construction of buildings. PMID- 20543009 TI - Pancreas-specific Gsalpha deficiency has divergent effects on pancreatic alpha- and beta-cell proliferation. AB - The ubiquitously expressed G protein alpha-subunit G(s)alpha mediates the intracellular cAMP response to glucagon-like peptide 1 (GLP1) and other incretin hormones in pancreatic islet cells. We have shown previously that mice with beta cell-specific G(s)alpha deficiency (betaGsKO) develop severe early-onset insulin deficient diabetes with a severe defect in beta-cell proliferation. We have now generated mice with G(s)alpha deficiency throughout the whole pancreas by mating G(s)alpha-floxed mice with Pdx1-cre transgenic mice (PGsKO). PGsKO mice also developed severe insulin-deficient diabetes at a young age, confirming the important role of G(s)alpha signaling in beta-cell growth and function. Unlike in betaGsKO mice, islets in PGsKO mice had a relatively greater proportion of alpha cells, which were spread throughout the interior of the islet. Similar findings were observed in mice with pancreatic islet cell-specific G(s)alpha deficiency using a neurogenin 3 promoter-cre recombinase transgenic mouse line. Studies in the alpha-cell line alphaTC1 confirmed that reduced cAMP signaling increased cell proliferation while increasing cAMP produced the opposite effect. Therefore, it appears that G(s)alpha/cAMP signaling has opposite effects on pancreatic alpha- and beta-cell proliferation, and that impaired GLP1 action in alpha- and beta cells via G(s)alpha signaling may be an important contributor to the reciprocal effects on insulin and glucagon observed in type 2 diabetics. In addition, PGsKO mice show morphological changes in exocrine pancreas and evidence for malnutrition and dehydration, indicating an important role for G(s)alpha in the exocrine pancreas as well. PMID- 20543010 TI - Primary total hip arthroplasty versus hemiarthroplasty for displaced intracapsular hip fractures in older patients: systematic review. AB - OBJECTIVE: To determine whether total hip arthroplasty is associated with lower reoperation rates, mortality, and complications, and better function and quality of life than hemiarthroplasty for displaced fractures of the femoral neck in older patients. DESIGN: Systematic review and meta-analysis of randomised trials, quasirandomised trials, and cohort studies. DATA SOURCES: Medline, Embase, Cochrane register of controlled trials, publishers' databases, and manual search of bibliographies. STUDY SELECTION: Randomised controlled trials, quasirandomised trials, and cohort studies (retrospective and prospective) comparing hemiarthroplasty with total hip arthroplasty for treating displaced femoral neck fractures in patients aged more than 60 years. DATA EXTRACTION: Relative risks, risk differences, and mean differences from each trial, aggregated using random effects models. Analyses were stratified for experimental and non-experimental designs, and two way sensitivity analyses and tests for interaction were done to assess the influence of various criteria of methodological quality on pooled estimates. DATA SYNTHESIS: 3821 references were identified. Of the 202 full papers inspected, 15 were included (four randomised controlled trials, three quasirandomised trials, and eight retrospective cohort studies, totalling 1890 patients). Meta-analysis of 14 studies showed a lower risk of reoperation after total hip arthroplasty compared with hemiarthroplasty (relative risk 0.57, 95% confidence interval 0.34 to 0.96, risk difference 4.4%, 95% confidence interval 0.2% to 8.5%), although this effect was mainly driven by investigations without concealed treatment allocation. Total hip arthroplasty consistently showed better ratings in the Harris hip score (three studies, 246 patients, weighted mean difference 5.4, 95% confidence interval 2.7 to 8.2) after follow-up periods of 12 to 48 months. The standardised mean difference of different scores from five studies was 0.42 (95% confidence interval 0.24 to 0.61), indicating a medium functional advantage of total hip arthroplasty over hemiarthroplasty. Total hip arthroplasty was associated with a slightly higher risk of dislocation (relative risk 1.48, 95% confidence interval 0.89 to 2.46) and general complications (1.14, 0.87 to 1.48). CONCLUSION: Single stage total hip arthroplasty may lead to lower reoperation rates and better functional outcomes compared with hemiarthroplasty in older patients with displaced femoral neck fractures. However, heterogeneity across the available trials and distinct subgroup effects preclude definitive statements and require further research in this area. PMID- 20543011 TI - Malaria control beyond 2010. PMID- 20543012 TI - Treatment of displaced intracapsular hip fractures in older patients. PMID- 20543014 TI - NICE rejects drug for metastatic breast cancer because of cost and poor efficacy. PMID- 20543015 TI - Mutants in phospholipid signaling attenuate the behavioral response of adult Drosophila to trehalose. AB - In Drosophila melanogaster, gustatory receptor genes (Grs) encode putative G protein-coupled receptors (GPCRs) that are expressed in gustatory receptor neurons (GRNs). One of the Gr genes, Gr5a, encodes a receptor for trehalose that is expressed in a subset of GRNs. Although a role for the G protein, Gsalpha, has been shown in Gr5a-expressing taste neurons, there is the residual responses to trehalose in Gsalpha mutants which could suggest additional transduction mechanisms. Expression and genetic analysis of the heterotrimeric G-protein subunit, Gq, shown here suggest involvement of this Galpha subunit in trehalose perception in Drosophila. A green fluorescent protein reporter of Gq expression is detected in gustatory neurons in the labellum, tarsal segments, and wing margins. Animals heterozygous for dgq mutations and RNA interference-mediated knockdown of dgq showed reduced responses to trehalose in the proboscis extension reflex assay and feeding behavior assay. These defects were rescued by targeted expression of the wild-type dgqalpha transgene in the GRNs. These data together with observations from other mutants in phospholipid signaling provide insights into the mechanisms of taste transduction in Drosophila. PMID- 20543016 TI - Tongue pressure and submental surface electromyography measures during noneffortful and effortful saliva swallows in healthy women. AB - PURPOSE: The effortful swallow, a compensatory technique frequently employed by speech-language pathologists for their patients with dysphagia, is still not fully understood in terms of how it modifies the swallow. In particular, although age-related changes are known to reduce maximum isometric tongue pressure, it is not known whether age affects people's ability to perform the effortful swallow. In this study, differences were explored between younger and older healthy women in execution of the effortful swallowing maneuver through a comparative analysis of effortful and noneffortful swallows. METHOD: Eighty healthy women (40 age 18 35 years and 40 age 60 and older) participated. Peak amplitude measures and the timing of signal onset to peak were measured using concurrent tongue pressure and submental surface electromyography. Result Statistically significant main effects of age group were not observed in the amplitude data, but older participants showed slower rise times to peak anterior tongue-palate pressure. CONCLUSIONS: Despite the general age-related deterioration of the swallowing musculature due to the phenomenon of sarcopenia, older women can still produce noneffortful and effortful swallows with lingual pressure and submental surface electromyography amplitudes similar to younger women. PMID- 20543017 TI - Synthesized speech output and children: a scoping review. AB - PURPOSE: Many computer-based augmentative and alternative communication systems in use by children have speech output. This article (a) provides a scoping review of the literature addressing the intelligibility and listener comprehension of synthesized speech output with children and (b) discusses future research directions. METHOD: Studies investigating synthesized speech intelligibility and/or comprehension with children as listeners were systematically identified and coded according to their objectives and methodology. RESULTS: Ten studies were identified. They were organized according to the following variables: intelligibility variables related to the stimuli (context and rate), intelligibility variables related to aspects of the listener (age of the child, the language or languages spoken by the listener, experience, and practice effects), and comprehension. Each of these factors-and the research support with child participants-was discussed. CONCLUSIONS: Overall, there is a paucity of research investigating synthesized speech for use with children. Available evidence suggests that children produce similar trends but lower levels of intelligibility performance when compared with adults. Future areas of applied research are required to adequately define this relationship and the variables that may contribute to improving the intelligibility and comprehension of synthesized speech for children. PMID- 20543018 TI - The effects of 'on-call/out of hours' physical therapy in acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. AB - OBJECTIVE: To assess the effectiveness of an on-call physical therapy programme in the management of acute exacerbations of chronic obstructive pulmonary diseases. DESIGN: Randomized controlled trial. SETTING: Secondary care level, rural hospital. SUBJECTS: Thirty-eight patients with acute exacerbations of chronic obstructive pulmonary disease. INTERVENTIONS: Regular physical therapy and on-call physical therapy was given to two groups of patients with 19 in each arm. On-call physical therapy included providing respiratory physical therapy as required by the patient out of business hours. MAIN MEASURES: Peak expiratory flow rate, sustained maximal inspiration, six-minute walk distance and rating of perceived exertion post six-minute walk test. RESULTS: In the group receiving on call physical therapy, peak expiratory flow rate and six-minute walk test showed a significant difference (52.1 L/min and 98.16 m, respectively) when compared with the control group (211.57 +/- 51.12 L/min and 159.47 +/- 67.78 L/min; P =0.01 and 387.89 +/- 110.1 m and 289.73 +/- 103.2 m; P=0.004 respectively). The difference in peak expiratory flow rate (Delta peak expiratory flow rate) was seen to be more in the on-call group (120 L/min) when compared to the control group (50 L/min), P =0.002. Improvements in sustained maximal inspiration and Borg's rating of perceived exertion after the six-minute walk test were also observed (P>0.05). CONCLUSION: On-call physical therapy brings about a significant increase in peak expiratory flow rates, six-minute walk distance and sustained maximal inspiration. PMID- 20543019 TI - Butler's neuromobilizations combined with proprioceptive neuromuscular facilitation are effective in reducing of upper limb sensory in late-stage stroke subjects: a three-group randomized trial. AB - QUESTION: Are Butler's neuromobilizations combined with proprioceptive neuromuscular facilitation and traditional post-stroke therapy more effective in reducing affected upper extremity sensory deficits in late-stage stroke subjects than proprioceptive neuromuscular facilitation combined with traditional therapy or traditional therapy alone? DESIGN: Pretest-posttest three-group randomized clinical experimental design. PARTICIPANTS: A total of 96 late-stage stroke subjects were randomly assigned to three groups. INTERVENTION: The therapeutic programme in the control group was based on traditional post-stroke methods. The second group (experimental 1) received in addition individual therapy based on the proprioceptive neuromuscular facilitation method. The third group (experimental 2) received a combination: traditional therapeutic programme plus individual proprioceptive neuromuscular facilitation exercises plus neuromobilization of the affected upper extremity. All groups received 18 training sessions lasting about 45 minutes each. OUTCOME MEASURES: Assessment of the two-point discriminatory sense (distance between the tips of the compass when the subject indicated two-point sensation), stereognosia (identification up to 10 objects by touch) and thermaesthesia (using hot and cold cylinders on dermatomes C6-C8) were performed. RESULTS: Analysis of change scores showed that two-point discriminatory sense for experimental group 2 was significantly better than that in the two other groups (P<0.001). Similar results were registered for thermaesthesia (experimental 2 versus experimental 1 P<0.01; experimental 2 versus control P<0.001). For stereognosia the only significant difference was found between experimental group 2 and the control group (P<0.05). CONCLUSION: In our subjects, application of Butler's neuromobilizations combined with proprioceptive neuromuscular facilitation showed greater effectiveness in reducing sensory deficits than proprioceptive neuromuscular facilitation or traditional therapy alone. PMID- 20543020 TI - Do rehabilitation professionals need to consider their clients' health literacy for effective practice? AB - OBJECTIVE: To discuss the importance of integrating health literacy into rehabilitation practice. BACKGROUND: The effectiveness of rehabilitation interventions and clients' long-term health might depend on various factors, including health literacy. Health literacy is defined as the ability to access, understand, evaluate and communicate information as a way to promote, maintain and improve health in a variety of settings over the life-course. Rehabilitation professionals are often uniformed about and neglect health literacy in their interventions. METHOD: The scientific and grey literature on health and, more specifically, rehabilitation and health promotion was reviewed. The MEDLINE, OTDBASE, CINAHL, AMED and MANTIS databases were searched by combining the keyword (1) 'health literacy' with the keywords (2) 'rehabilitation', 'physical therapy', 'occupational therapy' or 'health promotion'. RESULTS: Health literacy is one of the foundations of individual health and might have an impact on interventions, the individual and society. All papers addressing both health literacy and rehabilitation (n = 10) specifically mentioned that rehabilitation professionals need to consider their clients' health literacy. Rehabilitation is particularly linked to health literacy because both stress the importance of (1) capacities, functioning, participation and empowerment of clients; (2) holistic approach; (3) client-centred practice; (4) teaching of information and methods; and (5) access to services and equity issues. CONCLUSIONS: Based on these results, we think it is important that rehabilitation professionals be aware of the importance of health literacy and intervene to improve it. The challenge is now to better understand how health literacy influences the effectiveness of rehabilitation and health outcomes. PMID- 20543021 TI - Efficacy and usability of assistive technology for patients with cognitive deficits: a systematic review. AB - OBJECTIVE: To determine the efficacy of portable electronic aids such as personal digital assistants (PDAs), pagers or mobile phones for patients with cognitive deficits by means of a systematic review. The usability of these aids is also briefly discussed. DATA SOURCES: PubMed, CINAHL, PsychINFO, EMBASE and MEDLINE were searched up to February 2009. The references of identified and relevant articles were scanned to find additional relevant titles. REVIEW METHODS: Papers referring to 'electronic aids', 'cognition' and 'brain injury' were included. The population had to be adult and have cognitive impairments as a result of acquired brain injury. Outcome measures were change in cognitive or occupational performance or the level of participation in daily life. The criteria of Cicerone et al. were used to evaluate the quality of the retrieved studies. RESULTS: Twenty-eight papers presenting 25 studies were reviewed. The total number of participants was 423. Most identified papers described case reports or non randomized clinical trials. Only one randomized controlled trial was identified, in which the NeuroPage proved effective in supporting prospective memory. Other kinds of assistive technology such as PDAs and voice recorders showed positive results in supporting retrospective and prospective memory. CONCLUSION: The efficacy of assistive technology in general is not yet sufficiently studied in randomized controlled trials, although promising results has been reported. Furthermore, several survey studies established that both potential users and clinicians have optimistic expectations about the usability of assistive technology. PMID- 20543022 TI - Effectiveness of an online fatigue self-management programme for people with chronic neurological conditions: a randomized controlled trial. AB - OBJECTIVE: To evaluate an online fatigue self-management programme in a sample of adults with chronic neurological conditions. DESIGN: Randomized controlled trial. SETTING: Online fatigue self-management programme delivered across Australia. PARTICIPANTS: Ninety-five people with fatigue secondary to multiple sclerosis, Parkinson's disease or post-polio syndrome. INTERVENTIONS: An online fatigue self management programme, an information-only fatigue self-management programme and a control group. MAIN MEASURES: Groups were compared at pre test, post test and at three months on primary outcomes using the Fatigue Impact Scale, Activity Card Sort and Personal Wellbeing Index. RESULTS: With the exception of the Personal Wellbeing Index at post test (F = 3.519; P =0.034) and the Physical Subscale of the Fatigue Impact Scale at follow-up (F = 3.473; P =0.035) there were no significant differences between the three groups on primary outcomes. Post-hoc testing showed the differences to be between the information-only and control groups (P = 0.036 and P = 0.030 respectively). Improvement in the information only group was unexpected but appears to be similar to results of other online interventions. The fatigue self-management and information-only groups performed better than the control on some secondary outcome measures. Low power in the analysis may have contributed to the findings. Repeated-measures ANCOVA showed that the fatigue self-management and the information-only groups improved over time on the Fatigue Impact Scale and the Activity Card Sort (P<0.05). The control group showed no improvements over time. CONCLUSIONS: Although the fatigue self management group improved over time, results did not demonstrate additional benefit in most outcome measures when compared with the control group. PMID- 20543023 TI - The language phenotype of children and adolescents with Noonan syndrome. AB - PURPOSE: This study presents an analysis of language skills in individuals with Noonan syndrome (NS), an autosomal dominant genetic disorder. We investigated whether the language impairments affecting some individuals arise from deficits specifically within the linguistic system or whether they are associated with cognitive, perceptual, and motor factors. Comparisons of language abilities among the different NS genotypes were also conducted. METHOD: Sixty-six children and adolescents with NS were evaluated using standardized speech, language, and literacy assessments. Additional cognitive, perceptual, and motor tasks were administered to examine the relation of these factors to language development. Genotype was noted for those who underwent genetic testing. RESULTS: Language impairments were more frequent in NS than in the general population and were associated with higher risk for reading and spelling difficulties. Language was significantly correlated with nonverbal cognition, hearing ability, articulation, motor dexterity, and phonological memory. Genotype analyses suggest that the higher performance of SOS1-positive than PTPN11-positive individuals on language tasks was largely mediated by differences in cognitive ability. CONCLUSIONS: Our results indicate that variation in language skill in NS is closely related to cognitive, perceptual, and motor factors. It does not appear that specific aspects of language are selectively affected in this syndrome. PMID- 20543025 TI - Effects of a conversation intervention on the expressive vocabulary development of prekindergarten children. AB - PURPOSE: The purpose of this study was to determine the effectiveness of a conversation intervention including 500 min of linguistically and cognitively complex talk on the expressive vocabulary growth of prekindergarten children. METHOD: Children (N = 73) were randomly assigned to control or a 10-week experimental intervention condition. Twice weekly, children in the intervention condition received 25 min of intensive conversation with an adult emphasizing use of rare words, linguistic recasts, and open-ended questions. Expressive vocabulary was measured using the Expressive Vocabulary Test (EVT; Williams, 1997) and lexical diversity obtained through a language sample. RESULTS: Children in the intervention group showed greater growth on the EVT than controls. Children in the intervention group with low vocabulary at pretest also showed greater growth in lexical diversity than controls. CLINICAL IMPLICATIONS: Findings suggest that relatively small amounts of linguistically and cognitively complex conversation with a trained adult can be a useful strategy for improving the expressive vocabulary skills of children with low vocabularies. PMID- 20543024 TI - Differentiating the effects of phonotactic probability and neighborhood density on vocabulary comprehension and production: a comparison of preschool children with versus without phonological delays. AB - PURPOSE: To differentiate the effect of phonotactic probability from that of neighborhood density on a vocabulary probe administered to preschool children with or without phonological delays. METHOD: Twenty preschool children with functional phonological delays and 34 preschool children with typical language development completed a 121-item vocabulary probe in both an expressive and receptive response format. Words on the vocabulary probe orthogonally varied on phonotactic probability and neighborhood density but were matched on age of acquisition, word frequency, word length, semantic set size, concreteness, familiarity, and imagability. RESULTS: Results show a Phonotactic Probability x Neighborhood Density interaction with variation across groups. Specifically, the optimal conditions for typically developing children were rare phonotactic probability with sparse neighborhoods and common phonotactic probability with dense neighborhoods. In contrast, only rare phonotactic probability with sparse neighborhoods was optimal for children with phonological delays. CONCLUSIONS: Rare sound sequences and sparse neighborhoods may facilitate triggering of word learning for typically developing children and children with phonological delays. In contrast, common sound sequences and dense neighborhoods may facilitate configuration and engagement for typically developing children but not for children with phonological delays because of their weaker phonological and/or lexical representations. PMID- 20543026 TI - Pharmacotherapy and children with autism spectrum disorder: a tutorial for speech language pathologists. AB - PURPOSE: The purpose of this tutorial is to provide speech-language pathologists (SLPs) with general information regarding the most commonly prescribed medications for children with autism spectrum disorder (ASD; e.g., central nervous system stimulants, noradrenergic reuptake inhibitors, alpha-2 adrenergic agonists, antipsychotics, anticonvulsants, selective serotonin reuptake inhibitors, benzodiazepines) in regard to their mechanism of action, behaviors treated, and potential side effects. METHOD: This clinical resource was compiled to support SLPs who need to understand the functions and effects of medications that have been prescribed to a child with ASD to whom they have or will be providing assessment and intervention services. CONCLUSIONS: SLPs play an important role in the education, assessment, and treatment of children with ASD. Although there is no definitive cure for ASD, up to 70% of children with ASD are prescribed psychoactive medications to ameliorate disruptive behaviors associated with ASD such as hyperactivity, inattention, impulsivity, aggression, irritability, self-injury, obsessive compulsiveness, anxiety, and mood disorders. The entire health care team, including SLPs, should be involved in monitoring children with ASD for efficacy, tolerability, and potential side effects when medications are prescribed. PMID- 20543027 TI - The deubiquitinating enzyme AMSH3 is required for intracellular trafficking and vacuole biogenesis in Arabidopsis thaliana. AB - Ubiquitination, deubiquitination, and the formation of specific ubiquitin chain topologies have been implicated in various cellular processes. Little is known, however, about the role of ubiquitin in the development of cellular organelles. Here, we identify and characterize the deubiquitinating enzyme AMSH3 from Arabidopsis thaliana. AMSH3 hydrolyzes K48- and K63-linked ubiquitin chains in vitro and accumulates both ubiquitin chain types in vivo. amsh3 mutants fail to form a central lytic vacuole, accumulate autophagosomes, and mis-sort vacuolar protein cargo to the intercellular space. Furthermore, AMSH3 is required for efficient endocytosis of the styryl dye FM4-64 and the auxin efflux facilitator PIN2. We thus present evidence for a role of deubiquitination in intracellular trafficking and vacuole biogenesis. PMID- 20543028 TI - The Mg-chelatase H subunit of Arabidopsis antagonizes a group of WRKY transcription repressors to relieve ABA-responsive genes of inhibition. AB - The phytohormone abscisic acid (ABA) plays a vital role in plant development and response to environmental challenges, but the complex networks of ABA signaling pathways are poorly understood. We previously reported that a chloroplast protein, the magnesium-protoporphyrin IX chelatase H subunit (CHLH/ABAR), functions as a receptor for ABA in Arabidopsis thaliana. Here, we report that ABAR spans the chloroplast envelope and that the cytosolic C terminus of ABAR interacts with a group of WRKY transcription factors (WRKY40, WRKY18, and WRKY60) that function as negative regulators of ABA signaling in seed germination and postgermination growth. WRKY40, a central negative regulator, inhibits expression of ABA-responsive genes, such as ABI5. In response to a high level of ABA signal that recruits WRKY40 from the nucleus to the cytosol and promotes ABAR-WRKY40 interaction, ABAR relieves the ABI5 gene of inhibition by repressing WRKY40 expression. These findings describe a unique ABA signaling pathway from the early signaling events to downstream gene expression. PMID- 20543030 TI - Re: "Identification of patients with nonmelanoma skin cancer using health maintenance organization claims data". PMID- 20543029 TI - EOBII, a gene encoding a flower-specific regulator of phenylpropanoid volatiles' biosynthesis in petunia. AB - Floral scent, which is determined by a complex mixture of low molecular weight volatile molecules, plays a major role in the plant's life cycle. Phenylpropanoid volatiles are the main determinants of floral scent in petunia (Petunia hybrida). A screen using virus-induced gene silencing for regulators of scent production in petunia flowers yielded a novel R2R3-MYB-like regulatory factor of phenylpropanoid volatile biosynthesis, EMISSION OF BENZENOIDS II (EOBII). This factor was localized to the nucleus and its expression was found to be flower specific and temporally and spatially associated with scent production/emission. Suppression of EOBII expression led to significant reduction in the levels of volatiles accumulating in and emitted by flowers, such as benzaldehyde, phenylethyl alcohol, benzylbenzoate, and isoeugenol. Up/downregulation of EOBII affected transcript levels of several biosynthetic floral scent-related genes encoding enzymes from the phenylpropanoid pathway that are directly involved in the production of these volatiles and enzymes from the shikimate pathway that determine substrate availability. Due to its coordinated wide-ranging effect on the production of floral volatiles, and its lack of effect on anthocyanin production, a central regulatory role is proposed for EOBII in the biosynthesis of phenylpropanoid volatiles. PMID- 20543031 TI - Efficient genome-wide association testing of gene-environment interaction in case parent trios. AB - Complex trait variation is likely to be explained by the combined effects of genes, environmental factors, and gene x environment (G x E) interaction. The authors introduce a novel 2-step method for detecting a G x E interaction in a genome-wide association study (GWAS) of case-parent trios. The method utilizes 2 sources of G x E information in a trio sample to construct a screening step and a testing step. Across a wide range of models, this 2-step procedure provides substantially greater power to detect G x E interaction than a standard test of G x E interaction applied genome-wide. For example, for a disease susceptibility locus with minor allele frequency of 15%, a binary exposure variable with 50% prevalence, and a GWAS scan of 1 million markers in 1,000 case-parent trios, the 2-step method provides 87% power to detect a G x E interaction relative risk of 2.3, as compared with only 25% power using a standard G x E test. The method is easily implemented using standard software. This 2-step scan for G x E interaction is independent of any prior scan that may have been conducted for genetic main effects, and thus has the potential to uncover new genes in a GWAS that have not been previously identified. PMID- 20543032 TI - Positive and negative experiences of social support and long-term mortality among middle-aged Dutch people. AB - This study investigated the relation between positive and negative experiences of social support and mortality in a population-based sample. Data were derived from Dutch men and women aged 20-59 years who participated in the Doetinchem Cohort Study in 1987-1991. Social support was measured at baseline and after 5 years of follow-up by using the Social Experiences Checklist indicating positive (n = 11,163) and negative (n = 11,161) experiences of support. Mortality data were obtained from 1987 until 2008. Cox proportional hazards regression models, adjusted for age and sex, showed that low positive experiences of support at baseline were associated with an increased mortality risk after, on average, 19 years of follow-up (hazard ratio = 1.26, 95% confidence interval: 1.04, 1.52). Even after additional adjustment for socioeconomic factors, lifestyle factors, and indicators of health status, the increased mortality risk remained statistically significant (hazard ratio = 1.23, 95% confidence interval: 1.01, 1.49). For participants with repeated measurements of social support at 5-year intervals, a stable low level of positive experiences of social support was associated with a stronger increase in age- and sex-adjusted mortality risk (hazard ratio = 1.57, 95% confidence interval: 1.03, 2.39). Negative experiences of social support were not related to mortality. PMID- 20543033 TI - Methods for testing association between uncertain genotypes and quantitative traits. AB - Interpretability and power of genome-wide association studies can be increased by imputing unobserved genotypes, using a reference panel of individuals genotyped at higher marker density. For many markers, genotypes cannot be imputed with complete certainty, and the uncertainty needs to be taken into account when testing for association with a given phenotype. In this paper, we compare currently available methods for testing association between uncertain genotypes and quantitative traits. We show that some previously described methods offer poor control of the false-positive rate (FPR), and that satisfactory performance of these methods is obtained only by using ad hoc filtering rules or by using a harsh transformation of the trait under study. We propose new methods that are based on exact maximum likelihood estimation and use a mixture model to accommodate nonnormal trait distributions when necessary. The new methods adequately control the FPR and also have equal or better power compared to all previously described methods. We provide a fast software implementation of all the methods studied here; our new method requires computation time of less than one computer-day for a typical genome-wide scan, with 2.5 M single nucleotide polymorphisms and 5000 individuals. PMID- 20543034 TI - Characterization of a gne::IS629 O rough:H7 Escherichia coli strain from a hemorrhagic colitis patient. AB - Shiga-toxigenic Escherichia coli strains that are O rough:H7 due to gne::IS629 were thought to be rare and to have unknown pathogenic potential. Recently, an O rough:H7 strain caused by gne::IS629 was isolated from a hemorrhagic colitis patient, suggesting that these strains are pathogenic and may not be as rare as anticipated. PMID- 20543035 TI - Improved dsrA-based terminal restriction fragment length polymorphism analysis of sulfate-reducing bacteria. AB - To better describe the community structure of sulfate-reducing bacteria in environmental systems, we compared several dissimilatory sulfite reductase (dsr) primer sets for terminal restriction fragment length polymorphism application. A new reverse primer that increased allelic diversity estimates up to 5-fold was applied to hydrocarbon seep samples to examine the relationship between guild activity and diversity. PMID- 20543036 TI - Distribution of Shiga-toxigenic Escherichia coli O157 in the gastrointestinal tract of naturally O157-shedding cattle at necropsy. AB - Shiga-toxigenic Escherichia coli (STEC) O157 occurrence was determined along the entire gastrointestinal tract (GIT) of each of four naturally shedding cattle and at three sites in 61 slaughter cattle. STEC O157 was distributed along the entire GIT, though interanimal distribution was variable. Neither feces nor rectoanal junction samples accurately predicted the STEC O157-negative status of any particular animal. PMID- 20543037 TI - Targeted chromosomal knockouts in Mycoplasma pneumoniae. AB - Most gene knockouts in mycoplasmas are achieved through labor-intensive transposon mutagenesis. Here, we describe a method for making targeted deletions in Mycoplasma pneumoniae by use of homologous recombination. In this method, M. pneumoniae is transformed with a plasmid carrying an antibiotic resistance marker flanked by 1-kb regions surrounding the target gene. Following selection for the antibiotic resistance, colonies are screened for double crossovers which indicate complete deletion of the target open reading frame. PMID- 20543039 TI - Association of the melioidosis agent Burkholderia pseudomallei with water parameters in rural water supplies in Northern Australia. AB - We analyzed water parameters and the occurrence of the melioidosis agent Burkholderia pseudomallei in 47 water bores in Northern Australia. B. pseudomallei was associated with soft, acidic bore water of low salinity but high iron levels. This finding aids in identifying water supplies at risk of contamination with this pathogenic bacterium. PMID- 20543038 TI - Population turnover in a Microcystis bloom results in predominantly nontoxigenic variants late in the season. AB - Surface samples of the 2007 Microcystis bloom occurring in Copco Reservoir on the Klamath River in Northern California were analyzed genetically by sequencing clone libraries made with amplicons at three loci: the internal transcribed spacer of the rRNA operon (ITS), cpcBA, and mcyA. Samples were taken between June and October, during which time two cell count peaks occurred, in mid-July and early September. The ITS and cpcBA loci could be classified into four or five allele groups, which provided a convenient means for describing the Microcystis population and its changes over time. Each group was numerically dominated by a single, highly represented sequence. Other members of each group varied by changes at 1 to 3 nucleotide positions, while groups were separated by up to 30 nucleotide differences. As deduced by a partial sampling of the clone libraries, there were marked population turnovers during the season, indicated by changes in allele composition at both the ITS and cpcBA loci. Different ITS and cpcBA genotypes appeared to be dominant at the two population peaks. Toxicity (amount of microcystin per cell) and toxigenic potential (mcyB copy number) were lower during the second peak, and the mcyB copy number fell further as the bloom declined. PMID- 20543040 TI - Occurrence and molecular characteristics of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius in an academic veterinary hospital. AB - Recently, methicillin-resistant Staphylococcus aureus (MRSA) and methicillin resistant Staphylococcus pseudintermedius (MRSP) have been increasingly isolated from veterinarians and companion animals. With a view to preventing the spread of MRSA and MRSP, we evaluated the occurrence and molecular characteristics of each in a veterinary college. MRSA and MRSP were isolated from nasal samples from veterinarians, staff members, and veterinary students affiliated with a veterinary hospital. Using stepwise logistic regression, we identified two factors associated with MRSA carriage: (i) contact with an identified animal MRSA case (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 2.2 to 21.6) and (ii) being an employee (OR, 6.2; 95% CI, 2.0 to 19.4). The majority of MRSA isolates obtained from individuals affiliated with the veterinary hospital and dog patients harbored spa type t002 and a type II staphylococcal cassette chromosome mec (SCCmec), similar to the hospital-acquired MRSA isolates in Japan. MRSA isolates harboring spa type t008 and a type IV SCCmec were obtained from one veterinarian on three different sampling occasions and also from dog patients. MRSA carriers can also be a source of MRSA infection in animals. The majority of MRSP isolates (85.2%) carried hybrid SCCmec type II-III, and almost all the remaining MRSP isolates (11.1%) carried SCCmec type V. MRSA and MRSP were also isolated from environmental samples collected from the veterinary hospital (5.1% and 6.4%, respectively). The application of certain disinfection procedures is important for the prevention of nosocomial infection, and MRSA and MRSP infection control strategies should be adopted in veterinary medical practice. PMID- 20543041 TI - Complementation of Listeria monocytogenes null mutants with selected Listeria seeligeri virulence genes suggests functional adaptation of Hly and PrfA and considerable diversification of prfA regulation in L. seeligeri. AB - While Listeria seeligeri and L. monocytogenes contain the main Listeria virulence gene cluster, only L. monocytogenes is considered an intracellular pathogen. Initial evolutionary analyses showed that the virulence genes prfA, hly, and plcA are conserved in L. seeligeri, with specific Hly and PrfA amino acid residues showing evidence for positive selection in L. seeligeri. Our data also show that temperature-dependent transcript patterns for prfA, which encodes a transcriptional regulator of virulence genes, differed between L. monocytogenes and L. seeligeri. To further investigate the divergence of virulence gene function and regulation, L. seeligeri prfA (prfA(LS)), hly (hly(LS)), and plcA (plcA(LS)), as well as prfA(LS) constructs with different prfA promoter regions, were introduced into appropriate L. monocytogenes null mutants. Only when prfA(LS) was under the control of the L. monocytogenes prfA promoters (P1- and P2prfA) (P1P2(LM) prfA(LS)) was prfA(LS) able to fully complement the Delta prfA(LM) deletion. hly(LS) introduced into an L. monocytogenes background under its native promoter showed transcript levels similar to those of hly(LM) and was able to partially restore L. monocytogenes wild-type-level hemolysis and intracellular growth, even though Hly(LM) and Hly(LS) showed distinct patterns of cell- and supernatant-associated hemolytic activities. Our data indicate that (i) regulation of prfA expression differs between L. monocytogenes and L. seeligeri, although hly transcription is temperature dependent in both species, and (ii) PrfA and Hly functions are largely, but not fully, conserved between L. seeligeri and L. monocytogenes. Virulence gene homologues and their expression thus appear to have adapted to distinct but possibly related functions in these two species. PMID- 20543042 TI - Using chemobiosynthesis and synthetic mini-polyketide synthases to produce pharmaceutical intermediates in Escherichia coli. AB - Recombinant microbial whole-cell biocatalysis is a valuable approach for producing enantiomerically pure intermediates for the synthesis of complex molecules. Here, we describe a method to produce polyketide intermediates possessing multiple stereogenic centers by combining chemobiosynthesis and engineered mini-polyketide synthases (PKSs). Chemobiosynthesis allows the introduction of unnatural moieties, while a library of synthetic bimodular PKSs expressed from codon-optimized genes permits the introduction of a variety of ketide units. To validate the approach, intermediates for the synthesis of trans 9,10-dehydroepothilone D were generated. The designer molecules obtained have the potential to greatly reduce the manufacturing cost of epothilone analogues, thus facilitating their commercial development as therapeutic agents. PMID- 20543043 TI - Facilitation of direct conditional knockout of essential genes in Bacillus licheniformis DSM13 by comparative genetic analysis and manipulation of genetic competence. AB - The genetic manageability of the biotechnologically important Bacillus licheniformis is hampered due to its poor transformability, whereas Bacillus subtilis efficiently takes up DNA during genetic competence, a quorum-sensing dependent process. Since the sensor histidine kinase ComP, encoded by a gene of the quorum-sensing module comQXPA of B. licheniformis DSM13, was found to be inactive due to an insertion element within comP, the coding region was exchanged with a functional copy. Quorum sensing was restored, but the already-poor genetic competence dropped further. The inducible expression of the key regulator for the transcription of competence genes, ComK, in trans resulted in highly competent strains and facilitated the direct disruption of genes, as well as the conditional knockout of an essential operon. As ComK is inhibited at low cell densities by a proteolytic complex in which MecA binds ComK and such inhibition is antagonized by the interaction of MecA with ComS (the expression of the latter is controlled by cell density in B. subtilis), we performed an in silico analysis of MecA and the hitherto unidentified ComS, which revealed differences for competent and noncompetent strains, indicating that the reduced competence possibly is due to a nonfunctional coupling of the comQXPA-encoded quorum module and ComK. The obtained increased genetic tractability of this industrial workhorse should improve a wide array of scientific investigations. PMID- 20543044 TI - Xer site-specific recombination, an efficient tool to introduce unmarked deletions into mycobacteria. AB - Genetic manipulation of mycobacteria still represents a serious challenge due to the lack of tools and selection markers. In this report, we describe the development of an intrinsically unstable excisable cassette for introduction of unmarked mutations in both Mycobacterium smegmatis and Mycobacterium tuberculosis. PMID- 20543046 TI - Specific and rapid enumeration of viable but nonculturable and viable-culturable gram-negative bacteria by using flow cytometry. AB - An issue of critical concern in microbiology is the ability to detect viable but nonculturable (VBNC) and viable-culturable (VC) cells by methods other than existing approaches. Culture methods are selective and underestimate the real population, and other options (direct viable count and the double-staining method using epifluorescence microscopy and inhibitory substance-influenced molecular methods) are also biased and time-consuming. A rapid approach that reduces selectivity, decreases bias from sample storage and incubation, and reduces assay time is needed. Flow cytometry is a sensitive analytical technique that can rapidly monitor physiological states of bacteria. This report outlines a method to optimize staining protocols and the flow cytometer (FCM) instrument settings for the enumeration of VBNC and VC bacterial cells within 70 min. Experiments were performed using the FCM to quantify VBNC and VC Escherichia coli O157:H7, Pseudomonas aeruginosa, Pseudomonas syringae, and Salmonella enterica serovar Typhimurium cells after staining with different fluorescent probes: SYTO 9, SYTO 13, SYTO 17, SYTO 40, and propidium iodide (PI). The FCM data were compared with those for specific standard nutrient agar to enumerate the number of cells in different states. By comparing results from cultures at late log phase, 1 to 64% of cells were nonculturable, 40 to 98% were culturable, and 0.7 to 4.5% had damaged cell membranes and were therefore theoretically dead. Data obtained using four different gram-negative bacteria exposed to heat and stained with PI also illustrate the usefulness of the approach for the rapid and unbiased detection of dead versus live organisms. PMID- 20543045 TI - Alteration of microbial communities colonizing leaf litter in a temperate woodland stream by growth of trees under conditions of elevated atmospheric CO2. AB - Elevated atmospheric CO(2) can cause increased carbon fixation and altered foliar chemical composition in a variety of plants, which has the potential to impact forested headwater streams because they are detritus-based ecosystems that rely on leaf litter as their primary source of organic carbon. Fungi and bacteria play key roles in the entry of terrestrial carbon into aquatic food webs, as they decompose leaf litter and serve as a source of nutrition for invertebrate consumers. This study tested the hypothesis that changes in leaf chemistry caused by elevated atmospheric CO(2) would result in changes in the size and composition of microbial communities colonizing leaves in a woodland stream. Three tree species, Populus tremuloides, Salix alba, and Acer saccharum, were grown under ambient (360 ppm) or elevated (720 ppm) CO(2), and their leaves were incubated in a woodland stream. Elevated-CO(2) treatment resulted in significant increases in the phenolic and tannin contents and C/N ratios of leaves. Microbial effects, which occurred only for P. tremuloides leaves, included decreased fungal biomass and decreased bacterial counts. Analysis of fungal and bacterial communities on P. tremuloides leaves via terminal restriction fragment length polymorphism (T RFLP) and clone library sequencing revealed that fungal community composition was mostly unchanged by the elevated-CO(2) treatment, whereas bacterial communities showed a significant shift in composition and a significant increase in diversity. Specific changes in bacterial communities included increased numbers of alphaproteobacterial and cytophaga-flavobacter-bacteroides (CFB) group sequences and decreased numbers of betaproteobacterial and firmicutes sequences, as well as a pronounced decrease in overall gram-positive bacterial sequences. PMID- 20543047 TI - Control of the type 3 secretion system in Vibrio harveyi by quorum sensing through repression of ExsA. AB - The type 3 secretion system (T3SS) genes of Vibrio harveyi are activated at low cell density and repressed at high cell density by quorum sensing (QS). Repression requires LuxR, the master transcriptional regulator of QS-controlled genes. Here, we determine the mechanism underlying the LuxR repression of the T3SS system. Using a fluorescence-based cell sorting approach, we isolated V. harveyi mutants that are unable to express T3SS genes at low cell density and identified two mutations in the V. harveyi exsBA operon. While LuxR directly represses the expression of exsBA, complementation and epistasis analyses reveal that it is the repression of exsA expression, but not exsB expression, that is responsible for the QS-mediated repression of T3SS genes at high cell density. The present work further defines the genes in the V. harveyi QS regulon and elucidates a mechanism demonstrating how multiple regulators can be linked in series to direct the expression of QS target genes specifically at low or high cell density. PMID- 20543048 TI - Decreasing trend of overlapping multilocus sequence types between human and chicken Campylobacter jejuni isolates over a decade in Finland. AB - We describe the long-term multilocus sequence typing (MLST) analysis of the population structure and dynamics of 454 Finnish human Campylobacter jejuni isolates, as well as 208 chicken isolates, collected during the mid-1990s to 2007. The sequence type clonal complexes (ST CC) ST-45 CC, ST-21 CC, and ST-677 CC were the most common ones found among all isolates, and they covered 73.9% of all isolates. The ST-283 CC also was found frequently among chicken isolates (8.2%). The predominant STs among all isolates were ST-45, ST-50, and ST-677. ST 137 and ST-230 were common among human isolates, and ST-267 was found more frequently among chicken isolates than human isolates. The ST-45 CC was significantly associated with chicken isolates (P < 0.01), whereas the ST-21 CC was associated with human isolates (P < 0.001). The ST-677 CC was not associated with any host (P = 0.5), and an opposite temporary trend of this complex was seen among chicken and human isolates, with an increase in the former and a decrease in the latter during the study period. Furthermore, the ST-22 and ST-48 CCs were significantly associated with human isolates (P < 0.01), but neither of the CCs was found in chicken isolates. The annual overlap between STs from human and chicken isolates decreased from 76% at the beginning of the study to 58% at the end. Our results suggest that the importance of chicken as a reservoir for strains associated with human infections has declined despite the consumption of domestic chicken meat increasing during the follow-up period by 83%. PMID- 20543049 TI - Improved molecular detection of Angiostrongylus cantonensis in mollusks and other environmental samples with a species-specific internal transcribed spacer 1-based TaqMan assay. AB - Angiostrongylus cantonensis is the most common cause of human eosinophilic meningitis. Humans become infected by ingesting food items contaminated with third-stage larvae that develop in mollusks. We report the development of a real time PCR assay for the species-specific identification of A. cantonensis in mollusk tissue. PMID- 20543050 TI - Recombineering using RecTE from Pseudomonas syringae. AB - In this report, we describe the identification of functions that promote genomic recombination of linear DNA introduced into Pseudomonas cells by electroporation. The genes encoding these functions were identified in Pseudomonas syringae pv. syringae B728a based on similarity to the lambda Red Exo/Beta and RecET proteins encoded by the lambda and Rac bacteriophages of Escherichia coli. The ability of the pseudomonad-encoded proteins to promote recombination was tested in P. syringae pv. tomato DC3000 using a quantitative assay based on recombination frequency. The results show that the Pseudomonas RecT homolog is sufficient to promote recombination of single-stranded DNA oligonucleotides and that efficient recombination of double-stranded DNA requires the expression of both the RecT and RecE homologs. Additionally, we illustrate the utility of this recombineering system to make targeted gene disruptions in the P. syringae chromosome. PMID- 20543051 TI - Redirecting reductant flux into hydrogen production via metabolic engineering of fermentative carbon metabolism in a cyanobacterium. AB - Some aquatic microbial oxygenic photoautotrophs (AMOPs) make hydrogen (H(2)), a carbon-neutral, renewable product derived from water, in low yields during autofermentation (anaerobic metabolism) of intracellular carbohydrates previously stored during aerobic photosynthesis. We have constructed a mutant (the ldhA mutant) of the cyanobacterium Synechococcus sp. strain PCC 7002 lacking the enzyme for the NADH-dependent reduction of pyruvate to D-lactate, the major fermentative reductant sink in this AMOP. Both nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) metabolomic methods have shown that autofermentation by the ldhA mutant resulted in no D lactate production and higher concentrations of excreted acetate, alanine, succinate, and hydrogen (up to 5-fold) compared to that by the wild type. The measured intracellular NAD(P)(H) concentrations demonstrated that the NAD(P)H/NAD(P)(+) ratio increased appreciably during autofermentation in the ldhA strain; we propose this to be the principal source of the observed increase in H(2) production via an NADH-dependent, bidirectional [NiFe] hydrogenase. Despite the elevated NAD(P)H/NAD(P)(+) ratio, no decrease was found in the rate of anaerobic conversion of stored carbohydrates. The measured energy conversion efficiency (ECE) from biomass (as glucose equivalents) converted to hydrogen in the ldhA mutant is 12%. Together with the unimpaired photoautotrophic growth of the ldhA mutant, these attributes reveal that metabolic engineering is an effective strategy to enhance H(2) production in AMOPs without compromising viability. PMID- 20543052 TI - Determining UV inactivation of Toxoplasma gondii oocysts by using cell culture and a mouse bioassay. AB - The effect of UV exposure on Toxoplasma gondii oocysts has not been completely defined for use in water disinfection. This study evaluated UV-irradiated oocysts by three assays: a SCID mouse bioassay, an in vitro T. gondii oocyst plaque (TOP) assay, and a quantitative reverse transcriptase real-time PCR (RT-qPCR) assay. The results from the animal bioassay show that 1- and 3-log(10) inactivation is achieved with 4 mJ/cm(2) UV and 10 mJ/cm(2) low-pressure UV, respectively. TOP assay results, but not RT-qPCR results, correlate well with bioassay results. In conclusion, a 3-log(10) inactivation of T. gondii oocysts is achieved by 10 mJ/cm(2) low-pressure UV, and the in vitro TOP assay is a promising alternative to the mouse bioassay. PMID- 20543053 TI - Requirement of the type II secretion system for utilization of cellulosic substrates by Cellvibrio japonicus. AB - Cellulosic biofuels represent a powerful alternative to petroleum but are currently limited by the inefficiencies of the conversion process. While gram positive and fungal organisms have been widely explored as sources of cellulases and hemicellulases for biomass degradation, gram-negative organisms have received less experimental attention. We investigated the ability of Cellvibrio japonicus, a recently sequenced gram-negative cellulolytic bacterium, to degrade bioenergy related feedstocks. Using a newly developed biomass medium, we showed that C. japonicus is able to utilize corn stover and switchgrass as sole sources of carbon and energy for growth. We also developed tools for directed gene disruptions in C. japonicus and used this system to construct a mutant in the gspD gene, which is predicted to encode a component of the type II secretion system. The gspD::pJGG1 mutant displayed a greater-than-2-fold decrease in endoglucanase secretion compared to wild-type C. japonicus. In addition, the mutant strain showed a pronounced growth defect in medium with biomass as a carbon source, yielding 100-fold fewer viable cells than the wild type. To test the potential of C. japonicus to undergo metabolic engineering, we constructed a strain able to produce small amounts of ethanol from biomass. Collectively, these data suggest that C. japonicus is a useful platform for biomass conversion and biofuel production. PMID- 20543054 TI - Validation of a nylon-flocked-swab protocol for efficient recovery of bacterial spores from smooth and rough surfaces. AB - In order to meet planetary-protection requirements, culturable bacterial spore loads are measured representatively for the total microbial contamination of spacecraft. However, the National Aeronautics and Space Administration's (NASA's) cotton swab protocols for spore load determination have not changed for decades. To determine whether a more efficient alternative was available, a novel swab was evaluated for recovery of different Bacillus atrophaeus spore concentrations on stainless steel and other surfaces. Two protocols for the nylon-flocked swab (NFS) were validated and compared to the present NASA standard protocol. The results indicate that the novel swab protocols recover 3- to 4-fold more (45.4% and 49.0% recovery efficiency) B. atrophaeus spores than the NASA standard method (13.2%). Moreover, the nylon-flocked-swab protocols were superior in recovery efficiency for spores of seven different Bacillus species, including Bacillus anthracis Sterne (recovery efficiency, 20%). The recovery efficiencies for B. atrophaeus spores from different surfaces showed a variation from 5.9 to 62.0%, depending on the roughness of the surface analyzed. Direct inoculation of the swab resulted in a recovery rate of about 80%, consistent with the results of scanning electron micrographs that allowed detailed comparisons of the two swab types. The results of this investigation will significantly contribute to the cleanliness control of future life detection missions and will provide significant improvement in detection of B. anthracis contamination for law enforcement and security efforts. PMID- 20543055 TI - Outer membrane proteins A (OmpA) and X (OmpX) are essential for basolateral invasion of Cronobacter sakazakii. AB - Cronobacter sakazakii is an opportunistic pathogen that actively invades host eukaryotic cells. To identify invasion factors responsible for the intestinal translocation of C. sakazakii, we constructed for the first time outer membrane protein X (OmpX) and A (OmpA) deletion mutants using the lambda Red recombination system. The ompX and ompA deletion mutants showed significantly reduced invasion of human enterocyte-like epithelial Caco-2 and human intestinal epithelial INT 407 cells, and significantly fewer mutant cells were recovered from the livers and spleens of rat pups. Furthermore, compared with intact target cells, the invasion and initial association potentials of the mutants increased at a rate similar to that of the wild type in tight-junction-disrupted target cells, suggesting that OmpX and OmpA are involved in basolateral invasion by C. sakazakii. This is the first report of C. sakazakii virulence determinants that are essential for basolateral invasion and that may be critical for the virulence of C. sakazakii. PMID- 20543056 TI - Novel florfenicol and chloramphenicol resistance gene discovered in Alaskan soil by using functional metagenomics. AB - Functional metagenomics was used to search for florfenicol resistance genes in libraries of cloned DNA isolated from Alaskan soil. A gene that mediated reduced susceptibility to florfenicol was identified and designated pexA. The predicted PexA protein showed a structure similar to that of efflux pumps of the major facilitator superfamily. PMID- 20543057 TI - Biosynthesis and biodegradation of 3-hydroxypropionate-containing polyesters. AB - 3-Hydroxypropionate (3HP) is an important compound in the chemical industry, and the polymerized 3HP can be used as a bioplastic. In this review, we focus on polyesters consisting of 3HP monomers, including the homopolyester poly(3 hydroxypropionate) and copolyesters poly(3-hydroxybutyrate-co-3 hydroxypropionate), poly(3-hydroxypropionate-co-3-hydroxybutyrate-co-3 hydroxyhexanoate-co-3-hydroxyoctanoate), poly(4-hydroxybutyrate-co-3 hydroxypropionate-co-lactate), and poly(3-hydroxybutyrate-co-3-hydroxypropionate co-4-hydroxybutyrate-co-lactate). Homopolyesters like poly(3-hydroxybutyrate) are often highly crystalline and brittle, which limits some of their applications. The incorporation of 3HP monomers reduces the glass transition temperature, the crystallinity, and also, at up to 60 to 70 mol% 3HP, the melting point of the copolymer. This review provides a survey of the synthesis and physical properties of different polyesters containing 3HP. PMID- 20543058 TI - Hydroxyapatite-mediated separation of double-stranded DNA, single-stranded DNA, and RNA genomes from natural viral assemblages. AB - Metagenomics can be used to determine the diversity of complex, often unculturable, viral communities with various nucleic acid compositions. Here, we report the use of hydroxyapatite chromatography to efficiently fractionate double stranded DNA (dsDNA), single-stranded DNA (ssDNA), dsRNA, and ssRNA genomes from known bacteriophages. Linker-amplified shotgun libraries were constructed to generate sequencing reads from each hydroxyapatite fraction. Greater than 90% of the reads displayed significant similarity to the expected genomes at the nucleotide level. These methods were applied to marine viruses collected from the Chesapeake Bay and the Dry Tortugas National Park. Isolated nucleic acids were fractionated using hydroxyapatite chromatography followed by linker-amplified shotgun library construction and sequencing. Taxonomic analysis demonstrated that the majority of environmental sequences, regardless of their source nucleic acid, were most similar to dsDNA viruses, reflecting the bias of viral metagenomic sequence databases. PMID- 20543059 TI - A second soluble Hox-type NiFe enzyme completes the hydrogenase set in Thiocapsa roseopersicina BBS. AB - Three functional NiFe hydrogenases were previously characterized in Thiocapsa roseopersicina BBS: two of them are attached to the periplasmic membrane (HynSL and HupSL), and one is localized in the cytoplasm (HoxEFUYH). The ongoing genome sequencing project revealed the presence of genes coding for another soluble Hox type hydrogenase enzyme (hox2FUYH). Hox2 is a heterotetrameric enzyme; no indication for an additional subunit was found. Detailed comparative in vivo and in vitro activity and expression analyses of HoxEFUYH (Hox1) and the newly discovered Hox2 enzyme were performed. Functional differences between the two soluble NiFe hydrogenases were disclosed. Hox1 seems to be connected to both sulfur metabolism and dark/photofermentative processes. The bidirectional Hox2 hydrogenase was shown to be metabolically active under specific conditions: it can evolve hydrogen in the presence of glucose at low sodium thiosulfate concentration. However, under nitrogen-fixing conditions, it can oxidize H(2) but less than the other hydrogenases in the cell. PMID- 20543060 TI - Biochemical properties of pectate lyases produced by three different Bacillus strains isolated from fermenting cocoa beans and characterization of their cloned genes. AB - Pectinolytic enzymes play an important role in cocoa fermentation. In this study, we characterized three extracellular pectate lyases (Pels) produced by bacilli isolated from fermenting cocoa beans. These enzymes, named Pel-22, Pel-66, and Pel-90, were synthesized by Bacillus pumilus BS22, Bacillus subtilis BS66, and Bacillus fusiformis BS90, respectively. The three Pels were produced under their natural conditions and purified from the supernatants using a one-step chromatography method. The purified enzymes exhibited optimum activity at 60 degrees C, and the half-time of thermoinactivation at this temperature was approximately 30 min. Pel-22 had a low specific activity compared with the other two enzymes. However, it displayed high affinity for the substrate, about 2.5 fold higher than those of Pel-66 and Pel-90. The optimum pHs were 7.5 for Pel-22 and 8.0 for Pel-66 and Pel-90. The three enzymes trans-eliminated polygalacturonate in a random manner to generate two long oligogalacturonides, as well as trimers and dimers. A synergistic effect was observed between Pel-22 and Pel-66 and between Pel-22 and Pel-90, but not between Pel-90 and Pel-66. The Pels were also strongly active on highly methylated pectins (up to 60% for Pel-66 and Pel-90 and up to 75% for Pel-22). Fe(2+) was found to be a better cofactor than Ca(2+) for Pel-22 activity, while Ca(2+) was the best cofactor for Pel-66 and Pel 90. The amino acid sequences deduced from the cloned genes showed the characteristics of Pels belonging to Family 1. The pel-66 and pel-90 genes appear to be very similar, but they are different from the pel-22 gene. The characterized enzymes form two groups, Pel-66/Pel-90 and Pel-22; members of the different groups might cooperate to depolymerize pectin during the fermentation of cocoa beans. PMID- 20543061 TI - Nuclear dynamics during germination, conidiation, and hyphal fusion of Fusarium oxysporum. AB - In many fungal pathogens, infection is initiated by conidial germination. Subsequent stages involve germ tube elongation, conidiation, and vegetative hyphal fusion (anastomosis). Here, we used live-cell fluorescence to study the dynamics of green fluorescent protein (GFP)- and cherry fluorescent protein (ChFP)-labeled nuclei in the plant pathogen Fusarium oxysporum. Hyphae of F. oxysporum have uninucleated cells and exhibit an acropetal nuclear pedigree, where only the nucleus in the apical compartment is mitotically active. In contrast, conidiation follows a basopetal pattern, whereby mononucleated microconidia are generated by repeated mitotic cycles of the subapical nucleus in the phialide, followed by septation and cell abscission. Vegetative hyphal fusion is preceded by directed growth of the fusion hypha toward the receptor hypha and followed by a series of postfusion nuclear events, including mitosis of the apical nucleus of the fusion hypha, migration of a daughter nucleus into the receptor hypha, and degradation of the resident nucleus. These previously unreported patterns of nuclear dynamics in F. oxysporum could be intimately related to its pathogenic lifestyle. PMID- 20543062 TI - beta(1-3)Glucanosyltransferase Gel4p is essential for Aspergillus fumigatus. AB - The beta(1-3)glucanosyltransferase GEL family of Aspergillus fumigatus contains 7 genes, among which only 3 are expressed during mycelial growth. The role of the GEL4 gene was investigated in this study. Like the other Gelps, it encodes a glycosylphosphatidylinositol (GPI)-anchored protein. In contrast to the other beta(1-3)glucanosyltransferases analyzed to date, it is essential for this fungal species. PMID- 20543063 TI - Two components of a velvet-like complex control hyphal morphogenesis, conidiophore development, and penicillin biosynthesis in Penicillium chrysogenum. AB - Penicillium chrysogenum is the industrial producer of the antibiotic penicillin, whose biosynthetic regulation is barely understood. Here, we provide a functional analysis of two major homologues of the velvet complex in P. chrysogenum, which we have named P. chrysogenum velA (PcvelA) and PclaeA. Data from array analysis using a DeltaPcvelA deletion strain indicate a significant role of PcVelA on the expression of biosynthesis and developmental genes, including PclaeA. Northern hybridization and high-performance liquid chromatography quantifications of penicillin titers clearly show that both PcVelA and PcLaeA play a major role in penicillin biosynthesis in a producer strain that underwent several rounds of UV mutagenesis during a strain improvement program. Both regulators are further involved in different developmental processes. While PcvelA deletion leads to light-independent conidial formation, dichotomous branching of hyphae, and pellet formation in shaking cultures, a DeltaPclaeA strain shows a severe impairment in conidiophore formation under both light and dark conditions. Bimolecular fluorescence complementation assays provide evidence for a velvet-like complex in P. chrysogenum, with structurally conserved components that have distinct developmental roles, illustrating the functional plasticity of these regulators in genera other than Aspergillus. PMID- 20543064 TI - Methylenetetrahydrofolate reductase activity is involved in the plasma membrane redox system required for pigment biosynthesis in filamentous fungi. AB - Methylenetetrahydrofolate reductases (MTHFRs) play a key role in biosynthesis of methionine and S-adenosyl-l-methionine (SAM) via the recharging methionine biosynthetic pathway. Analysis of 32 complete fungal genomes showed that fungi were unique among eukaryotes by having two MTHFRs, MET12 and MET13. The MET12 type contained an additional conserved sequence motif compared to the sequences of MET13 and MTHFRs from other eukaryotes and bacteria. Targeted gene replacement of either of the two MTHFR encoding genes in Fusarium graminearum showed that they were essential for survival but could be rescued by exogenous methionine. The F. graminearum strain with a mutation of MET12 (FgDeltaMET12) displayed a delay in the production of the mycelium pigment aurofusarin and instead accumulated nor-rubrofusarin and rubrofusarin. High methionine concentrations or prolonged incubation eventually led to production of aurofusarin in the MET12 mutant. This suggested that the chemotype was caused by a lack of SAM units for the methylation of nor-rubrofusarin to yield rubrofusarin, thereby imposing a rate-limiting step in aurofusarin biosynthesis. The FgDeltaMET13 mutant, however, remained aurofusarin deficient at all tested methionine concentrations and instead accumulated nor-rubrofusarin and rubrofusarin. Analysis of MET13 mutants in F. graminearum and Aspergillus nidulans showed that both lacked extracellular reduction potential and were unable to complete mycelium pigment biosynthesis. These results are the first to show that MET13, in addition to its function in methionine biosynthesis, is required for the generation of the extracellular reduction potential necessary for pigment production in filamentous fungi. PMID- 20543065 TI - Melanin externalization in Candida albicans depends on cell wall chitin structures. AB - The fungal pathogen Candida albicans produces dark-pigmented melanin after 3 to 4 days of incubation in medium containing l-3,4-dihydroxyphenylalanine (l-DOPA) as a substrate. Expression profiling of C. albicans revealed very few genes significantly up- or downregulated by growth in l-DOPA. We were unable to determine a possible role for melanin in the virulence of C. albicans. However, we showed that melanin was externalized from the fungal cells in the form of electron-dense melanosomes that were free or often loosely bound to the cell wall exterior. Melanin production was boosted by the addition of N-acetylglucosamine to the medium, indicating a possible association between melanin production and chitin synthesis. Melanin externalization was blocked in a mutant specifically disrupted in the chitin synthase-encoding gene CHS2. Melanosomes remained within the outermost cell wall layers in chs3Delta and chs2Delta chs3Delta mutants but were fully externalized in chs8Delta and chs2Delta chs8Delta mutants. All the CHS mutants synthesized dark pigment at equivalent rates from mixed membrane fractions in vitro, suggesting it was the form of chitin structure produced by the enzymes, not the enzymes themselves, that was involved in the melanin externalization process. Mutants with single and double disruptions of the chitinase genes CHT2 and CHT3 and the chitin pathway regulator ECM33 also showed impaired melanin externalization. We hypothesize that the chitin product of Chs3 forms a scaffold essential for normal externalization of melanosomes, while the Chs8 chitin product, probably produced in cell walls in greater quantity in the absence of CHS2, impedes externalization. PMID- 20543066 TI - Phosphorylation and dephosphorylation among Dif chemosensory proteins essential for exopolysaccharide regulation in Myxococcus xanthus. AB - Myxococcus xanthus social gliding motility, which is powered by type IV pili, requires the presence of exopolysaccharides (EPS) on the cell surface. The Dif chemosensory system is essential for the regulation of EPS production. It was demonstrated previously that DifA (methyl-accepting chemotaxis protein [MCP] like), DifC (CheW-like), and DifE (CheA-like) stimulate whereas DifD (CheY-like) and DifG (CheC-like) inhibit EPS production. DifD was found not to function downstream of DifE in EPS regulation, as a difD difE double mutant phenocopied the difE single mutant. It has been proposed that DifA, DifC, and DifE form a ternary signaling complex that positively regulates EPS production through the kinase activity of DifE. DifD was proposed as a phosphate sink of phosphorylated DifE (DifE approximately P), while DifG would augment the function of DifD as a phosphatase of phosphorylated DifD (DifD approximately P). Here we report in vitro phosphorylation studies with all the Dif chemosensory proteins that were expressed and purified from Escherichia coli. DifE was demonstrated to be an autokinase. Consistent with the formation of a DifA-DifC-DifE complex, DifA and DifC together, but not individually, were found to influence DifE autophosphorylation. DifD, which did not inhibit DifE autophosphorylation directly, was found to accept phosphate from autophosphorylated DifE. While DifD approximately P has an unusually long half-life for dephosphorylation in vitro, DifG efficiently dephosphorylated DifD approximately P as a phosphatase. These results support a model where DifE complexes with DifA and DifC to regulate EPS production through phosphorylation of a downstream target, while DifD and DifG function synergistically to divert phosphates away from DifE approximately P. PMID- 20543067 TI - Genomic identification of a novel mutation in hfq that provides multiple benefits in evolving glucose-limited populations of Escherichia coli. AB - Beneficial mutations in diversifying glucose-limited Escherichia coli populations are mostly unidentified. The genome of an evolved isolate with multiple differences from that of the ancestor was fully assembled. Remarkably, a single mutation in hfq was responsible for the multiple benefits under glucose limitation through changes in at least five regulation targets. PMID- 20543068 TI - Changes in the Min oscillation pattern before and after cell birth. AB - The Min system regulates the positioning of the cell division site in many bacteria. In Escherichia coli, MinD migrates rapidly from one cell pole to the other. In conjunction with MinC, MinD helps to prevent unwanted FtsZ rings from assembling at the poles and to stabilize their positioning at midcell. Using time lapse microscopy of growing and dividing cells expressing a gfp-minD fusion, we show that green fluorescent protein (GFP)-MinD often paused at midcell in addition to at the poles, and the frequency of midcell pausing increased as cells grew longer and cell division approached. At later stages of septum formation, GFP-MinD often paused specifically on only one side of the septum, followed by migration to the other side of the septum or to a cell pole. About the time of septum closure, this irregular pattern often switched to a transient double pole to-pole oscillation in the daughter cells, which ultimately became a stable double oscillation. The splitting of a single MinD zone into two depends on the developing septum and is a potential mechanism to explain how MinD is distributed equitably to both daughter cells. Septal pausing of GFP-MinD did not require MinC, suggesting that MinC-FtsZ interactions do not drive MinD-septal interactions, and instead MinD recognizes a specific geometric, lipid, and/or protein target at the developing septum. Finally, we observed regular end-to-end oscillation over very short distances along the long axes of minicells, supporting the importance of geometry in MinD localization. PMID- 20543069 TI - The importance of the small RNA chaperone Hfq for growth of epidemic Yersinia pestis, but not Yersinia pseudotuberculosis, with implications for plague biology. AB - Yersinia pestis, the etiologic agent of plague, has only recently evolved from Yersinia pseudotuberculosis. hfq deletion caused severe growth restriction at 37 degrees C in Y. pestis but not in Y. pseudotuberculosis. Strains from all epidemic plague biovars were similarly affected, implicating Hfq, and likely small RNAs (sRNAs), in the unique biology of the plague bacillus. PMID- 20543070 TI - Transcriptional activation of the aldehyde reductase YqhD by YqhC and its implication in glyoxal metabolism of Escherichia coli K-12. AB - The reactive alpha-oxoaldehydes such as glyoxal (GO) and methylglyoxal (MG) are generated in vivo from sugars through oxidative stress. GO and MG are believed to be removed from cells by glutathione-dependent glyoxalases and other aldehyde reductases. We isolated a number of GO-resistant (GO(r)) mutants from Escherichia coli strain MG1655 on LB plates containing 10 mM GO. By tagging the mutations with the transposon TnphoA-132 and determining their cotransductional linkages, we were able to identify a locus to which most of the GO(r) mutations were mapped. DNA sequencing of the locus revealed that it contains the yqhC gene, which is predicted to encode an AraC-type transcriptional regulator of unknown function. The GO(r) mutations we identified result in missense changes in yqhC and were concentrated in the predicted regulatory domain of the protein, thereby constitutively activating the product of the adjacent gene yqhD. The transcriptional activation of yqhD by wild-type YqhC and its mutant forms was established by an assay with a beta-galactosidase reporter fusion, as well as with real-time quantitative reverse transcription-PCR. We demonstrated that YqhC binds to the promoter region of yqhD and that this binding is abolished by a mutation in the potential target site, which is similar to the consensus sequence of its homolog SoxS. YqhD facilitates the removal of GO through its NADPH dependent enzymatic reduction activity by converting it to ethadiol via glycolaldehyde, as detected by nuclear magnetic resonance, as well as by spectroscopic measurements. Therefore, we propose that YqhC is a transcriptional activator of YqhD, which acts as an aldehyde reductase with specificity for certain aldehydes, including GO. PMID- 20543071 TI - Genome sequence of a cellulose-producing bacterium, Gluconacetobacter hansenii ATCC 23769. AB - The Gram-negative bacterium Gluconacetobacter hansenii is considered a model organism for studying cellulose synthesis. We have determined the genome sequence of strain ATCC 23769. PMID- 20543072 TI - Catabolite repression of the TodS/TodT two-component system and effector dependent transphosphorylation of TodT as the basis for toluene dioxygenase catabolic pathway control. AB - The TodS/TodT two-component system of Pseudomonas putida regulates the expression of the toluene dioxygenase (tod) operon for the metabolism of toluene, benzene, and ethylbenzene. The sensor kinase TodS has a complex domain arrangement containing two functional modules, each harboring a sensor and an autokinase domain separated by a receiver domain. The TodT protein is the cognate response regulator that activates transcription of the toluene dioxygenase (TOD) pathway genes at the P(todX) promoter. We report in this study that the todST operon is transcribed from a main promoter and that the +1 initiation point is located 31 nucleotides upstream from the A of the first ATG codon and is preceded by a -10/ 35 canonical promoter. Expression from P(todS) is under catabolite control, and in cells growing with glucose, the level of expression from this promoter is reduced, which in turn translates to low levels of the TodS/TodT regulators and results in a decrease of transcription from the P(todX) promoter. Thus, the main underlying regulatory mechanisms of the tod structural genes are at the levels of catabolite repression control from P(todS) and transcription activation, mediated by the TodT response regulator through a regulatory cascade in which the effector enhances autophosphorylation of TodS by ATP, with subsequent transphosphorylation of TodT. PMID- 20543073 TI - Identification of the biosynthetic gene cluster for the Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid. AB - L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is a potent antibiotic and toxin produced by Pseudomonas aeruginosa. Using a novel biochemical assay combined with site-directed mutagenesis in strain PAO1, we have identified a five-gene cluster specifying AMB biosynthesis, probably involving a thiotemplate mechanism. Overexpression of this cluster in strain PA7, a natural AMB-negative isolate, led to AMB overproduction. PMID- 20543074 TI - Characterization of the transposase encoded by IS256, the prototype of a major family of bacterial insertion sequence elements. AB - IS256 is the founding member of the IS256 family of insertion sequence (IS) elements. These elements encode a poorly characterized transposase, which features a conserved DDE catalytic motif and produces circular IS intermediates. Here, we characterized the IS256 transposase as a DNA-binding protein and obtained insight into the subdomain organization and functional properties of this prototype enzyme of IS256 family transposases. Recombinant forms of the transposase were shown to bind specifically to inverted repeats present in the IS256 noncoding regions. A DNA-binding domain was identified in the N-terminal part of the transposase, and a mutagenesis study targeting conserved amino acid residues in this region revealed a putative helix-turn-helix structure as a key element involved in DNA binding. Furthermore, we obtained evidence to suggest that the terminal nucleotides of IS256 are critically involved in IS circularization. Although small deletions at both ends reduced the formation of IS circles, changes at the left-hand IS256 terminus proved to be significantly more detrimental to circle production. Taken together, the data lead us to suggest that the IS256 transposase-mediated circularization reaction preferentially starts with a sequence-specific first-strand cleavage at the left hand IS terminus. PMID- 20543075 TI - A novel spore protein, ExsM, regulates formation of the exosporium in Bacillus cereus and Bacillus anthracis and affects spore size and shape. AB - Bacillus cereus spores are assembled with a series of concentric layers that protect them from a wide range of environmental stresses. The outermost layer, or exosporium, is a bag-like structure that interacts with the environment and is composed of more than 20 proteins and glycoproteins. Here, we identified a new spore protein, ExsM, from a beta-mercaptoethanol extract of B. cereus ATCC 4342 spores. Subcellular localization of an ExsM-green fluorescent protein (GFP) protein revealed a dynamic pattern of fluorescence that follows the site of formation of the exosporium around the forespore. Under scanning electron microscopy, exsM null mutant spores were smaller and rounder than wild-type spores, which had an extended exosporium (spore length for the wt, 2.40 +/- 0.56 microm, versus that for the exsM mutant, 1.66 +/- 0.38 microm [P < 0.001]). Thin section electron microscopy revealed that exsM mutant spores were encased by a double-layer exosporium, both layers of which were composed of a basal layer and a hair-like nap. Mutant exsM spores were more resistant to lysozyme treatment and germinated with higher efficiency than wild-type spores, and they had a delay in outgrowth. Insertional mutagenesis of exsM in Bacillus anthracis DeltaSterne resulted in a partial second exosporium and in smaller spores. In all, these findings suggest that ExsM plays a critical role in the formation of the exosporium. PMID- 20543076 TI - Environment and vascular bed origin influence differences in endothelial transcriptional profiles of coronary and iliac arteries. AB - Atherosclerotic plaques tend to form in the major arteries at certain predictable locations. As these arteries vary in atherosusceptibility, interarterial differences in endothelial cell biology are of considerable interest. To explore the origin of differences observed between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of harvested porcine coronary (CECs) and iliac artery endothelial cells (IECs) grown in static culture out to passage 4. Fewer differences were observed between the transcriptional profiles of CECs and IECs in culture compared with in vivo, suggesting that most differences observed in vivo were due to distinct environmental cues in the two arteries. One-class significance of microarrays revealed that most in vivo interarterial differences disappeared in culture, as fold differences after passaging were not significant for 85% of genes identified as differentially expressed in vivo at 5% false discovery rate. However, the three homeobox genes, HOXA9, HOXA10, and HOXD3, remained underexpressed in coronary endothelium for all passages by at least nine-, eight-, and twofold, respectively. Continued differential expression, despite removal from the in vivo environment, suggests that primarily heritable or epigenetic mechanism(s) influences transcription of these three genes. Quantitative real-time polymerase chain reaction confirmed expression ratios for seven genes associated with atherogenesis and over- or underexpressed by threefold in CECs relative to IECs. The present study provides evidence that both local environment and vascular bed origin modulate gene expression in arterial endothelium. The transcriptional differences observed here may provide new insights into pathways responsible for coronary artery susceptibility. PMID- 20543077 TI - Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. AB - It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat. PMID- 20543078 TI - Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes. AB - Cardiac complications and heart failure are the leading cause of death in type 2 diabetic patients. Mitochondrial dysfunction is central in the pathogenesis of the type 2 diabetic heart. However, it is unclear whether this dysfunction is specific for a particular subcellular region. The purpose of this study was to determine whether mitochondrial dysfunction in the type 2 diabetic heart is specific to a spatially distinct subset of mitochondria. We investigated mitochondrial morphology, function, and proteomic composition of subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) in 18-wk-old db/db mice. Oxidative damage was assessed in subpopulations through the measurement of lipid peroxidation byproducts and nitrotyrosine residues. Proteomic profiles and posttranslational modifications were assessed in mitochondrial subpopulations using iTRAQ and multi-dimensional protein identification technologies, respectively. SSM from db/db hearts had altered morphology, including a decrease in size and internal complexity, whereas db/db IFM were increased in internal complexity. Db/db SSM displayed decreased state 3 respiration rates, electron transport chain activities, ATP synthase activities, and mitochondrial membrane potential and increased oxidative damage, with no change in IFM. Proteomic assessment revealed a greater impact on db/db SSM compared with db/db IFM. Inner mitochondrial membrane proteins, including electron transport chain, ATP synthesis, and mitochondrial protein import machinery, were predominantly decreased. We provide evidence that mitochondrial dysfunction in the type 2 diabetic heart is associated with a specific subcellular locale. Furthermore, mitochondrial morphological and functional indexes are impacted differently during type 2 diabetic insult and may result from the modulation of spatially distinct mitochondrial proteomes. PMID- 20543079 TI - Peripheral mu-opioid receptors attenuate the augmented exercise pressor reflex in rats with chronic femoral artery occlusion. AB - Recently, opioid receptors have been shown to be expressed on group III and IV afferents, which comprise the sensory arm of the exercise pressor reflex. Although the stimulation of opioid receptors in the central nervous system has been shown to attenuate the exercise pressor reflex, the effect on the reflex of their stimulation in the periphery is unknown. We therefore tested the hypothesis that the activation of peripheral mu-opioid receptors attenuates the exercise pressor reflex. The pressor responses to static contraction were compared before and after the injection of the mu-opioid receptor agonist [d-Ala(2),N MePhe(4),Gly-ol(5)]enkephalin (DAMGO; 1 microg) into the abdominal aorta of decerebrated rats in which one femoral artery had been occluded 72 h previously (n = 10) and in control rats whose femoral arteries were freely perfused (n = 8). DAMGO attenuated the peak pressor response to contraction in rats whose femoral arteries had been occluded (before: increase of 34 + or - 3 mmHg and after: increase of 22 + or - 2 mmHg, P = 0.008); the inhibitory effect of DAMGO was prevented by the injection of naloxone (100 microg) into the abdominal aorta (before: increase of 29 + or - 5 mmHg and after: increase of 29 + or - 5 mmHg, P = 0.646, n = 7). An intravenous injection of DAMGO (1 microg, n = 6) had no effect on the peak pressor response to contraction in both groups of rats. DAMGO had no effect on the peak pressor response to contraction in rats whose femoral arteries were freely perfused (before: Delta 23 + or - 4 mmHg, after: Delta 23 + or - 3 mmHg, n = 6) but appeared to have a small effect on topography of the response. DAMGO had no effect on the peak pressor response to tendon stretch in both groups of rats (both P > 0.05). We conclude that the stimulation of peripheral mu-opioid receptors attenuates the exercise pressor reflex in rats whose femoral arteries have been ligated for 72 h. PMID- 20543080 TI - Does Na+ really play a role in Ca2+ homeostasis in hypertension? PMID- 20543081 TI - Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity. AB - Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart. PMID- 20543083 TI - Nucleoside/nucleobase transport and metabolism by microvascular endothelial cells isolated from ENT1-/- mice. AB - Nucleoside and nucleobase uptake is integral to mammalian cell function, and its disruption has significant effects on the cardiovasculature. The predominant transporters in this regard are the equilibrative nucleoside transporter subtypes 1 (ENT1) and 2 (ENT2). To examine the role of ENT1 in more detail, we have assessed the mechanisms by which microvascular endothelial cells (MVECs) from ENT1(-/-) mice transport and metabolize nucleosides and nucleobases. Wild-type murine MVECs express mainly the ENT1 subtype with only trace levels of ENT2. These cells also have a Na(+)-independent equilibrative nucleobase transport mechanism for hypoxanthine (ENBT1). In the ENT1(-/-) cells, there is no change in ENT2 or ENBT1, resulting in a very low level of nucleoside uptake in these cells, but a high capacity for nucleobase accumulation. Whereas there were no significant changes in nucleoside transporter subtype expression, there was a dramatic increase in adenosine deaminase and adenosine A(2a) receptors (both transcript and protein) in the ENT1(-/-) tissues compared with WT. These changes in adenosine deaminase and A(2a) receptors likely reflect adaptive cellular mechanisms in response to reduced adenosine flux across the membranes of ENT1(-/ ) cells. Our study also revealed that mouse MVECs have a nucleoside/nucleobase transport profile that is more similar to human MVECs than to rat MVECs. Thus mouse MVECs from transgenic animals may prove to be a useful preclinical model for studies of the effects of purine metabolite modifiers on vascular function. PMID- 20543082 TI - Inducible nitric oxide synthase gene deletion exaggerates MAPK-mediated cyclooxygenase-2 induction by inflammatory stimuli. AB - Cyclooxygenase (COX)-2 and inducible nitric oxide (NO) synthase (iNOS) are responsive to a wide array of inflammatory stimuli, have been localized to vascular smooth muscle cells (SMCs), and are intimately linked to the progression of vascular disease, including atherosclerotic lesion formation. We and others have shown that the production and subsequent impact of COX products appear to be correlative with the status of NO synthesis. This study examined the impact of inflammation-driven NO production on COX-2 expression in SMCs. Concurrent stimulation of quiescent rat aortic SMCs with lipopolysaccharide (LPS) and interferon (IFN)-gamma increased COX-2, iNOS, and nitrite production. Pharmacological inhibition of NO synthase (N(G)-monomethyl-l-arginine) concentration- and time-dependently magnified LPS + IFN-gamma-mediated COX-2 mRNA and protein induction in a cGMP-independent manner. COX-2 induction was associated with activation of the ERK, p38, and JNK mitogen-activated protein kinase (MAPK) pathways. Interestingly, NO synthase inhibition enhanced ERK, p38, and to a lesser extent JNK phosphorylation but suppressed MAPK phosphatase (MKP) 1 induction in response to LPS + IFN-gamma. Similarly, the exposure of SMCs from iNOS(-/-) mice to LPS + IFN-gamma produced an enhancement of COX-2 induction, p38, and JNK phosphorylation and an attenuated upregulation of MKP-1 versus their wild-type counterparts. Taken together, our data indicate that NO, in part derived from iNOS, negatively regulates the immediate early induction of COX-2 in response to inflammatory stimuli. PMID- 20543084 TI - Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury. AB - The phosphodiesterase type-5 inhibitor sildenafil has powerful cardioprotective effects against ischemia-reperfusion injury. PKG-mediated signaling has been implicated in this protection, although the mechanism and the downstream targets of this kinase remain to be fully elucidated. In this study we assessed the role of phospholemman (PLM) phosphorylation, which activates the Na(+)/K(+)-ATPase, in cardioprotection afforded by sildenafil administered during reperfusion. Isolated perfused mouse hearts were optimally protected against infarction (indexed by tetrazolium staining) by 0.1 muM sildenafil treatment during the first 10 min of reperfusion. Extended sildenafil treatment (30, 60, or 120 min at reperfusion) did not alter the degree of protection provided. This protection was PKG dependent, since it was blocked by KT-5823. Western blot analysis using phosphospecific antibodies to PLM showed that sildenafil at reperfusion did not modulate PLM Ser63 or Ser68 phosphorylation but significantly increased Ser69 phosphorylation. The treatment of isolated rat ventricular myocytes with sildenafil or 8-bromo-cGMP (PKG agonist) enhanced PLM Ser69 phosphorylation, which was bisindolylmaleimide (PKC inhibitor) sensitive. Patch-clamp studies showed that sildenafil treatment also activated the Na(+)/K(+)-ATPase, which is anticipated in light of PLM Ser69 phosphorylation. Na(+)/K(+)-ATPase activation during reperfusion would attenuate Na(+) overload at this time, providing a molecular explanation of how sildenafil guards against injury at this time. Indeed, using flame photometry and rubidium uptake into isolated mouse hearts, we found that sildenafil enhanced Na(+)/K(+)-ATPase activity during reperfusion. In this study we provide a molecular explanation of how sildenafil guards against myocardial injury during postischemic reperfusion. PMID- 20543085 TI - Acute AT(1)-receptor blockade reverses the hemodynamic and baroreflex impairment in adult sheep exposed to antenatal betamethasone. AB - To accelerate lung development and protect neonates from other early developmental problems, synthetic steroids are administered maternally in the third trimester, exposing fetuses that are candidates for premature delivery to them. However, steroid exposure at this point of gestation may lead to elevated blood pressure [mean arterial pressure (MAP)] during adolescence. We hypothesize that fetal exposure to steroids activates the renin-angiotensin system, inducing an elevation in blood pressure and attenuation of baroreflex sensitivity (BRS) that is angiotensin II dependent in early adulthood. To test this hypothesis, fetal sheep were exposed to betamethasone (Beta) or vehicle (control) administered to ewes at day 80 of gestation and delivered at full term. At 1.8 yr of age, male offspring were instrumented for conscious recording of MAP, heart rate, and measurement of BRS [as low-frequency-alpha, high-frequency-alpha, sequence (seq) UP, seq DOWN, and seq TOTAL]. Beta-exposed sheep (n = 6) had higher MAP than control sheep (n = 5) (93 + or - 2 vs. 84 + or - 2 mmHg, P < 0.01). Acute blockade of angiotensin type 1 receptors with candesartan (0.3 mg/kg iv) normalized MAP in Beta-exposed sheep (85 + or - 4 mmHg), with no effect in control sheep (82 + or - 3 mmHg). Before angiotensin type 1 blockade, BRS maximum gain was significantly lower in Beta-exposed vs. control sheep (11 + or - 3 vs. 26 + or - 3 ms/mmHg, P < 0.0.01). However, 45 min after candesartan injection, BRS was increased in Beta-exposed (21 + or - 5 ms/mmHg) and control (35 + or - 4 ms/mmHg) sheep. Heart rate variability (HRV) and blood pressure variability (BPV) revealed lower HRV (SD of beat-to-beat interval and root mean square of successive beat-to-beat differences in R-R interval duration) and higher BPV (SD of MAP, systolic arterial pressure in low-frequency range) in Beta-exposed sheep. Candesartan partially restored HRV in Beta-exposed sheep and fully corrected BPV. Thus, in utero exposure to synthetic glucocorticoids causes long-lasting programming of the cardiovascular system via renin-angiotensin system-dependent mechanisms. PMID- 20543086 TI - Na(+)-K(+)-ATPase and Ca(2+) clearance proteins in smooth muscle: a functional unit. AB - The Na(+)-K(+)-ATPase (NKA) can affect intracellular Ca(2+) concentration regulation via coupling to the Na(+)-Ca(2+) exchanger and may be important in myogenic tone. We previously reported that in mice carrying a transgene for the NKA alpha(2)-isoform in smooth muscle (alpha(2sm+)), the alpha(2)-isoform protein as well as the alpha(1)-isoform (not contained in the transgene) increased to similar degrees (2-7-fold). Aortas from alpha(2sm+) mice relaxed faster from a KCl-induced contraction, hypothesized to be related to more rapid Ca(2+) clearance. To elucidate the mechanisms underlying this faster relaxation, we therefore measured the expression and distribution of proteins involved in Ca(2+) clearance. Na(+)-Ca(2+) exchanger, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), and plasma membrane Ca(2+)-ATPase (PMCA) proteins were all elevated up to approximately fivefold, whereas actin, myosin light chain, and calponin proteins were not changed in smooth muscle from alpha(2sm+) mice. Interestingly, the corresponding Ca(2+) clearance mRNA levels were unchanged. Immunocytochemical data indicate that the Ca(2+) clearance proteins are distributed similarly in wild-type and alpha(2sm+) aorta cells. In studies measuring relaxation half-times from a KCl-induced contraction in the presence of pharmacological inhibitors of SERCA and PMCA, we estimated that together these proteins were responsible for approximately 60-70% of relaxation in aorta. Moreover, the percent contribution of SERCA and PMCA to relaxation rates in alpha(2sm+) aorta was not significantly different from that in wild-type aorta. The coordinate expressions of NKA and Ca(2+) clearance proteins without change in the relative contributions of each individual protein to smooth muscle function suggest that NKA may be but one component of a larger functional Ca(2+) clearance system. PMID- 20543087 TI - Short-term type 1 diabetes alters the mechanism of endothelium-dependent relaxation in the rat carotid artery. AB - The aim of the present study was to examine the effect of an early stage of streptozotocin-induced diabetes on the mechanism(s) of endothelium-dependent relaxation. Diabetes was induced by a single injection of streptozotocin (48 mg/kg iv), and the ACh-induced relaxation of rat carotid arteries was examined 6 wk later. A diabetes-induced increase in superoxide levels, determined by L-012 induced chemiluminescence, from carotid arteries was associated with endothelial nitric oxide (NO) synthase (eNOS) uncoupling and increased catalytic subunit of NADPH oxidase expression. The sensitivity and maximum response to ACh were similar in normal and diabetic rats despite a decrease in NO release detected by 4-amino-5-methylamino-2',7'-difluorofluorescein. In normal rats, N-nitro-l arginine (100 microM) plus 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (10 microM), to inhibit NOS and soluble guanylate cyclase (sGC), respectively, abolished ACh-induced relaxation, whereas in diabetic rats, the maximum relaxation to ACh was attenuated (maximum relaxation: 25 + or - 5%), but not abolished, by that treatment. The remaining ACh-induced relaxation was abolished by NO scavengers, cupric chloride (to degrade nitrosothiols), or blockers of endothelial K(+) channels. Western blot analysis of the carotid arteries indicated that diabetes significantly increased the expression of eNOS but decreased the proportion of eNOS expressed as the dimer. These findings demonstrate that in early diabetes, ACh-induced relaxation is maintained but is resistant to NOS inhibition. In early diabetes, nitrosothiol-mediated opening of K(+) channels may act in conjunction with NO stimulation of sGC to maintain endothelium-dependent relaxation despite the increase in vascular superoxide levels. PMID- 20543088 TI - Stress signaling by Tec tyrosine kinase in the ischemic myocardium. AB - Nonreceptor tyrosine kinases have an increasingly appreciated role in cardiac injury and protection. To investigate novel tasks for members of the Tec family of nonreceptor tyrosine kinases in cardiac phenotype, we examined the behavior of the Tec isoform in myocardial ischemic injury. Ischemia-reperfusion, but not cardiac protective agents, induced altered intracellular localization of Tec, highlighting distinct actions of this protein compared with other isoforms, such as Bmx, in the same model. Tec is abundantly expressed in cardiac myocytes and assumes a diffuse intracellular localization under basal conditions but is recruited to striated structures upon various stimuli, including ATP. To characterize Tec signaling targets in vivo, we performed an exhaustive proteomic analysis of Tec-binding partners. These experiments expand the role of the Tec family in the heart, identifying the Tec isoform as an ischemic injury-induced isoform, and map the subproteome of its interactors in isolated cells. PMID- 20543089 TI - Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine. AB - The role of adenosine and contraction for secretion of vascular endothelial growth factor (VEGF) in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted in the thigh muscle of seven male subjects, and dialysate was collected at rest, during infusion of adenosine, and during knee extensor exercise. The dialysate was analyzed for content of VEGF protein and adenosine. The mechanism of VEGF secretion from muscle cells in culture was examined in resting and electrostimulated cells and in response to the adenosine analog NECA and the adenosine A(2A) receptor specific analog CGS-21680. Adenosine receptors A(1), A(2A), and A(2B) were blocked with DPCPX, ZM-241385, and enprofylline, respectively. cAMP-dependent protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) were inhibited by H-89 and PD-98509, respectively. The human experiment showed that adenosine infusion enhanced (P < 0.05) the interstitial concentration of VEGF protein approximately fourfold above baseline. Exercise increased (P < 0.05) the interstitial VEGF concentration approximately sixfold above rest in parallel with an approximately threefold increase in adenosine concentration. In accordance, in cultured muscle cells, NECA and contraction caused secretion of VEGF (P < 0.05). The contraction-induced secretion of VEGF was abolished by the A(2B) antagonist enprofylline and by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells and that the contraction-induced secretion of VEGF protein is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction-induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent, revealing involvement of additional pathways in VEGF secretion. PMID- 20543090 TI - The development of the vasculature and its extracellular matrix: a gradual process defined by sequential cellular and matrix remodeling events. PMID- 20543091 TI - Role of iNOS and peroxynitrite-matrix metalloproteinase-2 signaling in myocardial late preconditioning in rats. AB - We have previously shown that the inhibition of myocardial nitric oxide (NO) and peroxynitrite-matrix metalloproteinase (MMP) signaling by early preconditioning (PC) is involved in its cardioprotective effect. Therefore, in the present study, we investigated the role of NO and peroxynitrite-MMP signaling in the development of late PC. PC was performed by five consecutive cycles of 4-min coronary occlusion and 4-min reperfusion in anesthetized rats in vivo. Twenty-four hours later, hearts were subjected to a 30-min coronary occlusion followed by 180-min reperfusion to measure infarct size. In separate experiments, heart tissue was sampled to measure biochemical parameters before and 3, 6, 12, or 24 h after the PC protocol, respectively. Late PC decreased infarct size, increased cardiac inducible NO synthase (iNOS) activity and gene expression, and decreased SOD activity at 24 h significantly compared with sham-operated controls. Late PC increased cardiac superoxide levels significantly at 24 h; however, it did not change cardiac NO levels. Cardiac peroxynitrite levels were significantly decreased. Downstream cellular targets of peroxynitrite, MMP-2 and MMP-9 activities were decreased in the late PC group at 24 h compared with the sham operated group. To verify if PC-induced inhibition of MMPs had a causative role in the reduction of infarct size, in separate experiments, we measured infarct size after the pharmacological inhibition of MMPs by ilomastat and found a significant reduction of infarct size compared with the vehicle-treated group. In conclusion, this is the first demonstration that the inhibition of cardiac peroxynitrite-MMP signaling contributes to cardioprotection by late PC and that pharmacological inhibition of MMPs is able to reduce infarct size in vivo. Furthermore, increased expression of iNOS may play a role in the development of late PC; however, increased iNOS activity does not lead to increased NO production in late PC. PMID- 20543092 TI - Peroxisomal hydrogen peroxide is coupled to biotic defense responses by ISOCHORISMATE SYNTHASE1 in a daylength-related manner. AB - While it is well established that reactive oxygen species can induce cell death, intracellularly generated oxidative stress does not induce lesions in the Arabidopsis (Arabidopsis thaliana) photorespiratory mutant cat2 when plants are grown in short days (SD). One interpretation of this observation is that a function necessary to couple peroxisomal hydrogen peroxide (H(2)O(2))-triggered oxidative stress to cell death is only operative in long days (LD). Like lesion formation, pathogenesis-related genes and camalexin were only induced in cat2 in LD, despite less severe intracellular redox perturbation compared with SD. Lesion formation triggered by peroxisomal H(2)O(2) was modified by introducing secondary mutations into the cat2 background and was completely absent in cat2 sid2 double mutants, in which ISOCHORISMATE SYNTHASE1 (ICS1) activity is defective. In addition to H(2)O(2)-induced salicylic acid (SA) accumulation, the sid2 mutation in ICS1 abolished a range of LD-dependent pathogen responses in cat2, while supplementation of cat2 with SA in SD activated these responses. Nontargeted transcript and metabolite profiling identified clusters of genes and small molecules associated with the daylength-dependent ICS1-mediated relay of H(2)O(2) signaling. The effect of oxidative stress in cat2 on resistance to biotic challenge was dependent on both growth daylength and ICS1. We conclude that (1) lesions induced by intracellular oxidative stress originating in the peroxisomes can be genetically reverted; (2) the isochorismate pathway of SA synthesis couples intracellular oxidative stress to cell death and associated disease resistance responses; and (3) camalexin accumulation was strictly dependent on the simultaneous presence of both H(2)O(2) and SA signals. PMID- 20543093 TI - An mRNA blueprint for C4 photosynthesis derived from comparative transcriptomics of closely related C3 and C4 species. AB - C(4) photosynthesis involves alterations to the biochemistry, cell biology, and development of leaves. Together, these modifications increase the efficiency of photosynthesis, and despite the apparent complexity of the pathway, it has evolved at least 45 times independently within the angiosperms. To provide insight into the extent to which gene expression is altered between C(3) and C(4) leaves, and to identify candidates associated with the C(4) pathway, we used massively parallel mRNA sequencing of closely related C(3) (Cleome spinosa) and C(4) (Cleome gynandra) species. Gene annotation was facilitated by the phylogenetic proximity of Cleome and Arabidopsis (Arabidopsis thaliana). Up to 603 transcripts differ in abundance between these C(3) and C(4) leaves. These include 17 transcription factors, putative transport proteins, as well as genes that in Arabidopsis are implicated in chloroplast movement and expansion, plasmodesmatal connectivity, and cell wall modification. These are all characteristics known to alter in a C(4) leaf but that previously had remained undefined at the molecular level. We also document large shifts in overall transcription profiles for selected functional classes. Our approach defines the extent to which transcript abundance in these C(3) and C(4) leaves differs, provides a blueprint for the NAD-malic enzyme C(4) pathway operating in a dicotyledon, and furthermore identifies potential regulators. We anticipate that comparative transcriptomics of closely related species will provide deep insight into the evolution of other complex traits. PMID- 20543094 TI - Trend of income-related inequality of child oral health in Australia. AB - It is important that we monitor socio-economic inequality in health. Inequality in child oral health has been expected to widen because of widening socio economic inequality. This study aimed to evaluate trends in income-related inequality in caries experience of Australian children. Cross-sectional studies in 1992/93 and 2002/03 collected data on deciduous caries experience of 5- to 10 year-olds and permanent caries experience of 6- to 12-year-olds. Household composition and income was used to calculate quartiles of equivalized income. Slope Index of Inequality (SII), Concentration Index (CI), and regression-based rate ratios were used to quantify income-related inequality and to evaluate trends. Income-related inequality in caries experience was evident regardless of time and dentition. The three indicators of inequality indicate a significant increase in income-related inequality in child deciduous caries experience during the decade. The income inequality in permanent caries experience did not change significantly. Income inequalities increased in deciduous teeth, but not in permanent teeth, among Australian children. PMID- 20543095 TI - Role of sphingolipid mediator ceramide in obesity and renal injury in mice fed a high-fat diet. AB - The present study tested a hypothesis that excess accumulation of sphingolipid, ceramide, its metabolites, or a combination contributes to the development of obesity and associated kidney damage. Liquid chromatography/mass spectrometry analysis demonstrated that C57BL/6J mice on the high-fat diet (HFD) had significantly increased plasma total ceramide levels compared with animals fed a low-fat diet (LFD). Treatment of mice with the acid sphingomyelinase (ASMase) inhibitor amitriptyline significantly attenuated the HFD-induced plasma ceramide levels. Corresponding to increase in plasma ceramide, the HFD significantly increased the body weight gain, plasma leptin concentration, urinary total protein and albumin excretion, glomerular damage index, and adipose tissue ASMase activity compared with the LFD-fed mice. These HFD-induced changes were also significantly attenuated by treatment of mice with amitriptyline. In addition, the decline of plasma glucose concentration after an intraperitoneal injection of insulin (0.15 U/kg b.wt.) was more sustained in mice on the HFD with amitriptyline than on the HFD alone. Intraperitoneal injection of glucose (3 g/kg b.wt.) resulted in a slow increase followed by a rapid decrease in the plasma glucose concentration in LFD and HFD plus amitriptyline-treated mice, but such blood glucose response was not observed in HFD-fed mice. Immunofluorescence analysis demonstrated a decrease in the podocin and an increase in the desmin in the glomeruli of HFD-fed mice compared with the LFD and HFD plus amitriptyline treated mice. In conclusion, our results reveal a pivotal role for ceramide biosynthesis in obesity, metabolic syndrome, and associated kidney damage. PMID- 20543096 TI - Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors. AB - ATP-gated purinergic P2X4 receptors (P2X4Rs) are expressed in the central nervous system and are sensitive to ethanol at intoxicating concentrations. P2XRs are trimeric; each subunit consists of two transmembrane (TM) alpha-helical segments, a large extracellular domain, and intracellular amino and carboxyl terminals. Recent work indicates that position 336 (Met336) in the TM2 segment is critical for ethanol modulation of P2X4Rs. The anthelmintic medication ivermectin (IVM) positively modulates P2X4Rs and is believed to act in the same region as ethanol. The present study tested the hypothesis that IVM can antagonize ethanol action. We investigated IVM and ethanol effects in wild-type and mutant P2X4Rs expressed in Xenopus oocytes by using a two-electrode voltage clamp. IVM antagonized ethanol-induced inhibition of P2X4Rs in a concentration-dependent manner. The size and charge of substitutions at position 336 affected P2X4R sensitivity to both ethanol and IVM. The first molecular model of the rat P2X4R, built onto the X-ray crystal structure of zebrafish P2X4R, revealed a pocket formed by Asp331, Met336, Trp46, and Trp50 that may play a role in the actions of ethanol and IVM. These findings provide the first evidence for IVM antagonism of ethanol effects in P2X4Rs and suggest that the antagonism results from the ability of IVM to interfere with ethanol action on the putative pocket at or near position 336. Taken with the building evidence supporting a role for P2X4Rs in ethanol intake, the present findings suggest that the newly identified alcohol pocket is a potential site for development of medication for alcohol use disorders. PMID- 20543097 TI - Long-acting phosphodiesterase-5 inhibitor tadalafil attenuates doxorubicin induced cardiomyopathy without interfering with chemotherapeutic effect. AB - Doxorubicin (DOX) is one of the most effective anticancer drugs. However, its cardiotoxicity remains a clinical concern that severely restricts its therapeutic usage. We designed this study to investigate whether tadalafil, a long-acting phosphodiesterase-5 (PDE-5) inhibitor, protects against DOX-induced cardiotoxicity. We also sought to delineate the cellular and molecular mechanisms underlying tadalafil-induced cardioprotection. Male CF-1 outbred mice were randomized into three groups (n = 15-24/group) to receive either saline (0.2 ml i.p.), DOX (15 mg/kg, given by a single intraperitoneal injection), or tadalafil (4 mg/kg p.o. daily for 9 days) plus DOX. Left ventricular function was subsequently assessed by transthoracic echocardiography and Millar conductance catheter. Cardiac contractile function was impaired by DOX, and it was significantly improved by cotreatment with tadalafil. Tadalafil attenuated DOX induced apoptosis and depletion of prosurvival proteins, including Bcl-2 and GATA 4, in myocardium. Cardiac oxidative stress was attenuated and antioxidant capacity was enhanced by tadalafil possibly via up-regulation of mitochondrial superoxide dismutase (MnSOD). Moreover, the tadalafil-treated group demonstrated increased cardiac cGMP level and protein kinase G (PKG) activity. Tadalafil did not interfere with the efficacy of DOX in killing human osteosarcoma cells in vitro or its antitumor effect in vivo in tumor xenograft model. We conclude that tadalafil improved left ventricular function and prevented cardiomyocyte apoptosis in DOX-induced cardiomyopathy through mechanisms involving up regulation of cGMP, PKG activity, and MnSOD level without interfering with the chemotherapeutic benefits of DOX. PMID- 20543098 TI - Suppressor of cytokine signaling 2 regulates IL-15-primed human NK cell function via control of phosphorylated Pyk2. AB - NK cells are capable of killing virus-infected or tumor cells and producing IFN gamma. Resting NK cells, however, have only minimal cytolytic activity and secrete a low level of IFN-gamma. The cytokine IL-15 can promote the expression of effector functions by resting NK cells. In this study, we demonstrate that suppressor of cytokine signaling 2 (SOCS2) has a novel role in IL-15-primed human NK cell function. SOCS2 expression was upregulated in NK cells following stimulation with IL-15. During IL-15-mediated NK cell priming, SOCS2 interacted with phosphorylated proline-rich tyrosine kinase 2 (Pyk2) at tyrosine 402 (p Pyk2(Tyr402)) and induced the proteasome-mediated degradation of p-Pyk2(Tyr402) via ubiquitination. Knockdown of SOCS2 resulted in the accumulation of p Pyk2(Tyr402) and blocked NK cell effector functions. In addition, NK cell cytolytic activity and IFN-gamma production were inhibited by overexpression of the wild-type of Pyk2 but not by the overexpression of tyrosine 402 mutant of Pyk2. These results suggest that SOCS2 regulates human NK cell effector functions via control of phosphorylated Pyk2 depending on IL-15 existence. PMID- 20543099 TI - Low-level exposure to HIV induces virus-specific T cell responses and immune activation in exposed HIV-seronegative individuals. AB - HIV-specific T cells response and T cell activation are frequently seen in exposed seronegative individuals (ESN). In this study, we report HIV-specific response and level of T cell activation in ESN partners of HIV-infected patients presenting low or undetectable levels of HIV-RNA. We evaluated 24 HIV serodiscordant couples. ESN were classified into three categories of exposure to HIV (very low, low, and moderate-high), considering levels of HIV-RNA in their infected partner and frequency of sexual high-risk practices within the last 12 mo. HIV-specific T cell responses and activation levels in T cell subsets were evaluated by flow cytometry. We reported that 54% of ESN had detectable HIV specific T cells response, being the highest prevalence seen in the low exposure group (64%). Several T cell subsets were significantly increased in ESN when compared with controls: CD4(+)CD38(+) (p = 0.006), CD4(+)HLA-DR(-)CD38(+) (p = 0.02), CD4(+)CD45RA(+)CD27(+)HLA-DR(-)CD38(+) (p = 0.002), CD8(+)CD45RA(+)CD27(+)CD38(-)HLA-DR(+) (p = 0.02), and CD8(+)CD45RA(+)CD27( )CD38(+)HLA-DR(+) (p = 0.03). Activation of CD8(+) T cells was increased in ESN with detectable HIV T cell responses compared with ESN lacking these responses (p = 0.04). Taken together, these results suggest that persistent but low sexual HIV exposure is able to induce virus-specific T cells response and immune activation in a high proportion of ESN, suggesting that virus exposure may occur even in conditions of maximal viral suppression in the HIV-infected partner. PMID- 20543100 TI - Allergen-induced airway remodeling is impaired in galectin-3-deficient mice. AB - The role played by the beta-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knockout (KO) mice were subjected to repetitive allergen challenge with OVA up to 12 wk, and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, subepithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal 3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared with that WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, found in inflammatory zone 1, and TGF-beta were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal 3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared with that of WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil specific chemokines and profibrogenic and angiogenic mediators. PMID- 20543101 TI - An IL-2 paradox: blocking CD25 on T cells induces IL-2-driven activation of CD56(bright) NK cells. AB - Daclizumab (Dac), an Ab against the IL-2R alpha-chain, inhibits brain inflammation in patients with multiple sclerosis, while expanding CD56(bright) immunoregulatory NK cells in vivo. We hypothesized that this unexpected expansion is paradoxically IL-2 driven; caused by the increased availability of T cell derived IL-2 for NK cell signaling. To this end, we performed ex vivo functional analyses of CD56(bright) NK cells and T cells from patients in clinical trials with Dac. We developed in vitro models to investigate mechanisms for ex vivo observations. We observed that Dac treatment caused decreased numbers and proliferation of FoxP3(+) T regulatory cells (Tregs), a model T cell population known to be dependent on IL-2 for proliferation and survival. As anticipated, Dac therapy inhibited IL-2 signaling in all T cells; however, we also observed functional adaptation of T cells to low IL-2 signal in vivo, characterized by the concomitant enhancement of IL-7 signaling on all T cells and parallel increase of CD127 expression by Tregs. In contrast, IL-2 signaling on CD56(bright) NK cells was not inhibited by Dac and their in vivo proliferation and cytotoxicity actually increased. Mechanistic studies indicated that the activation of CD56(bright) NK cells was likely IL-2 driven, as low doses of IL-2, but not IL 15, mimicked this activation in vitro. Our study provides insight into the role that IL-2 and CD25 play in functional regulation of two important immunoregulatory cell populations in humans: FoxP3(+) Tregs and CD56(bright) NK cells. PMID- 20543102 TI - Long peptide vaccination can lead to lethality through CD4+ T cell-mediated cytokine storm. AB - The optimization of anticancer therapeutic vaccines can lead to better efficacy but also to stronger adverse effects. In a mouse model of antitumor vaccination using a long peptide (LP), which included MHC class I- and II-restricted male (H Y) epitopes, we observed unexpected mortality. Mice with an increased frequency of anti-H-Y CD4 T cells were primed with LP+CpG and boosted 10 d later. Within hours of boost, they displayed shock-like signs with high mortality. Serum cytokine levels were high. TNF-alpha secreted by the CD4 T cells was identified as the key effector molecule. Priming with a short peptide (SP), which included the MHC class II-restricted epitope, was a more efficient primer than LP, but did not lead to mortality when used as boost. The high mortality induced by LP compared with SP was probably related to its specific ability to be presented by B cells. Finally, targeting the LP sequence to dendritic cells allowed tumor protection without side effects. Our data: 1) confirm that the immune system can be very dangerous; 2) caution against the use of systemic activation of high frequency Ag-specific T cells as induced by high doses of LP; and 3) underline the benefit of targeting Ag to dendritic cells. PMID- 20543103 TI - Francisella tularensis suppresses the proinflammatory response of endothelial cells via the endothelial protein C receptor. AB - Various bacterial pathogens activate the endothelium to secrete proinflammatory cytokines and recruit circulating leukocytes. In contrast, there is a distinct lack of activation of these cells by Francisella tularensis, the causative agent of tularemia. Given the importance of endothelial cells in facilitating innate immunity, we investigated the ability of the attenuated live vaccine strain and virulent Schu S4 strain of F. tularensis to inhibit the proinflammatory response of HUVECs. Living F. tularensis live vaccine strain and Schu S4 did not stimulate secretion of the chemokine CCL2 by HUVECs, whereas material released from heat killed bacteria did. Furthermore, the living bacteria suppressed secretion in response to heat-killed F. tularensis. This phenomenon was dose and contact dependent, and it occurred rapidly upon infection. The living bacteria did not inhibit the activation of HUVECs by Escherichia coli LPS, highlighting the specificity of this suppression. The endothelial protein C receptor (EPCR) confers anti-inflammatory properties when bound by activated protein C. When the EPCR was blocked, F. tularensis lost the ability to suppress activation of HUVECs. To our knowledge, this is the first report that a bacterial pathogen inhibits the host immune response via the EPCR. Endothelial cells are a critical component of the innate immune response to infection, and suppression of their activation by F. tularensis is likely a mechanism that aids in bacterial dissemination and evasion of host defenses. PMID- 20543104 TI - Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance. AB - Despite accumulating evidence for the importance of allospecific CD8(+) regulatory T cells (Tregs) in tolerant rodents and free immunosuppression transplant recipients, mechanisms underlying CD8(+) Treg-mediated tolerance remain unclear. By using a model of transplantation tolerance mediated by CD8(+) Tregs following CD40Ig treatment in rats, in this study, we show that the accumulation of tolerogenic CD8(+) Tregs and plasmacytoid dendritic cells (pDCs) in allograft and spleen but not lymph nodes was associated with tolerance induction in vascularized allograft recipients. pDCs preferentially induced tolerogenic CD8(+) Tregs to suppress CD4(+) effector cells responses to first donor Ags in vitro. When tolerogenic CD8(+) Tregs were not in contact with CD4(+) effector cells, suppression was mediated by IDO. Contact with CD4(+) effector cells resulted in alternative suppressive mechanisms implicating IFN-gamma and fibroleukin-2. In vivo, both IDO and IFN-gamma were involved in tolerance induction, suggesting that contact with CD4(+) effector cells is crucial to modulate CD8(+) Tregs function in vivo. In conclusion, CD8(+) Tregs and pDCs interactions were necessary for suppression of CD4(+) T cells and involved different mechanisms modulated by the presence of cell contact between CD8(+) Tregs, pDCs, and CD4(+) effector cells. PMID- 20543105 TI - Serine protease inhibitor 6 protects iNKT cells from self-inflicted damage. AB - The role played by apoptosis in the homeostasis of effector cells of the innate immune system is unclear. Serine protease inhibitor 6 (Spi6) is an inhibitor of granzyme B (GrB) that protects cytotoxic T lymphocytes of the adaptive immune system from apoptosis. To determine whether Spi6 also protects cells of the innate immune system from self-inflicted damage we have examined invariant NKT (iNKT) cells. Spi6-deficient iNKT cells harbored increased levels of GrB after TCR stimulation with the PBS-57 glycolipid Ag and were susceptible to apoptosis. The increased apoptosis of Spi6 knock-out (KO) iNKT cells lead to a complete loss in the production of IL-4 and IFN-gamma by Spi6 KO iNKT cells after PBS-57 challenge. The increased activation-induced apoptosis resulted in impaired survival and a decreased clonal burst size of Spi6 KO iNKT cells, which could be corrected by GrB deficiency. However, the clonal burst of Spi6 KO iNKT cells after TCR-independent activation with lymphocytic choriomeningitis virus was not affected. Our findings demonstrate that Spi6 protects cytotoxic cells of the innate immune system from GrB-mediated self-inflicted triggered by the recognition of Ag. PMID- 20543106 TI - The relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate. AB - During granulomatous inflammatory reactions, myeloid cells can differentiate into activated phagocytic macrophages, wound-healing macrophages, foreign body giant cells, and bone-resorbing osteoclasts. Although it is appreciated that a variety of stimuli, including cytokines, cell-matrix interactions, and challenge with foreign materials can influence myeloid cell fate, little is known of how these signals integrate during this process. In this study, we have investigated the cross talk between receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis and particle phagocytosis-induced activation of human monocytes. Understanding interconnected signals is of particular importance to disorders, such as periprosthetic osteolysis, in which granulomatous inflammation is initiated by particle phagocytosis in proximity to bone and leads to inflammatory bone loss. Using cell-based osteoclastogenesis and phagocytosis assays together with expression analysis of key regulators of osteoclastogenesis, we show in this study that phagocytosis of disease-relevant particles inhibits RANKL-mediated osteoclastogenesis of human monocytes. Mechanistically, phagocytosis mediates this effect by downregulation of RANK and c-Fms, the receptors for the essential osteoclastogenic cytokines RANKL and M-CSF. RANKL pretreatment of monocytes generates preosteoclasts that are resistant to RANK downregulation and committed to osteoclast formation, even though they retain phagocytic activity. Thus, the relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate. PMID- 20543107 TI - IL-33 reduces macrophage foam cell formation. AB - The development of atherosclerosis, a chronic inflammatory disease characterized by the formation of arterial fibrotic plaques, has been shown to be reduced by IL 33 in vivo. However, whether IL-33 can directly affect macrophage foam cell formation, a key feature of atherosclerotic plaques, has not been determined. In this study, we investigated whether IL-33 reduces macrophage foam cell accumulation in vivo and if IL-33 reduces their formation in vitro using THP-1 and primary human monocyte-derived macrophages. In Apolipoprotein E(-/-) mice fed on a high fat diet, IL-33 treatment significantly reduced the accumulation of macrophage-derived foam cells in atherosclerotic plaques. IL-33 also reduced macrophage foam cell formation in vitro by decreasing acetylated and oxidized low density lipoprotein uptake, reducing intracellular total and esterified cholesterol content and enhancing cholesterol efflux. These changes were associated with IL-33-mediated reduction in the expression of genes involved in modified low-density lipoprotein uptake, such as CD36, and simultaneous increase in genes involved in cholesterol efflux, including Apolipoprotein E, thereby providing a mechanism for such an action for this cytokine. IL-33 also decreased the expression of key genes implicated in cholesterol esterification and triglyceride storage, including Acyl-CoA:cholesterol acyltransferase 1 and Adipocyte differentiation-related protein. Furthermore, using bone marrow-derived macrophages from ST2(-/-) mice, we demonstrate that the IL-33 receptor, ST2, is integral to the action of IL-33 on macrophage foam cell formation. In conclusion, IL-33 has a protective role in atherosclerosis by reducing macrophage foam cell formation suggesting that IL-33 maybe a potential therapeutic agent against atherosclerosis. PMID- 20543108 TI - The exocytosis of lytic granules is impaired in Vti1b- or Vamp8-deficient CTL leading to a reduced cytotoxic activity following antigen-specific activation. AB - The exocytosis of cytotoxic proteins stored in lytic granules of activated CTL is a key event during killing of target cells. Membrane fusion events that are mediated by soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins are crucial, as demonstrated by patients with familial hemophagocytic lymphohistocytosis type 4 who have mutations in the SNARE protein syntaxin-11 that result in an impaired degranulation of cytotoxic cells. We found an increased mRNA expression of the SNARE protein genes Vti1b and Vamp8 during Ag specific activation of CTL from TCR-transgenic OT-I mice. Therefore, we investigated the cytolytic activity of CTL from TCR-transgenic Vti1b and Vamp8 knockout mice. At 3 d as well as at 4 d of Ag-specific stimulation, the degranulation of CTL was significantly reduced in Vti1b and Vamp8 knockout mice, as determined by cell surface expression of the degranulation marker CD107a. After 3 d of Ag-specific stimulation, the cytolytic activity of Vti1b- and Vamp8 deficient CTL was reduced to approximately 50% compared with heterozygous controls. However, 4 d after stimulation, the cytotoxic activity of Vti1b- as well as Vamp8-deficient CTL was not impaired anymore. The capacity of Vti1b- and Vamp8-deficient dendritic cells to process Ags and to stimulate the proliferation of CTL was not reduced, arguing against an indirect effect on the activation of CTL. These findings suggest a role of the SNARE proteins vti1b and vesicle associated membrane protein 8 in the degranulation of CTL. However, a deficiency can apparently be compensated and affects only transiently the cytotoxic activity of CTL during their development to armed effector cells. PMID- 20543110 TI - Umbilical cord blood T cells respond against the Melan-A/MART-1 tumor antigen and exhibit reduced alloreactivity as compared with adult blood-derived T cells. AB - Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells to treat a variety of disorders. UCB transplant is associated with comparatively reduced incidence of graft-versus-host disease, robust graft versus leukemia effect, and relatively high incidence of opportunistic infections, three processes in which donor-derived T lymphocytes are known to be predominantly involved. To examine the differential functionality of UCB T cells, CD8(+) T cells specific for the melanoma-associated HLA-A2-restricted Melan-A(26 35) A27L peptide were isolated from HLA-A2(+) and HLA-A2(-) UCB samples and HLA A2(+) and HLA-A2(-) adult peripheral blood using A2/Melan-A tetramers. In UCB samples, A2/Melan-A(+) CD8(+) T cells were detected at a frequency of 0.04%, were more frequent in HLA-A2(+) UCB, and were polyclonal and mostly naive. Consistent with Ag-driven expansion, the frequency of A2/Melan-A(+) CD8(+) T cells was increased following stimulation with cognate peptide or polyclonal activation, they acquired cell-surface markers reflective of effector/memory differentiation, their TCR repertoire became oligoclonal, and they expressed cytolytic activity and produced IFN-gamma. Although functional properties of A2/Melan-A(+) CD8(+) T cells derived from HLA-A2(+) UCB resembled those of HLA-A2(+) adult peripheral blood, they were more likely to reach terminal differentiation following polyclonal stimulation and produced less IFN-gamma in response to cognate peptide. A2/Melan-A(+) CD8(+) T cells from HLA-A2(-) UCB were poorly cytolytic, produced little IFN-gamma, and were predominantly monofunctional or nonfunctional. These properties of UCB-derived CD8(+) T cells could contribute to the reduced incidence of graft-versus-host disease and heightened incidence of opportunistic infections observed following UCB transplant. PMID- 20543109 TI - Enhancement of antiviral immunity by small molecule antagonist of suppressor of cytokine signaling. AB - Suppressors of cytokine signaling (SOCSs) are negative regulators of both innate and adaptive immunity via inhibition of signaling by cytokines such as type I and type II IFNs. We have developed a small peptide antagonist of SOCS-1 that corresponds to the activation loop of JAK2. SOCS-1 inhibits both type I and type II IFN activities by binding to the kinase activation loop via the kinase inhibitory region of the SOCS. The antagonist, pJAK2(1001-1013), inhibited the replication of vaccinia virus and encephalomyocarditis virus in cell culture, suggesting that it possesses broad antiviral activity. In addition, pJAK2(1001 1013) protected mice against lethal vaccinia and encephalomyocarditis virus infection. pJAK2(1001-1013) increased the intracellular level of the constitutive IFN-beta, which may play a role in the antagonist antiviral effect at the cellular level. Ab neutralization suggests that constitutive IFN-beta may act intracellularly, consistent with recent findings on IFN-gamma intracellular signaling. pJAK2(1001-1013) also synergizes with IFNs as per IFN-gamma mimetic to exert a multiplicative antiviral effect at the level of transcription, the cell, and protection of mice against lethal viral infection. pJAK2(1001-1013) binds to the kinase inhibitory region of both SOCS-1 and SOCS-3 and blocks their inhibitory effects on the IFN-gamma activation site promoter. In addition to a direct antiviral effect and synergism with IFN, the SOCS antagonist also exhibits adjuvant effects on humoral and cellular immunity as well as an enhancement of polyinosinic-polycytidylic acid activation of TLR3. The SOCS antagonist thus presents a novel and effective approach to enhancement of host defense against viruses. PMID- 20543112 TI - IL-13 induces esophageal remodeling and gene expression by an eosinophil independent, IL-13R alpha 2-inhibited pathway. AB - Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression, including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice with pulmonary (but not esophageal) overexpression of IL-13 evidenced esophageal IL-13 accumulation and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, collagen deposition, and increased circumference. IL-13 induced notable changes in esophageal transcripts that overlapped with the human EE esophageal transcriptome. IL-13-induced esophageal eosinophilia was dependent on eotaxin-1 (but not eotaxin-2). However, remodeling occurred independent of eosinophils as demonstrated by eosinophil lineage deficient, IL-13 transgenic mice. IL-13-induced remodeling was significantly enhanced by IL-13Ralpha2 deletion, indicating an inhibitory effect of IL 13Ralpha2. In the murine system, there was partial overlap between IL-13-induced genes in the lung and esophagus, yet the transcriptomes were divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in a pattern of esophageal gene expression and extensive tissue remodeling that resembles human EE. Notably, we identified a pathway that induces EE-like changes and is IL-13-driven, eosinophil-independent, and suppressed by IL-13Ralpha2. PMID- 20543111 TI - Fine-scale staging of T cell lineage commitment in adult mouse thymus. AB - T cell development is marked by the loss of alternative lineage choices accompanying specification and commitment to the T cell lineage. Commitment occurs between the CD4 and CD8 double-negative (DN) 2 and DN3 stages in mouse early T cells. To determine the gene regulatory changes that accompany commitment, we sought to distinguish and characterize the earliest committed wild type DN adult thymocytes. A transitional cell population, defined by the first downregulation of surface c-Kit expression, was found to have lost the ability to differentiate into dendritic cells and NK cells when cultured without Notch-Delta signals. In the presence of Notch signaling, this subset generates T lineage descendants in an ordered precursor-product relationship between DN2, with the highest levels of surface c-Kit, and c-Kit-low DN3 cells. These earliest committed cells show only a few differences in regulatory gene expression, compared with uncommitted DN2 cells. They have not yet established the full expression of Notch-related and T cell differentiation genes characteristic of DN3 cells before beta selection. Instead, the downregulation of select stem cell and non-T lineage genes appears to be key to the extinction of alternative lineage choices. PMID- 20543113 TI - The adaptor molecule Act1 regulates BAFF responsiveness and self-reactive B cell selection during transitional B cell maturation. AB - The transitional stage is a key check-point for elimination of autoreactive B cells in the periphery. This selection process requires fine regulation of signals received through BCR and B cell activating factor (BAFF) receptor. We previously identified the adaptor molecule Act1 as a negative regulator of BAFF mediated signaling. Deficiency of Act1 in mice results in peripheral B cell hyperplasia and development of autoimmunity. In this study, we demonstrate that Act1 plays a critical role in the regulation of transitional B cell survival and maturation. We found that the ratio of late-transitional (T2) to early transitional (T1) cells was increased in spleens from Act1-deficient mice. Moreover, BAFF stimulation induced better T1 cell survival and promoted more efficient maturation of T1 cells into T2 cells ex vivo in the absence of Act1. BAFF stimulation induced higher levels of the anti-apoptotic Bcl-2 member Mc1-l in Act1-deficient T1 cells than in wild-type control cells, suggesting that Mcl-1 might be one of the key effector molecules for BAFF-mediated survival of the Act1 deficient transitional B cells. Importantly, costimulation with BAFF was able to rescue Act1-deficient T1 cells from BCR-induced apoptosis more effectively than Act1-sufficient T1 B cells. Finally, by using hen egg lysozyme double transgenic mice, we demonstrated that Act1 deficiency can promote the maturation of Ag specific autoreactive B cells. Taken together, our results suggest that the transitional stage is a critical point of action of Act1 in the elimination of autoreactive B cells and in the regulation of peripheral B cell homeostasis. PMID- 20543114 TI - The transwall gradient across the mouse colonic circular muscle layer is carbon monoxide dependent. AB - Gastric and small intestinal circular smooth muscle layers have a transwall resting membrane potential (RMP) gradient that is dependent on release of carbon monoxide (CO) from interstitial cells of Cajal (ICCs). Our aim was to determine whether a RMP gradient exists in the mouse colon and whether the gradient is CO dependent. Microelectrodes were used to record RMPs from muscle cells at different depths of the circular muscle layer from wild-type and heme oxygenase-2 knockout (HO-2-KO) mice. A transwall RMP gradient was present in wild-type mice. The CO scavenger oxyhemoglobin (20 MUM) and the heme oxygenase inhibitor chromium mesoporphyrin IX (CrMP, 5 MUM) abolished the transwall gradient. The gradient was absent in HO-2-KO mice. Tetrodotoxin (1 MUM) caused a significant depolarization in circular smooth muscle cells throughout the circular muscle layer and abolished the transwall gradient. Removal of the submucosal neurons abolished the gradient. The majority of submucosal neurons contained HO-2 immunoreactivity (HO 2-IR), while ICCs did not. These data show for the first time that a transwall gradient exists across the circular smooth muscle layer of the mouse colon, that the gradient is due to CO, and that the source of CO is the submucosal neurons. PMID- 20543115 TI - Partition of aerobic and anaerobic swimming costs related to gait transitions in a labriform swimmer. AB - Members of the family Embiotocidae exhibit a distinct gait transition from exclusively pectoral fin oscillation to combined pectoral and caudal fin propulsion with increasing swimming speed. The pectoral-caudal gait transition occurs at a threshold speed termed U(p-c). The objective of this study was to partition aerobic and anaerobic swimming costs at speeds below and above the U(p c) in the striped surfperch Embiotoca lateralis using swimming respirometry and video analysis to test the hypothesis that the gait transition marks the switch from aerobic to anaerobic power output. Exercise oxygen consumption rate was measured at 1.4, 1.9 and 2.3 L s(-1). The presence and magnitude of excess post exercise oxygen consumption (EPOC) were evaluated after each swimming speed. The data demonstrated that 1.4 L s(-1) was below the U(p-c), whereas 1.9 and 2.3 L s( 1) were above the U(p-c). These last two swimming speeds included caudal fin propulsion in a mostly steady and unsteady (burst-assisted) mode, respectively. There was no evidence of EPOC after swimming at 1.4 and 1.9 L s(-1), indicating that the pectoral-caudal gait transition was not a threshold for anaerobic metabolism. At 2.3 L s(-1), E. lateralis switched to an unsteady burst and flap gait. This swimming speed resulted in EPOC, suggesting that anaerobic metabolism constituted 25% of the total costs. Burst activity correlated positively with the magnitude of the EPOC. Collectively, these data indicate that steady axial propulsion does not lead to EPOC whereas transition to burst-assisted swimming above U(p-c) is associated with anaerobic metabolism in this labriform swimmer. PMID- 20543116 TI - Snout allometry in seahorses: insights on optimisation of pivot feeding performance during ontogeny. AB - As juvenile life-history stages are subjected to strong selection, these stages often show levels of performance approaching those of adults, or show a disproportionately rapid increase of performance with age. Although testing performance capacity in aquatic suction feeders is often problematic, in pivot feeders such as seahorses models have been proposed to estimate whether snout length is optimal to minimise the time needed to reach the prey. Here, we investigate whether the same model can also explain the snout lengths in an ontogenetic series of seahorses, explore how pivot feeding kinematics change during ontogeny, and test whether juveniles show disproportionate levels of performance. Our analysis shows that the dimensions of the snout change during ontogeny from short and broad to long and narrow. Model calculations show that the snout lengths of newborn and juvenile seahorses are nearly optimal for minimising prey reach time. However, in juveniles the centre of head rotation in the earth-bound frame of reference is located near the posterior end of the head, whereas in adults it is shifted forward and is located approximately above the eye. Modelling shows that this forward shift in the centre of rotation has the advantage of decreasing the moment of inertia and the torque required to rotate the head, but has the disadvantage of slightly increasing the time needed to reach the prey. Thus, the snout lengths of juvenile seahorses appear to be close to optimal, suggesting that they reach levels of performance close to adult levels, which illustrates the pervasive nature of selection on performance in juveniles. PMID- 20543117 TI - Hydrodynamic determination of the moving direction of an artificial fin by a harbour seal (Phoca vitulina). AB - Harbour seals can use their vibrissal system to detect and follow hydrodynamic trails left by moving objects. In this study we determined the maximum time after which a harbour seal could indicate the moving direction of an artificial fish tail and analysed the hydrodynamic parameters allowing the discrimination. Hydrodynamic trails were generated using a fin-like paddle moving from left to right or from right to left in the calm water of an experimental box. The blindfolded seal was able to recognise the direction of the paddle movement when the hydrodynamic trail was up to 35 s old. Particle Image Velocimetry (PIV) revealed that the seal might have perceived and used two different hydrodynamic parameters to determine the moving direction of the fin-like paddle. The structure and spatial arrangement of the vortices in the hydrodynamic trail and high water velocities between two counter-rotating vortices are characteristic of the movement direction and are within the sensory range of the seal. PMID- 20543118 TI - The mechanical function of linked muscles in the guinea fowl hind limb. AB - Although mechanical linkages between the proximal and distal limb are present in a range of species, their functional significance is unknown. We have investigated the mechanical function of the flexor cruris lateralis pars pelvica (FCLP), flexor cruris lateralis pars accessoria (FCLA) and gastrocnemius intermedia (GI), a system of linked muscles spanning proximal and distal limb segments in the guinea fowl (Numida meleagris) hind limb. The FCLP, which is in the anatomical position of a hamstring muscle, is the primary component of the linkage. It is connected to the distal femur via the FCLA, the tarsometatarsus via the tendon of insertion of the GI and the common Achilles tendon, and the tibiotarsus via a distal tendon of insertion. The FCLP may, therefore, potentially exert moments at the hip, knee and ankle joints depending on the joint angles and the relative states of activation in the three muscles. Evidence presented here suggests that the GI and FCLA act as actively controlled links that alter distal action of the FCLP. The FCLP and GI are coactive in the late swing and early stance phases of the stride, forming a triarticular complex, and likely act together to resist and control ankle flexion immediately after foot down in addition to providing hip extension and knee flexion moments. The FCLP and FCLA are coactive from mid-through to late stance, acting together as a uniarticular hip extensor. Available evidence suggests that this role of the FCLP and FCLA is of increased importance in inclined running and accelerations. This linkage between a proximal muscle and alternate distal connections allows for functional flexibility, both in terms of the site at which the muscle exerts force and the nature of the muscle's mechanical function. The interactions generated between the proximal and distal limb by linkages of this type suggest that less emphasis should be placed on the distinct functional roles of specific anatomical classes of muscle within proximal and distal limb segments. PMID- 20543119 TI - Oxygen limitation and thermal tolerance in two terrestrial arthropod species. AB - Recent studies of marine invertebrates and fish have suggested that lower and upper critical temperatures (CT(min) and CT(max)) are coupled by a common mechanism: oxygen and capacity limitation of thermal tolerance (OCLT). Using thermolimit respirometry, we tested the predictions of this theory for terrestrial arthropods by measuring maxima and minima for both critical temperatures and metabolic rate in two arthropods, the isopod Porcellio scaber and the beetle Tenebrio molitor, at 40%, 21%, 10% and 2.5% ambient O(2). Critical temperatures were identified as particular points on both activity and traces in four ways. In the first two instances, we identified the inflection points in regressions of absolute difference sum (ADS) residuals calculated for activity (aADS) and (VI), respectively. In the third, we visually identified the lowest point before the post-mortal peak in CO(2) release (PMV). Finally, we pinpointed the sudden drop in at death, where fell outside the 95% confidence intervals of the 5 min period immediately preceding the drop-off (CI). Minimum and maximum metabolic rates were determined using CO(2) traces, and the temperatures corresponding to these identified as T(MetMin) and T(MetMax). For both species, ambient oxygen concentration did not influence CT(min), minimum metabolic rate, or T(MetMin). By contrast, severe hypoxia (2.5% O(2)) caused a 6.9 degrees C decline in activity-based CT(max) for T. molitor and a 10.6 degrees C decline for P. scaber, relative to normoxia (21% O(2)). The magnitude of this decrease differed between methods used to estimated critical thermal limits, highlighting the need for a standard method to determine these endpoints during thermolimit respirometry. Maximum metabolic rate also declined with decreasing ambient oxygen in both species. The combination of increasing metabolic rate and oxygen limitation affected upper thermal limits in these arthropods only in severe hypoxia (2.5% O(2)). In both species, CT(min) and CT(max) responded differently to oxygen limitation, suggesting that this is not a common mechanism coupling upper and lower limits in terrestrial arthropods. PMID- 20543120 TI - Asymmetry of different brain structures in homing pigeons with and without navigational experience. AB - Homing pigeons (Columba livia f.d.) are well-known for their homing abilities, and their brains seem to be functionally adapted to homing as exemplified, e.g. by their larger hippocampi and olfactory bulbs. Their hippocampus size is influenced by navigational experience, and, as in other birds, functional specialisation of the left and right hemispheres ('lateralisation') occurs in homing pigeons. To show in what way lateralisation is reflected in brain structure volume, and whether some lateralisation or asymmetry in homing pigeons is caused by experience, we compared brains of homing pigeons with and without navigational experience referring to this. Fourteen homing pigeons were raised under identical constraints. After fledging, seven of them were allowed to fly around the loft and participated successfully in races. The other seven stayed permanently in the loft and thus did not share the navigational experiences of the first group. After reaching sexual maturity, all individuals were killed and morphometric analyses were carried out to measure the volumes of five basic brain parts and eight telencephalic brain parts. Measurements of telencephalic brain parts and optic tectum were done separately for the left and right hemispheres. The comparison of left/right quotients of both groups reveal that pigeons with navigational experience show a smaller left mesopallium in comparison with the right mesopallium and pigeons without navigational experience a larger left mesopallium in comparison with the right one. Additionally, there are significant differences between left and right brain subdivisions within the two pigeon groups, namely a larger left hyperpallium apicale in both pigeon groups and a larger right nidopallium, left hippocampus and right optic tectum in pigeons with navigational experience. Pigeons without navigational experience did not show more significant differences between their left and right brain subdivisions. The results of our study confirm that the brain of homing pigeons is an example for mosaic evolution and indicates that lateralisation is correlated with individual life history (experience) and not exclusively based on heritable traits. PMID- 20543121 TI - Oxidative stress and information content of black and yellow plumage coloration: an experiment with greenfinches. AB - Carotenoid and melanin pigments in the plumage of birds are hypothesized to be sensitive to oxidative stress. We manipulated oxidative status of captive greenfinches (Carduelis chloris L.) by the administration of buthionine sulfoximine (BSO), a selective inhibitor of the synthesis of glutathione (GSH), an intracellular antioxidant. Half of the birds in the treated group, as well as in the control group, also received dietary carotenoid (lutein) supplementation. BSO treatment reduced erythrocyte GSH levels and caused oxidative damage as indicated by the increased concentration of plasma malondialdehyde (MDA), an end product of lipid peroxidation. BSO treatment also reduced the brightness (i.e. increased blackness) of the tips of tail feathers grown during the experiment. These results show that a low systemic GSH level is required for development of eumelanin plumage coloration and that such a low GSH level is also potentially dangerous for the organism. Carotenoid supplementation increased plasma carotenoid levels and chroma of the yellow parts of the feathers grown during the experiment. However, carotenoid supplementation did not reduce plasma MDA levels. Manipulation of GSH did not affect plasma carotenoids or carotenoid-based plumage coloration. These findings argue against the antioxidant function of lutein in vivo and carotenoid signaling of antioxidant status. PMID- 20543122 TI - Chirping response of weakly electric knife fish (Apteronotus leptorhynchus) to low-frequency electric signals and to heterospecific electric fish. AB - Brown ghost knife fish (Apteronotus leptorhynchus) can briefly increase their electric organ discharge (EOD) frequency to produce electrocommunication signals termed chirps. The chirp rate increases when fish are presented with conspecific fish or high-frequency (700-1100 Hz) electric signals that mimic conspecific fish. We examined whether A. leptorhynchus also chirps in response to artificial low-frequency electric signals and to heterospecific electric fish whose EOD contains low-frequency components. Fish chirped at rates above background when presented with low-frequency (10-300 Hz) sine-wave stimuli; at 30 and 150 Hz, the threshold amplitude for response was 1 mV cm(-1). Low-frequency (30 Hz) stimuli also potentiated the chirp response to high-frequency ( approximately 900 Hz) stimuli. Fish increased their chirp rate when presented with two heterospecific electric fish, Sternopygus macrurus and Brachyhypopomus gauderio, but did not respond to the presence of the non-electric fish Carassius auratus. Fish chirped to low-frequency (150 Hz) signals that mimic those of S. macrurus and to EOD playbacks of B. gauderio. The response to the B. gauderio playback was reduced when the low-frequency component (<150 Hz) was experimentally filtered out. Thus, A. leptorhynchus appears to chirp specifically to the electric signals of heterospecific electric fish, and the low-frequency components of heterospecific EODs significantly influence chirp rate. These results raise the possibility that chirps function to communicate to conspecifics about the presence of a heterospecific fish or to communicate directly to heterospecific fish. PMID- 20543123 TI - The fish eye view: are cichlids conspicuous? AB - The extent of animal colouration is determined by an interplay between natural and sexual selection. Both forces probably shape colouration in the speciose, rock-dwelling cichlids of Lake Malawi. Sexual selection is thought to drive male colouration, overcoming natural selection to create conspicuous colour patterns via female mate choice and male-male competition. However, natural selection should make female cichlids cryptic because they mouthbrood their young. We hypothesize that as a result of both sexual and natural selection, males will have colours that are more conspicuous than female colours. Cichlid spectral sensitivity, especially in the ultraviolet, probably influences how colours appear to them. Here we use simple models of the trichromatic colour space of cichlid visual systems to compare the conspicuousness of male and female nuptial colours of nine species. Conspicuousness of colours was evaluated as their Euclidian distance in colour space from environmental backgrounds and from other colours on the same fish. We find in six of the nine species that breeding males have colours that are statistically more conspicuous than female colours. These colours contrast strongly with each other or with the backgrounds, and they fall within a range of spectra best transmitted in the habitat. Female colour distances were sometimes smaller, suggesting that females of some species are more cryptic than males. Therefore, selection can differentially act to generate male colours that are more conspicuous than those in females. However, in two species, females had colours that were more conspicuous than male colours, suggesting that other selective forces and possibly sexual conflicts are acting in this system. PMID- 20543124 TI - Neuropeptides in the Drosophila central complex in modulation of locomotor behavior. AB - The central complex is one of the most prominent neuropils in the insect brain. It has been implicated in the control of locomotor activity and is considered as a pre-motor center. Several neuropeptides are expressed in circuits of the central complex, and thus may be modulators of locomotor behavior. Here we have investigated the roles of two different neuropeptides, Drosophila tachykinin (DTK) and short neuropeptide F (sNPF), in aspects of locomotor behavior. In the Drosophila brain, DTK and sNPF are expressed in interneurons innervating the central complex. We have directed RNA interference (RNAi) towards DTK and sNPF specifically in different central complex neurons. We also expressed a temperature-sensitive dominant negative allele of the fly ortholog of dynamin called shibire(ts1), essential in membrane vesicle recycling and endocytosis, to disrupt synaptic transmission in central complex neurons. The spontaneous walking activity of the RNAi- or shibire(ts1)-expressing flies was quantified by video tracking. DTK-deficient flies displayed drastically increased center zone avoidance, suggesting that DTK is involved in the regulation of spatial orientation. In addition, DTK deficiency in other central complex neurons resulted in flies with an increased number of activity-rest bouts. Perturbations in the sNPF circuit indicated that this peptide is involved in the fine regulation of locomotor activity levels. Our findings suggest that the contribution of DTK and sNPF to locomotor behavior is circuit dependent and associated with particular neuronal substrates. Thus, peptidergic pathways in the central complex have specific roles in the fine tuning of locomotor activity of adult Drosophila. PMID- 20543125 TI - Chewing rates among domestic dog breeds. AB - The mammalian masticatory rhythm is produced by a brainstem timing network. The rhythm is relatively fixed within individual animals but scales allometrically with body mass (M(b)) across species. It has been hypothesized that sensory feedback and feed-forward adjust the rhythm to match the jaw's natural resonance frequency, with allometric scaling being an observable consequence. However, studies performed with adult animals show that the rhythm is not affected by jaw mass manipulations, indicating that either developmental or evolutionary mechanisms are required for allometry to become manifest. The present study was performed to tease out the relative effects of development versus natural selection on chewing rate allometry. Thirty-one dog breeds and 31 mass-matched non-domestic mammalian species with a range in M(b) from approximately 2 kg to 50 kg were studied. Results demonstrated that the chewing rhythm did not scale with M(b) among dog breeds (R=0.299, P>0.10) or with jaw length (L(j)) (R=0.328, P>0.05). However, there was a significant relationship between the chewing rhythm and M(b) among the non-domestic mammals (R=0.634, P<0.001). These results indicate that scaling is not necessary in the adult animal. We conclude that the central timing network and related sensorimotor systems may be necessary for rhythm generation but they do not explain the 1/3rd to 1/4th allometric scaling observed among adult mammals. The rhythm of the timing network is either adjusted to the physical parameters of the jaw system during early development only, is genetically determined independently of the jaw system or is uniquely hard-wired among dogs and laboratory rodents. PMID- 20543126 TI - Effects of wing deformation on aerodynamic forces in hovering hoverflies. AB - We studied the effects of wing deformation on the aerodynamic forces of wings of hovering hoverflies by solving the Navier-Stokes equations on a dynamically deforming grid, employing the recently measured wing deformation data of hoverflies in free-flight. Three hoverflies were considered. By taking out the camber deformation and the spanwise twist deformation one by one and by comparing the results of the deformable wing with those of the rigid flat-plate wing (the angle of attack of the rigid flat-plate wing was equal to the local angle of attack at the radius of the second moment of wing area of the deformable wing), effects of camber deformation and spanwise twist were identified. The main results are as follows. For the hovering hoverflies considered, the time courses of the lift, drag and aerodynamic power coefficients of the deformable wing are very similar to their counterparts of the rigid flat-plate wing, although lift of the deformable wing is about 10% larger, and its aerodynamic power required about 5% less than that of the rigid flat-plate wing. The difference in lift is mainly caused by the camber deformation, and the difference in power is mainly caused by the spanwise twist. The main reason that the deformation does not have a very large effect on the aerodynamic force is that, during hovering, the wing operates at a very high angle of attack (about 50 deg) and the flow is separated, and separated flow is not very sensitive to wing deformation. Thus, as a first approximation, the deformable wing in hover flight could be modeled by a rigid flat-plate wing with its angle of attack being equal to the local angle of attack at the radius of second moment of wing area of the deformable wing. PMID- 20543127 TI - The effects of turbulent eddies on the stability and critical swimming speed of creek chub (Semotilus atromaculatus). AB - The effect of turbulent eddy diameter, vorticity and orientation on the 2 min critical swimming speed and stability of creek chub (Semotilus atromaculatus) is reported. Turbulent eddies were visualized and their properties were quantified using particle image velocimetry (PIV). Flow fields with an increasing range in eddy diameter were created by inserting cylinder arrays upstream from the swimming test section. Eddy vorticity increased with increasing velocity. Two orientations of eddies, eddies spinning about a vertical axis and eddies spinning about a horizontal (wall-to-wall) axis, were investigated. Stability challenges were not observed until the largest (95th percentile) eddy diameters reached 76% of the fish body total length. Under these conditions fish were observed to spin in an orientation consistent with the rotational axis of the large eddies and translate downstream. These losses in postural control were termed 'spills'. Spills were 230% more frequent and lasted 24% longer in turbulent flow fields dominated by horizontal eddies than by vertical eddies of the same diameter. The onset of spills coincided with a 10% and 22% reduction in critical swimming speed in turbulent flows dominated by large vertical and horizontal eddies, respectively. These observations confirm predictions by Pavlov et al., Cada and Odeh, Lupandin, and Liao that the eddy diameter, vorticity and orientation play an important role in the swimming capacity of fishes. PMID- 20543128 TI - Collision avoidance by running insects: antennal guidance in cockroaches. AB - Cockroaches were observed with videographic methods as escape running was initiated, but with obstacles in the path of their run. The goal was to determine the repertoire of possible responses to obstacles and the sensory cues used to trigger the responses. Intact cockroaches collided with obstacles on only about 10% of trials. The most common collision avoidance strategy was simply to stop running prior to impact. However, occasionally animals moved vertically and climbed over the barrier, or turned and navigated an edge of the obstacle, or completely reversed run direction. The avoidance strategies chosen depended on the size and configuration of the obstacle. Tests for the use of vision in detecting obstacles showed that its role, if any, is small. However, all manipulations that altered the antennal system changed behavior in a way consistent with the hypothesis that antennal mechanosensation plays a major role in collision avoidance. For example, reducing antennal length, or severing the main antennal nerve without altering the length produced significant increases in the frequency of collisions. Tests with tethered insects showed that (1) the antennae are preferentially directed forward as animals run, and (2) nearly simultaneous contact with both antennae is required to make the cockroach stop. Our data indicate that running cockroaches employ strategies that set their sensorimotor systems in a mode of readiness to deal with obstacles and they suggest that sensory information about the presence and configuration of obstacles is used to make choices, at very short latencies, about how to respond to obstructions. PMID- 20543129 TI - Motor patterns associated with crawling in a soft-bodied arthropod. AB - Soft-bodied animals lack distinct joints and levers, and so their locomotion is expected to be controlled differently from that of animals with stiff skeletons. Some invertebrates, such as the annelids, use functionally antagonistic muscles (circumferential and longitudinal) acting on constant-volume hydrostatics to produce extension and contraction. These processes form the basis for most theoretical considerations of hydrostatic locomotion in organisms including larval insects. However, caterpillars do not move in this way, and their powerful appendages provide grip independent of their dimensional changes. Here, we show that the anterograde wave of movement seen in the crawling tobacco hornworm, Manduca sexta, is mediated by co-activation of dorsal and ventral muscles within a body segment, rather than by antiphasic activation, as previously believed. Furthermore, two or three abdominal segments are in swing phase simultaneously, and the activities of motor neurons controlling major longitudinal muscles overlap in more than four segments. Recordings of muscle activity during natural crawling show that some are activated during both their shortening and elongation. These results do not support the typical peristaltic model of crawling, but they do support a tension-based model of crawling, in which the substrate is utilized as an anchor to generate propulsion. PMID- 20543130 TI - Evidence for glutamate, GABA and NO in coordinating behaviour in the sponge, Ephydatia muelleri (Demospongiae, Spongillidae). AB - The view that sponges lack tissue level organisation, epithelia, sensory cells and coordinated behaviour is challenged by recent molecular studies showing the existence in Porifera of molecules and proteins that define cell signalling systems in higher order metazoans. Demonstration that freshwater sponges can contract their canals in an organised manner in response to both external and endogenous stimuli prompted us to examine the physiology of the contraction behaviour. Using a combination of digital time-lapse microscopy, high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, immunocytochemistry and pharmacological manipulations, we tested the role of the diffusible amino acids glutamate and gamma-aminobutyric acid (GABA) and a short-lived diffusible gas, nitric oxide (NO), in triggering or modulating contractions in Ephydatia muelleri. We identified pools of glutamate, glutamine and GABA used to maintain a metabotropic glutamate and GABA receptor signalling system. Glutamate induced contractions and propagation of a stereotypical behaviour inflating and deflating the canal system, acting in a dose-dependent manner. Glutamate-triggered contractions were blocked by the metabatropic glutamate receptor inhibitor AP3 and by incubation of the sponge in an allosteric competitive inhibitor of glutamate, Kynurenic acid. Incubation in GABA inhibited glutamate-triggered contractions of the sponge. Nitric oxide synthase, involved in the formation of the diffusible gas NO, was localised using NADPH-diaphorase to mesenchyme cells in the osculum and pinacoderm. A cGMP assay showed the same cells were labelled suggesting that the NO system is functional. Our findings suggest sponges coordinate behaviour using chemical messenger systems common to other animals. PMID- 20543131 TI - Effect of laboratory acclimation on the variation of reproduction-related characters in Drosophila melanogaster. AB - The natural variation of sex-specific characters between populations can favor their behavioral isolation, eventually leading to the formation of new species. Marked variations for male courtship, mating and the production of sex pheromones - three complex characters potentially inducing sexual isolation - were found between Drosophila melanogaster populations of various origins acclimated for many generations in research laboratories. However, the natural variation of these three characters between natural populations and their evolution after long term acclimation in the laboratory remains unknown. We measured many traits involved in these characters in six stocks initiated with distinct populations sampled in a restricted geographic area. Several sex-specific traits varied between stocks freshly brought back to the laboratory. After 100 generations spent in the laboratory without any experimental selection, traits varied in a strain-dependent manner. This variation was not related to a reduction of their variance except for copulation duration. This indicates that reproduction-related characters can diverge between neighboring D. melanogaster populations, and differently adapt to stable laboratory conditions. PMID- 20543132 TI - Cardiovascular performance of six species of field-acclimatized centrarchid sunfish during the parental care period. AB - Parental care is an energetically costly period of the life history of many fish species characterized by extended high intensity activity. To date, there have been no studies that have investigated the cardiovascular correlates of extended parental care in fish. Using Doppler flow probes, the cardiovascular performance of six syntopic centrarchid fish species (N=232) that provide sole, male parental care was examined across a range of water temperatures that encompass their reproductive periods (14-26 degrees C). Experiments were restricted to males but included both nesting and non-nesting individuals to evaluate the cardiovascular performance of fish during parental care. Resting values for cardiac output (Q) and heart rate (f(H)) tended to be higher for nesting fish when adjusted for variation in temperature. Both of these cardiac variables also increased with water temperature. Stroke volume (V(S)) was similar among nesting and non-nesting fish and was generally thermally insensitive. When exposed to exhaustive exercise, nesting fish took longer to exhaust than non-nesting individuals. The high resting levels found in nesting fish accompanied by only minor increases in maximal values typically resulted in reductions in cardiac scope. Cardiovascular variables recovered more quickly in nesting fish, which could facilitate the high activity and bursting associated with parental care. Interspecifically, several cardiovascular variables were correlated with parental care activity. Parental care investment became more energetically expensive as the degree of cardiac frequency modulation decreased. Additionally, as the duration of parental care increased, so did the time required for fish to become exhausted, although this relationship was probably influenced by the fact that the larger species (e.g. smallmouth bass Micropterus dolomieu; largemouth bass Micropterus salmoides) provided the lengthiest care. Collectively, these data indicate that fish that provide parental care possess adaptations, including sufficient phenotypic plasticity, such that they can enhance their ability to provide high intensity protracted care, and emphasize the nexus between behavior and physiology. PMID- 20543133 TI - Inhibition of glutamine synthetase during ammonia exposure in rainbow trout indicates a high reserve capacity to prevent brain ammonia toxicity. AB - Glutamine synthetase (GSase), the enzyme that catalyses the conversion of glutamate and ammonia to glutamine, is present at high levels in vertebrate brain tissue and is thought to protect the brain from elevated ammonia concentrations. We tested the hypothesis that high brain GSase activity is critical in preventing accumulation of brain ammonia and glutamate during ammonia loading in the ammonia intolerant rainbow trout. Trout pre-injected with saline or the GSase inhibitor methionine sulfoximine (MSOX, 6 mg kg(-1)), were exposed to 0, 670 or 1000 micromol l(-1) NH(4)Cl in the water for 24 and 96 h. Brain ammonia levels were 3- to 6-fold higher in ammonia-exposed fish relative to control fish and MSOX treatment did not alter this. Brain GSase activity was unaffected by ammonia exposure, while MSOX inhibited GSase activity by approximately 75%. Brain glutamate levels were lower and glutamine levels were higher in fish exposed to ammonia relative to controls. While MSOX treatment had little impact on brain glutamate, glutamine levels were significantly reduced by 96 h. With ammonia treatment, significant changes in the concentration of multiple other brain amino acids occurred and these changes were mostly reversed or eliminated with MSOX. Overall the changes in amino acid levels suggest that multiple enzymatic pathways can supply glutamate for the production of glutamine via GSase during ammonia exposure and that alternative transaminase pathways can be recruited for ammonia detoxification. Plasma cortisol levels increased 7- to 15-fold at 24 h in response to ammonia and MSOX did not exacerbate this stress response. These findings indicate that rainbow trout possess a relatively large reserve capacity for ammonia detoxification and for preventing glutamate accumulation during hyperammonaemic conditions. PMID- 20543134 TI - Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. AB - BACKGROUND: When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. METHODS AND RESULTS: Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP >=25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater increases in left ventricular end-diastolic pressure and was associated with blunted increases in heart rate, systemic vasodilation, and cardiac output. Exercise-induced pulmonary hypertension was present in 88% of patients with HFpEF and was related principally to elevated PCWP, as pulmonary vascular resistances dropped similarly in both groups. Exercise PCWP and pulmonary artery systolic pressure were highly correlated. An exercise pulmonary artery systolic pressure >=45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity. CONCLUSIONS: Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure. Earlier and more accurate diagnosis using exercise hemodynamics may allow better targeting of interventions to treat and prevent HFpEF progression. PMID- 20543135 TI - Identification of BERP (brain-expressed RING finger protein) as a p53 target gene that modulates seizure susceptibility through interacting with GABA(A) receptors. AB - p53 is a central player in responses to cellular stresses and a major tumor suppressor. The identification of unique molecules within the p53 signaling network can reveal functions of this important transcription factor. Here, we show that brain-expressed RING finger protein (BERP) is a gene whose expression is up-regulated in a p53-dependent manner in human cells and in mice. We generated BERP-deficient mice by gene targeting and demonstrated that they exhibit increased resistance to pentylenetetrazol-induced seizures. Electrophysiological and biochemical studies of cultured cortical neurons of BERP deficient mice showed a decrease in the amplitude of GABA(A) receptor (GABA(A)R) mediated miniature inhibitory postsynaptic currents as well as reduced surface protein expression of GABA(A)Rs containing the gamma2-subunit. However, BERP deficiency did not decrease GABA(A)Rgamma2 mRNA levels, raising the possibility that BERP may act at a posttranscriptional level to regulate the intracellular trafficking of GABA(A)Rs. Our results indicate that BERP is a unique p53 regulated gene and suggest a role for p53 within the central nervous system. PMID- 20543136 TI - Auxin regulates distal stem cell differentiation in Arabidopsis roots. AB - The stem cell niche in the root meristem is critical for the development of the plant root system. The plant hormone auxin acts as a versatile trigger in many developmental processes, including the regulation of root growth, but its role in the control of the stem cell activity remains largely unclear. Here we show that local auxin levels, determined by biosynthesis and intercellular transport, mediate maintenance or differentiation of distal stem cells in the Arabidopsis thaliana roots. Genetic analysis shows that auxin acts upstream of the major regulators of the stem cell activity, the homeodomain transcription factor WOX5, and the AP-2 transcription factor PLETHORA. Auxin signaling for differentiation of distal stem cells requires the transcriptional repressor IAA17/AXR3 as well as the ARF10 and ARF16 auxin response factors. ARF10 and ARF16 activities repress the WOX5 transcription and restrict it to the quiescent center, where WOX5, in turn, is needed for the activity of PLETHORA. Our investigations reveal that long distance auxin signals act upstream of the short-range network of transcriptional factors to mediate the differentiation of distal stem cells in roots. PMID- 20543137 TI - Two-photon single-cell optogenetic control of neuronal activity by sculpted light. AB - Recent advances in optogenetic techniques have generated new tools for controlling neuronal activity, with a wide range of neuroscience applications. The most commonly used approach has been the optical activation of the light gated ion channel channelrhodopsin-2 (ChR2). However, targeted single-cell-level optogenetic activation with temporal precessions comparable to the spike timing remained challenging. Here we report fast (< or = 1 ms), selective, and targeted control of neuronal activity with single-cell resolution in hippocampal slices. Using temporally focused laser pulses (TEFO) for which the axial beam profile can be controlled independently of its lateral distribution, large numbers of channels on individual neurons can be excited simultaneously, leading to strong (up to 15 mV) and fast (< or = 1 ms) depolarizations. Furthermore, we demonstrated selective activation of cellular compartments, such as dendrites and large presynaptic terminals, at depths up to 150 microm. The demonstrated spatiotemporal resolution and the selectivity provided by TEFO allow manipulation of neuronal activity, with a large number of applications in studies of neuronal microcircuit function in vitro and in vivo. PMID- 20543138 TI - mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. AB - Synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is regulated by the mTOR pathway in mammalian cells. The mTOR kinase localizes to tRNA and 5S rRNA genes, providing an opportunity for direct control. Its presence at these sites can be explained by interaction with TFIIIC, a DNA-binding factor that recognizes the promoters of these genes. TFIIIC contains a TOR signaling motif that facilitates its association with mTOR. Maf1, a repressor that binds and inhibits pol III, is phosphorylated in a mTOR-dependent manner both in vitro and in vivo at serine 75, a site that contributes to its function as a transcriptional inhibitor. Proximity ligation assays confirm the interaction of mTOR with Maf1 and TFIIIC in nuclei. In contrast to Maf1 regulation in yeast, no evidence is found for nuclear export of Maf1 in response to mTOR signaling in HeLa cells. We conclude that mTOR associates with TFIIIC, is recruited to pol III-transcribed genes, and relieves their repression by Maf1. PMID- 20543139 TI - B-cell signaling networks reveal a negative prognostic human lymphoma cell subset that emerges during tumor progression. AB - Human tumors contain populations of both cancerous and host immune cells whose malignant signaling interactions may define each patient's disease trajectory. We used multiplexed phospho-flow cytometry to profile single cells within human follicular lymphoma tumors and discovered a subpopulation of lymphoma cells with impaired B cell antigen receptor (BCR) signaling. The abundance of BCR insensitive cells in each tumor negatively correlated with overall patient survival. These lymphoma negative prognostic (LNP) cells increased as tumors relapsed following chemotherapy. Loss of antigen receptor expression did not explain the absence of BCR signaling in LNP tumor cells, and other signaling responses were intact in these cells. Furthermore, BCR signaling responses could be reactivated in LNP cells, indicating that BCR signaling is not missing but rather specifically suppressed. LNP cells were also associated with changes to signaling interactions in the tumor microenvironment. Lower IL-7 signaling in tumor infiltrating T cells was observed in tumors with high LNP cell counts. The strength of signaling through T cell mediator of B cell function CD40 also stratified patient survival, particularly for those whose tumors contained few LNP cells. Thus, analysis of cell-cell interactions in heterogeneous primary tumors using signaling network profiles can identify and mechanistically define new populations of rare and clinically significant cells. Both the existence of these LNP cells and their aberrant signaling profiles provide targets for new therapies for follicular lymphoma. PMID- 20543140 TI - Dynamic motors for bacterial flagella. PMID- 20543141 TI - Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency. AB - Recombinant proteins are important therapeutics due to potent, highly specific, and nontoxic actions in vivo. However, they are expensive medicines to manufacture, chemically unstable, and difficult to administer with low patient uptake and compliance. Small molecule drugs are cheaper and more bioavailable, but less target-specific in vivo and often have associated side effects. Here we combine some advantages of proteins and small molecules by taking short amino acid sequences that confer potency and selectivity to proteins, and fixing them as small constrained molecules that are chemically and structurally stable and easy to make. Proteins often use short alpha-helices of just 1-4 helical turns (4 15 amino acids) to interact with biological targets, but peptides this short usually have negligible alpha-helicity in water. Here we show that short peptides, corresponding to helical epitopes from viral, bacterial, or human proteins, can be strategically fixed in highly alpha-helical structures in water. These helix-constrained compounds have similar biological potencies as proteins that bear the same helical sequences. Examples are (i) a picomolar inhibitor of Respiratory Syncytial Virus F protein mediated fusion with host cells, (ii) a nanomolar inhibitor of RNA binding to the transporter protein HIV-Rev, (iii) a submicromolar inhibitor of Streptococcus pneumoniae growth induced by quorum sensing pheromone Competence Stimulating Peptide, and (iv) a picomolar agonist of the GPCR pain receptor opioid receptor like receptor ORL-1. This approach can be generally applicable to downsizing helical regions of proteins with broad applications to biology and medicine. PMID- 20543142 TI - Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism. AB - A high saturated fat diet induces free cholesterol and phospholipid accumulation in the plasma of phospholipid transfer protein (Pltp)-deficient mice. In this study, we examined the atherogenic consequence of this phenomenon and investigated the possible mechanism(s). Pltp KO/Apoe KO mice that were fed a coconut oil-enriched high-fat diet (COD) for 7 weeks had higher plasma free cholesterol (149%), phospholipids (15%), and sphingomyelin (54%) than Apoe KO controls. In contrast to chow-fed animals, COD-fed Pltp KO/Apoe KO mice had the same atherosclerotic lesion size as that of Apoe KO mice. Similar to Pltp KO mice, plasma from COD-fed Pltp KO/Apoe KO mice contained VLDL/LDL-sized lamellar particles. Bile measurement indicated that COD-fed Pltp KO mice have 33% less hepatic cholesterol output than controls. In conclusion, COD-fed, Pltp-deficient mice are no longer protected from atherosclerosis and have impaired biliary lipid secretion, which is associated with free cholesterol and phospholipid accumulation. PMID- 20543143 TI - On the shoulders of giants. PMID- 20543144 TI - Letter to the editor: Low-dose whole body irradiation: a potential therapeutic modality? PMID- 20543146 TI - Throwing arm dominance in collegiate baseball pitching: a biomechanical study. AB - BACKGROUND: Left-handed individuals make up about 10% of the general population, yet left-handers comprise approximately 30% of the pitching staffs in Major League and Division I college baseball. Despite speculation regarding differences between right- and left-handed pitchers, distinction between right- and left handed pitching mechanics has not been documented in the literature at any level of play. HYPOTHESIS: Left-hand-dominant pitchers display similar pitching mechanics and upper extremity joint loads when compared to their right-hand dominant counterparts. STUDY DESIGN: Controlled laboratory study. METHODS: Three dimensional, high-speed (240-Hz) video data were collected on fastballs from 84 collegiate baseball pitchers. Kinematic parameters related to pitching mechanics and resultant kinetics on the throwing shoulder and elbow were calculated. The 28 left-handed pitchers in the database were matched with 28 right-handed pitchers for age, height, mass, and ball velocity, and paired t tests were used to compare the kinematic and kinetic parameters. RESULTS: Six parameters were found to have statistically significant differences between left- and right-handed pitchers. Passive nonthrowing shoulder external rotation (right, 113 degrees +/- 9 degrees ; left, 124 degrees +/- 8 degrees ), elbow flexion at stride-foot contact (right, 79 degrees +/- 16 degrees ; left, 94 degrees +/- 20 degrees ), and shoulder abduction during acceleration (right, 72 degrees +/- 11 degrees ; left, 105 degrees +/- 8 degrees ) were greater in left-handed pitchers than right-handed pitchers. Shoulder abduction at stride-foot contact (right, 115 degrees +/- 13 degrees ; left, 73 degrees +/- 10 degrees ), shoulder horizontal abduction at stride-foot contact (right, 25 degrees +/- 12 degrees ; left, 15 degrees +/- 12 degrees ), and peak horizontal adduction angular velocity (right, 707 +/- 185 deg/s; left, 551 +/- 160 deg/s) were less for the left-handed pitchers. CONCLUSION: Biomechanical differences between left- and right-handed pitchers have been demonstrated in a collegiate population. CLINICAL RELEVANCE: The results of the current study indicate that left-handed pitchers may be at increased risk for certain shoulder injuries compared with their right-handed counterparts. Information has been provided for athletes, coaches, and sports medicine providers to further improve preventive and rehabilitative protocols for college pitchers. The results of the study also suggest that different normative data sets may need to be developed for left- and right-handed pitchers, independently of one another. PMID- 20543147 TI - Subcoracoid bursitis as an unusual cause of painful anterior shoulder snapping in a weight lifter. PMID- 20543148 TI - Halostagnicola alkaliphila sp. nov., an alkaliphilic haloarchaeon from commercial rock salt. AB - A Gram-negative, pleomorphic, aerobic, haloalkaliphilic archaeon, strain 167 74(T), was isolated from commercial rock salt imported into Japan from China. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that strain 167-74(T) is closely related to Halostagnicola larsenii XH-48(T) (98.3 %) and Halostagnicola kamekurae 194-10(T) (97.2 %). The major polar lipids of the isolate were C(20)C(20) and C(20)C(25) derivatives of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. A glycolipid was not detected, in contrast to the two existing, neutrophilic species of the genus Halostagnicola. The DNA G+C content of strain 167-74(T) was 60.7 mol%. and it gave DNA-DNA reassociation values of 19.5 and 18.8 %, respectively, with Hst. larsenii JCM 13463(T) and Hst. kamekurae 194-10(T). Therefore, strain 167-74(T) represents a novel species, for which the name Halostagnicola alkaliphila sp. nov. is proposed, with the type strain 167-74(T) ( = JCM 16592(T) = CECT 7631(T)). PMID- 20543149 TI - Jishengella endophytica gen. nov., sp. nov., a new member of the family Micromonosporaceae. AB - A novel endophytic actinomycete, designated strain 202201(T), was isolated from an Acanthus illicifolius root collected from the mangrove reserve zone in Hainan Province, China. Phylogenetic analysis based on 16S rRNA gene sequences suggested that strain 202201(T) fell within the family Micromonosporaceae. The strain formed an extensively branched substrate mycelium, which carried uneven warty surfaced spores. Cell walls of strain 202201(T) contained meso-diaminopimelic acid and xylose, mannose, arabinose, ribose and glucose were detected as whole cell sugars. The acyl type of the cell-wall polysaccharides was glycolyl. The major menaquinones were MK-9(H(4)), MK-9(H(6)), MK-9(H(8)) and MK-10(H(4)). The polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylserine. The major cellular fatty acids were 10-methyl-C(17 : 0), iso-C(15 : 0), iso-C(16 : 0) and C(17 : 1)omega8c. The DNA G+C content was 72.3 mol%. On the basis of the morphological and chemotaxonomic characteristics, phylogenetic analysis and characteristic patterns of 16S rRNA gene signature nucleotides, strain 202201(T) ( = CGMCC 4.5597(T ) = DSM 45430(T)) represents a novel species of a new genus within the family Micromonosporaceae, for which the name Jishengella endophytica gen. nov., sp. nov. is proposed. PMID- 20543150 TI - Halorubrum aquaticum sp. nov., an archaeon isolated from hypersaline lakes. AB - Two halophilic archaea, strains EN-2(T) and SH-4, were isolated from the saline lakes Erliannor and Shangmatala, respectively, in Inner Mongolia, China. Cells were strictly aerobic, motile rods. Colonies were red. Strains EN-2(T) and SH-4 were able to grow at 25-50 degrees C (optimum 35-40 degrees C), with 2.5-5.0 M NaCl (optimum 3.4 M NaCl) and at pH 6.0-9.0 (optimum pH 7.5). MgCl(2) was not required for growth. Cells lysed in distilled water and the lowest NaCl concentration that prevented cell lysis was 12 % (w/v). On the basis of 16S rRNA gene sequence analysis, strains EN-2(T) and SH-4 were closely related to Halorubrum cibi B31(T) (97.9 and 98.0 % similarity, respectively), Hrr. tibetense 8W8(T) (97.3 and 97.7 %), Hrr. alkaliphilum DZ-1(T) (96.8 and 97.1 %), Hrr. luteum CGSA15(T) (96.8 and 97.0 %) and Hrr. lipolyticum 9-3(T) (96.8 and 97.0 %). DNA-DNA hybridization showed that strains EN-2(T) and SH-4 did not belong to the same species as any of these strains (<= 45 % DNA-DNA relatedness) but that they are members of the same species (>70 % DNA-DNA relatedness). Polar lipid analysis revealed that strains EN-2(T) and SH-4 contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, sulfated diglycosyl diethers and several unidentified glycolipids. The DNA G+C content of both isolates was 62.1 mol%. It was concluded that strains EN-2(T) and SH-4 represent a novel species of the genus Halorubrum, for which the name Halorubrum aquaticum sp. nov. is proposed. The type strain is EN-2(T) ( = CECT 7174(T) = CGMCC 1.6377(T) = JCM 14031(T)). PMID- 20543151 TI - Paracoccus isoporae sp. nov., isolated from the reef-building coral Isopora palifera. AB - A bacterial strain, designated SW-3(T), was isolated from the reef-building coral Isopora palifera, from Southern Taiwan, and was characterized by using a polyphasic taxonomic approach. Cells of strain SW-3(T) were Gram-reaction negative, aerobic, rod-shaped and motile by means of monopolar flagella and formed cream-white colonies. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain SW-3(T) belonged to the genus Paracoccus and its most closely related neighbours were P. aestuarii B7(T), P. homiensis DD-R11(T), P. marinus KKL-A5(T), P. denitrificans DSM 413(T) and P. zeaxanthinifaciens R 1512(T), with sequence similarities of 96.8, 96.6, 96.1, 95.8 and 94.9 %, respectively. Strain SW-3(T) exhibited optimal growth at 25-30 degrees C and pH 9-10 and in 3-5 % (w/v) NaCl. The predominant cellular fatty acid was summed feature 8 (C(18 : 1)omega7c and/or C(18 : 1)omega6c; 75 %). The major respiratory quinone was Q-10. The polar lipid profile consisted of a mixture of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and several uncharacterized polar lipids. The DNA G+C content of strain SW-3(T) was 63.7 mol%. The results of physiological and biochemical tests allowed clear phenotypic differentiation of this isolate from recognized species of the genus Paracoccus. It is evident from the genotypic, phenotypic and chemotaxonomic data that strain SW-3(T) represents a novel species of the genus Paracoccus, for which the name Paracoccus isoporae sp. nov. is proposed. The type strain is SW-3(T) ( = LMG 25205(T) = BCRC 17967(T)). PMID- 20543152 TI - Paenibacillus tianmuensis sp. nov., isolated from soil. AB - Two closely related, Gram-stain-negative, rod-shaped, spore-forming strains, B27(T) and F6-B70, were isolated from soil samples of Tianmu Mountain National Natural Reserve in Zhejiang, China. Phylogenetic analysis based on 16S rRNA gene and rpoB sequences indicated that the isolates were members of the genus Paenibacillus. Both isolates were closely related to Paenibacillus ehimensis IFO 15659(T), Paenibacillus elgii SD17(T) and Paenibacillus koreensis YC300(T) (>= 95.2 % 16S rRNA gene sequence similarity). DNA-DNA relatedness between strain B27(T) and P. ehimensis DSM 11029(T), P. elgii NBRC 100335(T) and P. koreensis KCTC 2393(T) was 21.2, 28.6 and 16.8 %, respectively. The major cellular fatty acids of strains B27(T) and F6-B70 were anteiso-C(15 : 0) and iso-C(15 : 0). The cell wall contained meso-diaminopimelic acid. The two isolates differed from their closest neighbours in terms of phenotypic characteristics and cellular fatty acid profiles (such as variable for oxidase, negative for methyl red test, unable to produce acid from d-fructose and glycogen and relatively higher amounts of iso-C(15 : 0) and lower amounts of C(16 : 0) and iso-C(16 : 0)). Strains B27(T) and F6-B70 represent a novel species of the genus Paenibacillus, for which the name Paenibacillus tianmuensis sp. nov. is proposed. The type strain is B27(T) ( = DSM 22342(T) = CGMCC 1.8946(T)). PMID- 20543153 TI - Vagococcus acidifermentans sp. nov., isolated from an acidogenic fermentation bioreactor. AB - A Gram-staining-positive, coccus-shaped, non-spore-forming, facultatively anaerobic bacterium, designated AC-1(T), was isolated from an acidogenic fermentation bioreactor treating food wastewater. On the basis of 16S rRNA gene sequence analysis, strain AC-1(T) was shown to belong to the genus Vagococcus. The closest phylogenetic relatives were Vagococcus elongatus PPC9(T) (97.4 % 16S rRNA gene sequence similarity), Vagococcus penaei CD276(T) (96.7 %) and Vagococcus carniphilus ATCC BAA-640(T) (96.6 %). The major fatty acids were C(18 : 1)omega9c (24.8 %) and C(16 : 0) (19.5 %) and the G+C content of genomic DNA was 44.2 mol%, which supported the affiliation of strain AC-1(T) to the genus Vagococcus. Strain AC-1(T) and V. elongatus DSM 21480(T) exhibited 11 % DNA-DNA relatedness. Physiological and biochemical tests differentiated strain AC-1(T) from the type strains of recognized species of the genus Vagococcus. Therefore, strain AC-1(T) is considered to represent a novel species, for which the name Vagococcus acidifermentans sp. nov. is proposed. The type strain is AC-1(T) ( = KCTC 13418(T) = LMG 24798(T)). PMID- 20543154 TI - Streptohalobacillus salinus gen. nov., sp. nov., a moderately halophilic, Gram positive, facultative anaerobe isolated from subsurface saline soil. AB - A Gram-stain-positive, rod-shaped, non-sporulating, motile and moderately halophilic bacterium, designated strain H96B60(T), was isolated from a saline soil sample of the Qaidam basin, China. The strain was facultatively anaerobic. Major end products formed from glucose fermentation were acetate, ethanol and lactic acid. The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The isoprenoid quinone component was menaquinone-6 (MK-6). The predominant cellular fatty acids were C(16: 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). The genomic DNA G+C content of strain H96B60(T) was 36.2 mol%. Phylogenetic analysis based on comparative 16S rRNA gene sequences indicated that strain H96B60(T) represented a novel phyletic lineage within the family Bacillaceae and was related most closely to Halolactibacillus species (96.1-96.4 % similarity). Based on the phenotypic, chemotaxonomic and phylogenetic data presented, strain H96B60(T) is considered to represent a novel species of a new genus, for which the name Streptohalobacillus salinus gen. nov., sp. nov. is proposed. The type strain of Streptohalobacillus salinus is H96B60(T) ( = DSM 22440(T) = CGMCC 1.7733(T)). PMID- 20543156 TI - Desertibacter roseus gen. nov., sp. nov., a gamma radiation-resistant bacterium in the family Rhodospirillaceae, isolated from desert sand. AB - A Gram-negative, rod-shaped, strictly aerobic bacterium, strain 2622(T), was isolated from gamma-irradiated soil sampled from the Taklimakan desert in Xinjiang, China. Phylogenetic analyses showed that strain 2622(T) formed a distinct lineage in the family Rhodospirillaceae and shared 91.7 and 90.1 % 16S rRNA gene sequence similarity with its closest relatives, the type strains of Skermanella xinjiangensis and Skermanella aerolata, respectively. The DNA G+C content of strain 2622(T) was 71.4 mol% and the isoprenoid quinone was ubiquinone Q-10. Based on phenotypic and chemotaxonomic data and phylogenetic analysis, strain 2622(T) is considered to represent a novel species of a new genus in the family Rhodospirillaceae, for which the name Desertibacter roseus gen. nov., sp. nov. is proposed. The type strain of Desertibacter roseus is strain 2622(T) ( = CCTCC AB 208152(T) = KCTC 22436(T)). PMID- 20543155 TI - Hansschlegelia zhihuaiae sp. nov., isolated from a polluted farmland soil. AB - A novel Gram-negative, aerobic, coccoid-shaped strain designated S 113(T) was isolated from a polluted-soil sample collected in Jiangsu Province, China. A polyphasic taxonomic study including phylogenetic analysis based on the 16S rRNA gene sequence and determination of phenotypic characteristics was performed on the new isolate. The highest 16S rRNA gene sequence similarity was 96.8 %, with Hansschlegelia plantiphila S(1)(T). The predominant respiratory quinone was ubiquinone 10 (Q-10). The major fatty acids were C(18 : 1)omega7c and C(16 : 0). The G+C content of the DNA was about 65.7 mol%. DNA-DNA hybridization experiments showed 44.9 % relatedness for strain S 113(T) with its closest relative, H. plantiphila NCIMB 14035(T). The dominant phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine and phosphatidylcholine. The results of our polyphasic taxonomic analysis indicate that strain S 113(T) represents a novel species within the genus Hansschlegelia, for which the name Hansschlegelia zhihuaiae sp. nov. is proposed. The type strain is S 113(T) ( = DSM 18984(T) = CCTCC AB 206143(T) = KCTC 12880(T)). PMID- 20543157 TI - Brachybacterium squillarum sp. nov., isolated from salt-fermented seafood. AB - A Gram-positive bacterium, strain M-6-3(T), was isolated from salt-fermented seafood in Korea. The organism grew in 0-10 % (w/v) NaCl and at 25-37 degrees C, with optimal growth occurring in 5 % NaCl and at 28-30 degrees C. The peptidoglycan type was variation A4gamma with meso-diaminopimelic acid as the diagnostic cell-wall diamino acid. The polar lipid profile of strain M-6-3(T) consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unknown glycolipid. Strain M-6-3(T) contained MK-7 as the major component of the quinone system and anteiso-C(15 : 0) (62.1 %) as the predominant fatty acid. Based on 16S rRNA gene sequence similarity studies, strain M-6-3(T) was most closely related to Brachybacterium rhamnosum LMG 19848(T) (98.5 %). The G+C content of the genomic DNA was 71.5 mol% and the mean DNA-DNA hybridization value with reference strains was 14.32 +/- 2.0 %. Based on phenotypic, genotypic and phylogenetic analyses, it is proposed that strain M-6 3(T) represents a novel species for which the name Brachybacterium squillarum sp. nov. is proposed; the type strain is M-6-3(T) ( = KACC 14221(T) = JCM 16464(T)). PMID- 20543158 TI - Microstructures and electrical properties of TiO(2)-doped Al(2)O(3) ceramics. AB - Microstructures of TiO(2)-doped alpha-Al(2)O(3) ceramics used as electrostatic chucks (ESC) were investigated by transmission electron microscopy including energy-dispersive spectrometry (EDS) and electron energy loss spectroscopy (EELS) analyses in connection with their electrical properties. The lattice parameters of sintered Al(2)O(3) grains are almost independent of TiO(2) content as well as the sintering temperature, indicating immiscibility of the additive with Al(2)O(3). Scanning transmission electron microscopy (STEM)-EDS revealed that the grain boundaries of alpha-Al(2)O(3) are slightly enriched with Ti. It was shown in EELS that the segregated Ti is in a partially reduced state. The Ti-enriched grain boundaries, therefore, play a role as a conductive network, which is responsible for considerable improvement of electronic conductivity with TiO(2) doping. STEM-EDS and electron diffraction analyses confirmed that micrometre sized TiO(2) particles are dispersed in the alpha-Al(2)O(3) when sintering is operated at 1300 degrees C or lower, while the particles transform into Al(2)TiO(5) at higher temperature. EELS revealed that the TiO(2) grains are partially reduced into non-stoichiometric TiO(2-y), while Al(2)TiO(5) grains are in the fully oxidized state. The TiO(2-y)-dispersed alpha-Al(2)O(3) shows no dielectric relaxation and quite smooth dissipation of the electrostatic condensed charges. In contrast, alpha-Al(2)O(3) with Al(2)TiO(5) grains possesses pronounced dielectric relaxation, and the electrostatic dissipation takes such a longer time as 30 s. The former is preferable to application to ESC in terms of quick response. PMID- 20543159 TI - Dislocation structures and strain fields in [111] low-angle tilt grain boundaries in zirconia bicrystals. AB - Structures of <111> low-angle tilt grain boundaries in yttria-stabilized cubic zirconia bicrystals were characterized by conventional transmission electron microscopy, high-resolution transmission electron microscopy and high-angle annular dark-field scanning transmission electron microscopy. It is found that the 0.4 and 4.0 degrees tilt grain boundaries are composed of periodic arrays of edge dislocations with Burgers vectors . The experimentally estimated strain field of each dislocation in the 0.4 degrees tilt boundary was in good agreement with the theoretically predicted strain field from the Peierls-Nabarro model. On the other hand, the estimated strain field of each dislocation in the 4.0 degrees tilt boundary was clearly different from that in the 0.4 degrees tilt boundary, which suggests that the strain fields of neighbouring dislocations interact when the separation distance between dislocations is shorter than a critical value. PMID- 20543160 TI - Phase-shifting electron holography for atomic image reconstruction. AB - Phase-shifting electron holography was used to reconstruct the object-wave function of high-spatial-frequency specimens of HgCdTe, and the requirements for precise measurements were investigated. Fresnel fringes due to the electrostatic biprism caused serious calculation errors during the phase-shifting reconstruction. Uniform interference fringes, obtained by adjusting the biprism voltage to cancel out the Fresnel fringes, were needed to minimize these errors. High-resolution holograms of a HgCdTe single crystal were recorded with coarse interference fringes and a high visibility of 65% and then used to reconstruct the atomic-scale object wave. Although the spatial resolution (0.25 nm) of the transmission electron microscope was worse than the separation (0.16 nm) between Hg (or Cd) and Te columns, the crystal polarity was determined from the aberration-corrected object wave. PMID- 20543161 TI - Palliative care program for human immunodeficiency virus-infected patients: rebuilding of an academic urban program. AB - BACKGROUND: palliative care is extremely important for human immunodeficiency virus (HIV)-infected clientele. The impact of HIV infection is significant in the city of New Orleans. As of September 2009, a cumulative total of 29 548 HIV/acquired immunodeficiency syndrome (AIDS) cases and 12 267 HIV-related deaths were reported in Louisiana. METHODS: retrospective review of charts of patients enrolled in our palliative care program. RESULTS: as of September 2009, there were around 1800 active patients in our HIV outpatient clinic. A total of 5 (22%) patients had multidrug-resistant AIDS infection. Three (13%) referred patients had AIDS dementia. Progressive multifocal leukoencephalopathy (PML) and advanced HIV nephropathy were also reasons for referral (13% and 4% of referred patients, respectively). Around 9% of patients had advanced liver cancer with metastases. In all, 22% of patients had rapidly deteriorating functional status. The rest of the patients (26%) complained of cancer-related nausea and vomiting and progressive and nonresponsive weight loss. In terms of psychosocial assessment, the majority of referred patients had problems in areas such as social functioning, mood swings, unstable moods, problems with controlling temper, outbursts of anger, violence, and disturbing or unreal thoughts and beliefs. CONCLUSIONS: palliative care is extremely important in the care of patients with HIV/AIDS. More research is needed to elaborate on best palliative care practices in the care of HIV-infected patients. Interesting to note is that there is significant proportion of patients with mental issues (substance abuse, psychiatric problems, depression, and despair) for which better resources are needed. Integration of services among clinical, mental, and palliative care providers might be needed to better serve this population. PMID- 20543162 TI - Assessment of hospice patients' goals of care at the end of life. AB - OBJECTIVE: to evaluate satisfaction with inpatient hospice goals at the end of life and to determine steps for program improvement. STUDY DESIGN AND SETTING: prospective observational study of patients admitted to an inpatient Veterans Affairs Medical Center hospice unit, located in an urban setting with dedicated 16 hospice and 20 palliative care beds. Patients and their families are cared for by an interdisciplinary team. POPULATION: veteran population receiving care in an inpatient hospice unit whose goals are comfort care. INTERVENTION: two anonymous surveys of patient goals were distributed upon admission to hospice unit patients and families, who were asked to complete the first survey within 1 to 5 days of admission and the second survey 2 weeks after admission or later. OUTCOME MEASURE: patient and family centered end-of-life care outcomes, including meeting goals of care with desired symptom management, emotional support to the dying patient, coordinated care, shared decision making, and attending to the emotional needs of families. RESULTS: fifty patients were given surveys between June and September 2009. Response rate was 52% for the first survey and 36% for the second survey. Most important goals for 90% of veterans were control of symptoms and being with family. More than 90% of our patients' families, responding to our second survey, strongly agreed that these goals were achieved. We also identified other needs of hospice veterans, and family surveys showed that these were also accomplished. CONCLUSION: clarification and focus on goals of care improves satisfaction with end-of-life care. PMID- 20543163 TI - Northern Ireland disease surveillance, January to March 2010. PMID- 20543164 TI - Influences on the decision to study veterinary medicine: variation with sex and background. AB - A questionnaire was developed to look at attitudes to veterinary medicine as a career choice among students at different stages of the veterinary course at the Royal Veterinary College. Traditional-entry first-year and final-year students, as well as entry-level 'Gateway' (widening participation) students, were invited to participate. Wanting to work with animals and exposure to a veterinary role model through taking a sick animal to visit a veterinary surgeon appeared to be major factors in choosing a veterinary career for all undergraduates, regardless of their socioeconomic background. Overall, women were more strongly influenced by owning animals (P=0.014), and men were more positively influenced by the challenging reputation of the course (P=0.028). When the students were asked to indicate their top three reasons for wanting to become a vet, men were 9.5 times as likely as women to select 'Want to train as a scientist', 5.3 times as likely to select 'Join a profession' and 13.2 times as likely to select 'Hardest course to get in to'; the top choice for both sexes was 'Want to work with animals'. Thirty-one per cent of the students felt their careers adviser had been a negative influence on their decision to become a vet. PMID- 20543165 TI - Views on euthanasia and the rehoming of dogs in Norway and Iceland. AB - According to several previously published studies, large populations of dogs are sent to animal shelters in the UK and USA each year, and estimates indicate that a substantial percentage of the dogs in such shelters are euthanased annually. However, anecdotal evidence indicates a different situation in Norway and Iceland. This study explores the attitudes toward euthanasia of dogs in Norway and Iceland, and investigates the practice of rehoming of dogs in the two countries. A general reluctance toward euthanasia of dogs was expressed, and participants stressed the need to consider alternatives such as rehoming. Rehoming of dogs was found to be negligible in Norway relative to international trends, and less than 10 per cent of the dogs assigned for rehoming were euthanased. In Iceland, the rehoming of dogs is yet to reach levels that necessitate the setting up of animal shelters. There is, nevertheless, reason to continue to explore the attitudes toward euthanasia and rehoming of dogs in Norway and Iceland, because there is a lack of statistical data on the reasons behind the owners' decisions to give away or euthanase their dogs. PMID- 20543166 TI - Phenotypic and genotypic characterisation of Brucella strains isolated from cattle in the Gambia. AB - Thirty-five serum samples and six hygroma fluid samples were collected from sexually mature cattle in one herd with clinical signs of brucellosis (abortion and hygromas) in the Western Region of the Gambia in order to isolate and characterise Brucella species. Information on the sex, age, number of calvings, number of abortions, presence of hygromas, and presence of orchitis was also collected for each animal sampled. Twenty-six (74 per cent) of the serum samples were positive in the rose bengal test and 29 (83 per cent) were positive by indirect ELISA. Three isolates of Brucella, biotyped as Brucella abortus biovar 3, were cultured from six hygroma fluid samples. The multiple locus variable number tandem repeat analysis assay clustered the isolates as B abortus with the same profile for the three isolates, suggesting a common origin of contamination. PMID- 20543167 TI - Possible adverse reactions in sheep after vaccination with inactivated BTV vaccines. PMID- 20543168 TI - Prevention of PRRSV infection in large breeding herds using air filtration. PMID- 20543169 TI - Multiple congenital anomalies in an alpaca cria (Vicugna pacos). PMID- 20543174 TI - Seroprevalence of Fasciola hepatica in dairy herds. PMID- 20543175 TI - Change in Great Britain's bluetongue serotype 8 status. PMID- 20543176 TI - Treating ivermectin toxicity in cats. PMID- 20543181 TI - Prenatal alcohol exposure induces long-term changes in dendritic spines and synapses in the mouse visual cortex. AB - AIMS: To study the long-term changes of dendritic spine and synapse taking place in a mouse model of fetal alcohol spectrum disorders (FASDs). METHODS: Pregnant mice were intubated daily with ethanol (EtOH) from E5 to parturition. A DiI diolistic method was used to label dendritic spines of pyramidal cells in the visual cortex of EtOH-exposed and control pups over the period from postnatal (P) day P0 to P30; synaptic ultrastructure was also analyzed using transmission electron microscopy. RESULTS: Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length. The changes were dose dependent and persisted to P30. Ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls; ultrastructural changes also persisted to P30. CONCLUSIONS: Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure; these alterations probably reflect the developmental retardation of dendritic spines and synapses in visual cortex. These long-term changes are likely to contribute to lifelong mental retardation associated with childhood FASDs. PMID- 20543182 TI - Evaluating the diagnostic capacity of a single-question neuropathy screen (SQNS) in HIV positive Zambian adults. AB - A single-question neuropathy screen (SQNS) is routinely included in the enrolment data for people commencing antiretroviral therapy in publically funded clinics in Zambia. The authors assessed the sensitivity, specificity, positive and negative predictive value of this SQNS against the Brief Peripheral Neuropathy Screen (BPSN) in detecting HIV-associated sensory neuropathy in patients recruited from a rural and an urban hospital in Zambia. The SQNS was asked followed by conduct of the BPNS by the neurology resident assisted by a Zambian healthcare worker/translator. 77 patients (48 (62.3%) urban and 29 (37.7%) rural) were enrolled. 13 subjects were excluded due to altered mental status. The mean age was 33.7 years (range 15-53 years; SD+/-7.81). The SQNS was 95.7% sensitive and 80.0% specific, with 88.2% positive predictive value and 92.3% negative predictive value. Age, geographical location, gender and WHO stage were all unrelated to the performance of the SQNS (p>0.05). Despite its reliance on symptoms alone, this study suggests that the SQNS may be a valid research tool for identifying HIV-associated neuropathy among advanced stage HIV patients in Zambia. PMID- 20543184 TI - Neurological picture. Isolated abducens and facial nerve palsies due to a facial collicular plaque in multiple sclerosis. PMID- 20543183 TI - Neuroimaging of multimodal sensory stimulation in amyotrophic lateral sclerosis. AB - AIM: Structural and functional imaging techniques were combined to investigate sensory system function in amyotrophic lateral sclerosis (ALS). METHODS: Functional MRI (fMRI) was used to investigate cortical activity during visual, auditory and somatosensory stimulation in 14 ALS patients and 18 control subjects. Changes in amplitude, latency and duration of the blood oxygen level dependent response were modelled. Furthermore, diffusion tensor imaging was used to investigate changes in white matter networks. RESULTS: During visual stimulation, fMRI demonstrated a decreased response in secondary visual areas in ALS, possibly related to demyelination of sensory nerve fibres. Increasing brain activity in associative cortices was linked to a decrease in physical functioning and might represent a compensatory process. Additionally, reduced white matter functioning became evident for fibres projecting to the extrastriate visual cortex. For auditory stimulation, a delayed response in secondary auditory areas probably linked to prolonged nerve conductance time and an altered cortical pattern in areas involved in target processing/detection became evident in ALS patients. Structural white matter changes in the primary and secondary auditory cortices were observed. For somatosensory stimulation, a prolonged/reduced response in sensory integration areas of the parietal lobe was observed, perhaps linked to the reduced visceral inflow due to immobility. CONCLUSION: Multiparametric MRI suggests a progressive functional deficit in secondary/higher order sensory processing areas in ALS, probably associated with reduction of re afferent information flow due to progressive immobility. The changes described might also represent an expression of the disease process itself. Evidence for compensatory processes in multimodal associative cortices was found. PMID- 20543185 TI - Neurological picture. Spinal nerve root hypertrophy in chronic ataxic neuropathy with antiglycolipid IgM antibodies. PMID- 20543186 TI - Reproducibility and diagnostic accuracy of substantia nigra sonography for the diagnosis of Parkinson's disease. AB - OBJECTIVE: Transcranial sonography (TCS) shows characteristic hyperechogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD). Although this feature is well established, sufficient observer reliability and diagnostic accuracy are prerequisites for advancements of this method. METHODS: The authors investigated both aspects in a cross-sectional study with four blinded TCS raters in 22 PD patients and 10 healthy controls. RESULTS: As expected, the authors found significant bilateral SN hyperechogenicity in PD patients. Quantitative computerised SN planimetry had a substantial intra- (intraclass correlation coefficient (ICC) 0.97 and 0.93 respectively for both hemispheres) and inter rater reliability (ICC 0.84 and 0.89), while visual semiquantitative echogenicity grading of the SN revealed a moderate intrarater (weighted kappa 0.80 ipsilateral and 0.74 contralateral) and slight (0.33) to fair (0.51) inter-rater reliability only. Diagnostic accuracy measured as the area under the curve of receiver operating characteristics plots was highest in TCS of the SN opposite the clinically most affected body side (planimetry 0.821, echogenicity grading 0.792) with a hyperechogenic area of 0.24 cm(2) as the optimum cut-off value for the differentiation between PD and controls (sensitivity 79%, specificity 81%). CONCLUSIONS: The data demonstrate that the observer variability of SN planimetry is low in the hands of experienced investigators. This approach also offers adequate diagnostic accuracy. The authors conclude that reliable SN TCS data on PD can be achieved in clinical routine and multicentre trials when standardised analysis protocols and certain quality criteria of brain parenchyma sonography are met. PMID- 20543187 TI - Cognitive decline precedes late-life longitudinal changes in vascular risk factors. AB - INTRODUCTION: Although obesity, hypercholesterolaemia and hypertension in midlife are risk factors for dementia in late life, dementia is associated with lower body mass index, cholesterol levels and blood pressures. It is unclear whether declines in these vascular risk factors are preceded by declines in cognitive function or vice versa. METHODS: Within the Leiden 85-plus Study, a prospective population-based study of 599 subjects aged 85 years, the authors annually measured body mass index, total cholesterol, high-density lipoprotein (HDL) cholesterol, glucose levels and blood pressure, and assessed global cognitive function using the Mini Mental State Examination (MMSE) during a 5-year follow up. RESULTS: For the whole population who survived up to the age of 90 years, strong annual declines in MMSE score, body mass index, total cholesterol levels, glucose levels, and blood pressure, and an annual increase in HDL cholesterol levels were observed during the follow-up period (all p< or =0.010). Annual changes in MMSE score from age 85 to 87 years were associated positively with annual changes from age 87 to 90 years in total and HDL cholesterol levels (p=0.002 and p=0.013), systolic and diastolic blood pressure (p=0.008 and p=0.048), but not BMI. Parameter value changes from age 85 to 87 years were not associated with changes in MMSE score from age 87 to 90 years. DISCUSSION: In old age, cognitive decline precedes declines in total cholesterol levels, HDL cholesterol levels and blood pressure, and not vice versa. Possibly, brain lesions in metabolic and blood pressure regulation centres cause dysregulation of lipid metabolism and blood pressure. PMID- 20543188 TI - Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images. AB - OBJECTIVE: To evaluate visual assessment of [(11)C]PIB and [(18)F]FDDNP PET images as potential supportive diagnostic markers for Alzheimer's disease (AD). METHODS: Twenty-one AD patients and 20 controls were included. Parametric [(11)C]PIB and [(18)F]FDDNP global binding potential (BP(ND)) images were visually rated as 'AD' or 'normal.' Data were compared with ratings of [(18)F]FDG PET images and MRI-derived medial temporal lobe atrophy (MTA) scores. Inter-rater agreement and agreement with clinical diagnosis were assessed for all imaging modalities. In addition, cut-off values for quantitative global [(11)C]PIB and [(18)F]FDDNP BP(ND) were determined. Visual ratings were compared with dichotomised quantitative values. RESULTS: Agreement between readers was excellent for [(11)C]PIB, [(18)F]FDDNP and MTA (Cohen kappa kappa> or =0.85) and moderate for [(18)F]FDG (kappa=0.56). The highest sensitivity was found for [(11)C]PIB and [(18)F]FDG (both 1.0). The highest specificity was found for MTA (0.90) and [(11)C]PIB (0.85). [(18)F]FDDNP had the lowest sensitivity and specificity (0.67 and 0.53, respectively). The cut-off for quantitative [(11)C]PIB BP(ND) was 0.54 (sensitivity and specificity both 0.95) and for [(18)F]FDDNP BP(ND) 0.07 (sensitivity 0.80, specificity 0.73). Agreement between quantitative analyses and visual ratings was excellent for [(11)C]PIB (kappa=0.85) and fair for [(18)F]FDDNP (kappa=0.40). CONCLUSION: Visual assessment of [(11)C]PIB images was straightforward and accurate, showing promise as a supportive diagnostic marker for AD. Moreover, [(11)C]PIB showed the best combination of sensitivity and specificity. Visual assessment of [(18)F]FDDNP images was insufficient. The quantitative analysis of [(18)F]FDDNP data showed a considerably higher diagnostic value than the visual analysis. PMID- 20543189 TI - Antidepressants for neuropathic pain: a Cochrane review. PMID- 20543190 TI - Discovery and Characterization of HemQ: an essential heme biosynthetic pathway component. AB - Here we identify a previously undescribed protein, HemQ, that is required for heme synthesis in Gram-positive bacteria. We have characterized HemQ from Bacillus subtilis and a number of Actinobacteria. HemQ is a multimeric heme binding protein. Spectroscopic studies indicate that this heme is high spin ferric iron and is ligated by a conserved histidine with the sixth coordination site available for binding a small molecule. The presence of HemQ along with the terminal two pathway enzymes, protoporphyrinogen oxidase (HemY) and ferrochelatase, is required to synthesize heme in vivo and in vitro. Although the exact role played by HemQ remains to be characterized, to be fully functional in vitro it requires the presence of a bound heme. HemQ possesses minimal peroxidase activity, but as a catalase it has a turnover of over 10(4) min(-1). We propose that this activity may be required to eliminate hydrogen peroxide that is generated by each turnover of HemY. Given the essential nature of heme synthesis and the restricted distribution of HemQ, this protein is a potential antimicrobial target for pathogens such as Mycobacterium tuberculosis. PMID- 20543191 TI - Circulating endothelial progenitor cell levels and function in patients who experienced late coronary stent thrombosis. AB - AIMS: The pathogenesis of late coronary stent thrombosis may be related to impaired arterial healing. Endothelial progenitor cells (EPCs) have been shown to play an important role in repair and re-endothelialization following vascular injury. We hypothesized that patients who develop late stent thrombosis may have reduced or dysfunctional EPCs, and aimed to compare EPC level and function in patients who experienced stent thrombosis vs. matched controls. METHODS AND RESULTS: Patients who developed late (> 30 days) stent thrombosis within the past 3 years were compared with matched patients who underwent stenting and did not develop stent thrombosis. All patients had blood samples taken >= 3 months from the stent thrombosis or index procedure. The proportion of peripheral mononuclear cells (PMNCs) expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 was evaluated by flow cytometry. Endothelial progenitor cell colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. The two groups (n = 30 each) were well-matched (93.3% men, mean age 60-62 years, 33.3% diabetes, 73-80% DESs). The proportion of cells co-expressing VEGFR-2, CD133, and CD34 was lower in the stent thrombosis group compared with the control [VEGFR-2(+)CD133(+): 0.18% (0.03-0.41%) vs. 0.47% (0.16-0.66%), P = 0.01; VEGFR-2(+)CD34(+): 0.32% (0.22-0.70%) vs. 0.66% (0.24 1.1%), P = 0.03]. The number of EPC CFUs was also lower in the stent thrombosis group [3.9% (3.2-5.5%) vs. 8.3% (6.5-13.4%) colonies/well, respectively, P < 0.0001]. CONCLUSION: Patients who suffered late coronary stent thrombosis appear to have reduced levels of circulating EPCs and impaired functional properties of the cells. These findings require validation by further studies, but may contribute to understanding the pathogenesis of late stent thrombosis. PMID- 20543192 TI - Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. AB - AIMS: To assess the acute vasodilator response and long-term response to calcium channel blockers (CCB) in pulmonary arterial hypertension (PAH) with associated conditions. METHODS AND RESULTS: The response to acute vasodilator testing [>20% decrease in mean pulmonary artery pressure (mPAP) and total pulmonary resistance] was assessed in 663 consecutive PAH patients with connective tissue disease (CTD; n = 168), portal hypertension (PoPH; n = 153), anorexigen use (n = 127), human immunodeficiency virus infection (HIV; n = 124), congenital heart disease (CHD; n = 50), and pulmonary veno-occlusive disease or capillary haemangiomatosis (PVOD/PCH; n = 41). An acute vasodilator response was observed in 13.4% of PAH anorexigen patients, 12.2% of PVOD/PCH, 10.1% of CTD, 1.6% of HIV, 1.3% of PoPH, and was absent in CHD. A long-term response to CCB (marked haemodynamic improvement at 3-4 months and New York Heart Association functional class I or II after 1 year) was reported in 9.4% of PAH-anorexigen patients but was rare in HIV, PoPH, CTD (1.6, 0.7, and 0.6%, respectively) and absent in PVOD/PCH. All patients with a long-term CCB response were alive after 5 years; two deaths not related to PAH occurred after this time. Recent criteria for acute response based on the fall in mPAP to <40 mmHg are more specific to detect long-term responders to CCB. CONCLUSION: A long-term CCB response was reported in patients with PAH associated with anorexigen use, but was rare in patients with PoPH or HIV and absent in PVOD/PCH, CHD, and the vast majority of CTD. The prognosis of long-term responders was favourable and related to the underlying cause of PAH. PMID- 20543193 TI - Atrial asystole during ventricular pacing following radiofrequency catheter ablation of accessory pathways. AB - Sinus node bradycardia or sinus node arrest is a documented phenomenon during radiofrequency catheter ablation. In addition, sinus node inhibition during ventricular pacing has been described as an infrequent occurrence in the course of diagnostic electrophysiology studies. The proposed mechanism in both situations is intense stimulation of vagal afferent pathways leading to a Bezold Jarisch-like phenomenon. In the present report, we describe a series of three cases of atrial asystole during ventricular pacing following radiofrequency catheter ablation of accessory pathways. Potential pathophysiologic mechanisms are discussed. PMID- 20543194 TI - Inappropriate implantable cardioverter-defibrillator shocks due to temporary epicardial pacing. AB - Oversensing of external electrical signals can cause inappropriate therapy in cardiac rhythm management devices. In this report, a patient with an implantable cardioverter-defibrillator (ICD) is presented, who received inappropriate shocks due to temporary epicardial pacing after cardiothoracic surgery. PMID- 20543195 TI - TEE time? ICETEE time! IntraCardiac Echocardiography probe used for TransoEsophageal Echocardiography. PMID- 20543196 TI - The safety of MRI scanning of pacemakers and ICDs: what are the critical elements of safe scanning? Ask me again at 10,000. PMID- 20543197 TI - Defibrillation threshold decrease with the supradiaphragmatic extracardiac implantable cardioverter-defibrillator implantation technique. AB - Despite advances in implantable cardioverter-defibrillator (ICD) technology, the optimal ICD implantation technique for pediatric patients has not yet been established. One increasingly used option is totally extracardiac implantation. However, concern exists about the high defibrillation threshold (DFT) at the moment of implantation or during follow-up. We report the case of a 3-year-old boy with repetitive syncopal idiopathic ventricular tachycardia episodes treated with ICD implantation using the extracardiac technique. Changing device position from abdominal to a supradiaphragmatic, solved unsafe elevated discharge impedance and DFT during follow-up. PMID- 20543198 TI - Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation. AB - AIMS: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke and hypertension. Recently, the rs5063 SNP has been reported to confer an increased risk of AF development in a Chinese population. We sought to examine the associations of both rs5063 and rs5065 with AF in two separate North American cohorts of European ancestry. METHODS AND RESULTS: Patients with early-onset AF, along with healthy controls, were recruited at the University of Ottawa Heart Institute (UOHI) and the Massachusetts General Hospital (MGH). Study participants were genotyped for rs5063 and rs5065 using a combination of restriction fragment length polymorphism analysis and DNA microarrays. The study genotyped a total of 620 AF cases and 2446 healthy controls. The UOHI arm of the study identified an odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.42-1.24] for rs5063, whereas an OR of 1.33 (95% CI: 0.80-2.21) was observed in the MGH arm. The combined OR approximated unity (OR 0.99; 95% CI: 0.54-1.80). Analysis of rs5065 revealed an OR of 1.12 (95% CI: 0.84-1.48) in UOHI, 1.08 (95% CI 0.80-1.45) in MGH, and 1.10 (95% CI 0.90-1.35) when combined. CONCLUSION: Common non-synonymous genetic variants within NPPA in these two large North American cohorts of European ancestry are not associated with the development of AF. PMID- 20543199 TI - Survival in New York Heart Association class IV heart failure patients treated with cardiac resynchronization therapy compared with patients on optimal pharmacological treatment. AB - AIMS: Although the benefit of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well established, its effect on mortality in New York Heart Association (NYHA) class IV patients remains unclear. Our study evaluated the effect of CRT on urgent transplant-free survival in NYHA class IV patients treated with CRT, compared with medication-only treatment. METHODS AND RESULTS: Forty NYHA class IV patients treated with CRT (80% men, 62.5% ischaemic, mean age of 65) were matched 1:1 by age, gender and aetiology of cardiomyopathy with patients treated with optimal medical therapy (OPT group). No significant differences were found between the groups in left ventricular diastolic diameter (71 +/- 6 vs. 73 +/- 9 mm), left ventricular systolic diameter (58 +/- 7 vs. 61 +/- 11 mm), and left ventricular ejection fraction (23 +/- 5 vs. 22 +/- 6%). Mean follow-up was 13.2 +/- 9.5 months for the CRT group and 17.3 +/- 11.6 months for the OPT group. Time to all-cause death or urgent transplantation [hazard ratios (HR), 1.29; 95% CI: 0.59-2.83; P = 0.52] or to cardiovascular death or urgent transplantation (HR, 1.53; 95% CI: 0.64-3.67; P = 0.34) was not reduced significantly in patients treated with CRT. CONCLUSION: In this study, CRT did not significantly improve survival of NYHA class IV heart failure patients compared with pharmacological therapy. PMID- 20543200 TI - Hormonal contraception and risk of cancer. AB - BACKGROUND: Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance. METHODS: In this review, we included all cohort and case-control studies published in English up to December 2008. They were identified through a search of the literature using Pubmed and EMBASE. RESULTS: Data about breast cancer risk indicate a slightly increased risk among current users of oral contraceptives (OC), an effect which disappears 5-10 years after stopping. Combined OC have a significant protective effect on the risk of ovarian cancer, and the protection increases with duration of use (relative risk decreased by 20% for each 5 years of use). The significant risk reduction has been confirmed for BRCA 1 and 2 mutation carriers. The risk of endometrial cancer is reduced by about 50% in ever users, a benefit which is greater with increasing duration of use. An association has been found between increased risk of cervical cancer and long-term OC use. Current OC use has been associated with an excess risk of benign liver tumours and a modest increased risk of liver cancer. None of large prospective cohort studies with prolonged follow-up has observed an increased overall risk of cancer incidence or mortality among ever users of OC, indeed several have suggested important long-term benefits. Specifically, protective effect of OC can be used as chemoprevention in young women who are BRCA mutation carriers. CONCLUSIONS: Women wishing to use combined OC can be reassured that their decision is unlikely to place them at higher risk of developing cancer. PMID- 20543201 TI - Clinical and immunologic aspects of egg donation pregnancies: a systematic review. AB - BACKGROUND: Egg donation (ED) makes it possible for subfertile women to conceive. Pregnancies achieved using ED with unrelated donors are unique, since the entire fetal genome is allogeneic to the mother. The aims of this review were to evaluate the consequences of ED pregnancies and to place them in the special context of their atypical immunologic relationships. METHODS: This review comprised an online search of English language publications listed in Pubmed/Medline, up to 29 January 2010. Seventy-nine papers met inclusion criteria. Using the literature and the authors' own experience, the relevant data on pregnancy outcome and complications, placental pathology and immunology were evaluated. RESULTS: Multiple studies document that ED pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. The incidence of other perinatal complications, such as intrauterine growth restriction, prematurity and congenital malformations, is comparable to conventional IVF. During pregnancy, both local and systemic immunologic changes occur and in ED pregnancies these changes are more pronounced. There is almost no information in the literature on the long-term complications of ED pregnancies for the mother. CONCLUSIONS: ED pregnancies have a higher risk of maternal morbidity. Owing to the high degree of antigenic dissimilarity, ED pregnancies represent an interesting model to study complex immunologic interactions, as the fully allogeneic fetus is not rejected but tolerated by the pregnant woman. Knowledge of the immune system in ED pregnancies has broader significance, as it may also give insight into immunologic aspects of tolerance in solid organ transplantation. PMID- 20543202 TI - Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. AB - BACKGROUND: Large deletions of the NF1 gene region occur in approximately 5% of patients with neurofibromatosis type-1 (NF1) and are associated with particularly severe manifestations of the disease. However, until now, the genotype-phenotype relationship has not been comprehensively studied in patients harbouring large NF1 gene deletions of comparable extent (giving rise to haploinsufficiency of the same genes). METHOD: We have performed the most comprehensive clinical/neuropsychological characterisation so far undertaken in NF1 deletion patients, involving 29 patients with precisely determined type-1 NF1 (1.4 Mb) deletions. RESULTS: Novel clinical features found to be associated with type-1 NF1 deletions included pes cavus (17% of patients), bone cysts (50%), attention deficit (73%), muscular hypotonia (45%) and speech difficulties (48%). Type-1 NF1 deletions were found to be disproportionately associated with facial dysmorphic features (90% of patients), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and/or learning disabilities (93%) and mental retardation (IQ<70; 38%), as compared with the general NF1 patient population. Significantly increased frequencies (relative to the general NF1 population) of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and MPNSTs (21%) were also noted in the type-1 deletion patients. Further, 50% of the adult patients exhibited a very high burden of cutaneous neurofibromas (N>or=1000). CONCLUSION: These findings emphasise the importance of deletion analysis in NF1 since frequent monitoring of tumour presence and growth could potentiate early surgical intervention thereby improving patient survival. PMID- 20543203 TI - Germline mutations of the CBL gene define a new genetic syndrome with predisposition to juvenile myelomonocytic leukaemia. AB - BACKGROUND: CBL missense mutations have recently been associated with juvenile myelomonocytic leukaemia (JMML), an aggressive myeloproliferative and myelodysplastic neoplasm of early childhood characterised by excessive macrophage/monocyte proliferation. CBL, an E3 ubiquitin ligase and a multi adaptor protein, controls proliferative signalling networks by downregulating the growth factor receptor signalling cascades in various cell types. METHODS AND RESULTS: CBL mutations were screened in 65 patients with JMML. A homozygous mutation of CBL was found in leukaemic cells of 4/65 (6%) patients. In all cases, copy neutral loss of heterozygosity of the 11q23 chromosomal region, encompassing the CBL locus, was demonstrated. Three of these four patients displayed additional features suggestive of an underlying developmental condition. A heterozygous germline CBL p.Y371H substitution was found in each of them and was inherited from the father in one patient. The germline mutation represents the first hit, with somatic loss of heterozygosity being the second hit positively selected in JMML cells. The three patients display a variable combination of dysmorphic features, hyperpigmented skin lesions and microcephaly that enable a 'CBL syndrome' to be tentatively delineated. Learning difficulties and postnatal growth retardation may be part of the phenotype. CONCLUSION: A report of germline mutations of CBL in three patients with JMML is presented here, confirming the existence of an unreported inheritable condition associated with a predisposition to JMML. PMID- 20543204 TI - Leisure as a context for active living, recovery, health and life quality for persons with mental illness in a global context. AB - Globally, the mental health system is being transformed into a strengths-based, recovery-oriented system of care, to which the concept of active living is central. Based on an integrative review of the literature, this paper presents a heuristic conceptual framework of the potential contribution that enjoyable and meaningful leisure experiences can have in active living, recovery, health and life quality among persons with mental illness. This framework is holistic and reflects the humanistic approach to mental illness endorsed by the United Nations and the World Health Organization. It also includes ecological factors such as health care systems and environmental factors as well as cultural influences that can facilitate and/or hamper recovery, active living and health/life quality. Unique to this framework is our conceptualization of active living from a broad based and meaning-oriented perspective rather than the traditional, narrower conceptualization which focuses on physical activity and exercise. Conceptualizing active living in this manner suggests a unique and culturally sensitive potential for leisure experiences to contribute to recovery, health and life quality. In particular, this paper highlights the potential of leisure engagements as a positive, strengths-based and potentially cost-effective means for helping people better deal with the challenges of living with mental illness. PMID- 20543205 TI - The influence of parent-child relationship on safety belt use among school children in Beirut. AB - Parent-child relationships have been linked to the health and social well-being of adolescents. This relationship may be especially influential in areas of the world where family bonds remain the strongest for children. The association of parent-child relations and safety belt use has not been extensively documented. The objective of this research was to investigate the influence of parent-child relationship on adolescent safety belt use, controlling for other variables. To our knowledge, this is the first study to examine determinants of safety belt use among school students in Lebanon. A two-stage sampling design resulted in the inclusion of 3/3 public and 10/23 private schools. Over 2400 students in grades 6 12 completed a cross-sectional self administered survey. Current safety belt use included student report to wearing seat belts in the front seat only or the front and back seat. Parent-child relationship was measured through student reports of 'getting along with parents'. Other variables included socio-demographic status, health, lifestyle and social characteristics. Logistic regression was performed for variables significant at the bivariate level resulting in three models. Getting along with parents was a significant predictor of safety belt use in the bivariate and all multiple regression models. In the most comprehensive multiple regression model, having a good relationship with parents doubled the likelihood of using a safety belt (95% CI: 1.1-3.1). The study provides enhanced evidence of the importance of the parent-adolescent relationship. Interventions with parents are recommended to enhance their awareness of their influence on their children. PMID- 20543207 TI - Validation of the measure of processes of care for adults: a measure of client centred care. AB - OBJECTIVE: To assess the psychometric properties of the measure of processes of care for adults (MPOC-A), a measure of client-centredness of care for parents of children with disabilities, adapted for adult health-care settings. DESIGN: A validation study. SETTING: Regional orthopaedic service of a university affiliated hospital in ON, Canada. PARTICIPANTS: All patients and families who had had joint replacement surgery (Knee or Hip) between January and August of 2007. MAIN OUTCOME MEASURES: MPOC-A and the client satisfaction questionnaire (CSQ). RESULTS: One hundred and seventy-six questionnaires filled out by patients and 81 by family members were analysed. Scales demonstrated high internal consistency (Cronbach's alpha varying from 0.81 to 0.93 for patients and from 0.88 to 0.96 for family members). MPOC-A domain scores were moderately correlated with CSQ total scores (Pearson coefficients varying from 0.44 to 0.66 for patients and from 0.53 to 0.72 for family members). Moderate to good inter-rater agreement [intraclass correlation coefficient (ICC) from 0.50 to 0.74] and high test-retest reliability were found (ICCs varying from 0.73 to 0.83 for patients and from 0.75 to 0.91 for family members). CONCLUSIONS: MPOC-A has demonstrated good psychometric properties. As general satisfaction scores are notoriously poor indicators of the quality of care, this measure can help us understand the elements that contribute to overall judgements of satisfaction and provide a level of understanding that is important to improve service quality and delivery. PMID- 20543206 TI - Shear stress and the endothelial transport barrier. AB - The shear stress of flowing blood on the surfaces of endothelial cells that provide the barrier to transport of solutes and water between blood and the underlying tissue modulates the permeability to solutes and the hydraulic conductivity. This review begins with a discussion of transport pathways across the endothelium and then considers the experimental evidence from both in vivo and in vitro studies that shows an influence of shear stress on endothelial transport properties after both acute (minutes to hours) and chronic (hours to days) changes in shear stress. Next, the effects of shear stress on individual transport pathways (tight junctions, adherens junctions, vesicles and leaky junctions) are described, and this information is integrated with the transport experiments to suggest mechanisms controlling both acute and chronic responses of transport properties to shear stress. The review ends with a summary of future research challenges. PMID- 20543208 TI - Patient satisfaction and loyalty to the private hospitals in Sana'a, Yemen. AB - OBJECTIVE: To evaluate patients' satisfaction and loyalty to private hospitals and to identify factors influencing patient loyalty. DESIGN: A cross-sectional, population-based study was conducted between May and September of 2005. SETTING: Sana'a, the capital city of the Republic of Yemen. PARTICIPANTS: Eight hundred and nineteen respondents who were admitted for at least 1 day in a private hospital within last 6 months from the date of interview. MAIN OUTCOME MEASURES: The scores on the modified SERVQUAL market research instrument including six domains (tangibility, reliability, responsiveness, assurance, empathy and cost) that identify perceptions of service quality. In addition, the respondents were asked whether or not they would return to the same facility when they need future medical care (loyalty). RESULTS: Loyalty was higher among females [odds ratio (OR) = 1.44; P < 0.05], among those reporting higher reliability scores (OR = 1.24; P < 0.01), higher assurance scores (OR = 1.2; P < 0.01) and higher empathy scores (OR = 1.13; P < 0.05) and also among those reporting higher cost (OR = 1.15; P<0.05). No significant association was found between patient loyalty and, tangibility and responsiveness score. CONCLUSIONS: Improvements are required to achieve high-quality healthcare services in the private hospitals in Yemen and increase loyalty among patients. Findings from this study could inform private sector healthcare development in low- and middle-income countries. PMID- 20543209 TI - The role of quality improvement in strengthening health systems in developing countries. AB - Quality of care was recognized as a key element for improved health outcomes and efficiency in the World Health Organization's (WHO) widely adopted framework for health system strengthening in resource-poor countries. Although modern approaches to improving quality are increasingly used globally, their adoption remains sporadic in developing countries. Healthcare leaders and improvement experts representing 15 countries met in October 2008 to catalyze the adoption of quality improvement (QI) methods to improve healthcare quality in resource-poor settings. This paper describes the evidence used to frame deliberations, the proceedings and a proposal for incorporating QI methods into plans for strengthening health systems. The conference participants presented case reports and reviewed a growing body of evidence from peer-reviewed journals demonstrating that QI methods can make significant contributions in resource poor settings. Deliberations focused on the barriers to adoption of QI methods and potential strategies for addressing those barriers. Attendees concluded that QI has the potential to optimize the use of limited resources available from governments and global initiatives targeted at achieving shared aims. Demonstrable improvements in quality may encourage greater investment in health systems in developing countries by increasing donor, population and governmental confidence that resources are being used well. PMID- 20543210 TI - Clinical importance of an elevated circulating chemerin level in incident dialysis patients. AB - BACKGROUND: Circulating chemerin, a novel adipokine linked to obesity, glucose tolerance and hyperlipidaemia, was recently reported to be increased in chronic kidney disease (CKD) patients. We explored possible links between chemerin and various clinical, nutritional and biochemical markers as well as its association with 5-year all-cause mortality. METHODS: Fasting plasma samples were obtained from 252 CKD Stage 5 patients [median age 56 years, male 61%, glomerular filtration rate (GFR) 7 mL/min] enrolled at the initiation of dialysis. Serum chemerin was measured using commercial ELISA. Chemerin levels were related to clinical status and biomarkers of inflammation, glucose and lipid metabolism and body composition (body mass index and total and truncal fat mass by dual-energy X ray absorptiometry). Survival, censored for transplantation, was recorded for a follow-up time of 5 years. RESULTS: In univariate regression, circulating chemerin (119 +/- 26 ng/mL) was positively correlated with cholesterol (rho = 0.21; P = 0.001), triglycerides (rho = 0.22; P = 0.0007), apolipoprotein B (rho = 0.33; P < 0.0001), high-sensitivity C-reactive protein (rho = 0.18; P = 0.006), white blood cell count (rho = 0.23; P < 0.001), insulin (rho = 0.18; P < 0.05) and homeostatic model assessment (HOMA) index (rho = 0.17; P < 0.05), whereas we found a negative correlation with GFR (rho = -0.28; P = 0.007), high-density lipoprotein cholesterol (rho = -0.15; P < 0.05) and homocysteine (rho = -0.25; P = 0.001). Moreover, a high chemerin predicted a better survival (log-rank chi(2) = 3.85; P < 0.05). Also, in a Cox model, adjustments for age, sex and CRP did not alter this finding (hazard ratio = 1.98 [95% confidence interval = 1.13-3.50], P = 0.01). However, adjusting for GFR made the model non-significant. CONCLUSIONS: We report that, in incident dialysis patients, an elevated chemerin is associated with a survival advantage despite its significant positive association with markers of inflammation and dyslipidaemia. PMID- 20543211 TI - Effect of increasing dialysate flow rate on diffusive mass transfer of urea, phosphate and beta2-microglobulin during clinical haemodialysis. AB - BACKGROUND: Diffusive clearance depends on blood and dialysate flow rates and the overall mass transfer area coefficient (K(o)A) of the dialyzer. Although K(o)A should be constant for a given dialyzer, urea K(o)A has been reported to vary with dialysate flow rate possibly because of improvements in flow distribution. This study examined the dependence of K(o)A for urea, phosphate and beta(2) microglobulin on dialysate flow rate in dialyzers containing undulating fibers to promote flow distribution and two different fiber packing densities. METHODS: Twelve stable haemodialysis patients underwent dialysis with four different dialyzers, each used with a blood flow rate of 400 mL/min and dialysate flow rates of 350, 500 and 800 mL/min. Clearances of urea, phosphate and beta(2) microglobulin were measured and K(o)A values calculated. RESULTS: Clearances of urea and phosphate, but not beta(2)-microglobulin, increased significantly with increasing dialysate flow rate. However, increasing dialysate flow rate had no significant effect on K(o)A or K(o) for any of the three solutes examined, although K(o) for urea and phosphate increased significantly as the average flow velocity in the dialysate compartment increased. CONCLUSIONS: For dialyzers with features that promote good dialysate flow distribution, increasing dialysate flow rate beyond 600 mL/min at a blood flow rate of 400 mL/min is likely to have only a modest impact on dialyzer performance, limited to the theoretical increase predicted for a constant K(o)A. PMID- 20543212 TI - Nephrogenic syndrome of inappropriate antidiuresis. AB - The nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare, recently recognized disorder in water balance affecting not only infants but also adults. A new molecular mechanism responsible for NSIAD has recently been identified: a gain of function of the arginine vasopressin (AVP) receptor type 2 (V2R), causing the constitutive activation of the receptor. Clinical presentation and laboratory findings of NSIAD resemble those of the syndrome of inappropriate secretion of antidiuretic hormone and consist of hyponatraemia, seizures and the lack of urinary dilution; however, the AVP levels in plasma are undetectable or very low. An elucidation of the pathophysiology of this syndrome will provide more insight into the action of AVP. An effective treatment of NSIAD is available. It consists of fluid restriction and administration of oral urea. Reported experience with furosemide treatment in NSIAD is still lacking. PMID- 20543213 TI - Growth hormone therapy-related hyperglycaemia in a boy with renal cystic hypodysplasia and a new mutation of the HNF1 beta gene. AB - We provide a molecular and pathophysiological characterization of an 11-year-old male patient, with a diagnosis of renal hypodysplasia, cysts and chronic renal failure. Although previously normoglycaemic and with a negative familial history for diabetes mellitus, he developed fasting hyperglycaemia within 12 months of the start of treatment with recombinant human growth hormone (rhGH). Direct sequencing of the HNF1 beta gene revealed a de novo heterozygous mutation in exon 2, c.535delC [Pro118LeuX7]+[=]. The appearance of fasting hyperglycaemia following rhGH treatment in children with renal cystic hypodysplasia suggests that investigation of the HNF1 beta gene is warranted, even when familial history is negative for diabetes. This is particularly important in regard to genetic counselling. PMID- 20543214 TI - Change in glenohumeral rotation and scapular position after competitive high school baseball. AB - CONTEXT: Pathologies such as anterior instability and impingement are common in baseball and have been linked to decreases in internal rotation (IR) and concurrent increases in external rotation (ER). In addition, alterations to scapular position have been identified in this population, but the chronology of these adaptations is uncertain. OBJECTIVES: To determine whether there is a change in range of motion and scapular position after a single baseball season. DESIGN: Prospective cohort. SETTING: High school. PARTICIPANTS: 19 high school baseball players (age 16.6 +/- 0.8 y, mass 78.6 +/- 12.0 kg, height 180.3 +/- 6.2 cm). INTERVENTIONS: Subjects were measured for all dependent variables at preseason and postseason. MAIN OUTCOME MEASURES: Participants were measured for glenohumeral (GH) IR and ER with the scapula stabilized. Total GH range of motion was calculated as the sum of IR and ER. Scapular upward rotation was measured at 0 degrees, 60 degrees, 90 degrees, and 120 degrees of GH abduction in the scapular plane, and scapular protraction, at 0 degrees, hands on hips, and 90 degrees of GH abduction. RESULTS: Overall, the dominant arm had significantly less GH IR (11.4 degrees, P = .005) and significantly more ER (4.7 degrees, P = .001) than the nondominant arm. Total motion in the dominant arm was significantly less than in the nondominant arm (6.7 degrees, P = .001). Scapular upward rotation in the dominant arm significantly increased at 0 degrees (2.4 degrees, P = .002) and significantly decreased at 90 degrees (3.2 degrees, P = .001) and 120 degrees (3.2 degrees, P < .001) of abduction from preseason to postseason. Scapular protraction in the nondominant arm significantly decreased at 45 degrees (0.32 cm, P = .017) and 90 degrees (0.33 cm, P = .006) from preseason to postseason. CONCLUSION: These data suggest that scapular adaptations may be acquired over a relatively short period (12 wk) in a competitive baseball season. Competitive high school baseball players also presented with significant GH motion differences between their dominant and nondominant arms. Total motion was also significantly less in the dominant arm than in the nondominant arm. PMID- 20543215 TI - Influence of external ankle support on lower extremity joint mechanics during drop landings. AB - OBJECTIVE: To investigate the effects of external ankle support (EAS) on lower extremity joint mechanics and vertical ground-reaction forces (VGRF) during drop landings. DESIGN: A 1 x 3 repeated-measures, crossover design. SETTING: Biomechanics research laboratory. PATIENTS: 13 male recreationally active basketball players (age 22.3 +/- 2.2 y, height 177.5 +/- 7.5 cm, mass 72.2 +/- 11.4 kg) free from lower extremity pathology for the 12 mo before the study. INTERVENTIONS: Subjects performed a 1-legged drop landing from a standardized height under 3 different ankle-support conditions. MAIN OUTCOME MEASURES: Hip, knee, and ankle angular displacement along with specific temporal (TGRFz1, TGRFz2; s) and spatial (GRFz1, GRFz2; body-weight units [BW]) characteristics of the VGRF vector were measured during a drop landing. RESULTS: The tape condition (1.08 +/- 0.09 BW) demonstrated less GRFz1 than the control (1.28 +/- 0.16 BW) and semirigid conditions (1.28 +/- 0.21 BW; P < .0001), and GRFz2 was unaffected. For TGRFz1, no-support displayed slower time (0.017 +/- 0.004 s) than the semirigid (0.014 +/- 0.001 s) and tape conditions (0.014 +/- 0.002 s; P < .05). For TGRFz2, no-support displayed slower time (0.054 +/- 0.006 s) than the semirigid (0.050 +/- 0.006 s) and tape conditions (0.045 +/- 0.004 s; P < .05). Semirigid bracing was slower than the tape condition, as well (P < .05). Ankle joint displacement was less in the tape (34.6 degrees +/- 7.7 degrees) and semirigid (36.8 degrees +/- 9.3 degrees) conditions than in no-support (45.7 degrees +/- 7.3 degrees; P < .05). Knee-joint displacement was larger in the no support (45.1 degrees +/- 9.0 degrees) than in the semirigid (42.6 degrees +/- 6.8 degrees; P < .05) condition. Tape support (43.8 degrees +/- 8.7 degrees) did not differ from the semirigid condition (P > .05). Hip angular displacement was not affected by EAS (F(2,24) = 1.47, P = .25). CONCLUSIONS: EAS reduces ankle- and knee-joint displacement, which appear to influence the spatial and temporal characteristics of GRFz1 during drop landings. PMID- 20543216 TI - Reliability of measuring humeral retroversion using ultrasound imaging in a healthy nonthrowing population. AB - CONTEXT: Studies have reported the difference in humeral retroversion (HR) between the dominant and nondominant side in throwing athletes. However, there are few data concerning HR for the rest of the population. In addition, the relationship between HR and external (ER) and internal rotation (IR) at 90 degrees shoulder abduction has not been thoroughly investigated. OBJECTIVES: To investigate the reliability of ultrasound methodology to measure HR. In addition, using ultrasonography, the authors compare HR between the dominant and nondominant sides in healthy adult men and determine the relationship between HR and ER and IR at 90 degrees of shoulder abduction. DESIGN: Descriptive study. SETTING: Laboratory. PARTICIPANTS: Thirty-seven healthy male subjects (age 21.9 +/- 2.4 y, height 172.9 +/- 5.3 cm, weight 66.0 +/- 7.2 kg) with no history of shoulder or elbow injury, recruited from a convenience sample, volunteered for the study. MAIN OUTCOME MEASURES: Subjects were bilaterally examined for HR, ER, and IR. HR was measured by ultrasonography. RESULTS: The intrarater reliability of the ultrasound methodology was .91-.98, and the interrater reliability was .97. The HR angle on the dominant side (mean +/- SD: 68.5 degrees +/- 10.0 degrees) was significantly greater than that of the nondominant side (58.0 degrees +/- 8.4 degrees; P < .001). ER on the dominant side was significantly greater than on the nondominant side (P < .001), whereas IR on the dominant side was significantly smaller than on the nondominant side (P < .001). Total arc of motion for the dominant side was not significantly different from that of the nondominant side (P = .335). CONCLUSION: In the current study, ultrasound methodology to measure HR showed high interrater reliability, as well as high intrarater reliability. In addition, this study indicates that healthy Japanese adult men have side-to-side differences in HR. PMID- 20543217 TI - Ultrasonographic evaluation of the shoulder in elite wheelchair tennis players. AB - CONTEXT: Wheelchair tennis has been identified as a high-risk sport for shoulder injury, so understanding shoulder pathology in these athletes is important. OBJECTIVE: This study investigated the incidence and pattern of shoulder injuries in wheelchair tennis players using high-resolution ultrasonography. DESIGN: Descriptive study. SETTING: International Wheelchair Tennis Open. PARTICIPANTS: 33 elite-level wheelchair tennis players. OUTCOME MEASURES: Wheelchair tennis players completed a self-administered questionnaire, and shoulders of each athlete were investigated using high-resolution ultrasonography (linear probe 7.5 MHz). RESULTS: The most common pathology in the dominant shoulder was acromioclavicular pathology, in 21 players (63.6%). Full-thickness rotator-cuff tears involving the supraspinatus were found in 8 dominant shoulders and 6 nondominant shoulders. There were no correlations between identified shoulder pathology and the different variables studied, such as age, training time per day, length of wheelchair use, and length of career as a wheelchair tennis player. CONCLUSION: High prevalence of rotator-cuff and acromioclavicular pathology was found by ultrasonographic examination in the elite wheelchair tennis players in both dominant and nondominant shoulders. A high index of suspicion of these pathologies in wheelchair athletes is required. PMID- 20543218 TI - Effects of exercise training on heart-rate-variability indices in individuals with Down Syndrome. AB - OBJECTIVE: To investigate the effects of an exercise-training program on heart rate-variability (HRV) indices in individuals with Down syndrome (DS). DESIGN: Controlled clinical trial. PARTICIPANTS: 10 people with DS, age 24.2 +/- 5.1 y (group A), and 10 age-matched healthy sedentary individuals (group B). METHOD: At baseline all subjects underwent a clinical examination and an ambulatory 24-h Holter monitoring for the evaluation of cardiac autonomic-nervous-system (ANS) activity by time- and frequency-domain analysis. INTERVENTION: After initial evaluation, group A followed a 6-mo exercise-training program and thereafter underwent the same HRV analysis. RESULTS: At the beginning of the study, group A showed a higher LF:HF ratio than group B, indicating impaired sympathovagal balance, likely because of lesser vagal modulation. Moreover, both time- and frequency-domain indices in group A were significantly lower than in group B. At the end of the study, exercise training was found to improve the sympathovagal balance, mainly by increasing vagal activity, in group A. CONCLUSION: The results indicate that individuals with DS have ANS dysfunction that can be improved by exercise's increasing the parasympathetic modulation. PMID- 20543219 TI - The effects of jump-rope training on shoulder isokinetic strength in adolescent volleyball players. AB - OBJECTIVE: To investigate the effect of a 12-wk weighted-jump-rope training program on shoulder strength. DESIGN: Pretest to posttest experimental design. SETTING: University sports physiotherapy laboratory. PARTICIPANTS: 24 healthy volleyball players age 13-16 y. INTERVENTION: Group 1 took weighted-rope training (n = 9), group 2 took unweighted-rope training (n = 8), and group 3 did not train with any specific program (n = 7). MAIN OUTCOME MEASURES: Players' strength determined with an isokinetic dynamometer (Isomed 2000) at 180 and 60 degrees on external and internal rotators, supraspinatus peak torque, and total work of the dominant shoulder. Kruskal-Wallis and Mann-Whitney U tests were used to determine the difference among the groups. RESULTS: At pretraining evaluation, there were no significant differences in the test scores of the isokinetic test of full can and empty can between the groups at 60 and 180 degrees. There was no statistically significant difference for 60 and 180 degrees between pretraining and posttraining assessment (P > .05) except that total eccentric work increased in groups 1 and 3 but decreased in group 2 at 180 degrees during the full can (P < .05). There was no significant difference among the groups between the pretraining and posttraining testing at both 180 and 60 degrees for the empty can (P > .05). Internal-rotation values at 60 and 180 degrees decreased for both peak torque and total work for all groups. External-rotation peak torque and total work at 60 degrees increased for group 1. External-rotation peak torque and total work at 180 degrees increased for all groups. CONCLUSIONS: The results indicate that a jump-rope training program is a good conditioning method for overhead athletes because of its potential benefits to shoulder strength. PMID- 20543220 TI - A randomized, controlled study of a rehabilitation model to improve knee-function self-efficacy with ACL injury. AB - CONTEXT: The Knee Self-Efficacy Scale (K-SES) has good reliability, validity, and responsiveness for patients' perceived knee-function self-efficacy during rehabilitation after an anterior cruciate ligament (ACL) injury. Preoperative knee-function self-efficacy has also been shown to have a predictive ability in terms of outcome 1 y after ACL reconstruction. OBJECTIVE: To evaluate a new clinical rehabilitation model containing strategies to enhance knee-function self efficacy. DESIGN: A randomized, controlled study. SETTING: Rehabilitation clinic and laboratory. PATIENTS: 40 patients with ACL injuries. INTERVENTION: All patients followed a standardized rehabilitation protocol. Patients in the experimental group were treated by 1 of 3 physiotherapists who had received specific training in a clinical rehabilitation model. These physiotherapists were also given their patients' self-efficacy scores after the initial and 4-, 6-, and 12-mo follow-ups, whereas the 5 physiotherapists treating the patients in the control group were not given their patients' self-efficacy scores. MAIN OUTCOME MEASURES: The K-SES, the Tegner Activity Scale, the Physical Activity Scale, the Knee Injury and Osteoarthritis Outcome Score, and the Multidimensional Health Locus of Control. RESULTS: Twenty-four patients (12 in each group) completed all follow-ups. Current knee-function self-efficacy, knee symptoms in sports, and knee quality of life improved significantly (P = .05) in both groups during rehabilitation. Both groups had a significantly (P = .05) lower physical activity level at 12 mo than preinjury. No significant differences were found between groups. CONCLUSION: In this study there was no evidence that the clinical rehabilitation model with strategies to enhance self-efficacy resulted in a better outcome than the rehabilitation protocol used for the control group. PMID- 20543221 TI - The relationship between wearing incorrectly sized shoes and foot dimensions, foot pain, and diabetes. AB - CONTEXT: Wearing inappropriate shoes can cause biomechanical imbalance, foot problems, and pain and induce falls. OBJECTIVE: To verify the prevalence of wearing incorrectly sized shoes and the relationship between incorrectly sized shoes and foot dimensions, pain, and diabetes among older adults. DESIGN: A cross sectional study. PARTICIPANTS: 399 older adults (227 women and 172 men) age 60 to 90 y. MAIN OUTCOME MEASURES: The participants were asked about the presence of diabetes, pain in the lower limbs and back, and pain when wearing shoes. Foot evaluations comprised the variables of width, perimeter, height, length, first metatarsophalangeal angle, the Arch Index, and the Foot Posture Index. The data analysis was performed using a 2-sample t test and chi-square test. RESULTS: The percentage of the participants wearing shoe sizes bigger than their foot length was 48.5% for the women and 69.2% for the men. Only 1 man was wearing a shoe size smaller than his foot length. The older adults wearing the incorrect shoe size presented larger values for foot width, perimeter, and height than those wearing the correct size, but there were no significant differences between the groups with respect to the Arch Index and the Foot Posture Index. Incorrectly sized shoes were associated with ankle pain in women but not with diabetes. Men were more likely to wear incorrectly fitting shoes. The use of correctly sized shoes was associated with back pain in women. CONCLUSIONS: The use of incorrectly sized shoes was highly prevalent in the population studied and was associated with larger values for foot width, perimeter, and height and with ankle pain. PMID- 20543222 TI - The effectiveness of mobilization with movement at improving dorsiflexion after ankle sprain. AB - Ankle sprains are the most frequently occurring orthopedic injury among the physically active. The number 1 risk factor for suffering an ankle sprain is a history of a previous sprain. Those with a history of ankle sprain often report recurrent bouts of ankle instability and decreased functional capacity. Several mechanical and functional deficits have been identified that may contribute to residual symptoms, sequelae, and functional loss. One is decreased dorsiflexion range of motion. This deficit could predispose the patient to alterations in the ankle axis of rotation, changes in alignment and tracking of bony surfaces, and disrupted proprioceptive input to the sensorimotor system resulting in future ankle sprains or ankle osteoarthritis. Therefore, improving accessory and physiological motion at the talocrural joint is a clinical consideration. Joint mobilizations could be an effective intervention for addressing these alterations during rehabilitation. A joint-mobilization technique known as mobilization with movement (MWM) is of particular interest because this method is the concurrent application of an accessory mobilization with active or passive physiological movement. PMID- 20543223 TI - [Endoscopic skull base surgery]. PMID- 20543224 TI - [Stem cell therapy for cerebral ischemia]. PMID- 20543225 TI - [Angiographic analysis of variations and anomalous origin of the anterior choroidal artery and posterior communicating artery]. AB - OBJECT: The anterior choroidal artery (AchoA) is a very important artery for neurosurgeons and neuroendovascular surgeons. In fact the AchoA not only supplies the ventricles but also has important branches to the diencephalon, mesencephalon and cerebrum and also supplies motor and visual pathways. Review of the cerebrovascular embryology explains this variability in the anatomy of the developing AchoA and posterior communicating artery (PcomA)- posterior cerebral artery (PCA) distributions. CASE 1: A 47-year-old woman, with an unruptured left internal carotid artery (ICA) aneurysm. For the cerebral arterial aneurysm approximately 7 mm in size, we performed coil embolization with an assist balloon under general anaesthesia. CASE 2: A 63-year-old woman, with an unruptured right ICA aneurysm. Endeavouring to preserve the branch vessels, we undertook a craniotomy neck clipping operation. DISCUSSION AND CONCLUSION: It is thought that, usually, AchoA has its origin at the supraclinoid ICA distal to the PcomA. Our analysis of these two cases may be helpful for a better understanding of the vascular relations and anatomy of the AchoA and PcomA-PCA distributions. We emphasize the importance of recognizing such anomalies in planning surgical and interventional treatment. PMID- 20543226 TI - [Effects of abnormal muscle response monitoring on manipulation of microvascular decompression]. AB - OBJECTIVE: Intraoperative abnormal muscle response (AMR) monitoring is used as an indicator of postoperative outcome in patients with hemifacial spasm (HFS). We investigated whether AMR findings influence manipulation of microvascular decompression and improve the postoperative results. MATERIALS AND METHODS: Subjects were 102 HFS patients who underwent AMR monitoring during surgery. The value of AMR monitoring was classified into four categories: a guiding, a confirming, an indirect confirming, or an inconclusive role. The relationship between AMR monitoring results and surgical outcome was analyzed. RESULTS: The overall cure rate was 92.2%. A guiding role of AMR monitoring was apparent in 13.7% of patients, and a confirming role was demonstrated in 53.9% of patients. The cure rate was 92.9% in patients defined as guiding, and 96.4% in patients defined as confirming cases. When the AMR remained disappearance until completion of decompression in patients assigned in indirect confirming, 13 of 15 patients (86.7%) experienced resolution postoperatively. In patients defined as inconclusive cases, 14 of 16 patients (87.5%) in whom AMR still presented but its amplitude decreased at the end of surgery experienced complete resolution. CONCLUSIONS: This study demonstrates that meticulous evaluation of AMR findings intraoperatively can help to improve the results of surgery. We believe that intraoperative AMR monitoring is useful in microvascular decompression for HFS. PMID- 20543227 TI - [Clinical application of the Colorado-microdissection needle in neurosurgery]. AB - The steel scalpel and scalp clips have been commonly used for scalp incision in many neurosurgical procedures. Electrocautery is used mainly for subcutaneous and deep-layer dissection. The use of electrocautery on scalp incision has been avoided because of possible adverse events such as wound dehiscence and infection. We report our experience in Colorado-microdissection needle electrocautery for scalp incisions performed in our institution between November, 2006 and March, 2009. The rate of wound infection was compared in patients using the microdissection needle (100 procedures, n=93) and those using the steel scalpel/clips (n=261) during the same period. In patients using the microdissection needle, wound healing delay was not observed. Wound infection developed in only one procedure (1.0%) with the microdissection needle, and it developed in 6 procedures (2.2%) with the steel scalpel/clips, although this did not reach statistical significance (p=0.34). The use of electrocautery tended to cause little tissue distortion during fine dissection and it reduced blood loss. In conclusion, Colorado-microdissection needle electrocautery for scalp incisions could be safe and quite useful in neurosurgical procedures. PMID- 20543228 TI - [Unruptured aneurysm arising from fenestration of the horizontal (A1) segment in the anterior cerebral artery: a case report and review of the literature]. AB - Cerebral aneurysms arising from fenestration of the horizontal (A(1)) segment in the anterior cerebral artery (ACA) are very rare. In this paper, we report our case, discuss radiological features, and review previous cases. A 70-year-old male was referred to our hospital presenting with memory disturbance. His unruptured cerebral aneurysm in the A(1) segment was incidentally found by magnetic resonance angiography (MRA). Three dimensional computed tomographic angiography (3D-CTA) demonstrated this aneurysm arising from fenestration of the A(1) segment. Surgical neck clipping was performed via the pterional approach, while sacrificing one pair of the A(1) segment. The patient's post operative course was uneventful. Only 14 cases with an aneurysm arising from fenestration of the A(1) segment have been reported previously. In the present case, 3D-CTA was very useful for finding out where the aneurysm arose from, and we also had to be careful about perforating arteries from the A(1) segment during the surgery. PMID- 20543229 TI - [A case of cerebral amyloid angiopathy in which a restricted subarachnoid hemorrhage recurred in the cortical sulcus following a subcortical hemorrhage]. AB - Cerebral amyloid angiopathy (CAA) is predominantly recognized in elderly people and repeatedly causes a huge subcortical hemorrhage. Some cases of CAA can cause secondary subarachnoid hemorrhage (SAH), but cases in which it causes primary SAH is very rare. We describe a valuable reference case of a 75-year-old man in whom a restricted SAH recurred in the cortical sulcus following a huge subcortical hemorrhage. He presented with an unknown restricted SAH in the left frontal sulcus twice before neck clipping for a right IC-PC unruptured aneurysm. Postoperative computed tomography (CT) revealed a recurrent SAH in the left frontal lobe, and it spread gradually. T2(*) weighted imaging (T2(*)WI) revealed subarachnoid hemosiderosis and superficial cortical hemosiderosis in the frontal and parietal lobe. On the 21st postoperative day, he suddenly presented right hemiplegia and a huge subcortical hemorrhage was observed in the left frontal lobe on CT. Emergent removal of the hematoma was performed, but the patient had become bedridden. Pathological diagnosis of CAA was made. A recurrent restricted SAH in the frontal sulcus might have been a warning sign of a huge subcortical hemorrhage. In the aging society, a radiological prediction of CAA is very important. Although it is generally thought to be very difficult, T2(*)WI may be useful for predicting CAA. When we plan surgery for elderly people, we must always take CAA into consideration. PMID- 20543230 TI - [Reversible stenosis of posterior cerebral artery after surgical revascularization for quasi-moyamoya disease: a case report]. AB - The authors report a 32-year-old male who presented transient stenosis of the bilateral posterior cerebral artery (PCA) one week after right STA-MCA anastomosis and indirect bypass for quasi-moyamoya disease associated with Down syndrome. The bilateral PCA were intact on both cerebral angiography and MRA before surgery. One week after surgery, the patient suddenly developed left homonymous hemianopsia. Diffusion-weighted MRI revealed newly developed cerebral infarction in the bilateral MCA-PCA watershed zone. Simultaneous MRA revealed marked stenosis of the bilateral PCA. Follow-up MRA taken 5 months later showed that the stenosis of the bilateral PCA completely resolved. Although the precise mechanism of reversible PCA stenosis is still unknown, the phenomenon may play an important role in disease progression in patients with moyamoya or quasi-moyamoya disease. PMID- 20543231 TI - [Postpartum chronic subdural hematoma following spinal anesthesia: case report]. AB - Chronic subdural hematoma is a rare complication of epidural anesthesia. This report describes the case of a 34-year-old woman who presented with postpartum headache after she received epidural anesthesia for labor pain. The anesthesiologist's record did not show any anesthesia-related complication. Two days after the delivery (on day 2), the patient complained of headache. Postdural puncture headache was diagnosed, so she was administered analgesics, hydration therapy, and bed rest. On day 4, she reported a slight improvement and was discharged. The postural headache persisted even on day 7 after delivery. During the conservative treatment, she had suffered a mild head trauma. On day 13, she started to feel a non-postural and severe throbbing headache. On day 24, she was referred to our department. Bilateral chronic subdural hematoma was confirmed by a computed tomography scan. Physical examination revealed only mild right hemiparesis. Left burr hole trepanation was performed and this was followed by uneventful postoperative course. Right chronic subdural hematoma was managed by conservative treatment, and it completely recovered after 4 weeks. Chronic subdural hematoma should be considered when postpartum patients who have received epidural anesthesia present with mild to severe, persistent, and non-postural headache. PMID- 20543232 TI - [A case of progressive multifocal leukoencephalopathy with alcoholic liver dysfunction]. AB - Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection by JC virus and presents with progressive demyelinating lesions in the central nervous system. A 59-year-old man with a history of alcoholic liver dysfunction presented with progressive weakness of his left leg over a period of one month. MRI showed multiple white matter lesions that were of low intensity on the T1 image and high intensity on the T2 image, heterogeneously high intensity on the diffusion image, and were not enhanced with contrast media. The patient underwent open biopsy of the right parietal lesion. The histological findings were the demyelination and the enlargement of nuclei of oligodendrocytes. Electron microscopic examination showed numerous viral particles in the nuclei of the oligodendrocytes. Infection by JC virus in the central nervous system was diagnosed with the polymerase chain reaction (PCR) products sampled from the cerebrospinal fluid. The incidence of PML has significantly increased in immunosuppressive patients, such as AIDS (acquired immunodeficiency syndrome). We presented the first case of PML in an immune-compromised state with alcoholic liver dysfunction. PMID- 20543233 TI - [Understanding clinical neuropsychology: a basic approach (1) introduction:why do we study higher brain function?]. PMID- 20543234 TI - Mechanistic studies of AFM probe-driven Suzuki and Heck molecular coupling. AB - The initiation and high resolution control of surface confined chemical reactions would be both beneficial for nanofabrication and fundamentally interesting. In this work, mechanistic aspects of spatially confined Suzuki and Heck 'catalytic nanolithography' are investigated by varying the experimental parameters and noting their effects on apparent reactivity and lithographic yield. A variety of molecular couplings can be driven by the activated scanning probe with linewidths ultimately limited by its functional apex. On ramping the speed at which the probe traverses the surface confined reagent, one reaches a limit where the catalytic chemistry becomes limiting and reaction rates can be estimated. Self assembled monolayer (SAM) confined bromide reagents are observed to be more labile than their iodide analogues in Suzuki couplings. With Heck reactions, coupling rates are observed to be faster with the styrene surface confined than in the 'inverted configuration' with an aryl halide SAM, possibly because the accepted (solution phase) rate-determining step is bypassed in the former configuration. For both Heck and Suzuki coupling reactions, calculations indicate that catalyst turnover numbers per nanoparticle are an order of magnitude or more greater within the confines of the AFM probe-surface junction compared to solution phase reactions. A PVP matrix model is presented to account for these observations and the mechanism of catalytic nanolithography. PMID- 20543235 TI - Engineering the system of healthcare delivery. Introduction. PMID- 20543236 TI - Seeking care as a system. AB - Kim, aged 3 years, lies asleep, waiting for a miracle. Outside her room, the nurses on the night shift pad softly through the half-lighted corridors, stopping to count breaths, take pulses, or check the intravenous pumps. In the morning, Kim will have her heart fixed. She will be medicated and wheeled into the operating suite. Machines will take on the functions of her body: breathing and circulating blood. The surgeons will place a small patch over a hole within her heart, closing off a shunt between her ventricles that would, if left open, slowly kill her. Kim will be fine if the decision to operate on her was correct; if the surgeon is competent; if that competent surgeon happens to be trained to deal with the particular anatomic wrinkle that is hidden inside Kim's heart; if the blood bank cross-matched her blood accurately and delivered it to the right place; if the blood gas analysis machine works properly and on time; if the suture does not snap; if the plastic tubing of the heart-lung machine does not suddenly spring loose; if the recovery room nurses know that she is allergic to penicillin; if the "oxygen" and "nitrogen" lines in the anesthesia machine have not been reversed by mistake; if the sterilizer temperature gauge is calibrated so that the instruments are in fact sterile; if the pharmacy does not mix up two labels; and if when the surgeon says urgently, "Clamp, right now," there is a clamp on the tray. If all goes well, if ten thousand "ifs" go well, then Kim may sing her grandchildren to sleep some day. If not, she will be dead by noon tomorrow. If Kim were an astronaut, strapped into her seat at the top of some throbbing rocket, the crowd assembled would hold their breath in the morning Florida sun. "How can it possibly work?" they would whisper. "How many parts are there in that machine? A million? What if one fails? My toaster fails. Please let it all work right." The machine would bellow smoke, the gantry fall away, and slowly the monster would rise, Kim on top. If it worked, they would cheer. "A miracle," they would shout, in awe that the millions of tiny lines of effort, the millions of tiny lines of cause and effect, from job shops in Ohio and laboratories in Pasadena, criss-crossing through time and space, could converge so magnificently in a massive, gleaming rocket launched exactly right. Perfect. If it failed, they would cry. So would the rocket's makers, who had done their very best. No one wanted it to end this way. Poor Kim. What was the trouble? What went wrong? Why? The lines of cause will converge around Kim in the morning as she wheels toward the operating room. Thousands upon thousands of elements weaving a basket to hold her safely, all hope. No crowd holds its breath tonight; but wouldn't they if they knew? From: Berwick DM. Controlling variation in health care: a consultation from Walter Shewhart. Medical Care 1991; 29: 1212-1225. PMID- 20543238 TI - Aging: adding complexity, requiring skills. AB - The role of systems in addressing the needs of elderly and chronically ill populations remains a far from universal way of thinking, much less practice, in health care. Re-engineering the current fragmented system to align providers, patients and payment models to facilitate proactive management of conditions associated with advanced age and/or one or more chronic diseases - rather than responding to costly consequences of a health care system optimized for acute care conditions - will be a major challenge for all stakeholders. There are, however, promising success stories that are taking place in the United States today that may provide a model for improvement. The authors define the issues faced by the health care providers and payers that arise when providing care for the elderly and those with chronic conditions - issues that threaten to overwhelm the financial and human health care resources that exist to serve these populations. They define innovative ways of thinking about systems of care, and provide examples of unique systems that have applied theory into practice. These successful leaders may offer lessons in proactively managing complex health conditions, overcoming communication barriers and using technology to complement the necessary human touch that is essential to health care delivery. PMID- 20543237 TI - Patient safety - the role of human factors and systems engineering. AB - Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety. PMID- 20543239 TI - Palliative and end of life care. AB - Health care provided in the final year of life is typically costly and often delivers unintended outcomes. High value can be defined for end of life care. High value clinical practices exist for end of life care and a common set of high value processes can be identified. The current system structure of healthcare delivery does not consistently support those high value processes. An improved organizational schema could foster sustained delivery of high value delivery operations. The healthcare ecosystem needs to evolve to provide appropriate incentives and support for an appropriately designed care system. PMID- 20543240 TI - US health care costs: the crushing burden. AB - This chapter provides an overview of health care costs in the United States, including trends, sources and uses of funds, employers' role, and factors driving costs. It also reviews what analysts believe are cost drivers especially compared to other countries that have significantly lower health care costs and, often, better health outcomes. Within the US, there are also important differences by geography, further demonstrating that higher US costs do not reflect higher quality and greater patient and physician satisfaction. In fact, the opposite is often the case. PMID- 20543241 TI - Engineering information technology for actionable information and better health - balancing social values through desired outcomes, complementary standards and decision-support. AB - Information technology in health care (HIT) is getting a major boost in the United States through the passage of the American Recovery and Reinvestment Act (ARRA) of 2009. The portion of the Act that relates to health information technology (HITECH) seeks to achieve widespread implementation of electronic health records (EHRs) across the land and assure that these EHRs achieve sufficient levels of 'meaningful use' to improve care, reduce costs, and result in better outcomes. This chapter sets the stage for the other chapters that follow in this section. The chapter will review current thinking about how HIT will facilitate collection, dissemination, and evaluation of information throughout the system. Further, it will discuss the role and potential for HIT to support a learning organization [7,8]. Finally, it will outline the current widely identified barriers to progress, e.g., standards development, lack of interoperability and connectivity, and limited decision support that uses evidence-based guidelines created and maintained explicitly to be actionable through computer-based records and systems. Further, with the passage of HITECH, there is a continued attention given to privacy policy at the expense of access to person-specific health information for legitimate social purposes including research and community health. More will be said about this near the end of the chapter. Finally, the chapter will end with a discussion of the difference between information and communication and it will advocate for greater attention to the use of technology as a tool for improve communications and not simply storage and transmission of information. PMID- 20543242 TI - Electronic health records. AB - A radical change in technical approach is needed to achieve electronic health records suitable to support an engineered system of healthcare. This chapter suggests a redefinition of interoperable health information. It provides examples of how to break the electronic health record challenge into component parts to match computational technique to the scale of the problem handled by a component. PMID- 20543243 TI - Evidence-based medicine - engineering the Learning Healthcare System. AB - Whether for the generation or application of evidence to guide healthcare decisions, the success of evidence-based medicine is grounded in principles common to engineering. In the Learning Healthcare System envisioned by the Institute of Medicine's (IOM) Roundtable on Evidence-Based Medicine, evidence emerges as a natural by-product of care delivery, which is thoroughly documented, pooled for continuous monitoring and analysis, integrated with insights from related studies, and fed back seamlessly to improve the consistency and appropriateness of care decisions by clinicians and their patients. Drawing from lessons shared at the IOM/NAE symposium, Engineering a Learning Healthcare System, this paper provides an overview of the state-of-play in health care today, some of its key challenges, the vision and features of a learning healthcare system, applicable commonalties and principles from engineering, and potential collaborative opportunities moving forward to the benefit of both fields. PMID- 20543244 TI - Transforming healthcare through patient empowerment. AB - The United States faces tremendous challenges with its healthcare system. By any standard, it is expensive and performs poorly in most measures of health and thus, is in great need of reform. But how do we reform things without making the situation worse? Some of the more fundamental problems arise from the combination of a fee-for-service payment system for physicians with insurance-based financing care. This combination results in conflicts among the interests of patients, physicians and payers. This paper examines this issue from a decision analytic perspective, starting with a definition of the patient-centered view, and an assessment of the practicality of controlling costs by making healthcare more patient-centric. It then illustrates how fee-for-service models corrupt decision making and other solutions designed to reign in the abuses of the fee-for-service model and also negatively impacts the quality of decision making for individual patients. Whatever the strategies for health reform, the degree of patient centeredness of care is a benchmark that allows policy makers to understand how far they have had to deviate from optimal to achieve the desired ends of cost control. PMID- 20543245 TI - Health economics. AB - Health care spending and more importantly, health care spending growth rates, are unsustainable. Past strategies of price controls, reliance on administered pricing for Medicare and the dominance of a la carte fee for service reimbursement have been part of the problem and do not represent promising strategies for the future. Too much time has been spent debating whether Medicare has done better or worse than the private sector since neither represents an acceptable path going forward. Understanding the effects of innovative payment strategies - including those that affect the patient - will be an important part in learning how to "bend the curve". Making sure that there are strategies to implement the results of successful pilots and demonstrations will also be important. PMID- 20543246 TI - Pay for value. PMID- 20543247 TI - Reform incentives to create a demand for health system reengineering. AB - America needs a far more efficient health care financing and delivery system than the one we have. Our present system is a serious threat to public finances and is pricing itself out of reach. At the root of the problem are incentives and organization. The present fragmented fee-for-service small practice model is filled with cost-increasing incentives. There are some relatively efficient organized delivery systems, mostly based on large multi-specialty group practices. Unfortunately, most consumers are not offered the opportunity to save money and get better care by choosing such a system. This situation presents great opportunities for improvement in performance by re-engineering the system. However, for this to happen, incentives must be fundamentally changed so that everyone is cost conscious and care is organized in accountable care systems seeking improvement. PMID- 20543248 TI - Systems engineering and management. AB - This chapter offers a systems view of healthcare delivery and outlines a wide range of concepts, principles, models, methods and tools from systems engineering and management that can enable the transformation of the dysfunctional "as is" healthcare system to an agreed-upon "to be" system that will provide quality, affordable care for everyone. Topics discussed include systems definition, design, analysis, and control, as well as the data and information needed to support these functions. Barriers to implementation are also considered. PMID- 20543249 TI - Operations research - a valuable resource for improving quality, costs, access and satisfaction in health care delivery. PMID- 20543250 TI - Engineering healthcare as a service system. AB - Engineering has and will continue to have a critical impact on healthcare; the application of technology-based techniques to biological problems can be defined to be technobiology applications. This paper is primarily focused on applying the technobiology approach of systems engineering to the development of a healthcare service system that is both integrated and adaptive. In general, healthcare services are carried out with knowledge-intensive agents or components which work together as providers and consumers to create or co-produce value. Indeed, the engineering design of a healthcare system must recognize the fact that it is actually a complex integration of human-centered activities that is increasingly dependent on information technology and knowledge. Like any service system, healthcare can be considered to be a combination or recombination of three essential components - people (characterized by behaviors, values, knowledge, etc.), processes (characterized by collaboration, customization, etc.) and products (characterized by software, hardware, infrastructures, etc.). Thus, a healthcare system is an integrated and adaptive set of people, processes and products. It is, in essence, a system of systems which objectives are to enhance its efficiency (leading to greater interdependency) and effectiveness (leading to improved health). Integration occurs over the physical, temporal, organizational and functional dimensions, while adaptation occurs over the monitoring, feedback, cybernetic and learning dimensions. In sum, such service systems as healthcare are indeed complex, especially due to the uncertainties associated with the human centered aspects of these systems. Moreover, the system complexities can only be dealt with methods that enhance system integration and adaptation. PMID- 20543251 TI - Process engineering: a necessary step to a better public health system. AB - With its primary focus on community health, the public health system focuses on intervention and prevention of disease and injury to protect entire populations. As a federation of city, county and state entities operating independently under a complicated array of local, state and federal laws, public health can best be understood as a complex adaptive system. The dynamic nature of this system and the need for public health agencies to relate and respond to numerous stimuli in terms of new regulations, changing health status, emerging threats and shifting policy, can mask the commonality of underlying business processes performed within the public health sector. Heightened demand for interoperable, adaptive information systems across the broader US health system necessitates the recognition of this commonality and highlights the need for comprehensive analysis and understanding of these core business processes. In turn, this analysis paves the way for public health to apply proven systems engineering techniques to streamline, automate and facilitate those processes. Here, we look at the nature of the public health system and the evolution of a purpose-built methodology for process engineering within public health. We also present a case study based on the application of the methodology to develop requirements for public health laboratory information management systems. PMID- 20543252 TI - Engineering responses to pandemics. AB - Focusing on pandemic influenza, this chapter approaches the planning for and response to such a major worldwide health event as a complex engineering systems problem. Action-oriented analysis of pandemics requires a broad inclusion of academic disciplines since no one domain can cover a significant fraction of the problem. Numerous research papers and action plans have treated pandemics as purely medical happenings, focusing on hospitals, health care professionals, creation and distribution of vaccines and anti-virals, etc. But human behavior with regard to hygiene and social distancing constitutes a first-order partial brake or control of the spread and intensity of infection. Such behavioral options are "non-pharmaceutical interventions." (NPIs) The chapter employs simple mathematical models to study alternative controls of infection, addressing a well known parameter in epidemiology, R0, the "reproductive number," defined as the mean number of new infections generated by an index case. Values of R0 greater than 1.0 usually indicate that the infection begins with exponential growth, the generation-to-generation growth rate being R0. R0 is broken down into constituent parts related to the frequency and intensity of human contacts, both partially under our control. It is suggested that any numerical value for R0 has little meaning outside the social context to which it pertains. Difference equation models are then employed to study the effects of heterogeneity of population social contact rates, the analysis showing that the disease tends to be driven by high frequency individuals. Related analyses show the futility of trying geographically to isolate the disease. Finally, the models are operated under a variety of assumptions related to social distancing and changes in hygienic behavior. The results are promising in terms of potentially reducing the total impact of the pandemic. PMID- 20543253 TI - Understanding and enhancing the dental delivery system. AB - Dental decay is the most prevalent chronic disease among both children and adults in the U.S. The Surgeon General's Report on Oral Health found that there had been marked improvement in oral health in many Americans over the last 50 years and that good oral health could be achieved by all Americans largely due to the presence of safe and effective interventions to prevent and control oral disease However, recent national data suggest that several disparities in dental care exist. In this chapter, we present a model of the dental health system as well as key differences with the general medical health system. We further discuss the major issues that the dental care delivery system will have to address in order to ensure that all Americans have access to effective interventions to prevent and control disease in an environment of decreasing supply of dentists per capita and potentially increasing demand. We then discuss strategies and policies to address these emerging issues in the context of this model. Finally, we conclude with suggestions on how engineering techniques could be used to improve the system. PMID- 20543254 TI - Integrated health systems. AB - Before meaningful gains in improving the value of health care in the US can be achieved, the fragmented nature in which health care is financed and delivered must be addressed. One type of healthcare organization, the Integrated Delivery System (IDS), is poised to play a pivotal role in reform efforts. What are these systems? What is the current evidence regarding their performance? What are the current barriers to their establishment and how can these barriers be removed? This chapter addresses these important questions. Although there are many types of IDS' in the US healthcare landscape, the chapter begins by identifying the necessary healthcare components that encompass an IDS and discusses the levels of integration that are important to improving health care quality and value. Next, it explores the recent evidence regarding IDS performance which, while generally positive, is less than what it could be if there were greater focus on clinical integration. To highlight, the chapter discusses the efficacy of system engineering initiatives in two examples of large, fully integrated systems: Kaiser-Permanente and the Veterans Health Administration. The evidence here is strong that the impact of system engineering methods is enhanced through the integration of processes, goals and outcomes. Reforms necessary to encourage the development of IDS' include: 1) the development of payment mechanisms designed to increase greater inter-dependency of hospitals and physicians; 2) the modification or removal of several regulatory barriers to greater clinical integration; and 3) the establishment of a more robust data collection and reporting system to increase transparency and accountability. The chapter concludes with a framework for considering these reforms across strategic, structural, cultural, and technical dimensions. PMID- 20543255 TI - Academic health centers. AB - Academic Health Centers (AHCs) are comprised of academic, hospital, and clinical practice components that play a key role in healthcare delivery by their special ability to identify and implement improvements in outcomes, safety, cost-benefit, and satisfaction. They do this by utilizing a wide range of academic and clinical health professionals and disciplines to provide cutting-edge, highly specialized patient care as well as disproportionate uncompensated care in communities nationwide; to identify the effectiveness of different diagnostic and therapeutic approaches through clinical research; to foster new discoveries in biomedical science and technology and their clinical application; and to educate future generations of health professionals who apply these improvements. As the traditional homes of innovation in health and healing through research, and as the major sites of implementing change through education, AHCs have been at the forefront of improving healthcare. To successfully improve the effectiveness and efficiency of healthcare delivery, it is critical that AHCs continue to serve as uniquely integrated models for improving quality and value through novel approaches in education, research, and service. PMID- 20543256 TI - Government, health and system transformation. AB - All levels of government have an economic and social interest in health. In the United States, Federal, state and local government are involved in the development of health policy, funding health care, and maintaining or improving public health. Federal, State and most municipalities also engage in delivery of health services. As with the private sector, government is grappling with accelerating health care costs, increasing service demands generated by an aging and more chronically ill society, and accumulating evidence that American health outcomes are not commensurate with the resources invested. Unlike the private sector, attempts to improve value in health care - whether through legislation in Congress or regulation or program design in the Executive branch - are subject to the full intensity of the partisan political process. In order to engage effectively with government in health system transformation, an understanding of both the civic processes and the political dynamics is necessary. This chapter provides an overview of the major governmental roles in health care as formally structured and identifies points of influence in the political process. PMID- 20543257 TI - Barriers to change in engineering the system of health care delivery. AB - Significant reform of the health care system sufficient to achieve universal coverage, a value-driven system and administrative simplification faces enormous barriers at the level of our societal ecosystem - barriers as large as any that can be faced in public policy. These barriers exist within the health system itself as a complex adaptive system, and are structured by our economic, legal, cultural and political systems. Because there are so many barriers, significant reform is a relatively rare occurrence. Yet it does happen and there are some important examples of major health care reforms. There are a number of lessons to be learned from the successful enactment of the Medicare and Medicaid programs that appear relevant to current and future reform efforts. First, a necessary condition for achieving significant reform is the existence of large and sufficiently enduring social forces sufficient to disrupt legislative and policy stasis and drive the necessary political solutions. Second, public sentiment and electoral "mandates" might be necessary to significant reform, but they are not sufficient. Third, assuming the theoretical capacity to manage the constellation of systemic, economic, legal, cultural and legislative barriers, there remains a political "tipping point" that must be crossed and translated into a Congressional super-majority in order to enact significant nationwide reform. PMID- 20543258 TI - Prospects for change. AB - This chapter addresses the prospects for change in health care delivery. The focus is on value - high quality, affordable care for everyone. We consider three domains that participate in the flow of value and the nature of the interfaces among these domains. We also discuss strategic priorities that should align in various ways with these domains. Finally, we address the business transformations needed to enable the provision of value by enterprises that are viable and successful. PMID- 20543259 TI - Healthcare costs or investments? PMID- 20543260 TI - Hands, tables and groups make rehabilitation awesome! AB - Technology has helped improve rehabilitation programs by providing patients with engaging alternatives to otherwise monotonous and repetitive exercises. In recent years, therapists have looked towards multi-touch technologies to further enhance patient rehabilitation programs. So far, the focus has mainly been on single-user interaction, largely ignoring many of the benefits patients receive from socially interacting with therapists, caregivers and their peers. To make use of these valuable interactions, we have developed a suite of multi-touch activities for motor and cognitive rehabilitation. These applications can easily be adjusted to meet the needs of individual patients and enable therapists to quantitatively measure patient behavior and performance. We also reflect on design-related discussions we had with practicing occupational therapists and provide a set of design considerations to guide future rehabilitation activities. PMID- 20543261 TI - Intersubjectivity as a possible way to inhabit future cyberplaces. AB - A change of perspective in online interaction research, shifts attention from technologies to what people actually do online. It's time to study how subjects interact with others and how they 'take possession' of virtual environments on a perceptive, emotional and relational plan. This paper illustrates: a) how actors 'construct' themselves as subjects facing others during online interactions; b) the relationships actors establish with virtual environments and how actors transform 'simple' cyberspaces in cyberplaces; c) how actors - on the basis of a) and b) - 'bridge the gap' between them and their interlocutors using communication as a tool to give form to intersubjectivity, intended as an effective relational structure. A research program built around these three issues - both on the theoretical and empirical plan - should become the core of Social Psychology of Cyberplaces as this paper will demonstrate. PMID- 20543262 TI - Virtual reality adaptive stimulation of limbic networks in the mental readiness training. AB - A significant proportion of severe psychological problems in recent large-scale peacekeeping operations underscores the importance of effective methods for strengthening the stress resilience. Virtual reality (VR) adaptive stimulation, based on the estimation of the participant's emotional state from physiological signals, may enhance the mental readiness training (MRT). Understanding neurobiological mechanisms by which the MRT based on VR adaptive stimulation can affect the resilience to stress is important for practical application in the stress resilience management. After the delivery of a traumatic audio-visual stimulus in the VR, the cascade of events occurs in the brain, which evokes various physiological manifestations. In addition to the "limbic" emotional and visceral brain circuitry, other large-scale sensory, cognitive, and memory brain networks participate with less known impact in this physiological response. The MRT based on VR adaptive stimulation may strengthen the stress resilience through targeted brain-body interactions. Integrated interdisciplinary efforts, which would integrate the brain imaging and the proposed approach, may contribute to clarifying the neurobiological foundation of the resilience to stress. PMID- 20543263 TI - Interreality in the management of psychological stress: a clinical scenario. AB - The term "psychological stress" describes a situation in which a subject perceives that environmental demands tax or exceed his or her adaptive capacity. According to the Cochrane Database of Systematic Reviews, the best validated approach covering both stress management and stress treatment is the Cognitive Behavioral (CBT) approach. We aim to design, develop and test an advanced ICT based solution for the assessment and treatment of psychological stress that is able to improve the actual CBT approach. To reach this goal we will use the "interreality" paradigm integrating assessment and treatment within a hybrid environment, that creates a bridge between the physical and virtual worlds. Our claim is that bridging virtual experiences (fully controlled by the therapist, used to learn coping skills and emotional regulation) with real experiences (allowing both the identification of any critical stressors and the assessment of what has been learned) using advanced technologies (virtual worlds, advanced sensors and PDA/mobile phones) is the best way to address the above limitations. To illustrate the proposed concept, a clinical scenario is also presented and discussed: Paola, a 45 years old nurse, with a mother affected by progressive senile dementia. PMID- 20543264 TI - Neuropsychological testing through a Nintendo Wii console. AB - In recent years, videogames have demonstrated their positive effects in the psychological treatments and cognitive training of the old population. In this paper we present a pilot study in which a group of elderly people in an old people's home was requested to play a set of cognitive tasks administered through a popular videogames console, the Nintendo Wii. The results obtained by comparing the Wii cognitive games with traditional paper and pencil tests are described and discussed to orient further improvements. PMID- 20543265 TI - Influence of tracking feedback in user motor response in rehabilitation therapy. AB - In this experimental study, we present the results of user motor responses with and without the use of Tracking Feedback to complete correct movements in Virtual Rehabilitation Therapy. To carry out this study, we used a VRT system for standing balance rehabilitation. We applied it under two different conditions to twenty patients (with and without tracking feedback). We then analyzed their motor responses. By means of this analysis, we have confirmed the importance of Tracking Feedback in the achievement of rehabilitation goals. We also tested the possibility of eliminating the tracking components from the system to lower cost to make the integration of Virtual Rehabilitation systems available to more patients. Our results indicate that is currently not feasible. PMID- 20543266 TI - Virtual reality in the treatment of generalized anxiety disorders. AB - Generalized anxiety disorder (GAD) is a common anxiety disorder characterized by 6 months of "excessive anxiety and worry" about a variety of events and situations. Anxiety and worry are often accompanied by additional symptoms like restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension and disturbed sleep. GAD is usually treated with medications and/or psychotherapy. In particular, the two most promising treatments seem to be cognitive therapy and applied relaxation. In this study we integrated these approaches through the use of a biofeedback enhanced virtual reality (VR) system used both for relaxation and controlled exposure. Moreover, this experience is strengthened by the use of a mobile phone that allows patients to perform the virtual experience even in an outpatient setting. This paper describe the results of a controlled trial (NCT00602212) involving 20 GAD patients randomly assigned to the following groups: (1) the VR and Mobile group (VRMB) including biofeedback; (2) the VR and Mobile group (VRM) without biofeedback; (3) the waiting list (WL) group. The clinical data underlined that (a) VR can be used also in the treatment of GAD; (b) in a VR treatment, patients take advantage of a mobile device that delivers in an outpatient setting guided experiences, similar to the one experienced in VR. PMID- 20543267 TI - Effect of the mood produced by virtual reality exposure on body image disturbances. AB - Previous research suggests that negative mood increases body image disturbances. The aim of this study was to examine whether the mood produced by virtual reality exposure had any influence on such disturbances. As expected, dysphoric mood increased body image disturbances in patients with eating disorders. PMID- 20543268 TI - PDA self-register system for eating disorders: a study on acceptability and satisfaction. AB - Self-monitoring techniques, such as the use of dietary registers, are considered to be central to cognitive-behavioral treatment of Eating Disorders (ED). This information allows the clinician to identify the triggers of the behaviors associated to ED as purges and/or binges, and the associated thoughts and emotions, helping to carry out a more accurate assessment. Traditionally these registers are made with paper and pencil mode, where the patient has to register every eating and the emotions/thoughts associated; but this system has some problems, as low portability, low adherence or methodological difficulties. The use of PDA for self-registers can help to solve these problems. The aim of this study is to study the levels of acceptability and satisfaction with PDAs self register system specifically designed for assessment and treatment of ED. Samples of 30 subjects diagnosed with ED are receiving a PDA with software specifically designed for recording type and amount of food, emotions before and after eating and other behaviors. The participants are completing self-register daily during a week, and afterwards answer an acceptance and satisfaction questionnaire. This work is in progress at the moment. It is expected that the PDA system will show high levels of acceptance and satisfaction. PMID- 20543269 TI - Development of a computer based symmetry arrangement symptoms measures in obsessive-compulsive disorder. AB - BACKGROUND: Epidemiological studies indicated that compulsive ordering and arranging, and a preoccupation with symmetry are common presentations of obsessive-compulsive disorder (OCD). OBJECTIVE: The goal of the current study was to develop and obtain preliminary psychometric data for the objective and quantitative measurement of symmetry and arrangement symptoms in OCD. METHOD: Twenty-eight normal volunteers were administered computer based assessment tasks with 4 different conditions with or without target and distraction. Primary dependent variables included several indices of time and click of arranging behaviors. Construct validity for the task was examined by comparing the novel behavioral measures with standardized measures such as Symmetry, Ordering and Arranging Questionnaire (SOAQ), Obsessive Compulsive Inventory-Revised (OCI-R), Beck depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Quality of life scale (QOL). RESULT: We found significant positive correlation between behavioral parameters and standardized scales for OCD (total time and SOAQ: r(2)=0.623, P<0.001; total number of clicks and 'ordering' subscore of OCI-R: r(2)>=0.541, P<0.01). There was no significant correlation between behavioral parameters and other scales measuring constructs less relevant to ordering and arranging. A main effect of target only was observed on behavioral parameters. CONCLUSION: This study therefore provides preliminary data to support the use of this task as a novel behavioral measure of compulsive symptoms related with symmetry, ordering and arranging. PMID- 20543270 TI - Using virtual humans to alleviate social anxiety: preliminary report from a comparative outcome study. AB - Empirical studies have consistently shown the effectiveness of a multicomponent CBT treatment of social anxiety disorder (SAD). Previous outcome studies on virtual reality and SAD have focused on people suffering from fear of public speaking and not full blown SAD. In this study, 45 adults receiving a DSM-IV-TR diagnostic of social anxiety were randomly assigned to traditional CBT treatment (with in vivo exposure), CBT-VR combined treatment, or a waiting list. Results show significant reduction of anxiety on all questionnaires as well as statistically significant interactions between both treatment groups and the waiting list. PMID- 20543271 TI - eBaViR, easy balance virtual rehabilitation system: a study with patients. AB - eBaViR is a virtual rehabilitation system, which has been developed for balance rehabilitation for patients suffering from acquired brain injury. It is a game based system that uses a low-cost interface, the Nintendo Wii Balance Board. The games have been specifically designed with the help of experts in the rehabilitation of balance disorders and can be adapted to patients according to their needs. We present an experimental study that has been carried out using the system. The aim of the study is to determine whether this setup could be applied as a Virtual Rehabilitation System for balance rehabilitation in Acquired Brain Injury. We randomly divided patients into two groups: a trial group and a control group. The trial group used eBaViR system during the rehabilitation sessions, and the control group followed traditional rehabilitation sessions. We obtained encouraging results. PMID- 20543272 TI - Multimedia holistic rehabilitation method for patients after stroke-efficiency analysis. AB - The article presents the results of post-stroke rehabilitation of patients with brain dysfunctions causing cognitive impairments such as problems with concentrating, reasoning, logical thinking, and memory. Some of those patients suffered from various forms of aphasia as well. The holistic rehabilitation of the stroke patients was aided by specially designed computer systems offering an array of varied multimedia tasks. The research results presented below confirm the usability of the suggested method. PMID- 20543273 TI - Internet delivered images for exposure in specific phobia, design considerations for self-directed therapy. AB - Exposure to phobic stimuli in subjects with specific phobia typically results in increased anxiety, ranging from mild to severe, followed by gradual habituation. The Internet is a candidate medium for the delivery of phobic stimuli to phobic subjects, such as pictures, video clips or computer animations. Delivery of such images in home settings warrants careful attention to the range and time course of anxiety responses elicited, and to tailoring of progression through hierarchies of images. The agency of the user is paramount, they need to have the final say at all stages of exposure as to whether to proceed or not. We have incorporated solutions to these requirements in the design of an internet-based exposure program (FEARDROP). This employs a database repository of pictures and videos of phobic stimuli. Images are called up by the user engaging a tracking circle with their mouse and following it around the screen. The image fades out if the circle is not followed, a form of 'dead man's brake'. Anxiety responses are measured at intervals on a visual analogue scale and graphed for the user. Initial results show substantial habituation to spider pictures within minutes, with a controlled comparison to video images in progress. PMID- 20543274 TI - Virtual reality interoceptive exposure for the treatment of panic disorder and agoraphobia. AB - The efficacy of cognitive-behavioral therapy for panic disorder and agoraphobia (PDA) has been widely demonstrated. The exposure technique is the main component of these programs; interoceptive exposure also plays an important role. The virtual reality (VR) program for treating PDA developed by Botella's group can simulate physical sensations in a controlled manner while the user is immersed in the VR environments in the consultation room. These include audible effects, such as rapid heartbeat and panting, as well as visual effects, such as blurry vision, double vision and tunnel vision. This work examines the efficacy of the interoceptive exposure (IE) component in two treatment conditions: 1) VR Interoceptive Exposure Simultaneous Condition (VRIE-sim; N=14), and 2) Interoceptive Exposure Traditional Condition (IET; N=15). Results obtained showed that both treatment conditions significantly reduced the main clinical variables at post-treatment; these results were maintained or even improved at three month follow-up. Simultaneous VR interoceptive and VR external stimuli exposure is a new and effective way to apply PDA treatment. PMID- 20543275 TI - Use of immersive virtual reality for treating anger. AB - Poorly managed anger responses can be detrimental to one's physical and psychosocial well-being. Cognitive behavior therapies (CBT) have been found to be effective in treating anger disorders. A key component of CBT treatment is exposure to the anger arousing stimuli. Virtual reality (VR) environments can elicit potent reactions and may facilitate the treatment of anger. An anger VR environment with six video vignettes was developed by this study to examine the anger arousal potential of VR. Outcome measures included assessment of emotional reactivity, state anger, and presence. The results showed that significant anger arousal occurred during exposure to the VR environment, and arousal was greater when viewed in an immersive HMD than a non-immersive flat screen. In addition, presence was found to moderate the effects of VR. Low presence resulted in low reactivity regardless of the display modality. PMID- 20543276 TI - Accessible virtual reality therapy using portable media devices. AB - Simulated immersive environments displayed on large screens are a valuable therapeutic asset in the treatment of a range of psychological disorders. Permanent environments are expensive to build and maintain, require specialized clinician training and technical support and often have limited accessibility for clients. Ideally, virtual reality exposure therapy (VRET) could be accessible to the broader community if we could use inexpensive hardware with specifically designed software. This study tested whether watching a handheld non-immersive media device causes nausea and other cybersickness responses. Using a repeated measure design we found that nausea, general discomfort, eyestrain, blurred vision and an increase in salivation significantly increased in response to handheld non-immersive media device exposure. PMID- 20543277 TI - Executive functions in a virtual world: a study in Parkinson's disease. AB - In Parkinson's disease executive functions are altered. We used a Virtual Reality version of the Multiple Errand Test in order to evaluate decision-making ability in 12 patients and 14 controls. Patients with Parkinson's disease, even if not demented, showed strategies full of errors, suggesting that impulse control disorder, very frequent in course of disease, could precede cognitive dysfunctions. PMID- 20543278 TI - Presence, involvement and efficacy of a virtual reality intervention on pain. AB - We explored the impact of an interactive VR environment on pain cognitions (in vivo catastrophizing and pain self-efficacy) and pain-related measures: pain threshold, pain tolerance, Pain Sensitivity Range (PSR), pain intensity and time estimation in a sample of healthy students. Sense of presence is essential to conduct a psychological treatment; if patients are not able to involve themselves in a virtual world they cannot experience relevant emotions, and the desired processes that are necessary for most psychological treatments will not occur. However, some authors argue that presence must be distinguished from the degree of engagement, involvement in the portrayed environment. The results obtained in our study are consistent with this view, since the Involvement scale of the IPQ did not correlate with any of the measures related with the treatment's efficacy. PMID- 20543279 TI - Analysis of visual perception aspects of the virtual reality experience with transcranial Doppler monitoring. AB - Transcranial Doppler is a tool to measure blood flow velocity (BFV) in the main arteries of the brain that has been used in previous studies to analyze brain activity during virtual reality (VR) experiences. Increments in BFV were found during the exposure to virtual environments in comparison with baseline periods. However, due to the complexity of VR experiences, there are several factors that can be having an influence in these variations, so it is necessary to separately analyze those different aspects. In this work, we summarize our results related to visual perception. A method based on spectral analysis was used to analyze the magnitude and temporal evolution of the maximum BFV signal. Results showed that, in the presence of visual stimuli, BFV quickly rises to a maximum that is achieved after a few seconds. The contribution of the visual stimuli factor to the observed BFV variations during a VR experience can be estimated from the results of the developed work. PMID- 20543280 TI - Using robotics construction kits as metacognitive tools: a research in an Italian primary school. AB - The present paper is aimed at analyzing the process of building and programming robots as a metacognitive tool. Quantitative data and qualitative observations from a research performed in a sample of children attending an Italian primary school are described in this work. Results showed that robotics activities may be intended as a new metacognitive environment that allows children to monitor themselves and control their learning actions in an autonomous and self-centered way. PMID- 20543281 TI - Implementation of the multiple errands test in a NeuroVR-supermarket: a possible approach. AB - Our goal was to develop a tool for the assessment of executive functions by customizing a virtual reality (VR) version of the Multiple Errands Test (MET) [Shallice & Burgess, 1991; Fortin et al., 2003]. The MET is an assessment of executive functions in daily life which consists of tasks that abide by certain rules. It is performed in an actual shopping mall-like setting where there are items to be bought and information to be obtained. The specific goal of this study was to conduct a pilot study using the virtual version of MET (VMET) with both control subjects and patients with cognitive impairment derived from stroke. PMID- 20543282 TI - The moderating role of need for cognition on excessive searching bias: a case of finding romantic partners online. AB - Using online-dating websites to expand social networks and form close relationships is popular for people in information technology era. Wu and Chiou (2009) demonstrated that more options triggered excessive searching, leading to poorer decision-making and reduced selectivity. They proposed that the more-means worse effect refers to more searching leads to worse choices by reducing users' cognitive resources, distracting them with irrelevant information and reducing their ability to screen out inferior options. A 2 by 2 experimental study was conducted to investigate the moderating effect of individual differences in need for cognition (NFC) and number of available options on excessive searching and decision quality. A total of 120 undergraduates with experiences of online romantic relationships participated in the experiment. After participants were administrated their need for cognition, they were assigned to review either a small or a large number of options to search for their most desirable romantic partners via a popular online-dating website in Taiwan. Results indicated that high-NFC participants showed more excessive searching than did low-NFC participants. Moreover, the more-means-worse effect was more salient for high-NFC participants than high-NFC participants. The findings suggest that users with high NFC may be more vulnerable to the negative effect of excessive searching. PMID- 20543283 TI - Efficacy of virtual reality in triggering the craving to smoke: its relation to level of presence and nicotine dependence. AB - Virtual Reality environments that reproduce typical contexts associated with tobacco use may be useful for aiding smoking cessation. The main objective of this study was to assess the capacity of eight environments to produce the craving to smoke and determine the relation of craving to nicotine dependence and level of presence. The results show that all the environments were able to generate the desire to smoke; a direct relation was found between sense of presence and craving. PMID- 20543284 TI - Training presence: the importance of virtual reality experience on the "sense of being there". AB - Nature and origin of presence are still unclear. Although it can be characterized, under a neurophysiological perspective, as a process resulting from a synchrony between cognitive and perceptive systems, the multitude of associated processes reduces the chances of brain mapping presence. In this way, our study was designed in order to understand the possible role of VR experience on presence in a virtual environment. For our study, 16 participants (M=28.39 years; SD=13.44) of both genders without computer experience were selected. The study design consisted of two assessments (initial and final), where the participants were evaluated with BFI, PQ, ITQ, QC, MCSDS-SF, STAI, visual attention and behavioral measures after playing an first person shooter (FPS) game. In order to manipulate the level of VR experience the participants were trained on, a different FPS was used during the 12 weekly sessions of 30 minutes. Results revealed significant differences between the first and final assessment for presence (F(1,15)=11.583; MSE=775.538; p<01) and immersion scores (F(1,15)=6.234; MSE=204.962; p<05), indicating higher levels of presence and immersion in the final assessment. No statistical significant results were obtained for cybersickness or the behavioral measures. In summary, our results showed that training and the subsequent higher computer experience levels can increase immersion and presence. PMID- 20543285 TI - Analysis of distributed-collaborative activity during augmented reality exposure therapy for cockroach phobia. AB - Recent research presents Augmented Reality Exposure Therapy (ARET) for treatment of phobia of cockroaches as a potentially effective technique. However, to the authors' knowledge no studies have been published concerning the Human-Computer Interaction issues of such a system. The aim of this paper is to report some preliminary data on how patients, therapists and an Augmented Reality system collaborate and interact during the therapeutic process. The results show that the therapeutic process is distributed between individuals (patient and therapist) and artifacts (e.g. AR cockroaches, a computer screen, a Head Mounted Display (HMD), a keyboard, a swatter and therapists' notes on paper). The results are discussed in terms of possible improvement of the ARET system. PMID- 20543286 TI - Understanding the psychological motives behind microblogging. AB - This research aims to understand the psychological motives behind microblogging. We conducted two studies to investigate if social exclusion and existential anxiety would lead to a high tendency to microblog. Our results show that participants did not use microblogging to satisfy their needs for social connection and affiliation, but highly extraverted participants did use it to relieve their existential anxiety. PMID- 20543287 TI - Virtual/Real transfer of spatial learning: impact of activity according to the retention delay. AB - Within the framework of cognitive rehabilitation using virtual reality (VR), one of the major challenges is to study beforehand the effectiveness of the virtual real transfer of learning and to define cognitive aids. The aim of this experiment was to verify if, after learning spatial knowledge (i.e., a route) in VR, performances can be transferred to reality, then maintained in real time, and improved with the aid of an active navigation (i.e., using a joystick). Ninety student volunteers from the University of Bordeaux 2 (45 men and 45 women) participated in the experiment. The virtual environment (VE) used for learning was a replica of an area of Bordeaux. The factors tested were retention delay (Immediate vs. 48 hours) and type of navigation (Passive virtual vs. Active virtual vs. Real), using three recall tasks: wayfinding, freehand sketch and photograph classification. Our results showed that the virtual-real transfer was not degraded by a retention delay of 48 hours and that active navigation allowed performances to be optimized. PMID- 20543288 TI - SNSs usage among Chinese internet users: an empirical study. AB - Renren and Kaixin, which are Chinese versions of "Facebook", are the main Social Network Sites (SNSs) in China. Although many researchers have been exploring SNSs usage and have gained rich results, there are limited studies for the understanding of SNSs usage in China. In this present study, with 777 Chinese participants, we test variables influencing Chinese SNSs usage based on the technology acceptance model (TAM). Using structural equation modeling techniques, the empirical results confirm that the perceived ease of use significantly determines the perceived usefulness, which in turn influences SNSs use intensity. Meanwhile, the Internet self-efficacy could affect perceived ease of use and further determine SNSs use intensity indirectly. Overall, our results could be used to describe and predict SNSs usage among Chinese Internet users. PMID- 20543289 TI - The illusion of presence influences VR distraction: effects on cold-pressor pain. AB - This study investigated whether VR presence influences how effectively VR distraction reduces pain intensity during a cold-pressor experience. Thirty-seven healthy students underwent a cold pressor task while interacting with a VR distraction world. After the VR cold-pressor experience, each subject provided VAS ratings of the most intense pain experienced during the hand immersion and rated their illusion of having been inside the virtual world. Results showed that the amount of VR presence reported correlated significantly and negatively with ratings of pain intensity. The importance of using an appropriately designed VR to achieve effective VR analgesia is highlighted. PMID- 20543290 TI - The effects of augmented reality on learning. AB - In this study, a new approach to the implementation of Augmented Reality (AR) in the educational environment was taken by creating a Chemistry Augmented Reality Learning System (CARLS), using the existing teaching curriculum, together with physical activity. This system combined learning with three types of physical activity: aerobic fitness, muscle strength and flexibility fitness. This study reveals that the students using all three types of physical activity together with CARLS result in significantly higher academic performance compared to the traditional Keyboard-Mouse CAI (KMCAI). This improvement is most evident for the non-memorized knowledge component of Science. Moreover, the students in the AR group with 'muscle strength' physical activity had significantly more positive learning attitude change toward Science than those in the KMCAI group. A great additional benefit of our approach is that, students also obtained more physical fitness while learning. PMID- 20543291 TI - Indoor orientation and mobility for learners who are blind. AB - This study consisted of designing a mobile technology to identify the position and orientation of people who are blind in closed environments, such as a school, building or home, identifying the necessary infrastructure based on criteria of usability, reliability and accessibility, in order for PocketPC device interface developers to be able to define the technology to be used at an early stage. The technology consisted of using PocketPC devices with a data collecting application and another for the representation of space. We evaluated its usability, accessibility, reliability, efficiency, and availability. The results of the usability evaluation assured us that the interface designed and developed is usable for users who are blind, which is reaffirmed through the accessibility evaluation. The reliability, efficiency and availability evaluations of the system show that a user who is blind can use the system confidently, because it provides correct information for more independent navigation. PMID- 20543292 TI - The use of virtual reality for a human classical conditioning procedure. AB - The present study investigated the use of a VR stereoscopic figure as conditioned stimulus (CS). A differential conditioning procedure was applied on 67 participants, where a VR stereoscopic figure (CS+) was paired with electric shock and other VR stereoscopic figure (CS-) was presented without shock. Evaluative and expectancy measures were taken. Results showed that, after acquisition, the CS+ by itself became a more negative stimulus, as evidenced by the evaluative ratings. Besides, the presentation of the CS+ evoked an active expectancy of the unconditioned stimulus (US). The use of VR stereoscopic figures as CSs seems feasible to design innovative experimental paradigms. PMID- 20543293 TI - Teaching tactical combat casualty care using the TC3 sim game-based simulation: a study to measure training effectiveness. AB - The effectiveness of games as instructional tools has been debated over the past several decades. This is due to the lack of empirical data to support such claims. The US ARMY developed a game-based simulation to support Tactical Combat Casualty Care (TCCC) Training. The TC3 Game based Simulation is a first person game that allows a Soldier to play the role of a combat medic during an infantry squad mission in an urban environment. This research documents results from a training effectiveness evaluation conducted at the Department of Combat Medic Training (Ft Sam Houston) in an effort to explore the capability of the game based simulation as a potential tool to support the TCCC program of instruction. Reaction to training, as well as, acquisition of knowledge and transfer of skills were explored using Kirkpatrick's Model of Training Effectiveness Evaluation. Results from the evaluation are discussed. PMID- 20543294 TI - Visual properties of an object affect time to target in VR reaching tasks. AB - Virtual Reality is being used increasingly for upper limb rehabilitation. The type of virtual objects used for reaching tasks varies widely, but there has been little work exploring the effect of different characteristics of objects on target acquisition time. This study investigates how target acquisition times vary for virtual objects with different visual cues. Results suggest that the visual properties of an object may have a notable effect on target acquisition times. Simple (low polygon) objects with richer depth cues are acquired more easily than a standard sphere. PMID- 20543295 TI - Psychophysiological indicators of acute stress disorder. AB - AIM: The aim of the current study was to compare basal psychophysiology and startle reflexes in acute stress disorder (ASD) patients and controls. Stress reactions to traumatic event include acute and chronic reactions like ASD and posttraumatic stress disorder (PTSD). They are characterized by prominent psychophysiological symptoms that can give insight into the pathogenesis of PTSD. METHODS: We measured heart-rate (HR), respiratory sinus arrhythmia (RSA), electrodermal activity (EDA) and electromyography (EMG) of musculus orbicularis occuli during an acclimation period and during the presentation of startle stimuli in 29 ASD patients with different traumatic experiences and in 33 healthy controls. RESULTS: ASD subjects had similar habituation to the startle probe as healthy controls. EDA for individuals with ASD after traffic accident was higher then for healthy controls. There were no differences for heart-rate in two compared groups. CONCLUSION: EDA appears to offer the most reliable psychophysiological indices in the ASD following traffic accident. PMID- 20543296 TI - Presence is just an illusion: using fMRI to locate the brain area responsible to the meaning given to places. AB - Researchers have suggested different models to describe the feeling of presence. Most of them imply that presence is some kind of alternate state. Research conducted in our research team lead us to consider presence simply like a very powerful perceptual illusion, with the addition of challenging the meaning given to the place where the user actually is (i.e., being "there"). The aim of this study is to investigate the neural correlates of the illusion of presence in VR. Five right-handed adults were scanned in the fMRI and were immersed in two conditions: high and low presence, where the exact same stimulus was presented to participants during each condition but the context (narrative) provided differed significantly. Results show a clear, specific and statistically significant involvement of the parahippocampal area, the brain responsible for giving contextual meaning of places. PMID- 20543297 TI - Contributions of functional magnetic resonance in the field of psychological treatments with virtual reality. AB - Many studies have been developed using brain imaging methods to investigate psychological disorders. On the other hand, there are many studies that make use of virtual reality (VR) to simulate a real condition during psychological treatments. In this research, we plan to analyze brain activity during the exposure to a virtual environment related to phobias. Our first goal is to study the possibility of activating brain areas related to phobias, specifically phobias to small animals (spiders and cockroaches), using virtual reality as stimulus, while the patient is inside a functional magnetic resonance imaging (fMRI) machine. The second goal of the research is to analyze if there are differences in the activated areas after patients have followed a psychological treatment for this specific phobia. That is why two different sessions with fMRI will be performed, before and after an intensive treatment for the phobia. In the fMRI room, participants will wear special glasses to visualize the VR environments in which they have to navigate (using also a joystick adapted to fMRI). They will have to perform some tasks while being exposed to the phobic stimuli. The VR environment used in the fMRI sessions has three different conditions: first, a clean room without spiders or cockroaches; second, the same room, but dirty and disordered (giving the sensation of having small animals, although actually there are none); third, the same dirty room but having spiders and cockroaches. It is our hypothesis that the patients will get anxious in the situation in which it is possible that the animal appears and the patterns of brain activation will be different in this condition. PMID- 20543298 TI - Sounding better: fast audio cues increase walk speed in treadmill-mediated virtual rehabilitation environments. AB - Music or sound effects are often used to enhance Virtual Environments, but it is not known how this audio may influence gait speed. This study investigated the influence of audio cue tempo on treadmill walking with and without visual flow. The walking speeds of 11 individuals were recorded during exposure to a range of audio cue rates. There was a significant effect of audio tempo without visual flow, with a 16% increase in walk speed with faster audio cue tempos. Audio with visual flow resulted in a smaller but still significant increase in walking speed (8%). The results suggest that the inclusion of faster rate audio cues may be of benefit in improving walk speed in virtual rehabilitation. PMID- 20543299 TI - Multi-modal memory restructuring for patients suffering from combat-related PTSD: a pilot study. AB - The paper discusses the design and evaluation of a multimedia software application, which can be used in the treatment of combat-related posttraumatic stress disorder (PTSD). The application allows patients and therapist to visualize the patients' past experience using maps, personal photos, stories and self-created 3D virtual worlds. The tool aims to allow patients to restructure and relearn about their past experience involving the problematic stressors. Findings of a first experiment with non-patients (N=18) suggests that the tool can facilitate more detailed storytelling. Participants stated that using the application was appealing and enjoyable. Insights were also acquired with a case study of a veteran suffering from combat-related PTSD. This case study showed how a patient uses and interacts with the system in a therapeutic setting. PMID- 20543300 TI - Effectiveness of brief VR treatment for PTSD in war-fighters: a case study. AB - War-fighters exposed to combat are at high risk for developing posttraumatic stress disorder (PTSD), a complex and challenging condition to treat. Cognitive behavioral therapies (CBT) have been empirically validated as effective treatments for PTSD resulting from sexual assault, vehicular accidents, and disasters. Exposure, imaginal or in vivo, to the traumatic event is a central component of successful CBT treatment. Early studies indicate that CBT with brief virtual reality exposure (VRE) is beneficial in treating PTSD. The case study examined the effectiveness of brief VRE in treating combat-related PTSD. PMID- 20543301 TI - A myoelectric-controlled virtual hand for the assessment and treatment of phantom limb pain in trans-radial upper extremity amputees: a research protocol. AB - At least 90% of individuals of limb amputees experience phantom limb pain (PLP). Recent clinical research suggests that providing patients with the mirror image representation of the amputated limb may alleviate PLP. However, mirror therapy cannot be used with bilateral amputees, as visual feedback is dependent on the movement of the intact limb. To overcome this limitation, we designed a novel myoelectric-controlled virtual reality (VR) system for the treatment of phantom limb pain in trans-radial upper extremity amputees. The proposed system allows the patient to directly control the virtual limb by recognizing stump muscle patterns recorded with EMG sensors. The hypothesis behind this strategy is that the VR image of the amputated limb induces better limb imagery than the reflected image of their intact limb and, therefore, is more effective in reducing PLP. A research protocol to test this hypothesis is described. PMID- 20543302 TI - Combined functional electrical stimulation (FES) and robotic system for wrist rehabiliation after stroke. AB - Functional electrical stimulation (FES) and rehabilitation robots are techniques used to assist in post-stroke rehabilitation. However, FES and rehabilitation robots are still separate systems currently; and their combined training effects on persons after experiencing a stroke have not been well studied yet. In this work, a new combined FES-robot system driven by user's voluntary intention was developed for wrist joint training after stroke. The performance of the FES-robot assisted wrist tracking was evaluated on five subjects with chronic stroke. With simultaneous assistance from both the FES and robot parts of the system, the motion accuracy was improved and excessive activation in elbow flexor was reduced during wrist tracking. PMID- 20543303 TI - Lean on Wii: physical rehabilitation with virtual reality Wii peripherals. AB - In recent years, a growing number of occupational therapists have integrated video game technologies, such as the Nintendo Wii, into rehabilitation programs. 'Wiihabilitation', or the use of the Wii in rehabilitation, has been successful in increasing patients' motivation and encouraging full body movement. The non rehabilitative focus of Wii applications, however, presents a number of problems: games are too difficult for patients, they mainly target upper-body gross motor functions, and they lack support for task customization, grading, and quantitative measurements. To overcome these problems, we have designed a low cost, virtual-reality based system. Our system, Virtual Wiihab, records performance and behavioral measurements, allows for activity customization, and uses auditory, visual, and haptic elements to provide extrinsic feedback and motivation to patients. PMID- 20543304 TI - Therapeutic games to improve attachment capabilities and protect sexual health. AB - From the very beginning of life, man's fundamental needs for acceptance, security, trust, warmth and closeness can only be satisfied in relationships [1]. During infancy this is accomplished by body contact and the emotional experience of being taken care of, for instance by the sheltering manner in which an infant is held during breast-feeding. Through this parental loving care the modus of satisfying psychosocial fundamental needs by skin contact is learned by the infant and reinforced on a neuronal level, the way all processes of learning elementary skills generally are. According to present knowledge, chronic lack of security transmitted by frustration of psychosocial fundamental needs increases the probability of developing psychological and physical disorders. Furthermore it hinders overcoming prevailing diseases [2]. In developing therapeutic computer games this phylogenetically established programming for attachment in order to fulfill fundamental psychosocial needs will be the focus of interaction, cognitive triggers and strategic as well as emotional rules to be applied in the games which are designed in a modular way for difficult developmental phases (e.g. adolescence) or various chronic diseases. This is a new approach transferring sexological clinical experience into therapeutic computer games for prevention purposes and protection of sexual health. PMID- 20543305 TI - Seamless care: what is it; what is its value; what does it require; when might we get it? AB - The vision of a seamless care environment enabled through the use of health information technology opens the door to exciting possibilities. The first is the creation of a patient-centric Electronic Health Record that would contain all health-related data about a patient from all sources. That EHR would contribute to highest quality, safe, efficient, and low cost care. That same data would be used for multiple purposes, and, by integrating all requirements at the beginning, would meet all those multiple needs. Key to obtaining seamless care is the creation of a global master registry of data elements with attributes that would provide not only interoperability throughout seamless health care but also permit the coupling of knowledge with data. To accomplish this lofty vision will require making critical decisions, staying to the course, eliminating siloed approaches, and adopting universal, cooperative solutions to the use of HIT. PMID- 20543306 TI - Secondary use of clinical data. AB - Clinicians involved in clinical care generate daily volumes of important data. This data is important for continuity of care, referrals to specialists and back to the patient's medical home. The same data can be used to generate alerts to improve the practice and to generate care activities to ensure that all appropriate care services are provided for the patient given their known medical histories using electronic quality (eQuality) monitoring. For many years we have used patient records as a data source for human abstraction of clinical research data. With the advent of electronic health record (EHR) data we can now make use of computable EHR data that can perform retrospective research studies more rapidly and lower the activation energy necessary to ask the next important question using electronic studies (eStudies). Barriers to these eStudies include: the lack of interoperable data between and among practices, the lack of computable definitions of measures, the lack of training of health professionals to use Ontology based Informatics tools that allow the execution of this type of logic, common methods need to be developed to distribute computable best practice rules to ensure rapid dissemination of evidence, better translating research into practice. PMID- 20543307 TI - The role of architecture and ontology for interoperability. AB - Turning from organization-centric to process-controlled or even to personalized approaches, advanced healthcare settings have to meet special interoperability challenges. eHealth and pHealth solutions must assure interoperability between actors cooperating to achieve common business objectives. Hereby, the interoperability chain also includes individually tailored technical systems, but also sensors and actuators. For enabling corresponding pervasive computing and even autonomic computing, individualized systems have to be based on an architecture framework covering many domains, scientifically managed by specialized disciplines using their specific ontologies in a formalized way. Therefore, interoperability has to advance from a communication protocol to an architecture-centric approach mastering ontology coordination challenges. PMID- 20543308 TI - Patients' empowerment of their personal health record requires strong traceability to guarantee patients health care security. AB - Giving patients power over their personal health record is an unavoidable evolution in all industrialized countries which will reflect their active participation in the management of their own health. This would lead to patients sharing management with health professionals, which would need traceability of the data provider to maintain trust and transparency. The systematic use of electronic signatures by medical practitioners will be essential to provide sufficient guarantees and to clearly determine who has added what in the PEHR. PMID- 20543309 TI - Empowering patients with COPD using Tele-homecare technology. AB - This paper discusses how a tele-rehabilitation program using home tele-monitoring may empower patients with chronic obstructive pulmonary disease (COPD). The paper is based on preliminary findings from an ongoing research and innovation project, called "Tele-homecare, chronic patients and the integrated healthcare system" (the TELEKAT project) that employs triple interventions related to patients, professionals, and the organization of care. The ways COPD patients make use of home tele-monitoring in the TELEKAT project points to the relevance of a concept of empowerment rooted in ideologies of social action, and focusing on the improvement of both personal and social conditions at the intersection of individual, organizational and community development. PMID- 20543310 TI - Language games and patient-centred eHealth. AB - The sharing of clinical information between ehealth systems requires a common terminology, and SNOMED CT is seen as an acceptable solution for this task. Widespread adoption of SNOMED CT may mean that other terminologies, particularly those of citizens and patients, are sidelined or ignored. This paper considers the role of a citizen's "voice" in a connected ehealth world. PMID- 20543311 TI - Electronic interchange of lab test orders and results between laboratories reduces errors and gives full traceability. AB - Introduction of electronic lab test ordering and reporting corresponding results between laboratories when exchanging special tests for analysis in service labs, instead of manual paper based workflow, have reduced the fault rate by a factor 10 and reduced reporting time by 2 days compared to the manual workflow. Retyping orders and results into different IT systems is not longer needed as all 9 different labsystems in more than 60 laboratories are using the same standards and procedures resulting in full interoperability. The solution, challenges, implementation process and outcome is described in the paper. PMID- 20543312 TI - Quality improvements based on detailed and precise terminology. AB - This article describes a comparative study within intensive care where possibilities for quality monitoring have been examined regarding the data input. The study compared the results of making quality statistics based on ICD10 and on SNOMED CT. The article describes the method deployed for defining the subset used in the study and how the data comparison has been established. The study shows that the use of a more granulated, precise and well defined terminology used in daily clinical work can help clinicians doing better quality monitoring and quality development and at the same time may reduce time and costs in quality management. The study shows further that the use of an international terminology can increase the possibilities of international benchmarking and research. The article ends up by drawing attention to some challenges which must be dealt with especially regarding reimbursement. PMID- 20543313 TI - Risk assessment of integrated electronic health records. AB - The paper describes the security concerns related to Electronic Health Records (EHR) both in registration of data and integration of systems. A description of the current state of EHR systems in Iceland is provided, along with the Ministry of Health's future vision and plans. New legislation provides the opportunity for increased integration of EHRs and further collaboration between institutions. Integration of systems, along with greater availability and access to EHR data, requires increased security awareness since additional risks are introduced. The paper describes the core principles of information security as it applies to EHR systems and data. The concepts of confidentiality, integrity, availability, accountability and traceability are introduced and described. The paper discusses the legal requirements and importance of performing risk assessment for EHR data. Risk assessment methodology according to the ISO/IEC 27001 information security standard is described with examples on how it is applied to EHR systems. PMID- 20543314 TI - Meeting EHR security requirements: SeAAS approach. AB - In the last few years, Electronic Health Record (EHR) systems have received a great attention in the literature, as well as in the industry. They are expected to lead to health care savings, increase health care quality and reduce medical errors. This interest has been accompanied by the development of different standards and frameworks to meet EHR challenges. One of the most important initiatives that was developed to solve problems of EHR is IHE (Integrating the Healthcare Enterprise), which adapts the distributed approach to store and manage healthcare data. IHE aims at standardizing the way healthcare systems exchange information in distributed environments. For this purpose it defines several so called Integration Profiles that specify the interactions and the interfaces (Transactions) between various healthcare systems (Actors) or entities. Security was considered also in few profiles that tackled the main security requirements, mainly authentication and audit trails. The security profiles of IHE currently suffer two drawbacks. First, they apply end point security methodology, which has been proven recently to be insufficient and cumbersome in distributed and heterogeneous environment. Second, the current security profiles for more complex security requirements are oversimplified, vague and do not consider architectural design. This recently changed to some extend e.g., with the introduction of newly published white papers regarding privacy [5] and access control [9]. In order to solve the first problem we utilize results of previous studies conducted in the area of security-aware IHE-based systems and the state-of-the-art Security-as-a Service approach as a convenient methodology to group domain-wide security needs and overcome the end point security shortcomings. PMID- 20543315 TI - Improvement of cross-sector communication in the integrated health environment. AB - Patient care is a complex process with different providers located in various institutions co-operating within an integrated health environment. In spite of technical improvements in medical care, patient information is usually exchanged by paper. Digital and timely communication between regional care providers can improve the exchange of information. Different systems and missing data standards are challenges that have to be met. ByMedConnect, a project sponsored by the Bavarian State Ministry of the Environment and Public Health, develops and demonstrates a communication solution based on the EN 13606 standard. In a first step the dataset, which will be exchanged by the care providers, is defined. ByMedConnect develops the dataset in cooperation with practicing clinicians and converts it via modeling tools into archetypes that provide the base for reliable cross-sector communication. Existing heterogeneous systems are integrated via a dedicated module that transforms legacy data into a normalized representation. Information provided in a standardized form thereby enables semantic interoperability between different systems and allows medical add-on applications to connect. A secure digital communication network guarantees easy and direct data sharing. ByMedConnect aims to evaluate the achieved theoretical preliminary work in practice and to draft approaches, which can be applied beyond the pilot application. PMID- 20543316 TI - Design and implementation of a health data interoperability mediator. AB - The objective of this study is to design and implement a common-gateway oriented mediator to solve the health data interoperability problems that exist among heterogeneous health information systems. The proposed mediator has three main components: (1) a Synonym Dictionary (SD) that stores a set of global metadata and terminologies to serve as the mapping intermediary, (2) a Semantic Mapping Engine (SME) that can be used to map metadata and instance semantics, and (3) a DB-to-XML module that translates source health data stored in a database into XML format and back. A routine admission notification data exchange scenario is used to test the efficiency and feasibility of the proposed mediator. The study results show that the proposed mediator can make health information exchange more efficient. PMID- 20543317 TI - Ontology-based interoperability service for HL7 interfaces implementation. AB - Sharing information and knowledge among heterogeneous health information systems requires semantic interoperability. Most integration projects address semantic interoperability by implementing HL7 version 3 standard interfaces. However, it is challenging to achieve computable semantic interoperability with HL7 because of i) the complexity of the standard, requiring HL7 experts in the interface implementation process ii) inconsistencies and overlapping of the different HL7 information models (RIM, D-MIMs, R-MIMs, C-METs), and iii) instability of the different HL7 version 3 models. In this paper, an ontology-based service for health systems semantic interoperability is proposed. This service includes three main components: i) the conceptual model formalization component, responsible to represent the conceptual information models of the applications to be integrated as formal application ontologies; ii) the ontology mapper component; responsible to realize the semantic mapping between the formal application ontologies using a domain ontology, therefore solving inconsistencies found in the source application ontologies; (iii) the automatic interface generator, responsible to create and to maintain HL7 version 3 interfaces. The service presented in this paper is primary focused on the implementation of HL7 interfaces to integrate legacy systems. However being supported in an ontology-based mapping of HL7 information models, it can also support semantic interoperability among healthcare services and applications. PMID- 20543318 TI - Harmonizing the semantics of technical terms by the generic component model. AB - Working interoperability not only requires harmonized system's architectures, but also the same interpretation of technical specifications in order to guide the development process. This paper analyzes the commonly used terms to introduce different kinds of coded concepts by an alignment with the Generic Component Model (GCM). PMID- 20543319 TI - Challenges of interoperability using HL7 v3 in Czech healthcare. AB - The paper describes several classification systems that could improve patient safety through semantic interoperability among contemporary electronic health record systems (EHR-Ss) with support of the HL7 v3 standard. We describe a proposal and a pilot implementation of a semantic interoperability platform (SIP) interconnecting current EHR-Ss by using HL7 v3 messages and concepts mappings on most widely used classification systems. The increasing number of classification systems and nomenclatures requires designing of various conversion tools for transfer between main classification systems. We present the so-called LIM filler module and the HL7 broker, which are parts of the SIP, playing the role of such conversion tools. The analysis of suitability and usability of individual terminological thesauri has been started by mapping of clinical contents of the Minimal Data Model for Cardiology (MDMC) to various terminological classification systems. A national-wide implementation of the SIP would include adopting and translating international coding systems and nomenclatures, and developing implementation guidelines facilitating the migration from national standards to international ones. Our research showed that creation of such a platform is feasible; however, it will require a huge effort to adapt fully the Czech healthcare system to the European environment. PMID- 20543320 TI - ResearchEHR: use of semantic web technologies and archetypes for the description of EHRs. AB - In this paper, we present the ResearchEHR project. It focuses on the usability of Electronic Health Record (EHR) sources and EHR standards for building advanced clinical systems. The aim is to support healthcare professional, institutions and authorities by providing a set of generic methods and tools for the capture, standardization, integration, description and dissemination of health related information. ResearchEHR combines several tools to manage EHR at two different levels. The internal level that deals with the normalization and semantic upgrading of exiting EHR by using archetypes and the external level that uses Semantic Web technologies to specify clinical archetypes for advanced EHR architectures and systems. PMID- 20543321 TI - CEN EN13606 normalisation framework implementation experiences. AB - Since the approval of the CEN EN13606 norm for the electronic health record communication, a growing interest around the application of this specification has emerged. The main objective of the norm is to serve as a mechanism to achieve the semantic interoperability of clinical data. This will require an effort to use common terminologies, to normalise the clinical knowledge domain and to combine all these formalisations with the existing information systems. This paper presents a methodology and developed tools to reach the seamless semantic interoperability of health data in legacy systems and several study cases where the developed framework has been applied. PMID- 20543322 TI - Procuring interoperability at the expense of usability: a case study of UK National Programme for IT assurance process. AB - BACKGROUND: The allure of interoperable systems is that they should improve patient safety and make health services more efficient. The UK's National Programme for IT has made great strides in achieving interoperability; through linkage to a national electronic spine. However, there has been criticism of the usability of the applications in the clinical environment. METHOD: Analysis of the procurement and assurance process to explore whether they predetermine usability. RESULTS: Processes separate developers from users, and test products against theoretical assurance models of use rather than simulate or pilot in a clinical environment. The current process appears to be effective for back office systems and high risk applications, but too inflexible for developing applications for the clinical setting. CONCLUSIONS: For clinical applications agile techniques are more appropriate. Usability testing should become an integrated part of the contractual process and be introduced earlier in the development process. PMID- 20543323 TI - Health-Identity: mobile services for consumers of medicines. AB - New technologies for drug identification, traceability and mobile platforms make it possible to personalise the services provided to consumers of medicine. This paper presents the Health-Identity platform, a mobile application which gives consumers the assurance that the drug they have in their hands is a genuine product and can be consumed without risk according to their stored patient profile (allergies, health state, current medication, etc.). PMID- 20543324 TI - Alerts in clinical information systems: building frameworks and prototypes. AB - Alerts in Clinical Information Systems and CPOE are powerful tools for decision support. However, studies show that physicians override a large part of these alerts. Low specificity and high bandwidth of alerts lead to alert fatigue. Moreover, alerts seem to have usability issues as they are interrupting workflows and not always efficient to handle. This paper provides three different views on alerts: a system-based view, a human-computer interaction view and an organizational view. Based on this framework, we present a prototype of alert handling, which might ameliorate some of the problems with alerts. PMID- 20543325 TI - Tele-assistance for discharged patients supporting continuity of care. AB - The paper describes a tele-assistance / tele-monitoring system that assist discharged patients at their home. The system consists of units located at the homes of the monitored persons collecting and sending medical and environmental data from sensors and a call centre with a server for recording and monitoring the data. Here, specialized staff will support tele-surveillance and tele assistance services. The algorithm that describes the alarm processing related to the threshold conditions of the values read from the sensors is presented as one important part of the system functionalities. During the project an important activity was related to the integration of the devices used in the monitoring process. There were different devices and equipments from different companies and the integration was almost impossible. The solution was to create complex software that can make the things work together. PMID- 20543326 TI - Telemedicine fetal phonocardiography surveillance: an italian satisfactory experience. AB - In this paper we describe an Italian experience of fetal home monitor, organized using a portable phonocardiography system (product by Pentavox, Hungary), and the method utilized to evaluate its effectiveness in providing quality services and patient satisfaction. Patient satisfaction is an important dimension in the evaluation of quality care delivery. We used phonocardiography technique in our experience of fetal home monitoring as it is non invasive and passive in nature, low-cost and easy to use. A lightweight portable phonocardiograph (Fetaphon-home) was assigned to six selected patients, without effective pregnancy risk to monitor fetal heartbeat, uterine contractions and fetal movements at home or wherever they need it. The selected patients were instructed by trained personnel in the use of the monitoring device. Patients were asked to perform the recording two times a week and to transmit 20-min signal to the reference centre. The home monitoring sessions were performed in addition to the routine surveillance at a gynecologist's office; thus, the home monitoring did not replace clinic visits. The women were requested to fill a satisfaction questionnaire in order to evaluate their quality of life and anxiety state. Preliminary results have shown that home fetal surveillance appreciably reduces the need of travel for patients and consequently their stress. Furthermore, our results suggest that, after a short training, pregnant women are able to record and transmit long traces without troubles. Use of telemedicine system was generally well accepted by pregnant women since it increased the possibility of fetal long-term home surveillance which in turn could increase the efficiency of the service offered to them. PMID- 20543327 TI - Citizens, seamlessness, and care - inter-relationships and inter-operability. AB - Health care is currently fragmented, as are its IT systems, and each excludes partner care services which are important in supporting citizen health. Citizens see commercial international interoperability such as in banking, and wonder why the health sector cannot match that even at local level. The focus on inter operability priorities is on health system interoperability, in the context of a policy of full European interoperability by 2015. However, the priority for citizens is to see coordination of objectives and delivery of care and assurance of day-to-day delivery of integrated care involving not just health but other agencies. A change from international vertical healthcare inter-operability, to horizontal citizen-based inter-operability should be considered the priority. PMID- 20543328 TI - A framework for the development of patient safety education and training guidelines. AB - Patient Safety (PS) is a major concern that involves a wide range of roles in healthcare, including those who are directly and indirectly involved, and patients as well. In order to succeed into developing a safety culture among healthcare providers, carers and patients, there should be given great attention into building appropriate education and training tools, especially addressing those who plan patient safety activities. The framework described in this policy paper is based on the results of the European Network for Patient Safety (EUNetPaS) project and analyses the principles and elements of the guidance that should be provided to those who design and implement Patient Safety Education and training activities. The main principles that it should be based on and the core teaching objectives-expected outcomes are addressed. Once the main context and considerations are properly set, the guidance should define the general schema of the content that should be included in the Education and Training activities, as well as how these activities would be delivered. It is also important that the different roles of the recipients are clearly distinguished and linked to their role-specific methods, proper delivery platforms and success stories. Setting these principles into practice when planning and implementing interventions, primarily aims to enlighten and support those who are enrolled to design and implement Patient Safety education and training teaching activities. This is achieved by providing them with a framework to build upon, succeeding to build a collaborative, safety conscious and competent environment, in terms of PS. A guidelines web platform has been developed to support this process. PMID- 20543329 TI - Getting seamless care right from the beginning - integrating computers into the human interaction. AB - BACKGROUND: The digital age is coming to the health space, behind many other fields of society. In part this is because health remains heavily reliant on human interaction. The doctor-patient relationship remains a significant factor in determining patient outcomes. Whilst there are many benefits to E-Health, there are also significant risks if computers are not adequately integrated into this interaction and accurate data are consequently not available on the patient's journey through the health system. METHOD: Video analysis of routine clinical consultations in Australian and UK primary care. We analyzed 308 consultations (141+167 respectively) from these systems, with an emphasis on how the consultation starts. RESULTS: Australian consultations have a mean duration of 12.7 mins, UK 11.8 mins. In both countries around 7% of consultations are computer initiated. Where doctors engaged with computer use the patient observed the computer screen much more and better records were produced. However, there was suboptimal engagement and poor records and no coding in around 20% of consultations. CONCLUSIONS: How the computer is used at the start of the consultation can set the scene for an effective interaction or reflect disengagement from technology and creation of poor records. PMID- 20543330 TI - Analysis model for personal eHealth solutions and services. AB - In this paper, we present a framework for analysing and assessing various features of personal wellbeing information management services and solutions such as personal health records and citizen-oriented eHealth services. The model is based on general functional and interoperability standards for personal health management applications and generic frameworks for different aspects of analysis. It has been developed and used in the MyWellbeing project in Finland to provide baseline for the research, development and comparison of many different personal wellbeing and health management solutions and to support the development of unified "Coper" concept for citizen empowerment. PMID- 20543331 TI - Standardized and flexible health data management with an archetype driven EHR system (EHRflex). AB - To build a semantically interoperable Electronic Health Record is one of the most challenging research fields in health informatics. In order to reach this objective, EHR standards that formally describe health data structures have to be used. CEN EN13606 is one of the most promising approaches. It covers the technical needs for semantic interoperability and, at the same time, it incorporates a mechanism (archetype model) that enables clinical domain experts to participate in building an EHR system. In this paper we present EHRflex, a generic system based on archetypes. It empowers the clinician and allows him to manage his own EHR system in a simple and generic way, assuring that the user works with underlying standardized data structures. These can be exchanged with other people and systems when needed. EHRflex introduces EHR standards into the clinical routine delivering a technical platform which works directly on archetype based data. PMID- 20543332 TI - On a seamless transition from a running EPR system to a new one. AB - An approach is proposed to provide the transition from a running EPR system to a new one seamlessly and transparent for users. The essence of the approach is to use an industrial integration platform to build a transition platform for smooth transition. PMID- 20543333 TI - What is missing in health informatics standardization for pHealth? AB - Health systems turn everywhere, but with different speed, from organization centered to personalized eHealth or pHealth, i.e. ubiquitous care delivery independent of time and location of the resources involved. As interoperability is an important issue in such distributed, fully integrated, intelligent and individualized environment, pHealth solutions have to comply with advanced architectural solutions based on international standards. Representing concepts and their interrelations, such architectural framework perspectives' system architecture, domains, and development process can be described by the domains' ontologies. Therefore, advanced interoperability approaches have to refer to ontology principles, finally resulting in ontology-driven approaches to semantically interoperable and sustainable health information systems. The paper investigates functional requirements, interoperability levels, architectural approaches to pHealth systems, thereby analyzing and classifying related existing or emerging standards. PMID- 20543334 TI - Using collective intelligence to fine-tune public health policy. AB - The European Union Future Internet Assembly, the roadmap for the Web heading towards semantic interoperability and building on the UK's adoption of the Internet and social media are accelerating the development of Web 3.0. A number of health portals are opening, some with facilities for the capture of Patient Based Records. Collective Intelligence will be generated that, applied to health, has potential to support Public Health policy. By using the Internet, millions of people in the course of their daily activities contribute to uncertified data stores, some explicitly collaborating to create collective knowledge bases, some contributing implicitly through the patterns of their choices and actions. An application of soft computing, called Collective Health Intelligence, that reasons uncertified and certified data could enhance the social pool of existing health knowledge available to the public health agencies. Collective Health Intelligence could be used to complement national programmes by employing innovative sampling techniques, cost-effectively generating anonymous data trends that would quantify policy, indicate epidemiological effects and supply metrics to test policy efficacy. PMID- 20543335 TI - Quality evaluation of health information system's architectures developed using the HIS-DF methodology. AB - Requirement analysis, design, implementation, evaluation, use, and maintenance of semantically interoperable Health Information Systems (HIS) have to be based on eHealth standards. HIS-DF is a comprehensive approach for HIS architectural development based on standard information models and vocabulary. The empirical validity of HIS-DF has not been demonstrated so far. Through an empirical experiment, the paper demonstrates that using HIS-DF and HL7 information models, semantic quality of HIS architecture can be improved, compared to architectures developed using traditional RUP process. Semantic quality of the architecture has been measured in terms of model's completeness and validity metrics. The experimental results demonstrated an increased completeness of 14.38% and an increased validity of 16.63% when using the HIS-DF and HL7 information models in a sample HIS development project. Quality assurance of the system architecture in earlier stages of HIS development presumes an increased quality of final HIS systems, which supposes an indirect impact on patient care. PMID- 20543336 TI - Setting core standards: privacy, identity & interoperability. AB - This position paper focuses on strategic developments and underlying concepts emerging out of the standards and associated domains. It addresses the issue of personal privacy in the wider context of interoperability across an ever-growing range of e-health and social care support systems and processes. These will increasingly be driven by major growth in the elderly segment of national populations where unambiguous identification of both patients and care staff both in hospitals and the community will become significant issues. This is particularly so where remote patient monitoring and access control to personal data is concerned, and is further complicated where racial, cultural and linguistic barriers are prevalent. PMID- 20543337 TI - An improved method of measurement of ECG parameters for online medical diagnosis. AB - The accuracy in the online measurement of ECG parameters has a decisive role in the better diagnosis and effective treatment of the diseases. The present paper describes a Lab-VIEW based programming using Pan Tompkins method to extract out QRS complex whereas QT interval measurements were carried out using Mat-lab based math-script module. Hilbert transform has been applied on the ECG signal to convert it into an analytical signal for better peak detection. Peak detection and other parameters like RR interval, HR and several time domain measures of heart rate variability such as RR mean and standard deviations, HR mean and standard deviations, RMSSSD, NN50 count, pNN50 etc were calculated for several other clinical applications apart from online disease diagnosis. PMID- 20543338 TI - Evaluation of response time delay of a pen-tablet system in thin-client computing environments: implications for usability. AB - Changeover from the traditional paper-based patient records to the computerized patient records has been spreading rapidly in medical facilities. Since ordinary input devices such as a keyboard and mouse are often thought insufficient for the needs of medical workers using electronic patient records (EPR) compared with traditional pens and paper-based patient records, a pen-tablet system (PTS) as a digital pen interface tends to be used instead. On the other hand, with the growing adoption of thin-client computing (TCC) in medical facilities, the usability of PTS with TCC has come to be a concern because of possible reduction of the usability due to delays of response time occurring in TCC environments. To analyze the factors that influence the usability of PTS with TCC, the authors focused on the relationship between length and its scattering of the response time delay. The results indicated that the delay scattering could be a more influencing factor than the delay length itself and that values of the scattering should be within approximately 35 milliseconds for the best usability. This study would provide useful indicators for evaluating the usability of PTS in incorporating it into the EPR system with TCC environments. PMID- 20543339 TI - Development of an alarm management system to manage those alarms occurred during the illness prevention and management inside and outside the hospital environment. AB - A great amount of information is available to be exploited thanks to the use of information technologies. However, the systems that analyze this data lack the ability to alert the right clinical staff to important events, having some of the latest developments centered on the possibility of sending events from specific areas. The following system tries to solve these dependencies and offers a unique system capable of analyzing any data source and communicates the alarms through different means in an effective way. PMID- 20543340 TI - Metaboli-Net: online groupware system providing counseling guidance for patients with metabolic syndrome. AB - This study presented a newly developed online groupware system, Metaboli-Net, to yield counseling guidance on diet and exercise to patients with metabolic syndrome. A distinctive feature adopted in the system to maintain the retention rate of patients was the social network service (SNS) that enables the patients to share their dietary and relevant health information with other participants in the same group on the network. A pilot study was conducted to prove the effectiveness of the system in improving the patient's lifestyle and dietary health awareness. SNS also contributed to the participant's adherence to intervention programs. PMID- 20543341 TI - The potential of RFID technology in Blood Center processes. AB - Current RFID technology deployment is limited by safety, procedural and physical limitations in healthcare field. It is important to define and ensure safe operation of technologies without actual deployment in real operation. Potential problems could arise due to the consequences of technical and physical characteristics of RFID technology and its improper location. This article deals with manipulation of blood products and the definition of suitable places for radio identification. Each suitable place must undergo laboratory experiments and tests. The results can provide a convenient base for defining efficient and safe deployment of RFID technology in Blood Centers with substantial financial savings for Czech healthcare. PMID- 20543343 TI - Co-morbidity analysis and decision support on transplanted patients using machine learning techniques. AB - The A Coruna University Hospital Complex is developing an expert system to improve the decision support for transplanted patients. The system will access the data collected during the monitoring of patients and generate a database of statistics that will aid health professionals in several stages of the transplant process. All historical data will be revised to give an estimation of the patient's parameters evolution depending on his medical record and his actual treatment. We will use two different machine learning techniques to do both clustering and classification. PMID- 20543344 TI - Effective e-learning for health professional and medical students: the experience with SIAS-Intelligent Tutoring System. AB - Current e-learning systems are still inadequate to support the level of interaction, personalization and engagement demanded by clinicians, care givers, and the patient themselves. For effective e-learning to be delivered in the health context, collaboration between pedagogy and technology is required. Furthermore, e-learning systems should be flexible enough to be adapted to the students' needs, evaluated regularly, easy to use and maintain and provide students' feedback, guidelines and supporting material in different formats. This paper presents the implementation of an Intelligent Tutoring System (SIAS-ITS), and its evaluation compared to a traditional virtual learning platform (Moodle). The evaluation was carried out as a case study, in which the participants were separated in two groups, each group attending a virtual course on the WHO Integrated Management of Childhood Illness (IMCI) strategy supported by one of the two e-learning platforms. The evaluation demonstrated that the participants' knowledge level, pedagogical strategies used, learning efficiency and systems' usability were improved using the Intelligent Tutoring System. PMID- 20543345 TI - A communication standards ontology using basic formal ontologies. AB - Working interoperability not only requires harmonized system's architectures, but also the same interpretation of technical specifications in order to guide the development process. This paper analyses the commonly used structures of communication standards elaborated with HL7 Version 3 and proposes an ontological structure resulting in the so-called Communication Standards Ontology (CSO). As such a solution has to be developed within an architectural framework, the approach is aligned with the Generic Component Model (GCM). PMID- 20543346 TI - User-specific perspectives on ontologies. AB - Ontologies are more and more used in clinical informatics in different settings and supporting different functionalities. Most experts see the role of ontologies as operating in a black box and being invisible for the end-user. With respect to some of the systems that have recently been developed this is only partly possible. Therefore, we provide a methodology to create an end-user perspective on a clinical ontology. This will foster participation of the clinical expert in both ontology exploitation and ontology maintenance. This methodology does not only provide the basis for a better integration of the experts into the ontology based system, but it can be used to support patient empowerment by helping the patient to understand the content that is stored and partake in its management. PMID- 20543347 TI - Management of knowledge gaps: concept representation of things we don't know. AB - Suva (Swiss National Accident Insurance Fund) is the most important carrier of obligatory accident insurance in Switzerland. Its medical division supports doctors working in inpatient and outpatient care with comprehensive case management and with conciliar advice. The Suva hospitals provide inpatient rehabilitation. In 2002, Suva started the InWiM project. InWiM is an acronym and stands for "Integrierte Wissensbasen der Medizin", which can be translated as "Integrated Knowledge Bases in Medicine". Information retrieval within InWiM is achieved by means of the MeSH Index (Medical Subject Headings), the thesaurus of the United States National Library of Medicine (NLM). InWiM has now been extended towards the management not only of publications but also of areas where sound knowledge is missing, so called "knowledge gaps": Knowledge gaps are indexed with MeSH terms in a similar way to publications. This improves knowledge management: In particular it is possible to search and find knowledge gaps and solutions covering the same or a similar topic, thus allowing adequate collating and it prevents duplication of work. Furthermore, literature search strategies for the NML are predefined and do not need every time to be reinvented from scratch. PMID- 20543348 TI - An ontology-based tool for the correspondences between specialist and consumer medical lexicons for the geriatrics domain. AB - New services devoted to improve personalized healthcare are emerging from information technology developments. Personal health record systems allow the patients to participate actively in their healthcare process. However, the dissemination and use of personal health record systems face with some barriers, for example low health literacy that leads to discrepancy in understanding medical concepts. While it is important to present health information using consumer-familiar terms in consumer applications, consistently converting medical terms to consumer-familiar ones is a challenging task. We designed and developed both an ontology-like taxonomic structure devoted to the Geriatrics domain for the outpatient and a software tool, for carrying out the matching between the medical vocabulary of the consumer and that of the doctor from the outpatient's and their family point of view. PMID- 20543349 TI - Exploring the link between populomics and knowledge management: patient-oriented case exemplars. AB - The challenge of population-level health problems, such as healthcare disparities, encompasses socio-behavioural, community and biologic factors and advances in information and communication technologies (ICTs). These elements are reflected in the key ethos of contemporary knowledge management (KM), as knowledge emerges from the confluence of people, process and technology. This paper illustrates how knowledge-based health case studies can be used as effective exemplars to illuminate understanding and explore possible connections between populomics and KM. PMID- 20543350 TI - Standardized vectorial representation of medical data in patient records. AB - In this paper standardized vectorial (quantitative) representation of medical data is suggested for use in patient records. Vectorial representations are (as sequences of numbers) language independent, precise, directly comparable, and they allow advanced evaluation, e.g. similarity calculation using well defined distance functions. It is possible to search for a patient with a certain combination of diagnostic parameters on the Web records of patients with similar parameters. The information about chosen treatments and treatment outcome at these patients can be used anonymously or pseudonymously for decision support. Because patient records from all countries can be compared, in the long run this could open systematic access to a very large wealth of clinically relevant information. Here the technical principle is described and illustrated by examples (e.g. similarity search of heart sounds). Previously published material is integrated in parts for explanation of the motivation and background. PMID- 20543351 TI - Clinical events classification for using the EHR to provide better patient care. AB - The Healthcare Record has been used in a "Before and After" situation to improve patient care. The main paradigm of the modern Health Care is changing towards pervasive person-centric care including prevention and home care. Medical compunetics is a very important applicative field for improving the interoperability and the quality of the healthcare information system, especially in the current climate with the empowerment patients. The success depends on the choice of the Clinical Events Classification for structuring the span of clinical information. For the purposes of universalizing medical electronic data-bases, it is very important to organize the data regarding Clinical Events in such manner that it would be possible to use this information-structure in different fields of Clinical Practice: e.g., for the creation of the diagnostic and drug assistance protocols, for the evaluation of the quality of drug prescribing, and for communication with patients as well. For this purpose all Clinical Events were divided to 5 classes. This Paper will describe a "Before and After" situation consequent upon the introduction of the Clinical Events Classification and the introduction of Protocols for drug-prescribing. Use of the Protocol brought about a 50% reduction in mortality. PMID- 20543352 TI - Patient opportunities in the Estonian Electronic Health Record System. AB - Estonia is the first country which has implemented a nationwide electronic health record system and gives full access to its citizens. This provides new opportunities to citizens, healthcare providers and e-health developers. Combining health data, citizens' self added health and welfare data, decision support and possibilities of service oriented architecture of the Estonian Electronic Health Record System - a new era of e-health services can begin. PMID- 20543353 TI - Holism, health and data - managing the person-centred digital haystack. AB - There is currently very legitimate pressure to change the function of health information systems to more explicitly serve and support the individual. Concurrently other support services to health, including condition monitoring, social care and intelligent housing, add to the complexity of patient health related data. A paradigm shift is needed, to recognize that many agencies and systems outside as well as within the health sector all work to support the citizen's health, yet the essential integrated view is not being provided, even though much needed not least by the citizen and their agents. Broker technologies can enable this new paradigm. Moreover, a move to identifying the patient's appointments and support services would enable a daily life dimension to be given due weight, and would recognize the patient's viewpoint in wanting to live an ordered life, not one subservient and reactive to the delivery of care by providers. PMID- 20543354 TI - The mixed management of patients' medical records: responsibility sharing between the patient and the physician. AB - Through this article, we propose a mixed management of patients' medical records, so as to share responsibilities between the patient and the Medical Practitioner by making Patients responsible for the validation of their administrative information, and MPs responsible for the validation of their Patients' medical information. Our proposal can be considered a solution to the main problem faced by patients, health practitioners and the authorities, namely the gathering and updating of administrative and medical data belonging to the patient in order to accurately reconstitute a patient's medical history. This method is based on two processes. The aim of the first process is to provide a patient's administrative data, in order to know where and when the patient received care (name of the health structure or health practitioner, type of care: out patient or inpatient). The aim of the second process is to provide a patient's medical information and to validate it under the accountability of the Medical Practitioner with the help of the patient if needed. During these two processes, the patient's privacy will be ensured through cryptographic hash functions like the Secure Hash Algorithm, which allows pseudonymisation of a patient's identity. The proposed Medical Record Search Engines will be able to retrieve and to provide upon a request formulated by the Medical Practitioner all the available information concerning a patient who has received care in different health structures without divulging the patient's identity. Our method can lead to improved efficiency of personal medical record management under the mixed responsibilities of the patient and the MP. PMID- 20543355 TI - A context-aware approach to process-based PHR system security. AB - Healthcare delivery is a highly complex process involving a broad range of healthcare services, typically performed by a number of geographically distributed and organizationally disparate healthcare providers requiring increased collaboration and coordination of their activities in order to provide shared and integrated care. Under an IT-enabled, patient-centric model, health systems can integrate care delivery across the continuum of services, from prevention to follow-up, and also coordinate care across all settings. In particular, much potential can be realized if cooperation among disparate healthcare organizations is expressed in terms of cross-organizational healthcare processes, where information support is provided by means of PHR systems. This paper assumes a process-oriented PHR system and presents a security framework that addresses the authorization and access control issues arisen in these systems. The proposed framework ensures provision of tight, just-in-time permissions so that authorized users get access to specific objects according to the current context. These permissions are subject to continuous adjustments triggered by the changing context. Thus, the risk of compromising information integrity during task executions is reduced. PMID- 20543356 TI - Patient empowerment by the means of citizen-managed Electronic Health Records: web 2.0 health digital identity scenarios. AB - With the advent of more sophisticated and comprehensive healthcare information systems, system builders are becoming more interested in patient interaction and what he can do to help to improve his own health care. Information systems play nowadays a crucial and fundamental role in hospital work-flows, thus providing great opportunities to introduce and improve upon "patient empowerment" processes for the personalization and management of Electronic Health Records (EHRs). In this paper, we present a patient's privacy generic control mechanisms scenarios based on the Extended OpenID (eOID), a user centric digital identity provider previously developed by our group, which leverages a secured OpenID 2.0 infrastructure with the recently released Portuguese Citizen Card (CC) for secure authentication in a distributed health information environment. eOID also takes advantage of Oauth assertion based mechanisms to implement patient controlled secure qualified role based access to his EHR, by third parties. PMID- 20543357 TI - A neuro-fuzzy decision support system for the diagnosis of heart failure. AB - A neuro-fuzzy decision support system is proposed for the diagnosis of heart failure. The system comprises; knowledge base (database, neural networks and fuzzy logic) of both the quantitative and qualitative knowledge of the diagnosis of heart failure, neuro-fuzzy inference engine and decision support engine. The neural networks employ a multi-layers perception back propagation learning process while the fuzzy logic uses the root sum square inference procedure. The neuro-fuzzy inference engine uses a weighted average of the premise and consequent parameters with the fuzzy rules serving as the nodes and the fuzzy sets representing the weights of the nodes. The decision support engine carries out the cognitive and emotional filtering of the objective and subjective feelings of the medical practitioner. An experimental study of the decision support system was carried out using cases of some patients from three hospitals in Nigeria with the assistance of their medical personnel who collected patients' data over a period of six months. The results of the study show that the neuro fuzzy system provides a highly reliable diagnosis, while the emotional and cognitive filters further refine the diagnosis results by taking care of the contextual elements of medical diagnosis. PMID- 20543358 TI - Rules and access rights of the Estonian integrated e-Health system. AB - There should be a clear understanding that when implementing an electronic health record system (EHR), one of the hardest problems we have to solve is the access rights. In Estonia this process lasted for three years and involved all stakeholders of the healthcare sector. Special ethical committee was established to advise the decision makers and doctors to help them understand the ethical dilemmas from the patient's and society's point of view. In this article you will find a short overview of the access rights of the system, roles of the healthcare systems' employees. Descriptions of some specific situations like underage patients and representation of patient with restricted active legal capacity. PMID- 20543359 TI - From safe systems to patient safety. AB - In this introduction we summarize the contributions to the Fourth International Conference Information Technology in Health Care: Socio-technical Approaches. We argue that putting to use information systems in health care is a difficult and winding road. Systems may even compromise instead of improving patient safety. Designing and implementing systems requires a thorough understanding of the context in which technology is being used. But this understanding should also lead to better design and implementation methods. Therefore this conference wishes to address the challenges of safe systems and patient safety, ten years after the publication of the landmark reports on human error and quality of health care by the Institute of Medicine. PMID- 20543360 TI - Healthcare IT usability and suitability for clinical needs: challenges of design, workflow, and contractual relations. AB - While healthcare information technology (HIT) offers extraordinary promise of clinical improvement and greater efficiencies, the realization of the promise must confront and overcome a number of challenges caused by incomplete and inappropriate software design. In this paper, we review several types of HIT design and workflow decisions that limit the value and utility of HIT in electronic health (medical) record (EHR/EMR), computerized physician order entry (CPOE), and electronic medication administration record (eMAR) systems. While remedies for problems of design or workflow may be either easy or difficult, , the industry creates additional barriers in the contractual relationships it creates between itself (HIT vendors) and the clinical facilities (hospitals, clinics, and physician offices) that purchase its systems. We suggest that the structure of those relationships may retard the progress and responsiveness of HIT. PMID- 20543361 TI - Aggregated review of route cause analyses related to medication. AB - Since 2001 when the systematic analysis of serious patient safety incidents was implemented, a number of root cause analyses have been completed. Common to these is that the medication of the patient has been problematic and has had serious consequences for the patient. In the analyses the events causing the patient safety incidents are described in detail, the causes are identified and a plan of actions is created. PMID- 20543362 TI - Sustained participatory design and implementation of ITHC. AB - Participatory design includes engaging in large-scale information-systems development where participatory design approaches have been applied throughout design and organizational implementation. The keynote suggest to extend the iterative prototyping approach by (1) emphasizing participatory design experiments and pilot implementations as transcending traditional prototyping by evaluating fully integrated systems exposed to real work practices; (2) incorporating improvisational change management including anticipated, emergent, and opportunity-based change; and (3) extending initial design and development into a sustained and ongoing implementation that constitutes an overall technology-driven organizational change. This sustained participatory design and implementation approach is exemplified through a large-scale project in the Danish healthcare sector. PMID- 20543363 TI - Sociotechnical changing in healthcare. AB - This paper discusses a conceptual approach to the study of the implementation of ICTs in healthcare organizations. The paper uses some fundamental concepts from sociotechnical studies to address the complex process of change--the changing- that accompanies ICT innovations. The paper argues for the importance of the perspective of changing as a way to account for the dynamics as technology and people, organizations and institutions co-constitutively work-out their future together. PMID- 20543364 TI - The sociotechnical configuration of the problem of patient safety. AB - This paper discusses two approaches to "the sociotechnical", one coming from the Tavistock tradition and the other from actor network theory. These two differ in important ways and from the latter it follows that what patient safety means must be scrutinized and unpacked. The paper thus rudimentarily discusses central contributions to the problematization of patient safety. Last, it is argued that patient safety does not exist apart from the sociotechnical practices that seek to accomplish it, but is constructed in and through them, which is why it is pertinent to reflect on how those practices constructs what comes to qualify as patient safety. PMID- 20543365 TI - How to dwell in an EHR. The question concerning architecture EHR. AB - The article deals with architecture and EHRs on a conceptual and philosophical level. Architecture is seen as the essential human expression of being, exemplified through the thoughts and writings of the German architect Gottfried Semper, the American architect Philip Johnson and the German philosopher Martin Heidegger. It is the assumption of the article that the current versions of EHR architectures are the result of a technical and systemic perspective on architecture, as opposed to the thoughts of Semper, Johnson and Heidegger. The article has a value-based and phronetic approach to the topic field, and claims that construction of EHRs should be a matter of concern, and not, as it is for now, a matter of fact. PMID- 20543366 TI - Pilot users in agile development processes: motivational factors. AB - Despite a wealth of research on user participation, few studies offer insights into how to involve multi-organizational users in agile development methods. This paper is a case study of user involvement in developing a system for electronic laboratory requisitions using agile methodologies in a multi-organizational context. Building on an interpretive approach, we illuminate questions such as: How does collaboration between users and developers evolve and how might it be improved? What key motivational aspects are at play when users volunteer and continue contributing in the face of considerable added burdens? The study highlights how agile methods in themselves appear to facilitate mutually motivating collaboration between user groups and developers. Lessons learned for leveraging the advantages of agile development processes include acknowledging the substantial and ongoing contributions of users and their roles as co designers of the system. PMID- 20543367 TI - Designing shared electronic records for chronic care. AB - This paper reports preliminary findings from an ongoing research project on the development of IT support for communication and information sharing across institutional and professional boundaries within the Danish healthcare system. The project focuses on the treatment of patients with implanted ICDs (implantable cardioverter-defibrillator). These are chronic patients who usually see several different healthcare providers on a regular basis. The main findings so far are: (1) Most of the data produced and recorded as part of the care process are context-specific and often difficult to interpret unless you are an expert on the subject. Sharing these types of data across institutional and professional boundaries is not feasible. (2) Yet, it appears that a small subset of data can make sense across the different contexts and be of use to others. These data are good candidates for sharing. (3) In addition, there appears to be a need for creating new types of data specifically designed to meet the coordination needs across different contexts and expert domains. (4) The dilemma is, however, that the production of these new types of data must not require too much extra work. PMID- 20543368 TI - Participatory (re)design of a sociotechnical healthcare delivery system: the Group Health Patient-Centered Medical Home. AB - This paper describes one organization's interpretation of the Patient-Centered Medical Home concept and the healthcare delivery system that has emerged from their participatory redesign initiative. Group Health, a large integrated healthcare system based in Seattle, Washington, USA initiated a Patient-Centered Medical Home care delivery system transformation in January 2007. Current theories and evidence about the Patient-Centered Medical Home (PCMH), the Chronic Care Model, and effective primary care were interpreted via a facilitated group process and translated into a core set of 5 system design principles. These design principles guided all subsequent system transformation activities. The central organizing principle is supporting and sustaining the patient-primary care physician relationship. The emergent PCMH healthcare delivery system comprises both opportunistic point-of-care and outreach components, many of which leverage and enhance the organization's health information and communication technologies. PMID- 20543369 TI - Patients and professionals in collaborative testing of a web-based tool for integrated care: an evaluation study. AB - Since 2001, patients in Norway with long-term, complex needs for care have had a legal right to an "individual care plan", intended to increase efficiency and quality in health and social services, as well as patient involvement. Commonly, a responsible group is established to manage the planning process. A web-based application was developed and tested for three years in groups including both patients and professionals. Data were collected through questionnaires, interviews, project documentation and field notes. The findings showed that iterative testing improved usability. Participants expressed confidence in the online access and their enhanced control of planning and documentation. Testing in real-life environments added valuable and unforeseen information. It also showed that technical and organizational aspects influenced each other, and should not be considered separately. Despite the successful testing and improvement of the application, some participants and groups did not feel comfortable using it. Further research will be undertaken to address barriers to participation. PMID- 20543370 TI - Communication challenges in system development: involvement of system developers in small-scale IT projects. AB - A well-known challenge in system development is the aspect of user participation. In this paper we shift perspective from how to involve users in system development to how project managers with a clinical background, but without technical system knowledge, can involve system developers in IT projects. Using data from the development of an online patient book (an ICT application for clinical practice), we analyze challenges using the concept of language-games. We conclude that further research and development of participatory and communicative methods to involve system developers in IT projects, based in a clinical context, is needed. PMID- 20543371 TI - Sociotechnical integration of decision support in the dementia domain. AB - The need for improving dementia care has driven the development of the clinical decision support system DMSS (Dementia Management and Support System). A sociotechnical approach to design and development has been applied, with an activity-centered methodology and user participation throughout the process. Prototypes have been developed based on the characteristics of clinical practice and domain knowledge, while clinical practice has been subjected to different efforts for development such as education and organizational change. This paper addresses the lessons learned and role and impact DMSS has had, and is expected to have on the clinical assessment of dementia in different clinics in Sweden, South Korea and Japan. Furthermore, it will be described in what way the development of DMSS and the development of dementia care in these three areas are interlinked. Results indicate that the most important contribution of DMSS at the point of care, is the educational support that DMSS provides, part from the tailored explanatory support related to a patient case. This effect was partly manifested in a change of routines in the encounter with patients. PMID- 20543372 TI - Standardization--the iron cage of nurses' work? AB - This paper explores how nursing classification has been adopted and used in a local clinical practice. The study is inspired by the socio-technical approach to information system and illustrates some of the enabling and constraining properties of standardization. Findings from the study show how international standards have been embedded into local practice. At the same time, the use of locally developed standards has increased and many of these are similar to the international classification. This indicates that we need to move beyond the dichotomous perspective on nurses' use of classification and strive for more flexible solutions. PMID- 20543373 TI - Standardized nursing work: works in practice but not in theory? AB - Socio-technical approaches have established that ICT-supported standardization of healthcare work is difficult, if not impossible. We argue that standardization is neither straightforward nor uncontroversial, but discuss an interpretative case study where standardization of nursing work--to an interesting degree--has been achieved. Our case suggests that co-constructing of the standards is essential to standardization in practice. This is partly imposed from the top, and partly accomplished through the active involvement and ingenuity of users. PMID- 20543374 TI - Cafe seminars in a bottom-up organizational development project at a Danish Radiology Department. AB - The radiology department at a Danish regional university hospital implemented integrated RIS/PACS. In the process, it became clear that some aspects of the changes had been ignored and that the impact on the organization would be substantial. With that in mind this study was planned, and an interdisciplinary working group was appointed and tasked with implementing activities to improve the organizational environment and atmosphere in the department. One activity aimed at formulating a vision/activity plan by using cafe seminars to involve all employees. The plan for implementation included 35 activities to support the realization of the vision. Bottom-up organizational development does work - provided that responsibility for the process is delegated. PMID- 20543375 TI - Collaboration across organizational boarders, the referral case. AB - Referrals are requests for medical examination and evaluation by a specialist, outpatient clinic or a hospital. The referral can be sent from a GP, specialist or from one hospital to another. The referral transfers fully or partly the responsibility for further treatment of the patient. The diffusion of electronic referrals in the health sector has been slow in many countries despite the fact that EHR-systems, referral standards and technical infrastructure are available. This paper addresses shortcomings that have been seen in the Norwegian deployment process, and how collaboration can support, and be supported by, the involved actors in different organizations. Special attention is paid to how GPs that work in part time positions as practice consultants in Hospitals can act as boundary spanners in order to improve the collaborating actors understanding of each other's needs and work processes. Practice consultant should also be used actively in design of ICT-systems that support collaboration across organizational boarders in health care. PMID- 20543376 TI - Organizational considerations for the implementation of a computerized physician order entry. AB - Several studies stressed that the introduction of CPOE applications deteriorates the doctor-nurse communication. But there are many factors that might influence communication behaviors, as for example the way these communications are organized. The present study aims at showing that the impact of a CPOE system on the cooperative activities can be controlled given that a good understanding of the cooperative workflows support the implementation. By analyzing the doctors nurses communications during the medication use process, the study demonstrates that the technical system has no impact on the cooperative activities within a given organization. CPOE does not induce differences in the dialogs' durations and contents. PMID- 20543377 TI - Issue orders and discontinued EPR. AB - Users gave us 104 different reasons for the failure of implementing an EPR in a surgical clinic. We classify the reasons with the issue order model, where the first issue level is for simple and technical issues, the second one for more complex and combined issues, and the third one for political or ideological issues. However, what appears as a first order issue to a manager might be seen as an insurmountable third order issue for a worker and vice versa. The issues are interrelated, and solving one issue might have a substantial influence on other issues. Also, the issues seemed to accumulate and concentrate on points. The analysis helps focus on key problems, with consideration to related issues. PMID- 20543378 TI - Sustainable mobile information infrastructures in low resource settings. AB - Developing countries represent the fastest growing mobile markets in the world. For people with no computing access, a mobile will be their first computing device. Mobile technologies offer a significant potential to strengthen health systems in developing countries with respect to community based monitoring, reporting, feedback to service providers, and strengthening communication and coordination between different health functionaries, medical officers and the community. However, there are various challenges in realizing this potential including technological such as lack of power, social, institutional and use issues. In this paper a case study from India on mobile health implementation and use will be reported. An underlying principle guiding this paper is to see mobile technology not as a "stand alone device" but potentially an integral component of an integrated mobile supported health information infrastructure. PMID- 20543379 TI - Where Superman is not on staff--on implementation and lacking feedback. AB - Computer systems tend to deliver less than promised. In this article we investigate mechanisms that contribute to this gap through a computer system supposed to facilitate discharge planning. The aim of this system is to increase efficiency and quality, and make information exchange safer. We do the investigation from the perspective of Science and Technology Studies (STS) and skill acquisition. We find that information tends to be hindered from entering the system, rather than ending up in the wrong places as the case was before. Further knowledge that earlier was gleaned from person to person interaction is missing out. Despite being sparse and limited, the information stored in the system is sufficient to enable action. We therefore see that one risk is exchanged for another. In total, patient safety might suffer, and hence staff ought to compensate for this. This in turn reduces efficiency and hence also the promised gain from the system. PMID- 20543380 TI - Compliance or patient empowerment in online communities: reformation of health care services? AB - New technologies enable a different organization of the public's admission to health care services. The article discusses whether online support groups in patient treatment are to be understood in the light of patient empowerment or within the tradition of compliance. The back-ground material of the discussion is complementary data from quantitative research on characteristics of patient support groups, and from two qualitative, in depth studies of the impact of patient networks for lung patients and for women with fertility problems. We conclude that in spite of the potential of online communities of opening up health care to the critical voice of the public, the quantitative and qualitative studies surprisingly point to a synthesis of the otherwise opposite positions of empowerment and compliance in patient care. Thereby the critical potential of online communities in health care services seems reverted into configuring ideal patients from diverse users. PMID- 20543381 TI - Does telehomeconsultation lead to substitution of home visits? Analysis and implications of a telehomecare program. AB - This study's objective was to determine and to explain the potential substitution effects of a nurse-led video teleconsultation service for homecare clients. To that end the largest program in the Netherlands up till 2009 was analyzed. This program's aim was to realize partly substitution of homecare visits by telecare for carefully selected clients. The study was multi-method. Each video contact was registered, and a sample was described on forms during an 8- month period starting half a year after implementation. (Changes in) the homecare visit consumption of the subscribing (n=335) and of a non-subscribing group (n=288) were compared. Moreover, we interviewed care coordinators, clients, managers, and telenurses and observed the latter's work. Results show that the frequency of telehomecare contacts varied greatly. For this homecare client population the sheer provision of a video channel to nurses does not lead to substitution. Only for a few clients substitution of the regular homecare visits proved feasible The discussion section explains this disappointing outcome by technology push and an inconsistent implementation mode. It is argued that telehomecare can potentially serve four different goals, including substitution. For future research we propose consistent implementation modes to realize these goals. PMID- 20543382 TI - IT for learning diabetes. AB - This paper calls for IT supporting learning of diabetes self-management. Challenges of self-management and traditional IT tools for self-management are outlined--problems with data discipline, motivation of self-management, and learning as only an add-on to existing technologies. There is a call for IT focused on supporting learning in educational settings in an engaging manner. Two central self-management skills are identified: counting of carbohydrates and the understanding of the dynamics of diabetes factors. Three prototypes designed to support the learning of these skills are presented. Results from the prototype explorations emphasize the need for considering social aspects in learning with IT. PMID- 20543383 TI - Use of "serious health games" in health care: a review. AB - This inter-disciplinary literature review examines current and potential uses of so-called "Serious Games" in health care. Based on a core body of 51 articles about Serious Games (12 pertaining specifically to health care), it briefly examines examples of use for training professionals, but focuses mostly on how games are used for patient treatment or education and how they can be used for disease prevention and health promotion. This article highlights considerations that must be made when designing and implementing Serious Games for these purposes. PMID- 20543384 TI - From clinical practice guidelines, to clinical guidance in practice--implications for design of computerized guidance. AB - This paper presents a case study of clinical guidance within oncology clinics. Close to all patients treated within the observed clinics were treated according to a research or standard treatment protocol. The protocol artifacts were however rarely applied in clinical practice instead we found an extensive application of what we have named second order guiding artifacts. The deployed protocols underwent a local adaptation and transformation process when initiated. The protocols were adapted to match the local resources and transformed into several activity specific second order guiding artifacts. The transformation from protocols was executed according to a standard operating procedure. Each activity type had a standardized template ensuring uniformity across second order guiding artifacts within a clinic. The guiding artifacts were multi-functional and a wide variety of standardized graphical attributes were applied to support effortless appliance. The implications for computerization of clinical practice guidelines are discussed. PMID- 20543385 TI - Improving health IT through understanding the cultural production of safety in clinical settings. AB - Health IT is said to have the potential to improve the safety and effectiveness of care. However, it is known that the implementation of health IT can introduce new risks into the environment of care as a result of design failures, implementation failures, and unintended consequences. The design and implementation of health IT systems reflect explicit or implicit assumptions about what constitutes safe practice. These assumptions may clash with those held by patients and clinicians who are the intended users and subjects of the technology. Current perspectives on risk are discussed and an anthropological approach to understanding the construction of safe practices in the clinical setting is explored using research in barcode medication administration. PMID- 20543386 TI - Integrating technology-centric and user-centric system testing methods: ensuring healthcare system usability and safety. AB - The objective of this paper is to describe a framework for system testing in response to the need to ensure both the usability and safety of healthcare information systems. The approach includes consideration of methods that include both conventional computer software testing approaches (i.e. technology-centric approaches) and extends conventional testing to include consideration of system impact in terms of both usability and workflow (i.e. user-centric testing approaches) prior to system release. The paper describes these main approaches. It is argued that both technology and user-centered approaches should be employed before the release of a complex health information system in order to ensure that it is safe and does not inadvertently introduce error. PMID- 20543387 TI - Towards safer medication use--in practice. AB - We study the drug order and delivery process for patients receiving municipal home care services in Norway. Using interpretative qualitative methods we document an extensive but "invisible" manual and distributed quality assurance among the involved health care providers. We call for selective automation of medication use processes in this setting as these distributed, highly manual micro-practices are vital to quality assurance in practice. PMID- 20543388 TI - Patient safety and sociotechnical considerations for electronic handover tools in an Australian ehealth landscape. AB - The Australian Commission for Safety and Quality in Health Care (ACSQHC) coordinates national improvements in a range of complex health system problems including clinical handover, and has funded a range of handover improvement projects in Australia. One of these, the SafeTECH project in South Australia has developed guidelines for safe use of electronic handover tools. These guidelines were developed using evidence from three hospital case studies into the use of an electronic tool to support different types of shift-to-shift handover. This paper provides an overview of the project, and highlights challenges for patient safety in the design and use of electronic tools to support clinical handover in a busy clinical environment. The paper then considers these challenges within the broader context of the Australian ehealth landscape. Australia's National eHealth Transition Authority (NEHTA) is actively developing ehealth standards and infrastructure requirements for the electronic collection and secure exchange of health information. The paper argues for flexible standardisation in the design and implementation of electronic handover tools to ensure that all key dimensions of the challenges faced in ensuring patient safety are addressed. PMID- 20543389 TI - Patient safety, resilience and ICT. A reason for concern? AB - During my studies of the implementation of a new hospital wide information system for medical charts, the project's impact on patient safety emerged as a topic of interest for the clinicians involved. While Karl Weick [1] applies the law of requisite variety to illustrate the correlation between professional variety and medical errors, it is argued here that a similar notion could be applied to the variety in modes of information in hospitals. Based on this, the question is raised whether or not the introduction of standardized computer systems at the expense of existing solutions could pose a threat to this variety, and subsequently to the hospital's resilience in handling uncertainty. PMID- 20543390 TI - Socio-technical challenges in implementing safe patient handovers. AB - Ineffective handovers in patient care, including those where information loss occurs between care providers, have been identified as a risk to patient safety. Computerization of health information is often offered as a solution to improve the quality of care handovers and decrease adverse events related to patient safety. Drawing on three ethnographic case studies we identify and discuss socio technical issues which must be addressed if computerized health information systems are to achieve improvements in patient safety related to handovers in care. We suggest that the contextual nature of information, ethical and medico legal issues arising in relation to information handover and data standards and system integration warrant ongoing research in socio-technical aspects of care handovers. PMID- 20543391 TI - Recent advances in the study of candidate genes for adolescent idiopathic scoliosis. AB - We used a microarray approach to evaluate gene expression profiles in human AIS osteoblasts, and to identify genes that are differentially expressed following estrogen exposure in non-AIS and AIS human osteoblasts. We found that more than one gene is likely responsible for AIS. Furthermore, some of these genes are estrogen-regulated, suggesting a possible role of estrogens in the etiology of scoliosis. PMID- 20543392 TI - The role of remodeling and asymmetric growth in vertebral wedging. AB - BACKGROUND: Scoliosis with vertebral wedging is thought to be caused by asymmetric growth (Hueter-Volkmann law), but vertebral diaphyseal remodeling (Wolff's law) may also contribute to the deformity. We investigated whether vertebral wedging in scoliosis might involve both mechanisms. METHODS: An external fixator was used to impose a 30 degrees scoliosis and compression of 0.1 or 0.2 MPa to the tails of 10 5-week-old and 20 14-week-old Sprague-Dawley rats for 6 weeks. The rats were divided into three groups of 10 animals each: Group 1: 5-week-old animals with 0.1 MPa compression; Group 2: 14-week-old animals with 0.1 MPa compression; Group 3: 14-week-old animals with 0.2 MPa compression. Vertebral wedging and diaphyseal curvature were measured from micro CT scans performed at weeks 1, 3, and 6. Wedging due to asymmetrical growth and remodeling was calculated from a Calcein label administered at week 3 and a Xylenol label at week 6. RESULTS: The growth rate of the loaded vertebrae as a per cent of control vertebrae was 60% in Group 1, 40% in Group 2, and 30% in Group 3. The growth rate of control vertebrae in 14-week-old animals was 16% that of 5-week-old animals. The animals in all 3 groups developed a scoliosis with vertebral wedging that averaged 18.7 degrees in Group 1, 8.2 degrees in Group 2, and 10.1 degrees in Group 3. Asymmetric growth was much greater in Group 1 (5-week-old) animals. The ossified epiphyses became wedged and diaphyseal remodeling occurred in all groups. CONCLUSIONS: The major contribution to the vertebral wedging was asymmetric growth in the 5-week-old animals and diaphyseal remodeling in the 14 week-old animals. The results support the concept that if appropriate loads can be applied to human vertebrae through minimally invasive techniques, scoliosis and vertebral wedging can be corrected without a spinal fusion in both adolescents and adults. PMID- 20543393 TI - Improvements in three-dimensional back contour after spinal fusion for idiopathic scoliosis. AB - Quantec raster stereography has been recognized as an accurate and reliable tool for evaluating back contour and posterior truncal rotation in patients with scoliosis. In this prospective study, 35 patients with adolescent idiopathic scoliosis underwent both spinal radiography and Quantec three-dimensional evaluation of their idiopathic scoliosis before and after surgical intervention, consisting of anterior and/or posterior spinal fusion, with or without thoracoplasty. Comparison of established key parameters showed significant improvement in thoracic and thoracolumbar Cobb angle, as well as Quantec Q-angle. Thoracic rotation, Suzuki rib hump sum, and posterior trunk asymmetry also improved due to spinal fusion. PMID- 20543394 TI - Simple technique to evaluate thorax asymmetry in scoliosis: clinical usefulness to assess deformity and mobility. AB - In subjects with scoliosis the thoracic cage deformity is a complex 3D phenomenon. There is a deficiency of simple clinical methods of thorax shape evaluation. The study aimed to introduce and assess an anthropometric technique measuring transverse plane deformity of the thorax in patients with idiopathic scoliosis. Thirty scoliotic girls, aged 14.4+/-1.5 years, thoracic scoliosis type Lenke 1, mean Cobb 54.1+/-24.7 degrees, and 30 healthy volunteers matched for sex and age were examined. Using a Martin anthropometric caliper the length of the long and the short horizontal axes of the thorax were measured at the level of the xiphoid process (upper index) and of the costal arch (lower index), both on maximum inspiration and expiration. Asymmetry index, defined as difference of the length of the long and the short axes expressed as the percentage of the short one, was calculated. The upper asymmetry index in the study group was 35.2+/-18.6 (inspiration) while in the control group it was 13.6+/-13.6, difference significant, p<0.001. The lower asymmetry index in the study group was 26.2+/ 12.9 (inspiration) while in the control group it was 12.5+/-11.7, difference significant, p<0.001. In conclusion, thorax asymmetry index revealed significantly higher values in scoliotic patients. Asymmetry of respiratory movements could be measured. This simple technique may be used as a helpful tool for clinicians. PMID- 20543395 TI - Non-rigid surface shape registration to monitor change in back surface topography. AB - Measured back surface topographies can be useful to monitor the external manifestation of scoliosis to avoid exposure to large doses of radiation. Manual shape fitting of back surface topographies from successive clinical visits can then be used to detect differences. Automated matching of the measured topographies has been seen as a possible improvement on manual comparisons. Recognizing that two changed surface cannot be expected to be simple rigid replicas of each other, the goal of this research has been to develop a new algorithm based on a non-rigid surface matching algorithm, suited to matching the surfaces into same reference frame while also estimating the parameters of the scoliosis deformities, and eliminating noise due to normal body change caused by growth. Back surface topography data from laser optical scanning have been automatically matched by a least squares non-rigid matching algorithm. The algorithm includes new parameters able to model shape changes caused by normal growth and scoliosis deformation. This non-rigid matching algorithm returned r.m.s. values for surface closeness which were improved by at least 10% over rigid matching. Experiments on various scoliosis data demonstrate that the non rigid matching algorithm is able to accurately match the surfaces while simultaneously extracting parameters representing patient shape change. The non rigid algorithm has proven to be an improvement on the classical rigid surface matching approach which allows positional fit rather than shape fit. Measured back surface topographies can be closely matched to monitor the external manifestation of scoliosis. PMID- 20543397 TI - Design and evaluation of an MRI compatible axial compression device for 3D assessment of spinal deformity and flexibility in AIS. AB - Magnetic Resonance Imaging (MRI) offers a valuable research tool for the assessment of 3D spinal deformity in AIS, however the horizontal patient position imposed by conventional scanners removes the axial compressive loading on the spine. The objective of this study was to design, construct and test an MRI compatible compression device for research into the effect of axial loading on spinal deformity using supine MRI scans. The device was evaluated by performing unloaded and loaded supine MRI scans on a series of 10 AIS patients. The patient group had a mean initial (unloaded) major Cobb angle of 43+/-7 degrees, which increased to 50+/-9 degrees on application of the compressive load. The 7 degrees increase in mean Cobb angle is consistent with that reported by a previous study comparing standing versus supine posture in scoliosis patients (Torell et al, 1985. Spine 10:425-7). PMID- 20543396 TI - Application of 3-D ultrasound in assisting the fitting procedure of spinal orthosis to patients with adolescent idiopathic scoliosis. AB - Spinal orthosis is generally applied to the patients with adolescent idiopathic scoliosis (AIS) during puberty to mechanically support the spine and prevent further deterioration. However, the optimum location of pressure is not easy to be determined and the X-ray taken is not a real time presentation of the spinal curvature. With the advancement of clinical ultrasound, tracing spinal processes along a scoliotic spine becomes possible, which means spinous process angle (SPA) can be obtained from ultrasound images. Moreover, SPA is found to be highly correlated with Cobb's angle. Since the outcome of orthotic intervention for AIS is considered to be associated with accurate orthosis fitting, this study seeks to apply three-dimensional (3-D) ultrasound in the fitting procedure of spinal orthosis for patients with AIS. The accuracy of pressure pad location in brace can help to improve the effectiveness of spinal orthosis treatment. By means of the ultrasound assessments, spinous process angle is examined and used as the parameter to evaluate the optimal location for pressure pad. The intra-rater reliability [ICC (1, 3)] for using ultrasound to measure SPA is >0.9 (p<0.05). Furthermore, the correlation between Cobb's angle estimated from the measurement of SPA in 3-D ultrasound images and Cobb's angle measured from X-ray is highly significant (R=0.98, p<0.01). According to these findings, ultrasound can be further developed as a non-invasive real-time assessment tool for spinal curvature especially in fitting stage to improve the treatment effect of the spinal orthosis. PMID- 20543398 TI - Using ultrasound to guide the insertion of pedicle screws during scoliosis surgery. AB - Scoliosis surgery involves the insertion of screws and/or hooks into selected vertebrae to secure a pre-bent rod placed along the concave side of the spine. Usually conventional x-rays will be taken before the surgery to plan the alignment and positioning of the pedicle screws. However, reports state that perforation rate range from 6% to 54%. A misalignment of a pedicle screw can potentially cause permanent neurological spinal cord injury or even a life threatening vascular injury. Because of the importance of positioning and aligning of pedicle screws, we are working on an ultrasound method to guide the insertion of pedicle screws in real time. A pulse-echo immersion experiment was set up to study how well the edges of cortical bone could be detected using a bovine spinous process in-vitro. Two ultrasound frequencies (3.5 MHz and 5.0 MHz) were considered in this study. This preliminary study shows that ultrasound is able to penetrate cortical bone and reflect back from the outer boundary. All interfaces are clearly identified for both frequencies. Strong reflection signals are obtained when the beam is normal to the interface. Derived thickness values from the reflections are comparable with those from micro-CT image. The 5.0 MHz ultrasound frequency provided better resolution than the 3.0 MHz frequency. PMID- 20543399 TI - Towards a handheld probe based on optical coherence tomography for minimally invasive spine surgeries. AB - Minimally invasive surgical (MIS) techniques for the correction of scoliosis are under development. The installation of fusionless implants targeting the vertebral growth plate requires precise identification of spinal micro structures. During ex vivo studies, we demonstrate that optical coherence tomography (OCT) allows visualization of spinal tissues including the growth plate, the intervertebral disc and the vertebral body. This study aims at designing a handheld probe using OCT and assessing its potential for use in MIS. An OCT handheld probe was built which satisfies criteria for resolution, penetration and field of view required for spinal MIS techniques. Ex vivo images of rat tail and porcine vertebrae enabled differentiating musculoskeletal tissues of the spine (growth plate, intervertebral disc and vertebral body). Pending in vivo studies on porcine models, we evaluated the probe on a human finger and demonstrated its ability to image human tissues at video rate (25 fps) with proper imaging depth and resolution. These preliminary results showed the potential of the OCT probe for dynamic and precise imaging of spinal tissues. PMID- 20543400 TI - 3D visualization tool for minimally invasive discectomy assistance. AB - Multimodal fusion of 2D thoracoscopic images with a pre-operative 3D anatomical model of the spine is useful for minimally invasive surgical procedures using an angled monocular endoscope with varying focal length. An offline calibration procedure has been developed to compute initial endoscope parameters, such as lens distortion, focal length and optical center before surgery. An optical tracking system is used to update extrinsic parameters describing the position and orientation of the endoscope in real-time during the procedure. This calibration allows the registration of the thoracoscopic image sequence with a pre-operative MRI 3D model of the spine. Two visualization methods merging the 3D model and thoracoscopic image sequence have been developed using both augmented reality and augmented virtuality paradigms primarily as an aid for discectomy. Augmented views are generated by adding annotations and projecting the MRI 3D model onto real thoracoscopic images. Virtual views are generated by projecting the real thoracoscopic images on a virtual view of the 3D model. Experimental results showed that the calibration procedure accuracy obtained by computing the relative 3D reconstruction error on a known object was 1.0 mm. Two orthopedic surgeons assessed the generated views, confirming the relevance and added value of the proposed visualization tool for minimally invasive discectomy assistance. PMID- 20543401 TI - Rib length discrepancy in patients with adolescent idiopathic scoliosis. AB - The development of scoliosis in animal models with induced asymmetric rib growth suggested the possible role of asymmetric rib growth in the etiopathogenesis of adolescent idiopathic scoliosis (AIS). Asymmetric rib length is well recognized in idiopathic scoliosis, however, whether this rib asymmetry was primary or secondary has not been clearly documented. We measured the lengths of all ribs in 48 patients with AIS and 29 patients with scoliosis associated with syringomyelia and Chiari I malformation (SS). In both groups, ribs on the concave side were significantly longer than those on the convex side in apical area. The rib length difference was significantly associated with magnitude of the Cobb angle of thoracic curve. However, the rib length discrepancy showed no difference between AIS and SS group. The finding of similar asymmetry of rib length in both AIS and SS patients with thoracic curve indicated the discrepancy found in AIS might be secondary to the spinal deformity rather than its etiological factor. PMID- 20543402 TI - Pre-existent vertebral rotation in the human spine is influenced by body position. AB - Human bipedalism appears to be a prerequisite for the development of idiopathic scoliosis. The objective of this study was to examine the effect of different positions of the human spine on vertebral rotation in vivo. Thirty asymptomatic volunteers underwent MRI scanning of the spine in three different body positions; upright, quadrupedal-like and supine. Vertebral rotation in the local transverse plane was measured and compared at different spinal levels between the three body positions. It was shown that in all three positions the mid and lower thoracic vertebrae were predominantly rotated to the right. However, rotation was significantly less in certain areas of the spine in the quadrupedal-like position than in both the standing upright and supine positions. We hypothesize that the erect position of the human spine, but also the supine position, increases dorsally directed shear loads that may increase the tendency of certain spinal segments to rotate. PMID- 20543403 TI - Evaluation of reducibility of trunk asymmetry in lateral bending. AB - The value of the lateral bending test is important in the assessment of spinal curve mobility and prediction of surgical outcome in the treatment of adolescent idiopathic scoliosis (AIS). However, radiographic bending tests are unable to assess the reducibility of trunk asymmetry. This study aims to exploit surface topography measurement in order to evaluate the changes in shape of the trunk (a) between bending and neutral standing positions, and (b) between standing pre- and post-operative visits, in a cohort of adolescents with AIS having undergone surgical correction; and to correlate the differences measured in cases (a) and (b). Our cohort includes 13 patients with right thoracic AIS. Each patient had their 3D trunk surface digitized with a multi-head InSpeck system in standing posture (at the pre-op and post-op visits) and in maximum voluntary right and left bending (at the pre-op visit). We developed a novel trunk shape analysis method which produces a set of inclined trunk cross-sections allowing comparison between different postures. Two asymmetry indices, trunk rotation (TR) and back surface rotation (BSR), were computed in all cases and a statistical analysis was performed. Our correlation study (Pearson test) showed fair correlations in most cases between the changes in side-bending and those post-surgery, with the strongest relationship (p-value < 0.01) when combining the TR measurements from both bendings. These results provide evidence that the bending test can be used to assess trunk asymmetry reducibility. The proposed approach could provide a non invasive trunk asymmetry reducibility test for routine clinical use in AIS surgery planning. PMID- 20543404 TI - Identifying the best surface topography parameters for detecting idiopathic scoliosis curve progression. AB - There is no consensus on which surface topography (ST) parameters may be used to detect scoliosis progression. The sensitivity to change of common ST parameters has not yet been compared. The goal of this study was to determine which ST parameters are most sensitive to scoliosis progression in patients with adolescent idiopathic scoliosis (AIS) receiving conservative treatment. Fifty eight subjects with AIS were included whose Cobb angle had progressed by at least 5 degrees during a 1 year interval. All had had ST scans and frontal radiographs at a 12 month interval at our clinic. Commonly used back-only ST parameters and contributing scores were derived by one evaluator. Standardized response mean (SRM) and 95% confidence intervals (CI) were calculated using the absolute value of the changes between baseline and follow-up to reflect change in deformity, independent of direction. Decompensation, cosmetic score, Deformity in the Axial Plane Index (DAPI), trunk rotation, Hump Sum, and lordosis angle were highly sensitive to scoliosis progression (SRM>0.8). Cosmetic score, Posterior Trunk Symmetry Index (POTSI), and kyphosis angle had significantly poorer SRM values than the Cobb angle. All other ST parameters had SRM estimates that did not differ significantly from the Cobb angle, suggesting that they have a similar ability to detect progression The ST measures that were most sensitive to detection of scoliosis progression in the frontal, transverse, and sagittal planes were decompensation, trunk rotation, and lordosis angle, respectively. Absolute changes in surface parameters representing either worsening or improvement externally could reflect worsening of the internal deformity. The majority of ST parameters are potentially sensitive to scoliosis progression. PMID- 20543405 TI - Optimized use of multi-functional positioning frame features for scoliosis surgeries. AB - A multi-functional positioning frame (MFPF) has been developed which includes a number of positioning features allowing for hip flexion and extension, thorax vertical displacement, lateral leg displacement, pelvic torsion and thorax lateral displacement. The objective of this study was to develop a method allowing for optimized combined use of the MFPF features. Finite element models (FEMs) representing the osseo-ligamentous structures of the spine, ribcage, pelvis and lower limbs, including muscles, were created for three different curve types (main thoracic, double major, and triple major) using a radiographic bi planar reconstruction technique. Each FEM was subjected to an experimental design in which MFPF features were independently and simultaneously varied between extreme positions and the resultant changes in spinal geometry measured. Optimization of individual spinal geometrical parameters showed variability between curve types and some patterns such as minimum Cobb with lower limbs displaced laterally towards the convexity, pelvis raised on the side of concavity, and thorax laterally displaced towards the thoracic concavity. A weighted and normalized global optimization equation was developed which accounts for the relative importance and desired values of each geometrical parameter. Combined use of MFPF features and adjustments offers a wider range of possible intra-operative spinal geometries than their individual use. PMID- 20543406 TI - Finite element comparison of different growth sparring instrumentation systems for the early treatment of idiopathic scoliosis. AB - Fusionless growth sparring implants seek to restore spinal alignment through the early intervention of pediatric scoliosis. Amongst a growing number of concepts, the stainless steel (SS) staple, flexible tether and shape memory alloy (SMA) staple have demonstrated their validity by retarding convex vertebral growth while modifying spinal alignment. The purpose of this study was to explore the biomechanics of these devices in a human scoliotic finite element model (FEM) constructed from patient data. A FEM of a scoliotic anterior spine (28 degrees thoracic curve) was developed to include growth dynamics and shown to represent typical scoliotic progression. The explored implant concepts were alternatively introduced around the apical vertebra of the FEM (T5-T9). Immediate impact (asymmetrical loading of the vertebral growth plates and correction of scoliotic curve) and long term impact (correction of scoliotic curve after 2 years of growth) were simulated and compared to the behavior of the non-instrumented model and patient data. Results of the difference in asymmetrical growth plate stress between instrumented and non-instrumented models reveal: insignificant initial impact by the SS staple, a 52% reduction with the flexible tether, and a 31% reduction with the SMA staple. Initial and long term modifications of coronal spinal alignment following simulated growth was respectfully 28 degrees to 62 degrees in non-instrumented model and patient data, 28 degrees to 31 degrees with SS staple, 23 degrees to 31 degrees with flexible tether, and 27 degrees to 34 degrees with SMA staple. The interpretation of such methods suggests that the long term correction, achieved via growth modulation, would benefit from improved control of asymmetrical stresses within the growth plates. From a biomechanical perspective, fusionless growth sparring techniques for the early treatment of idiopathic scoliosis show promising preliminary results. PMID- 20543407 TI - Biomechanics of the intra-operative lateral decubitus position for the scoliotic spine: effect of the pelvic obliquity. AB - The intra-operative prone position used for the posterior instrumentation of scoliotic patients has been shown to reduce the spinal deformities prior to instrumentation by 37% on average. However, the effects of the lateral decubitus position used for anterior approaches and minimally invasive techniques have not been investigated. The objectives were to characterize, model and study the biomechanics of this intra-operative posture. Several clinical indices were measured on the pre- and intra-operative radiographs of six scoliotic patients. A personalized finite element mode (FEM) was developed using the pre-op 3D reconstruction, and a three-step method was developed to simulate the lateral decubitus positioning. Two additional intra-op postures, simulating different pelvic obliquities, were also tested by varying the inclination of L5. The radiographic evaluation of the lateral decubitus position showed a significant reduction of 44% of the major curve with 18 mm of apical vertebra translation. The FEM was able to reproduce the intra-op spine geometry with no significant difference with the measured values. Simulations also showed that the pelvic obliquity had different effects on the lumbar and major Cobb angles depending on the scoliotic curve type. The lateral decubitus posture reduces significantly the scoliotic curvatures prior to instrumentation, which was dependent on the pelvic obliquity. PMID- 20543408 TI - Gait in adolescent idiopathic scoliosis. Kinematics, electromyographic and energy cost analysis. AB - INTRODUCTION: Adolescent idiopathic scoliosis (AIS) can affect spine mobility and gait mechanisms. Nowadays little is known about the effects of scoliosis on gait. OBJECTIVES: To evaluate the effects of untreated scoliosis on gait. MATERIALS AND METHODS: Fifty-four females (13 healthy girls and 41 AIS with thoracolumbar/lumbar curve) were assessed by gait analysis. Xrays allowed classifying AIS patients into three groups, depending on the scoliosis severity. Gait analysis included synchronous bilateral kinematic and electromyographic (EMG) measurements, assessment of external (W(ext)), internal (W(int)), total mechanical work (W(tot)), oxygen consumption (V O(2)), energy cost (C) and muscular efficiency (W(tot)/C). RESULTS: Shoulder, pelvis and hip motions were significantly reduced in all AIS patients. The reduced motion correlated with decreased W(tot). V O(2) and C were increased by 30 %. Muscle efficiency was decreased by 29 %. Increased C correlated with prolonged timing activity of lumbo pelvic muscles (LPMTA). DISCUSSION: Reduction of W(tot) can be explained by decrease of external work. Increase of V O(2) and energy cost could be due to bilateral increase of LPMTA. CONCLUSION: Similar gait alterations were observed in all AIS patients, whatever the severity of the scoliosis. The observed alterations may be considered as the manifestation of an underlying neuromuscular disease or as a consequence of the stiffening effect of scoliosis. The observed "careful walking" strategy could also be a compensatory mechanism to minimize energy expenditure. PMID- 20543409 TI - Quantification of global intervertebral torques during gait: comparison between two subjects with different scoliosis severities. AB - The internal forces in the human body in motion could provide valuable information for the evaluation and follow-up of subjects with musculo-skeletal pathologies, such as scoliosis, but are still difficult to accurately measure. In this context, the objective of this study is to quantify the global intervertebral torques along the spine during walking, in order to compare the dynamical behavior between two subjects with different scoliosis severities. Practically, two patients, both with left lumbar adolescent idiopathic scoliosis (lumbar Cobb angles: 40 degrees), but with different apical axial rotations (20 degrees and 30 degrees) and different thoracic Cobb angles (20 degrees and 30 degrees), walked on a treadmill at 4 km/h. The acquisition system included optokinetic sensors (reflective markers), recording the 3D-joint coordinates, and a treadmill equipped with strain gauges, measuring the external forces independently applied to both feet. The global intervertebral torques were computed using an inverse dynamic model of the human body in 3D. As results, significant differences of the subject kinematics and ground reaction forces were recorded, which lead to different internal torque behavior in magnitude, maxima and minima when normalized to the subject mass. In conclusion in this preliminary study, different dynamical behavior was found between two subjects with different scoliosis severities, suggesting that the scoliosis severity could be affected by abnormal internal torques along the spine during gait (different than in the standing posture), which could lead to a supplementary asymmetric growth modulation of the vertebrae and the further progression of the scoliotic deformities in the framework of the Hueter-Volkman principle. Finally, this is a pilot study and the results will inform future studies and biomechanical modeling. PMID- 20543410 TI - The role of posteriorly directed shear loads acting on a pre-rotated growing spine: a hypothesis on the pathogenesis of idiopathic scoliosis. AB - Despite years of extensive research, the etiology of idiopathic scoliosis still has not been resolved. A hypothesis on the role of posteriorly directed shear loads was studied in several biomechanical and imaging studies. So far, it has been shown that: on the human erect spine these posteriorly directed shear loads act; these loads decrease the rotational stability of the spine vitro and in vivo; once rotation occurs, it logically follows an already built-in vertebral rotational pattern, that is pre-existent in the human spine; this pre-existent rotational pattern is related to organ anatomy, and not to handedness; certain areas in the female spine are more subject to posteriorly directed shear loads as certain areas in the female spine are more backwardly inclined. Although it is appreciated that the cause of idiopathic scoliosis is multi-factorial, we believe that the delicate upright spinal sagittal balance and the unique posteriorly directed shear loads acting on the erect human spine play a crucial role in the rotational stability of the human spine, and thus in the pathogenesis of idiopathic scoliosis. PMID- 20543411 TI - An integrated procedure for spine and full skeleton multi-sensor biomechanical analysis & averaging in posture gait and cyclic movement tasks. AB - Spine and posture disorders cover large interest in rehabilitation. Quantitative functional evaluation represents the main goal in Movement/Gait analysis. However very few studies outline the behaviour of spine during Posture and Movement/Gait analysis. To overcome such limits, several years ago our group started, a project to transfer into a complete fully 3D reliable and detailed representation, different segmental biomechanical models presented in literature. As result a complete 3D parametric biomechanical skeleton model has been developed to be used in quantitative analysis. Posture and Movement/Gait analysis are performed by 3D Opto-electronic stereophotogrammetric measurements of body landmarks labelled by passive markers. Depending on different analysis purposes, the model can work at different stages of complexity. Examples on the application of such model into biomechanical and clinical fields have been presented in literature. Our group is continuously working to add new features to such model, which is now able to fully integrate data deriving from force platforms, SEMG, foot pressure maps. By means of data fusion and optimisation procedures all these inputs are used in the model to assess lower limbs internal joint forces, torques and muscular efforts. The possibility to compute the average of cyclic or repetitive tasks has been included as well. Recently we added the possibility to assess internal joint forces and torques at each spine vertebral level and to correlate these latter with all the other model's features. The aim of this study is to present the methodological aspects of such new features and their potential applicability in clinical and biomechanical fields. PMID- 20543412 TI - Analysis of postural stability following posterior spinal fusion in adolescents with idiopathic scoliosis. AB - This study uses experimental data acquired from adolescents with idiopathic scoliosis to assess their postural control during quiet standing before and after posterior spinal fusion. Statistically significant differences were seen when comparing the pre- and post-surgical measures of balance calculated from data for three different test conditions. PMID- 20543413 TI - Prevalence of spondylolisthesis in a population of gymnasts. AB - Spondylolysis occurs in 6 % of the general population. Of these, approximately 75% will develop spondylolisthesis. According to multiple studies, an increased prevalence of spondylolysis and spondylolisthesis exists in groups of athletes practicing certain sports such as gymnastics. In the literature, prevalence of spondylolisthesis in gymnasts can reach up to 40 to 50 %. However, the specific risk factors associated with the development of spondylolisthesis in gymnasts are not known. The main purpose of this study was to evaluate the prevalence of spondylolysis and spondylolisthesis in a population of gymnasts, as well as the associated epidemiological characteristics. In order to achieve this goal, we presented our project to the two most renowned gymnastics centers in the city of Montreal, which allowed us to recruit a total of 93 gymnasts (19 males and 74 females). A radiological evaluation, with the low emission radiographic system, EOS, allowed us to identify the subjects that were affected by spondylolysis and spondylolisthesis. Additionally, standardized questionnaires allowed us to evaluate and compare different epidemiologic parameters such as age, height, weight, number of years of practice, number of hours of training per week. Of the 93 gymnasts evaluated clinically and radiographically, we identified 6 (1 male, 5 females) gymnasts presenting a spondylolysis and/or spondylolisthesis. This 6.5% prevalence found in our population is similar to the one reported in the general population. Gender did not seem to be a determinant factor. Also, gymnasts with and without spondylolysis and/or spondylolisthesis seemed to be similar in terms of height. However, gymnasts with spondylolysis and/or spondylolisthesis seemed to be heavier than gymnasts without one of these two affections, older and training with greater intensity. These results suggest that the real prevalence rate of spondylolysis and spondylolisthesis in gymnasts may have been overestimated in previous studies. A selection bias, due to the high competitive level in the two gymnastics centers where our recruitment took place, could be involved. Our findings could also be the result of new or different training methods compared to those used in past studies. This might suggest that with intense training schedules, heavier individuals could potentially be prone to increased loads at the lumbosacral junction, thus favoring the development of spondylolysis and spondylolisthesis. These hypotheses should be explored in further details in the near future, especially with investigation of radiological parameters of the spine and pelvis. PMID- 20543414 TI - Factors affecting distal end & global decompensation in coronal/sagittal planes 2 years after fusion. AB - INTRODUCTION: Decompensation of un-fused vertebrae is a potential complication of spinal instrumentation performed for adolescent idiopathic scoliosis (AIS). This can result in problems requiring revision surgery. The purpose of this study was to compare patients who decompensated in the sagittal/coronal plane and those who do not and to identify risk factors. METHODS: The Spinal Deformity Study Group data-base for AIS identified 908 patients at 2 years post-op. Coronal measures analyzed included coronal balance (CB), coronal position of the lower instrumented vertebra (CPL) and LIV tilt angle (LTA). Sagittal measures included sagittal balance (SB) and distal-junctional kyphosis (DJK). The incidence of decompensation at 2 years was: CB-16.83%, LTA-37.53%, CPL-21.17%, negative SB 51.88%, positive SB-7.62%, DJK-6.8%. Decompensated patients were compared to those who were not using preoperative, and 4-16 weeks post-op values. RESULTS: Numerous significant differences were found between patients who decompensated at 2 years and those who did not. CB was significantly influenced by larger height/weight, increased Cobb, preexisting CB and a thoracic LIV. In addition to other factors LTA decompensation was more likely to occur in JIS. CPL was associated with pelvic-obliquity and thoracic LIV. Post-operative sagittal balance could be predicted by pre-operative sagittal balance. DJK was also associated with larger weight and preoperative sagittal measures. DISCUSSION AND CONCLUSION: Less correction in sagittal/coronal planes is a risk factor for decompensation. Curve correction was significant in predicting coronal decompensation. Failure to control sagittal alignment was a risk factor in sagittal decompensation. PMID- 20543415 TI - Super Hybrid Method of scoliosis correction: minimum 2-year follow-up. AB - We applied a new surgical technique utilizing conventional hybrid instrumentation to achieve better correction of trunk deformity in adolescent idiopathic scoliosis. The purpose of this study is to introduce our "Super Hybrid Method" and to analyze the results at minimum 2-year follow-up. The technique consists of rib mobilization (2006), a rod rotation maneuver (1997) and a hook rotation maneuver (2007). Forty-four idiopathic cases (female: 43) with minimum 2-year follow-up were reviewed (24-39 months, average 32). The average age at surgery was 20.4 years (12-57). The average pre-operative Cobb angle was 56.7 degrees (40 93). The average pre-operative rib hump was 23.2mm in height and 14.3 degrees by scoliometer. The average post-op Cobb angle was 13.3 degrees at 3 weeks and 18.1 degrees at follow-up. The average initial overall correction at 3 weeks post-op was 78% (83% for age<18, 73% for age < or =18) and 70% at later follow up (75% for age<18, 67% for age < or =18). The average rib hump 2 years post-operatively was 12.4mm in height and 7.3 degrees. Sixty nine percent of patients (18/26) with a pre-operative rib hump < or =20mm (20-49) had a decrease in hump height by more than 10mm (10-34). In Moire analysis, the hump-sum measure (Suzuki) showed a statistically significant decrease from 13.4 preoperatively to 9.2 at 1 year post op (p<0.001). Correction of deformity was excellent with our new technique. It is a less expensive procedure and carries little inherent risks. PMID- 20543416 TI - Brace prescription patterns in patients referred to orthopaedic clinics for adolescent idiopathic scoliosis (AIS). AB - Even if braces for scoliosis are broadly used, there are no data on the orthopaedic medical practice to evaluate the circumstances of brace prescription. This study aims at comparing scoliosis brace prescription patterns with generally recognized standards. A cross-sectional study was carried out in 2006-2007 on all confirmed AIS patients referred to a paediatric scoliosis clinic for a first visit. Agreement between the actual brace prescription patterns and standards for immediate prescription was analyzed, following the recommendations of the Quebec Scoliosis Network (QSN), as well as the Scoliosis Research Society (SRS) therapeutic inclusion criteria. In addition, chi-2 tests and logistic regression models were used to identify variables related to brace prescription. Amongst the 321 AIS patients, immediate brace treatment was recommended in 70 cases, for about 50% of concordance with the defined criteria. Variables describing the patients' maturity (age, Risser, onset of menses) and deformity magnitude (Cobb angle and rib hump), as well as the treating physician, were the main determinants of brace prescription. Despite the professional consensus on immediate bracing norms, under and over-prescription of brace were documented in this study. Better understanding of these patterns would require documentation of motives associated with prescription at the individual level. PMID- 20543417 TI - European braces widely used for conservative scoliosis treatment. AB - A systematic examination of the braces commonly used in Europe lacks in literature. Therefore the objective of this report is the description of the European braces widely used. The history, design rationale, indications, biomechanics, outcomes and comparison between some braces are reported. Cheneau Brace is used in France and other European Countries. There are two Cheneau derivatives, namely the Rigo System Cheneau Brace used in Spain and the ScoliOlogiC "Cheneau light" used in Germany. The Lyonnaise Brace is used in France and Italy. The Dynamic Derotating Brace DDB is used in Greece. The TriaC brace is applied in the Netherlands. The Sforzesco brace based on the SPoRT concept and the Progressive Action Short Brace PASB are used in Italy. Correction of spinal deformities is achieved in conservative treatment with passive and active brace mechanisms. The mode of operation of modern braces is in accordance with various principles of correction, namely active or passive extension with the aid of a neck ring and correction by lateral pads, lateral pressure according to 3 - point principle, compression, bending the trunk towards the opposite side, active bracing and correction by means of pressure exerted by bands during movement and by means of metallic blades. Recently there has been an effort to expand our insight on the biomechanics, the treatment management principles and the outcome description of the above mentioned braces. The peer review publications on these studies mandate the use of the SOSORT and SRS inclusion and assessment criteria for conservative scoliosis treatment. PMID- 20543418 TI - Biomechanical analysis of pedicle screw placement: a feasibility study. AB - In spinal instrumentation surgery, the optimal placement of pedicle screws that takes into account the cortical/cancellous bone quality, geometry and property distribution, and screw design is still undetermined despite several in vitro experiments. The objective of this study was to evaluate the feasibility of using a detailed finite element model (FEM) of an instrumented vertebra to simulate screw axial pull-out and to analyze the bone-screw mechanical interaction. The FEM was built using CT-scan images of the L3 vertebra (0.6mm thick contiguous slices) of a 50th percentile human male volunteer, in order to virtually implant a fully customizable pedicle screw in a straight-forward position. The 753,000 elements model takes into account local cortical bone thickness and integrates advanced material behavior (elasto-plastic) laws that simulate bone failure. Screw axial pull-out was simulated and compared to in vitro experimental data, and the stress distribution at the screw thread-bone interface was analyzed. The simulated screw pull-out force (non-linear response with a failure at 640N) was within the range of experimental data (500-660N). Von Mises stresses in the bony structures were concentrated around the root of each internal thread, with the maximum stress located near the first proximal thread, in the cortical bone of the posterior wall of the pars. This study shows the feasibility and relevance of using a detailed FEM to simulate screw pull-out and to analyze the bone-screw mechanical interaction. PMID- 20543419 TI - Development and initial validation of a disease specific outcome measure for early onset scoliosis. AB - INTRODUCTION: Treatment of children with early onset scoliosis (EOS) seeks to improve natural history and health related quality of life (QOL). QOL measurement presents a significant challenge given the young age, comorbidities, and heterogeneity of this population. OBJECTIVE: To develop a disease specific measure reflecting issues of importance to EOS patients and caretakers. MATERIALS AND METHODS: Review of the literature and relevant measures informed development of semi-structured qualitative interviews. Interviews of caregivers of EOS patients were interpreted through the framework technique. A master-list of 75 items was created and responses were scaled on a 5-point Likert-scale. Psychometric analysis was performed to group items into domains, to maintain score distribution, to create a responsive instrument, and to identify question redundancy. RESULTS: Content validation revealed 8-items with low content validity indices. Item distribution analysis demonstrated 19-items with skewed distribution. Item reliability demonstrated redundant items within domains (r> or =0.5). Construct validity demonstrated unique domains measuring intended issues of interest. The resulting Early Onset Scoliosis Questionnaire (EOSQ) includes 33 items in 13-domains: General Health, Pain, Physical Function, Pulmonary Function, Daily Living, Fatigue, Emotion, Surgical Concerns, Satisfaction, Transfer, Financial Burden, Parental Burden, and Treatment Outcomes. CONCLUSION: The EOSQ reflects QOL and caregiver burden in the EOS population. The EOSQ will expand options for outcome assessment in this unique population. PMID- 20543420 TI - Radiological and clinical outcome of non surgical management for pediatric high grade spondylolisthesis. AB - OBJECTIVE: To describe and compare the quality of life of patients with pediatric high-grade spondylolisthesis managed non-operatively and operatively. SUMMARY OF BACKGROUND DATA: Some authors consider pediatric high-grade spondylolisthesis as an absolute indication for surgery, regardless of symptoms while others sometimes recommend observation in asymptomatic patients. Very little is known about the indications and outcome of non-operatively managed high-grade spondylolisthesis. METHODS: A prospective database comprising all the spondylolisthesis cases from a single pediatric institution was reviewed in order to identify all cases of high grade spondylolisthesis. Quality of life data from Short form (SF)-12 and Scoliosis Research Society (SRS)-22 questionnaires were collected. Non operatively treated patients were identified and compared to surgically treated patients at baseline and at last follow-up. RESULTS: 34 spondylolisthesis were identified as high grade and 5 of them were non-operatively treated. Quality of life questionnaires showed less impairment in the non-operative group when compared to the surgical group preoperatively. Moreover at last follow-up, quality of life questionnaires were similar between the two groups. There was no worsening of quality of life observed in non-operative patients during follow-up. CONCLUSION: The quality of life after surgical treatment of high grade spondylolisthesis is similar to that of patients with high grade spondylolisthesis and mild symptoms undergoing non-operative treatment. PMID- 20543421 TI - Developmental spondylolisthesis: is slip angle related to quality of life? AB - Lumbosacral kyphosis (LSK) is considered to be an important aspect of the deformity in adolescent developmental spondylolisthesis, but its clinical impact is not known. The purpose of this study was to clarify if slip angle (SA), a parameter commonly used to measure LSK, has a significant impact on the quality of life of patient with spondylolisthesis. Eighty-six patients with lumbosacral developmental spondylolisthesis were evaluated. There were 67 low-grade and 19 high-grade spondylolisthesis. All patients completed the SF-12v2 questionnaires. The score of the mental and physical component summary (MCS and PCS) of SF-12v2 were correlated with the slip angle. The correlation of SA was only significant with PCS and not with MCS. PCS decreased significantly with increasing SA (Spearman's rho=-0.40, p<0.001). LSK has a significant impact on the physical aspect of the quality of life of adolescent with spondylolisthesis. LSK is an important part of the deformity in developmental spondylolisthesis and should be included in the routine radiological evaluation of patient with spondylolisthesis. PMID- 20543422 TI - A survey of grid knowledge and grid perception in the public sector. AB - Grids have been developed to enable computational or data intensive scientific applications and to share resources. Existing infrastructures can benefit other possible user groups. This qualitative survey focuses on the public sector with universities, governments and hospitals. Interviews were performed to collect information on the perception of Grids by decision makers, system administrators and high level users in the sector. Application scenarios and main barriers for Grid adoption are discussed based on the users' and institutional interests. PMID- 20543423 TI - Privacy aware access controls for medical data disclosure on European healthgrids. AB - To be processed within a healthgrid environment, medical data goes through a complete lifecycle and several stages until it is finally used for the primary reason it has been collected for. This stage is not always the final occurrence of when the data would have been manipulated. The data could rather continue to be needed for secondary purposes of legitimate or non legitimate nature. Although other privacy issues are related to the processing of patient data while it is residing on a healthgrid environment, the control of data disclosure is our primary interest. When sharing medical data between different Healthcare and biomedical research organizations in Europe, it is important that the different parties involved in the sharing handle the data in the same way indicated by the legislation of the member state where the data was originally collected as the requirements might differ from one state to another. Privacy requirements, such as patient consent, may be subject to conflicting conditions between different national frameworks as well as between different legal and ethical frameworks within a single member state. These circumstances have made the compliance management process in European healthgrid very challenging. In this paper we are presenting an approach to tackle these issues by relying on several technologies contained in the semantic web stack. Our work suggests a direct mapping from high level legislation on privacy and data protection to operational level privacy aware controls. Additionally we suggest an architecture for the enforcement of these controls on access control models adopted by healthgrids security infrastructures. PMID- 20543425 TI - Hitting the ground running: Healthgrid deployment and adoption. AB - We consider the issues of healthgrid development, deployment and adoption in health care and research environments. While healthgrid technology could be deployed to support advanced medical research, we are not seeing its wide adoption. Understanding why this technology is not being exploited is one purpose of this paper. We do so in light of the seminal Healthgrid White Paper and the SHARE roadmap. We also address barriers to adoption and successes by presenting experiences in North America and Europe. By critically appraising where we are, we hope that we can hit the ground running in the near future. PMID- 20543424 TI - On transferring the grid technology to the biomedical community. AB - Natural scientists such as physicists pioneered the sharing of computing resources, which resulted in the Grid. The inter domain transfer process of this technology has been an intuitive process. Some difficulties facing the life science community can be understood using the Bozeman's "Effectiveness Model of Technology Transfer". Bozeman's and classical technology transfer approaches deal with technologies that have achieved certain stability. Grid and Cloud solutions are technologies that are still in flux. We illustrate how Grid computing creates new difficulties for the technology transfer process that are not considered in Bozeman's model. We show why the success of health Grids should be measured by the qualified scientific human capital and opportunities created, and not primarily by the market impact. With two examples we show how the Grid technology transfer theory corresponds to the reality. We conclude with recommendations that can help improve the adoption of Grid solutions into the biomedical community. These results give a more concise explanation of the difficulties most life science IT projects are facing in the late funding periods, and show some leveraging steps which can help to overcome the "vale of tears". PMID- 20543426 TI - Phylogenetic code in the cloud - can it meet the expectations? AB - Cloud computing has recently become very popular, and several bioinformatics applications exist already in that domain. The aim of this article is to analyse a current cloud system with respect to usability, benchmark its performance and compare its user friendliness with a conventional cluster job submission system. Given the current hype on the theme, user expectations are rather high, but current results show that neither the price/performance ratio nor the usage model is very satisfactory for large-scale embarrassingly parallel applications. However, for small to medium scale applications that require CPU time at certain peak times the cloud is a suitable alternative. PMID- 20543427 TI - Integrating TRENCADIS components in gLite to share DICOM medical images and structured reports. AB - The problem of sharing medical information among different centres has been tackled by many projects. Several of them target the specific problem of sharing DICOM images and structured reports (DICOM-SR), such as the TRENCADIS project. In this paper we propose sharing and organizing DICOM data and DICOM-SR metadata benefiting from the existent deployed Grid infrastructures compliant with gLite such as EGEE or the Spanish NGI. These infrastructures contribute with a large amount of storage resources for creating knowledge databases and also provide metadata storage resources (such as AMGA) to semantically organize reports in a tree-structure. First, in this paper, we present the extension of TRENCADIS architecture to use gLite components (LFC, AMGA, SE) on the shake of increasing interoperability. Using the metadata from DICOM-SR, and maintaining its tree structure, enables federating different but compatible diagnostic structures and simplifies the definition of complex queries. This article describes how to do this in AMGA and it shows an approach to efficiently code radiology reports to enable the multi-centre federation of data resources. PMID- 20543428 TI - Web service catalogue for Biomedical Grid infrastructure. AB - A great variety of services have been developed to address problems in the field of biomedicine. The EU project Advancing Clinico-Genomics Trials on Cancer (ACGT http://www.eu-acgt.org) provides a Grid-based platform for improved medical knowledge discovery and integration of biomedical data in clinical trials on cancer. Metadata describing biomedical services needs to be shared to enable discovery and service composition (as workflows). This paper reports a catalogue for knowledge-based discovery of service metadata and a software module to wrap existing command line programs as a secure Grid service able to handle sensitive information. PMID- 20543429 TI - Research traceability using provenance services for biomedical analysis. AB - We outline the approach being developed in the neuGRID project to use provenance management techniques for the purposes of capturing and preserving the provenance data that emerges in the specification and execution of workflows in biomedical analyses. In the neuGRID project a provenance service has been designed and implemented that is intended to capture, store, retrieve and reconstruct the workflow information needed to facilitate users in conducting user analyses. We describe the architecture of the neuGRID provenance service and discuss how the CRISTAL system from CERN is being adapted to address the requirements of the project and then consider how a generalised approach for provenance management could emerge for more generic application to the (Health)Grid community. PMID- 20543430 TI - Programming distributed medical applications with XWCH2. AB - Many medical applications utilise distributed/parallel computing in order to cope with demands of large data or computing power requirements. In this paper, we present a new version of the XtremWeb-CH (XWCH) platform, and demonstrate two medical applications that run on XWCH. The platform is versatile in a way that it supports direct communication between tasks. When tasks cannot communicate directly, warehouses are used as intermediary nodes between "producer" and "consumer" tasks. New features have been developed to provide improved support for writing powerfull distributed applications using an easy API. PMID- 20543431 TI - Grid-wide neuroimaging data federation in the context of the NeuroLOG project. AB - Grid technologies are appealing to deal with the challenges raised by computational neurosciences and support multi-centric brain studies. However, core grids middleware hardly cope with the complex neuroimaging data representation and multi-layer data federation needs. Moreover, legacy neuroscience environments need to be preserved and cannot be simply superseded by grid services. This paper describes the NeuroLOG platform design and implementation, shedding light on its Data Management Layer. It addresses the integration of brain image files, associated relational metadata and neuroscience semantic data in a heterogeneous distributed environment, integrating legacy data managers through a mediation layer. PMID- 20543432 TI - Decrypthon grid - grid resources dedicated to neuromuscular disorders. AB - Thanks to the availability of computational grids and their middleware, a seamless access to computation and storage resources is provided to application developers and scientists. The Decrypthon project is one example of such a high performance platform. In this paper, we present the architecture of the platform, the middleware developed to facilitate access to several servers deployed in France, and the data center for integrating large biological datasets over multiple sites, supported by a new query language and integration of various tools. The SM2PH project represents an example of a biological application that exploits the capacities of the Decrypthon grid. The goal of SM2PH is a better understanding of mutations involved in human monogenic diseases, their impact on the 3D structure of the protein and the subsequent consequences for the pathological phenotypes. PMID- 20543433 TI - Sentinel e-health network on grid: developments and challenges. AB - Grid technologies have proven their capabilities to settle challenging problems of medical data access. The grid ability to access distributed databases in a secure and reliable way while preserving data ownership opened new perspectives in medical data sharing and disease surveillance. This paper focuses on the implementation challenges of grid-powered sentinel networks within the e sentinelle project. This initiative aims to create a lightweight grid dedicated to cancer data exchange and enable automatic disease surveillance according to definition of epidemiological alarms. Particularly, issues related to security, patient identification, databases integration, data representation and medical record linkage are discussed. PMID- 20543434 TI - Using graphics processors to accelerate protein docking calculations. AB - Protein docking is the computationally intensive task of calculating the three dimensional structure of a protein complex starting from the individual structures of the constituent proteins. In order to make the calculation tractable, most docking algorithms begin by assuming that the structures to be docked are rigid. This article describes some recent developments we have made to adapt our FFT-based "Hex" rigid-body docking algorithm to exploit the computational power of modern graphics processors (GPUs). The Hex algorithm is very efficient on conventional central processor units (CPUs), yet significant further speed-ups have been obtained by using GPUs. Thus, FFT-based docking calculations which formerly took many hours to complete using CPUs may now be carried out in a matter of seconds using GPUs. The Hex docking program and access to a server version of Hex on a GPU-based compute cluster are both available for public use. PMID- 20543435 TI - Grid based evaluation of a liver segmentation method for contrast enhanced abdominal MRI. AB - Recent developments in MRI contrast agents give new perspectives in radiological diagnosis and therapy planning, but require specific image analysis methods. By employment of an academic research grid, we are currently validating and optimizing a recently developed fully automatic method for liver segmentation in Gd-EOB enhanced MRI. The grid enables extensive parameter scans and evaluation against expert's reference segmentation. The implementation layout and so far reached results are presented. Furthermore, experiences made in the production phase and consequences resulting for the exploitation of publicly funded research grids for Healthgrid applications are given. PMID- 20543436 TI - Visualization, analysis, and design of COMBO-FISH probes in the grid-based GLOBE 3D genome platform. AB - The genome architecture in cell nuclei plays an important role in modern microscopy for the monitoring of medical diagnosis and therapy since changes of function and dynamics of genes are interlinked with changing geometrical parameters. The planning of corresponding diagnostic experiments and their imaging is a complex and often interactive IT intensive challenge and thus makes high-performance grids a necessity. To detect genetic changes we recently developed a new form of fluorescence in situ hybridization (FISH) - COMBinatorial Oligonucleotide FISH (COMBO-FISH) - which labels small nucleotide sequences clustering at a desired genomic location. To achieve a unique hybridization spot other side clusters have to be excluded. Therefore, we have designed an interactive pipeline using the grid-based GLOBE 3D Genome Viewer and Platform to design and display different labelling variants of candidate probe sets. Thus, we have created a grid-based virtual "paper" tool for easy interactive calculation, analysis, management, and representation for COMBO-FISH probe design with many an advantage: Since all the calculations and analysis run in a grid, one can instantly and with great visual ease locate duplications of gene subsequences to guide the elimination of side clustering sequences during the probe design process, as well as get at least an impression of the 3D architectural embedding of the respective chromosome region, which is of major importance to estimate the hybridization probe dynamics. Beyond, even several people at different locations could work on the same process in a team wise manner. Consequently, we present how a complex interactive process can profit from grid infrastructure technology using our unique GLOBE 3D Genome Platform gateway towards a real interactive curative diagnosis planning and therapy monitoring. PMID- 20543437 TI - Grid heterogeneity in in-silico experiments: an exploration of drug screening using DOCK on cloud environments. AB - Large-scale in-silico screening is a necessary part of drug discovery and Grid computing is one answer to this demand. A disadvantage of using Grid computing is the heterogeneous computational environments characteristic of a Grid. In our study, we have found that for the molecular docking simulation program DOCK, different clusters within a Grid organization can yield inconsistent results. Because DOCK in-silico virtual screening (VS) is currently used to help select chemical compounds to test with in-vitro experiments, such differences have little effect on the validity of using virtual screening before subsequent steps in the drug discovery process. However, it is difficult to predict whether the accumulation of these discrepancies over sequentially repeated VS experiments will significantly alter the results if VS is used as the primary means for identifying potential drugs. Moreover, such discrepancies may be unacceptable for other applications requiring more stringent thresholds. This highlights the need for establishing a more complete solution to provide the best scientific accuracy when executing an application across Grids. One possible solution to platform heterogeneity in DOCK performance explored in our study involved the use of virtual machines as a layer of abstraction. This study investigated the feasibility and practicality of using virtual machine and recent cloud computing technologies in a biological research application. We examined the differences and variations of DOCK VS variables, across a Grid environment composed of different clusters, with and without virtualization. The uniform computer environment provided by virtual machines eliminated inconsistent DOCK VS results caused by heterogeneous clusters, however, the execution time for the DOCK VS increased. In our particular experiments, overhead costs were found to be an average of 41% and 2% in execution time for two different clusters, while the actual magnitudes of the execution time costs were minimal. Despite the increase in overhead, virtual clusters are an ideal solution for Grid heterogeneity. With greater development of virtual cluster technology in Grid environments, the problem of platform heterogeneity may be eliminated through virtualization, allowing greater usage of VS, and will benefit all Grid applications in general. PMID- 20543438 TI - CHOIS: enabling grid technologies for obesity surveillance and control. AB - CHOIS, the Child Health and Obesity Informatics System, is developed using open source portal technology with three-tiered Open Grid Services Architecture, an accepted standard for accessing Grid Computing and other services under Open Grid Collaborating Environments (OGCE). Its web application provides web based forms with 112 different fields to enter data ranging from demographic, height & weight for BMI, to genomic information. Automatic computation of BMI, BMI percentile and the risk of obesity alert are embedded into this system. After successful testing of the prototype, CHOIS is now ready to be used by the Illinois Department of Human Services (DHS) for obesity surveillance. This HIPAA & FERPA compliant secure system, integrating large databases in a high performance grid computing environment, enables school-nurse to collect data on school children and report statistical and surveillance information on BMI to identify those at-risk and obese for obesity prevention and intervention programs. PMID- 20543439 TI - Optimization of mean-shift scale parameters on the EGEE grid. AB - This paper studies the optimization of Mean-Shift (MS) image filtering scale parameters. A parameter sweep experiment representing 164 days of CPU is performed on the EGEE grid. The mathematical foundations of Mean-Shift and the grid environment used for the deployment are described in details. The experiments and results are then discussed highlighting the efficiency of gradient ascent algorithm for MS parameters optimization and a number of grid observations related to data transfers, reliability, task scheduling, CPU time and usability. PMID- 20543440 TI - Grid-based International Network for Flu observation (g-INFO). AB - The 2009 H1N1 outbreak has demonstrated that continuing vigilance, planning, and strong public health research capability are essential defenses against emerging health threats. Molecular epidemiology of influenza virus strains provides scientists with clues about the temporal and geographic evolution of the virus. In the present paper, researchers from France and Vietnam are proposing a global surveillance network based on grid technology: the goal is to federate influenza data servers and deploy automatically molecular epidemiology studies. A first prototype based on AMGA and the WISDOM Production Environment extracts daily from NCBI influenza H1N1 sequence data which are processed through a phylogenetic analysis pipeline deployed on EGEE and AuverGrid e-infrastructures. The analysis results are displayed on a web portal (http://g-info.healthgrid.org) for epidemiologists to monitor H1N1 pandemics. PMID- 20543441 TI - Support-based distributed optimisation: an approach to radiotherapy patient scheduling. AB - In the health system inefficiency leads to poor use of scarce expensive resources. Lengthy patient treatment waiting time can result from inefficiency in scheduling. The use of state-of-the art multi-agent and distributed computing technologies can provide a solution to address this problem. However, distributed optimisation in such a multi-agent setting poses an important challenge that requires protocols to enable agents to optimise shared objectives without necessarily revealing all of their private constraints. In this study we show that if the problem is expressed as a Dynamic Distributed Constraint Optimisation Problem a powerful algorithm such as SBDO can be deployed to solve it. As SBDO can be deployed in a grid all of the advantages of grid computing are also gained. PMID- 20543442 TI - Characterization of antigenetic serotypes from the dengue virus in Venezuela by means of Grid Computing. AB - This work determines the molecular epidemiology of dengue virus in Venezuela by means of phylogenetic calculations performed on the EELA-2 Grid infrastructure with the PhyloGrid application, an open source tool that allows users performing phylogeny reconstruction in their research. In this study, a total of 132 E nucleotide gene sequences of dengue virus from Venezuela recorded in GenBank(R) have been processed in order to reproduce and validate the topology described in the literature. PMID- 20543443 TI - HIV-K: an integrative knowledge base for semantic integration of AIDS-related malignancy data and treatment outcomes. AB - Technological innovations such as web services and collaborative Grid platforms like caGrid can create opportunities to converge the worlds of health care and clinical research, by facilitating access and integration of HIV-related malignancy clinical and outcomes data at more sophisticated, semantic levels. At the same time, large numbers of randomized clinical trial and outcomes data on AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) have been produced during the last few years. There is still much work to do, though, on obtaining clear conclusions from the integration of such information. This is a white paper on work in progress from Emory University's HIV/AIDS related malignancy data integrative knowledge base project (HIV-K). We are working to increase the understanding of available clinical trial data and outcomes of ADM such as lymphoma, as well as nADM such as anal cancer, Hodgkin lymphoma, or liver cancer. Our hypothesis is that, by creating prototypes of tools for semantics enabled integrative knowledge bases for HIV/AIDS-related malignancy data, we will facilitate the identification of patterns and potential new overall evidence, as well as the linking of integrated data and results to registries of interest. PMID- 20543444 TI - Grid selection of models of nucleotide substitution. AB - jModelTest is a Java program for the statistical selection of models of nucleotide substitution with thousands of users around the world. For large data sets, the calculations carried out by this program can be too expensive for many users. Here we describe the port of the jModeltest code for Grid computing using DRMAA. This work should facilitate the use of jModelTest on a broad scale. PMID- 20543445 TI - Enabling distributed processing and management of biological data using the grid and web technologies. AB - Transcriptomic technologies have dramatically reshaped modern biological research by deriving profiles of genome-wide expression of living organisms, and producing an unprecedented wealth of quantitative data. Given this characteristic, microarray experiments are considered high-throughput both in terms of data (data intensive) and processing (computationally intensive). GRISSOM Web Tools enable the exploitation of GRID resources for DNA microarray data distributed processing and management. It provides experts with a complete web-based solution for managing, searching and disseminating biological knowledge in the context of gene expression patterns on a genomic scale. Through the incorporation of novel workflows and various web services, the platform is gradually transformed to a powerful environment for knowledge discovery in the biomedical research. PMID- 20543446 TI - Use of NLM medical subject headings with the MeSH2010 thesaurus in the PORTAL DOORS system. AB - The NLM MeSH Thesaurus has been incorporated for use in the PORTAL-DOORS System (PDS) for resource metadata management on the semantic web. All 25588 descriptor records from the NLM 2010 MeSH Thesaurus have been exposed as web accessible resources by the PDS MeSH2010 Thesaurus implemented as a PDS PORTAL Registry operating as a RESTful web service. Examples of records from the PDS MeSH2010 PORTAL are demonstrated along with their use by records in other PDS PORTAL Registries that reference the concepts from the MeSH2010 Thesaurus. Use of this important biomedical terminology will greatly enhance the quality of metadata content of other PDS records thus improving cross-domain searches between different problem oriented domains and amongst different clinical specialty fields. PMID- 20543447 TI - Enabling secure, distributed collaborations for adrenal tumor research. AB - Many e-Health strategies rely on the secure integration of datasets that have previously resided in isolated locations, but can now in principle be accessed over the Internet. Of paramount importance in the health domain is the need for the security and privacy of data that is transmitted across these networks. One such collaboration, which spans several specialist centres across France, Germany, Italy and the UK, is ENSAT - the European Network for the Study of Adrenal Tumors. The rarity of the tumors under study means the value of accessing, aggregating and comparing data from many centres is great indeed. However this is especially challenging given that ENSAT require clinical and genomic data to be seamlessly linked, but in such a way that the information governance, ethics and privacy concerns of the patients and associated stakeholders involved are visibly satisfied. Key to this is the clear separation of clinical and genomic data sets and support for rigorous patient-identity protecting access control. This is especially challenging when such data sets exist across different organisational boundaries. In this paper we describe a prototype solution offering a security-oriented tailored portal supported by a layered encryption-driven linkage technology (VANGUARD) that offers precisely such patient-privacy protecting capabilities. We describe the architecture, implementation and use to date of this facility to support the ENSAT adrenal cancer research network. PMID- 20543448 TI - Parallel high-performance grid computing: capabilities and opportunities of a novel demanding service and business class allowing highest resource efficiency. AB - Especially in the life-science and the health-care sectors the huge IT requirements are imminent due to the large and complex systems to be analysed and simulated. Grid infrastructures play here a rapidly increasing role for research, diagnostics, and treatment, since they provide the necessary large-scale resources efficiently. Whereas grids were first used for huge number crunching of trivially parallelizable problems, increasingly parallel high-performance computing is required. Here, we show for the prime example of molecular dynamic simulations how the presence of large grid clusters including very fast network interconnects within grid infrastructures allows now parallel high-performance grid computing efficiently and thus combines the benefits of dedicated super computing centres and grid infrastructures. The demands for this service class are the highest since the user group has very heterogeneous requirements: i) two to many thousands of CPUs, ii) different memory architectures, iii) huge storage capabilities, and iv) fast communication via network interconnects, are all needed in different combinations and must be considered in a highly dedicated manner to reach highest performance efficiency. Beyond, advanced and dedicated i) interaction with users, ii) the management of jobs, iii) accounting, and iv) billing, not only combines classic with parallel high-performance grid usage, but more importantly is also able to increase the efficiency of IT resource providers. Consequently, the mere "yes-we-can" becomes a huge opportunity like e.g. the life-science and health-care sectors as well as grid infrastructures by reaching higher level of resource efficiency. PMID- 20543449 TI - Cell nucleus architecture in health and medicine: geometrical descriptors and their use in grid based case studies. AB - Adopting the world wide accessible Grid computing power and data management structures enables usage of large image data bases for individual diagnosis and therapy decisions. Here, we define several descriptors of the genome architecture of cell nuclei which are the basis of a detailed analysis for conclusions on the health state of an individual patient. All these descriptors can be accessed by automatic inspection of microscopic images of fluorescently labelled nuclei, obtained from cells from tissue sections or blood and subjected to standard biochemical protocols. We demonstrate how the combinatorial, geometrical and statistical parameters may be used in diagnosis and therapy monitoring. PMID- 20543450 TI - Development of an information platform for new grid users in the biomedical field. AB - Bringing new users into grids is a top priority for all grid initiatives and one of the most challenging tasks. Especially in life sciences it is essential to have a certain amount of users to establish a critical mass for a sustainable grid and give feedback back to the technological middleware layer. Based on the presumable lack of grid IT knowledge it is notably more arduous to satisfy user demands although here the requirements are especially demanding. Therefore, the development of an information- and learning platform could support the efforts of grid experts to guide new users. By providing a platform about grid technology and their feasibilities for users of the community of biomedicine potential, users could be supported using the high potential of their discipline. PMID- 20543451 TI - An approach to using care pathway records for research. AB - Previously, we have examined the use of integrated care pathways, a fine-grained form of medical guideline including the explicit recording of any deviation, or 'variance', for research purposes. Feeding the results of the analysis of variance into the development of a pathway could be an effective way of capturing evidence from practice. Building on this concept, in our principal case study we propose a system for extracting data from integrated care pathways (ICPs) using ontologies and a method for inferring ICPs from other patient records, combining these with data collected for retrospective and prospective studies in preimplantation genetic diagnosis (PGD) for assisted reproduction. PMID- 20543452 TI - Vascular cognitive impairment. PMID- 20543453 TI - Impairments of syntactic comprehension in Korean and the location of ischemic stroke lesions: a voxel-based lesion-symptom mapping study. AB - In order to assess the capacity of neurological patients to process syntactic features unique to Korean, such as the heavy dependence of parsing on syntactic morphemes rather than the word order in a sentence, the Korean Syntactic Comprehension Test (KSCT) was newly developed. To examine the correlation between lesion locations and the test performance, we did voxel-based lesion-symptom mapping (VLSM) analysis in a group of 39 patients with ischemic stroke. As a result, KSCT scores of the aphasic patients were significantly lower than those of 18 normal subjects. Within the patient group, VLSM analysis showed significant association between lower KSCT performance and the lesions mainly located in left perisylvian area and anterior temporal lobe. The KSCT results were also closely correlated with the results of two subtests in the Korean version-the Western Aphasia Battery. We conclude therefore that brain localization of syntactic comprehension in Korean native speakers is similar to that in other language speakers, despite the unique features of the Korean syntax, and that the KSCT will be of diagnostic value in assessing left fronto-temporal functions in Korean patients. PMID- 20543454 TI - The NIHSS-plus: improving cognitive assessment with the NIHSS. AB - BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) has been criticized for limited representation of cognitive dysfunction and bias towards dominant hemisphere functions. Patients may therefore receive a low NIHSS score despite a fairly large stroke. A broader scale including simple cognitive tests would improve the clinical and research utility of the NIHSS. METHODS: We studied 200 patients with acute non-dominant hemispheric stroke who underwent cognitive testing and had MRI with diffusion-weighted imaging (DWI) within 5 days of presentation. We measured DWI volumes and retrospectively calculated NIHSS scores. We used linear regression to determine the role of selected cognitive tests, when added to the NIHSS, in predicting DWI volume. RESULTS: The NIHSS predicted DWI volume in a univariate analysis, as did total line cancellation and a visual perception task. In a multivariate model, using log-transformed variables, the NIHSS (p=0.0002), line cancellation errors (p=0.02) and visual perception (p=0.004) each improved prediction of total infarct volume. CONCLUSION: The addition of line cancellation and visual perception tasks significantly adds to the model of NIHSS alone in predicting DWI volume. We propose that these two cognitive tests, which together can be completed in 2-3 minutes, could be combined with the NIHSS to create an "NIHSS-plus" that more accurately represents a patient's ischemic tissue volume after a stroke. This scale requires further validation in a prospective study. PMID- 20543455 TI - Rose-colored answers: neuropsychological deficits and patient-reported outcomes after stroke. AB - Patient-reported, subjective outcomes are promoted as a standard for ethical, valid studies in many neurological disorders. Such outcomes are considered potentially more sensitive and specific to important therapeutic effects, and may be more linked to disability and disease-related life losses than conventional assessments of impairment (e.g. ability to walk, performance on language tests, serological or radiological indices). Self-report is invaluable to identify social and emotional consequences of brain injury: depression, changes in intimate and family relationships, social role and community participation losses. However, common stroke-related neuropsychological deficits are likely to confound subjective stroke outcome measures. The scientific community focused on stroke-related health outcomes may arrive at {significantly underestimated} patient reports of stroke-related disability, caused by a failure to adjust for the effect on self-report of spatial neglect, deficits of magnitude estimation, pathologic alteration of self-awareness, and alteration in distributed cortical systems supporting emotional semantics and abstraction. PMID- 20543456 TI - The relative role of semantic and sublexical processes in reading, writing and repetition: evidence from a follow-up study. AB - The evolution in time of a number of language tasks in a longitudinal study of a 61-year-old aphasic patient is described. The patient, examined twice, in a 10 month follow-up, showed a dissociation between preserved reading with respect to impaired other modalities as well as a qualitative change in errors' type. A reduction of neologisms and phonologically based errors, with a concurrent increase of semantic paraphasias in naming and repetition, as well as an amelioration in reading, with a reduction of stress assignment errors was exhibited at the follow-up. The results are interpreted by postulating an improved performance of the phonological output processes, allowing non phonologically based errors to emerge, thus revealing the underlying semantic damage. The Summation Hypothesis [14] seems a general framework better interpreting these findings, more than highly specialized production models, which could explain separately only different modalities' impairments. PMID- 20543457 TI - Patterns of reading performance in acute stroke: A descriptive analysis. AB - One of the main sources of information regarding the underlying processes involved in both normal and impaired reading has been the study of reading deficits that occur as a result of brain damage. However, patterns of reading deficits found acutely after brain injury have been little explored. The observed patterns of performance in chronic stroke patients might reflect reorganization of the cognitive processes underlying reading or development of compensatory strategies that are not normally used to read. METHOD: 112 acute left hemisphere stroke patients were administered a task of oral reading of words and pseudowords within 1-2 days of hospital admission; performance was examined for error rate and type, and compared to that on tasks involving visual lexical decision, visual/auditory comprehension, and naming. RESULTS: Several distinct patterns of performance were identified. Although similarities were found between the patterns of reading performance observed acutely and the classical acquired dyslexias generally identified more chronically, some notable differences were observed. Of interest was the finding that no patient produced any pure semantic errors in reading, despite finding such errors in comprehension and naming. PMID- 20543458 TI - Dual task impairments in vascular dementia. AB - Several studies have shown that people with Alzheimer's disease (AD) demonstrate difficulties in doing two things at once or 'dual-tasking' and that this dual task impairment is insensitive to normal ageing, chronic depression or prodromal conditions like Mild Cognitive Impairment. It is not known, however, if this impairment is specific to AD, or also present in other dementias, such as vascular dementia (VaD). In this study 15 people with VaD, 25 healthy age-matched and 25 healthy young controls were assessed using a paper and pencil dual tasking paradigm and several measures of working and episodic memory. Age had no effect on dual task performance, but the VaD patients demonstrated a significant impairment in dual tasking ability. Performance on the memory measures was instead affected by age with a further deterioration in the VaD patients. Both dual tasking and memory ability were significantly correlated with disease severity, as assessed by the MMSE. These results indicate that performance on the dual task could be a specific indicator of pathological ageing. PMID- 20543459 TI - The dysexecutive syndrome associated with ischaemic vascular disease and related subcortical neuropathology: a Boston process approach. AB - The introduction of diagnostic criteria for vascular dementia has helped to re define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes. PMID- 20543460 TI - Association between hypotension, low ejection fraction and cognitive performance in cardiac patients. AB - BACKGROUND AND PURPOSE: Impaired cardiac function can adversely affect the brain via decreased perfusion. The purpose of this study was to determine if cardiac ejection fraction (EF) is associated with cognitive performance, and whether this is modified by low blood pressure. METHODS: Neuropsychological testing evaluating multiple cognitive domains, measurement of mean arterial pressure (MAP), and measurement of EF were performed in 234 individuals with coronary artery disease. The association between level of EF and performance within each cognitive domain was explored, as was the interaction between low MAP and EF. RESULTS: Adjusted global cognitive performance, as well as performance in visuoconstruction and motor speed, was significantly directly associated with cardiac EF. This relationship was not entirely linear, with a steeper association between EF and cognition at lower levels of EF than at higher levels. Patients with low EF and low MAP at the time of testing had worse cognitive performance than either of these alone, particularly for the global and motor speed cognitive scores. CONCLUSIONS: Low EF may be associated with worse cognitive performance, particularly among individuals with low MAP and for cognitive domains typically associated with vascular cognitive impairment. Further care should be paid to hypotension in the setting of heart failure, as this may exacerbate cerebral hypoperfusion. PMID- 20543461 TI - Expression of 2 transcripts of NGX6 gene in colorectal cancer and the correlation with carcinoembryonic antigen. AB - OBJECTIVE: To investigate the expression and function of NGX6-S (short transcript) and NGX6-L (long transcript) in colorectal cancer. METHODS: In situ hybridization was used to detect the expression of these 2 transcripts in colorectal cancer tissues and paired normal tissues, and analyze the correlation between NGX6 and carcinoembryonic antigen (CEA). RESULTS: The expression of NGX6 S was higher than that of NGX6-L in the colorectal cancer tissues (P=0.008). The expressions of NGX6-S and NGX6-L were not different among the 4 stages of colorectal cancer (P>0.05). The expression of NGX6-S in the colorectal cancer tissues of Duke A, B, and C stages had no difference with that of the paired normal tissues (P>0.05). Inversely, the expression of NGX6-S in the colorectal cancer tissues of Duke D stage was lower than that in the paired normal tissues (P=0.033). NGX6-L expression was not different between the colorectal cancer tissues and the paired normal tissues in 4 stages(P>0.05).The expression of NGX6 S and NGX6-L had no correlation with the serum concentration of CEA. CONCLUSION: NGX6-S may play an important role in colorectal cancer, and the lowered expression of NGX6-S may contribute to the distant metastasis of colorectal cancer. PMID- 20543462 TI - Effect of GnRH II and GnRH I on secretion of VEGF by eutopic and ectopic endometrial stromal cells of endometriosis patients. AB - OBJECTIVE: To determine the effect of GnRH I and GnRH II on the secretion of VEGF by eutopic and ectopic endometrial stromal cells cultured in vitro, and to provide theoretical basis for exploring new treatments for endometriosis (EMs). METHODS: Eutopic and ectopic endometrium stromal cells cultured in vitro were treated with different concentrations of GnRH II and a GnRH I (goserelin), and a control group was not treated by GnRH II and GnRH I. Enzyme linked immunosorbent assay (ELISA) was used to measure the content of vascular endothelial growth factor (VEGF) protein in the medium of the above 2 groups. RESULTS: (1) There was no difference in the VEGF protein secreted by eutopic and ectopic stromal cells in the medium after being cultured in vitro for 48 h (P>0.05). (2) 10(-10), 10( 8), and 10(-6) mol/L GnRH II dose-dependently reduced VEGF protein secreted by endometrial stromal cells (P<0.05),and the inhibition effect was stronger than that of GnRH I (P<0.05).(3)The inhibition effect of GnRH II on VEGF in ectopic stromal cells was stronger than that of eutopic stromal cells (P<0.05). CONCLUSION: (1) Ectopic stromal cells cultured in vitro can secrete VEGF,which has no difference from the eutopic stromal cells, and which may play an important role in the formation and development of EMs. (2) GnRH II can dose-dependently reduce VEGF protein secreted by ectopic and eutopic endometrial stromal cells cultured in vitro,and the inhibition effect is stronger than that of GnRH I, providing theoretical basis for exploring new treatments for EMs. PMID- 20543463 TI - Influence of intense pulsed light on the secretion of TGF-beta1 in cultured human fibroblasts and intervention of JNK inhibitor. AB - OBJECTIVE: To determine the influence of intense pulsed light (IPL) on the secretion of TGF-beta1 in cultured human fibroblasts and the intervention of JNK inhibitor. METHODS: The callan foreskin fibroblasts were cultured and divided into 2 groups. In the IPL treatment group, cells were irradiated with IPL with fluences of 0 (negative control), 10, 18, 27, 36, and 36 J/cm2*2 (irradiated with IPL with fluences of 36 J/cm2 twice). In the IPL+inhibitor group, cells were irradiated with IPL with fluences of 36 J/cm2 after incubation with the inhibitor SP600125 for 2 h. TGF-beta1 in the culture supernatant was evaluated 48 h after the irradiation using enzyme-linked immunosorbent assay. RESULTS: Compared with the negative control, TGF-beta1 in the culture supernatant decreased at the IPL irradiation of 10, 18, 27, and 36 J/cm2, whereas TGF-beta1 increased at the IPL irradiation of 36 J/cm2*2. In the IPL+inhibitor group, the concentration of TGF beta1 in the culture supernatant decreased compared with the controls (P<0.05). CONCLUSION: IPL can suppress the secretion of TGF-beta1 at the lower fluence and promote the secretion at a higher fluence. JNK inhibitor may play an inhibitive role when IPL regulates the TGF-beta1 secretion in cultured human fibroblasts. IPL may stimulate TGF-beta1 secretion of the fibroblast cells in human skin via JNK signal pathway. PMID- 20543464 TI - Endogenous stress contributes to cardiac injury after heart transplantation in rats. AB - OBJECTIVE: Stress effect plays an important role in the development of some myocardial diseases. We hypothesized it was important nosogenesis to myocardial damage and cardiac allograft vasculopathy. METHODS: The transplanted hearts from Lewis to Wister rats served as allografts and from Lewis to Lewis rats as isografts based Ono's model. The differential proteins in the transplanted hearts were separated by comparative proteome, and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and searched by Matrix Science software system. RESULTS: All transplanted hearts were characterized by lumen loss [(total vessel area-luminal area)/total vessel area] in the coronary artery 2 weeks after the operation [(2.07%+/-0.93%) vs. (27.58%+/ 11.14%), P<0.01], but more predominant after 8 weeks [(2.34%+/-1.06%) vs. (72.29%+/-20.57%), P<0.01]. All samples of the left ventricle were analyzed by proteomic techniques and 37 distinct proteins involving their respective isoforms and subunits were identified. Nine proteins were correlated to endoplasmic reticulum stress effect and myocardial damage, and 2 proteins were verified by Western blot. CONCLUSION: Stress plays an important role in cardiac allograft damage and the development of rat cardiac allograft vasculopathy. PMID- 20543465 TI - Effect of Naoling decoction on the expression of APP in hippocampal CA3 region in rats with synthetic Alzheimer's disease. AB - OBJECTIVE: To observe the effect of Naoling decoction on hippocamal histomorphology and the expression of amyloid precursor protein (APP) in CA3 region in rats with Alzheimer's disease (AD), and to explore the therapeutical and the potential mechanism. METHODS: Forty SD rats were classified into 5 groups: a normal group, a sham-operated group, an AD group, a Naoling decoction group, and a Naofukang group. Alzheimer's disease model was established by Abeta1 42 injected into the hippocamal in the rats. The faculty of learning and memory was evaluated by Morris water maze. The changes of cell morphology were detected by HE staining. Expression of APP in CA3 region was mea-sured with immunohistochemical staining. RESULTS: Morris water maze experiment showed that the escape latency of hidden platform in the AD group were delayed significantly (P<0.05) and the average times of passing was decreased (P<0.05). In the hippocampal CA3 field of the AD rats, HE staining and immunohistochemical test showed that pyramidal cells disturbed, neurons decreased significantly and expression of APP protein increased (P<0.05). Naoling decoction treatment improved pyramidal cellular disorders and decreased APP expression. CONCLUSION: Naoling decoction can distinctly improve the learning and memory ability, and reduce the expression of APP in the AD model rats, suggesting that Naoling decoction can be used for the treatment of AD in rats. PMID- 20543466 TI - [DJ-1 gene rearrangement mutation in patients with autosomal recessive early onset parkinsonism using real-time PCR]. AB - OBJECTIVE: To establish a technique platform of DJ-1 gene exon rearrangement using real-time PCR and to analyze DJ-1 gene exon rearrangement mutation in patients with autosomal recessive early-onset Parkinsonism(AREP). METHODS: Real time PCR was used to analyze DJ-1 gene exon rearrangement mutation in 22 probands with AREP from unrelated Chinese Han families and 30 normal controls. RESULTS: We obtained satisfactory real-time PCR reaction conditions and primers of DJ-1 gene coding exons No exon rearrangement mutation in the DJ-1 gene is detected in this group. CONCLUSION: We established platform of DJ-1 gene exon rearrangement using real-time PCR. Exon rearrangement mutation in the DJ-1 gene is rare in Chinese patients with AREP. PMID- 20543467 TI - [Effect of neferine combined with mdr-1shRNA on the expression of mdr-1/P-gp in K562/A02 cell line]. AB - OBJECTIVE: To determine the effect of neferine (Nef) combined with mdr-1shRNA on the expression of mdr/P-gp in K562/A02 cell line. METHODS: MTT assay was used to observe the cell proliferation. The expression level of P-gp was determined by Western blot and the transcription of mdr-1 gene was detected by semi quantitative RT-PCR. RESULTS: After K562/A02 cells were treated by Nef or mdr 1shRNA alone or both for 24 h, the proliferation of K562/A02 cells was significantly higher in the Nef combined with mdr-1shRNA treatment group than that of Nef or mdr-1shRNA alone group (P<0.01).The expression of mdr-1/P-gp in the Nef with mdr-1 shRNA group was significantly lower than that of Nef or mdr 1shRNA alone group. CONCLUSION: Nef enhances the inhibition of mdr-1shRNA expression vector on K562/A02 cell proliferation and on P-gp protein to effectively reverse multidrug resistance induced by mdr-1 gene encoding P-gp. PMID- 20543468 TI - [Effect of HMGB1 on human hepatoma cell line-HepG2 proliferation]. AB - OBJECTIVE: To investigate the effect of high mobility group box-1 protein (HMGB1) on the proliferative activity of human hepatoma cell line HepG2 and its potential regulating mechanism. METHODS: The cultured HepG2 cells were treated with recombinant HMGB1 (0, 10, 50, and 100 ng/mL, respectively) for 24 h. Cell proliferation was observed by MTT analysis. Western blot and reverse transcriptase-polymerase chain reaction were used to detect the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 protein and mRNA, respectively. RESULTS: Compared with the control group, HMGB1 at 10, 50, and 100 ng/mL obviously increased HepG2 cells proliferation, cyclin D1 and PCNA protein and mRNA expression after the treatment for 24 h, respectively (P<0.05). Anti HMGB1 significantly inhibited the proliferation and cyclin D1 and PCNA mRNA and protein expression of HMGB1 on HepG2 cells (P<0.05). CONCLUSION: Proliferation of HMGB1 on HepG2 cells may be associated with increasing cyclin D1 and PCNA expression. Anti-HMGB1 may have a therapeutic effect on hepatocellular carcinoma. PMID- 20543469 TI - [NMDA receptor and NOS in morphine tolerance in mice with bone cancer]. AB - OBJECTIVE: To set up a mouse model with bone cancer to simulate the morphine tolerance and explore its mechanism. METHODS: Forty C57BL/6 male mice were divided into 4 groups: Group 1 and Group 2 were firstly set up as bone cancer pain models. Morphine (10 mg/kg) was sequentially administered subcutaneously twice daily in Group 1 and normal saline was administered in Group 2 as the control group. Similar to Group 1 and Group 2, morphine (10 mg/kg) was administered subcutaneously twice daily in Group 3 and normal saline was administered in Group 4 as the control group. To set up morphine tolerance model, we injected morphine continuously for 7 days. From Day 1 to Day 7 after the morphine injection, we measured the mice hind paw withdrawal threshold in the von Frey hair test every other day. NMDA receptor 1 (NMDA1) and nitric oxide synthase (NOS) were measured on Day 7 after the morphine injection. RESULTS: The mice hind paw withdrawal threshold in the von Frey hair test in Group 1 increased on Day 1,3, and 5 after the morphine injection compared with the paw withdrawal threshold in Group 2 and had the same threshold as Group 2 on Day 7. The mice hind paw withdrawal threshold in the von Frey hair test in Group 3 increased on Day 1,3, and 5 after the morphine injection compared with the paw withdrawal threshold in Group 4 and had the same threshold as Group 4 on Day 7. The grey scales and integral optical density (IOD) of NMDAR1 and the level of NOS in the spinal dorsal horn were higher in Group 1, Group 2, and Group 3 compared with those in Group 4 (P<0.05 or P<0.01), and the grey scales and IOD of NMDAR1 in Group 2 was higher than that in Group 1 (P<0.05). CONCLUSION: NMDA receptors and NOS may play important roles in morphine tolerance in mice with bone cancer pain. PMID- 20543470 TI - [Effect of human bone morphogenetic protein 2, 3, 6, and 12 on osteosarcoma cell line UMR106]. AB - OBJECTIVE: To investigate the effect of human bone morphogenetic protein (hBMPs) 2/3/6 and 12 on osteosarcoma cell UMR106. METHODS: Adenovirus-BMP2/3/6 and 12 (AdBMP2/3/6 and12) were used to treat the cell line. Their proliferation, apoptosis, and transmigration were detected by Trypan blue exclusion test, TdT mediated biotinylated-dUTP nick end labeling (TUNEL), acridine orange-ethidium bromide (AO/EB) double fluorescent dye staining, and transwell-room test, respectively. The alkaline phosphatase (ALP) activity was detected to reflect the differentiation of tumors. RESULTS: Compared with the control groups, the cell survival rate of the experimental groups treated with AdBMP2/3/6 and 12 showed a significant time-dependent decrease (P<0.01). The apoptosis indexes were increased significantly (P<0.01) and the results from TUNEL and AO/EB method were consistent. The cell numbers of transmembrane significantly decreased at 24,48, and 72 h (P<0.01). AdBMP2/3/6 and 12 treatment enhanced the activity of ALP activity from day 3 and this effect might still be observed up to day 9 of the treatment (P<0.01). CONCLUSION: hBMPs2/3/6 and 12 can inhibit the proliferation and transmigration, and induce their apoptosis and differentiation in osteosarcoma cell line UMR106. PMID- 20543471 TI - [Cost-benefit of expanding cervical cancer screening]. AB - OBJECTIVE: To estimate the benefit and cost of increasing the coverage of cervical cancer screening. METHODS: Using an eleven year conventional screening data (universal strategy) and a representative population sample (expanding strategy) to analyze the health and economic impact. RESULTS: The screening coverage for all 30-59 women in Liuyang was increased from 7.20% to 66.67%. Early detection cases were increased from 20 to 45, and life years saved in one screening term increased from 103.46 years to 925.83 years with expanding strategy as compared with the conventional strategy. The incremental cost per life year saved was 6 917.07 Yuan. The benefit/cost ratio was 1.80:1 at the screening coverage of 66.67%, which was higher than that of the conventional strategy (1.40:1). Both strategies were cost-effective. CONCLUSION: With various uncertainties and data limitations, expanding screening coverage is more effective than conventional strategy, and more benefit is obtained when the number of early detection cases increases. PMID- 20543472 TI - [Dendritic cells and coronary collateral circulation in coronary heart disease]. AB - OBJECTIVE: To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD). METHODS: Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared. RESULTS: (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/ 0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003). CONCLUSION: In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation. PMID- 20543473 TI - [Stent-delayed implantation strategy of acute myocardial infarction with high thrombus burden in primary percutaneous coronary intervention]. AB - OBJECTIVE: To retrospectively evaluate the efficacy of stent-delayed implantation in patients with acute myocardial infarction (AMI) with high thrombus burden after thrombus extraction was performed. METHODS: Of 186 consecutive AMI patients, 56 were included according to thrombus score(TS)>or=2, and then were divided into 2 groups based on the thrombus score after thrombus extraction was executed: the stent-direct implantation group (TS=0 or 1)and the stent-delayed implantation group (TS>or=2) even if 3 times thrombus extraction were given. Thrombolysis in myocardial infarction(TIMI)flow grade and TIMI myocardial perfusion (TMP) were used to assess the coronary artery flow and myocardial perfusion,respectively. RESULTS: TIMI score in the stent-direct implantation group was lower than that in the stent-delayed implantation group. There was no significant difference(P=0.07). TMP score in the stent-direct implantation group was significantly lower than that in the stent-delayed implantation group (P<0.05). CONCLUSION: Stent-delayed implantation can remarkably improve myocardial perfusion in AMI patients with high thrombus burden after thrombus extraction and intensive anti-thrombosis therapy is administrated. PMID- 20543474 TI - [Pneumo-peritoneum helico-CT imaging in post-operative peritoneal adhesion]. AB - OBJECTIVE: To discuss the diagnostic value of pneumoperitoneum helico-CT imaging (PHCT) in cases of post-operative peritoneal adhesion (POPA). METHODS: We retrospectively analyzed the PHCT scan pictures from 32 consecutive patients with chronic abdominal pain or recurrent mechanical intestinal obstruction after abdominal operation. RESULTS: In a normal peritoneal cavity without adhesion, an air distended dome-like space would be demonstrated with the abdominal organs arranged smoothly on the bottom of the shadow. Any additional shadow appearing in the dome-space would suggest adhesion or something abnormal. Positive findings of peritoneal adhesion were found in 30 of the 32 patients (93.75%). A spot adhesion at the abdominal wall making a kinking of intestine usually showed a cuneiform bulging shadow pointed to the roof of the dome-space. Organs involved in the adhesion may be single or multiple, including the liver, stomach, small intestine, colon, uterus, and omentum. In all the 32 patients, PHCT diagnosis was confirmed by the subsequent laparoscopy treatment. CONCLUSION: PHCT imaging is valuable in making a definite diagnosis of POPA, particularly before a blind laparoscopic exploration. It is a replacement for laparoscopy but much simpler, and may offer a valuable help in dealing with the difficult cases of suspected POPA. A negative imaging is sometimes very important to an undetermined postoperative chronic abdominal pain. PMID- 20543475 TI - [Three-dimensional computed tomograph angiography and neuroendoscope assisted microsurgery for intracranial aneurysm]. AB - OBJECTIVE: To determine the role of 3-dimensional computed tomograph angiography (3D-CTA) and neuroendoscope in intracranial aneurysm, and to analyze its benefits. METHODS: A total of 38 patients with intracranial aneurysm were confirmed by operation. All the patients were examined by 3D-CTA before the operation and surgical simulation was conducted to ensure the location of aneurysm and its relationship with parent aneurysm artery. Endoscopy was used as an adjunct before and after the microsurgical treatment to observe the neck anatomic features and perforating branches and to verify the optimal clipping position. RESULTS: Pre-operative 3D-CTA clearly displayed the aneurysm and their relation with the parent aneurysm artery, the aneurysm, the periphery vessel, and bony structures, according to demonstration during the operation. Endoscope clearly showed the anatomy around aneurysm, especially the perforating branches. Postoperative 3D-CTA showed satisfactory aneurysm clipping. CONCLUSION: Simulation surgery of 3D-CTA is helpful in finding and exposing aneurysm. Neuroendoscope is very useful for protecting deep blood vessels. Combination of the two can increase the operation success ratio and reduce postoperative complications. PMID- 20543476 TI - [Stages of 3,547 patients with chronic kidney disease and relevant factor analysis]. AB - OBJECTIVE: To investigate the prevalence and distribution of chronic kidney disease(CKD) in Second Xiangya Hospital of Central South University. METHODS: We retrospectively analyzed the medical records of 3547 CKD patients (>or=14 years old) admitted to Second Xiangya Hospital for the 1st time from January 2003 to December 2008. Glomerular filtration rate (GFR) was estimated by using the MDRD equation abbreviated [eGFR=186.3*SCr-1.154*age-0.203*0.742 (for women) mL/min.1.73 m2]. Data of patients' gender, age, admission number, etiologic and functional diagnose, course of disease, blood pressure, hemoglobin, urine, renal function, blood albumin, and kidney ultra-B were collected. RESULTS: (1) The most common causes for CKD were primary glomerulonephritis(55.20%), hypertension (14.55%) and diabetes (11.78%). The composition of the causes during this 6 years was not significantly different (P>0.05). The proportion of chronic glomerulonephritis declined while that of hypertensive nephropathy and diabetic nephropathy increased as time passed. (2) Patients were respectively distributed from stage 3 to stage 5 at the following percentages: 11.59% (stage 3), 23.03% (stage 4), and 65.38% (stage 5). Middle-aged and young patients (41 years60 years) accounted for 36.88% of the CKD patients. Chronic glomerulonephritis was often seen at 21-40 and 41-60 year olds. Patients with lupus nephritis were younger, 48.35% of whom were 21-40 years old. On the contrary, patients with hypertensive nephropathy and diabetic nephropathy were much older. They were mainly seen in older than 40 year groups. (3) Obstructive nephropathy and gout nephropathy occurred mainly in men while it seemed much easier for women to suffer from lupus nephritis. (4) The majority of CKD patients was accompanied by anemia (94.28%) and hypertension (56.91%), and the incidence and degree of anemia and hypertension increased as CKD developed (P<0.005). CONCLUSION: The top 3 causes of CKD are chronic glomerulonephritis, hypertensive nephropathy, and diabetic nephropathy. The proportion of hypertensive nephropathy and diabetic nephropathy is on the rise. Elderly people are the high risk group for CKD. PMID- 20543477 TI - [Mevastatin inhibits the differentiation of thyroid-associated ophthalmopathy derived orbital preadipocytes]. AB - OBJECTIVE: To investigate the effect of mevastatin (Mev) on the expression of peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) mRNA and differentiation of Thyroid-associated ophthalmopathy (TAO) derived orbital preadipocytes in vitro. METHODS: Orbital adipose tissues were obtained from TAO patients undergoing orbital decompression surgery. The orbital preadipocytes cultured from the orbital adipose tissues were divided into Group A (a control group) and Group B (an intervention group). Group B was subdivided into Group B1 B5, all groups were stimulated to differentiate into mature adipocytes with cocktail differentiation medium.The entire course of differentiation was 10 d. The differentiation of orbital preadipocytes in Group A was induced with routine inducer,while at in Group B1,B2, and B3 was interfered with 5 micromol/L (B1), 10 micromol/L(B2),20 micromol/L (B3) mevastatin respectively during the whole process of differentiation. The differentiation of orbital preadipocytes in Group B4 and B5 was interfered with 10 micromol/L mevastatin day 4 (B4) or day 8 (B5) of the differentiation process until the entire course was over. Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining. The value of optical absorption was measured at 492 nm with enzyme linked immunosorbent assay. The expression of PPAR-gamma mRNA was detected by reverse transcription polymerase chain reaction. RESULTS: The light absorption value (A) and PPAR-gamma mRNA expression of differentiated cells in Group A,B1,B2,and B3 decreased successively,and there was significant difference in any of the 2 groups among Group A, B1 and B2, and B3 (P<0.05). The value A and PPAR gamma mRNA expression of differentiated cells in Group A, B4, and B2 decreased successively, and the difference in any of the 2 groups among these 3 groups was significant. However, there were no significant difference between Group A and B5. CONCLUSION: Mevastatin inhibits the differentiation of TAO derived orbital preadipocytes by blocking PPAR-gamma mRNA expression. The degree of inhibition is not only concentration-dependent but also associated with the stage of differentiation. The earlier the differentiation, the stronger the inhibition. PMID- 20543478 TI - [Expression and secretion of TGF-beta2 in human retinal pigment epithelium cell line D407 regulated by atropine]. AB - OBJECTIVE: To investigate the regulation of atropine to the expression and secretion of TGF-beta2 in retinal pigment epithelium (RPE) cells by observing the changes of those under different treatments of atropine and carbachol. METHODS: D407 cells were cultured conventionally and divided into 4 groups as follows: (1) An experimental group (Group A), cells were pretreated with 10(-4)-10(-8) mol/L atropine for 30 min, and then treated with 10(-5) mol/L carbachol; (2) a negative control group (Group B), cells were treated with 10(-4)-10(-8) mol/L atropine; (3) a positive control group (Group C), cells were treated with 10(-5) mol/L carbachol; (4) a blank control group (Group D). The concentration of TGF-beta2 in the supernate, and the level of TGF-beta2 mRNA and protein were measured by ELISA, RT-PCR, and Western blot after the 24-hour treatment. The data were analyzed by analysis of variance. RESULTS: The levels of TGF-beta2 mRNA and protein in the cytoplasm and the concentration of TGF-beta2 in the supernate in the experimental groups were lower than those of the positive control group. Atropine at 10-4 mol/L could completely inhibit the effect of carbachol at 10-5 mol/L. The effect of atropine was concentration-dependent (F=1,056.897,1,320.170, and 475.657; P<0.001). There was no change of TGF-beta2 level in the cytoplasm and supernate with the treatment of atropine alone (P>0.05). CONCLUSION: Carbachol can promote the expression and secretion of TGF-beta2 in human RPE cells and atropine could reverse it effectively, suggesting that M receptor may be involved. PMID- 20543479 TI - [Dentification ability of inbred strain mice tooth germs homologically transplanted into oral submucosa]. AB - OBJECTIVE: To establish a suitable environment for the bioengineered teeth in vivo by observing the dentification ability of BALB/C mice tooth germs homologically implanted into the oral submucosa. METHODS: The first molar tooth germs of BALB/C mice 4 days after birth were transplanted into the oral submucosa of BALB/C male mice, and then recycled for regular histological observation after 1, 2, 3, and 6 week transplantation. RESULTS: The tooth germs in the oral submucosa grew well with continuing developing enamelum and pulpodentinal complex, and the dentinal tubules were clear. CONCLUSION: The environment of the BALB/C male mice oral submucosa is favorable for the growth of tooth germs in inbred strain BALB/C mice, and it can provide a new environment for the development of bioengineered teeth in vivo. PMID- 20543480 TI - [Effect of body composition on bone mineral density in males with different glucose tolerance]. AB - OBJECTIVE: To investigate the effect of body composition on bone mineral density (BMD) in males with different glucose tolerance. METHODS: A total of 87 male subjects aged 35~64 years were divided into 2 groups by glucose tolerance test, 57 diagnosed T2DM and 30 with normal glucose tolerance(NGT). BMDs of anteroposterior lumbar vertebrae (AP), left femur neck (FN), total hip (T-hip), and total bone mineral density(TBMD)were measured by dual-energy-X-ray absorptiometry (DEXA). Body composition was also measured by DEXA, while fat tissue mass(FTM), lean tissue mass(LTM), percentage of truncal fat (Tru-fat%) and total fat (Fat%) were computed. The effect of body composition on the BMD of the 2 groups was analyzed. RESULTS: LTM and FN-BMD had a positive correlation in the NGT group, but no correlation in the T2DM group. The percentage of fat showed a negative relationship with the BMD of AP in the T2DM group, but not in the NGT group. The percentage of fat and total BMD had a negative association in both the NGT and the T2DM groups. In the NGT group, LTM was the independent predictor of BMD of AP,FN and hip (b=0.509, 0.411, and 0.585; P<0.01 or 0.05; R2=0.169~0.342). In the T2DM group, LTM was the independent predictor of BMD of AP (b=0.330, P<0.05, R2=0.109) and hip (b=0.462, P<0.01,R2=0.213), but not FN. CONCLUSION: LTM has an attenuated effect on the BMD in male patients with T2DM compared with patients with NGT. An increased percent of fat percent is harmful to preserve bone mass in male adults, regardless of normal glucose tolerance or T2DM. PMID- 20543481 TI - [Healing of pregnant patient with severe H1N1 and literature review]. PMID- 20543482 TI - Community-based participatory research as a tool to support civic engagement. PMID- 20543483 TI - Development of a theater-based nutrition and physical activity intervention for low-income, urban, African American adolescents. AB - BACKGROUND: Childhood overweight is disproportionately worse in minority and low income populations. Theater is a promising and effective tool for delivering health education to these underserved populations, but no known studies have examined the use of theater to promote both nutrition and physical activity to minority youth. OBJECTIVE: To develop an interactive, theater-based intervention that conveys health messages to low-income, urban, African Americans and engages them in learning ways to adopt a healthy lifestyle. METHODS: Community partners worked to develop a theater-based nutrition and physical activity intervention. A focus group provided urban adolescents' thoughts about their desires for the intervention. Based on input from all community partners, the group created a theater-based intervention. Researchers used a quasi-experimental (pre-/posttest) design with a community-based participatory research (CBPR) approach. Participants learned health messages through theater, dance, and music and gave feedback on the program sessions and materials. The program ended with a dinner theater performance showcasing information that students learned during the intervention. RESULTS: Participants received six theater-based health lessons. Learning objectives for each health education session were achieved. Each participant contributed to and performed in the final performance. All program participants were highly satisfied with the theater-based method of learning health messages. CONCLUSION: A community-academic partnership succeeded in developing a theater-based nutrition and physical activity intervention that satisfied participating adolescents. PMID- 20543485 TI - From community-based pilot testing to region-wide systems change: lessons from a local quality improvement collaborative. AB - BACKGROUND: A community-based collaborative conducted a 2-year pilot study to inform efforts for improving maternal and child health care practice and policy in Allegheny County, Pennsylvania. OBJECTIVES: (1) To test whether three small scale versions of an evidence-based, systems improvement approach would be workable in local community settings and (2) to identify specific policy/infrastructure reforms for sustaining improvements. METHODS: A mixed methods approach was used, including quantitative performance measurement supplemented with qualitative data about factors related to outcomes of interest, as well as key stakeholder interviews and a literature review/Internet search. RESULTS: Quantitative performance results varied; qualitative data revealed critical factors for the success and failure of the practices tested. Policy/infrastructure recommendations were developed to address specific practice barriers. This information was important for designing a region-wide quality improvement initiative focused on maternal depression. CONCLUSION: The processes and outcomes provide valuable insights for other communities interested in conducting similar quality improvement initiatives. PMID- 20543486 TI - Partnering to collect health services and public health data in hard-to-reach communities: a community-based participatory research approach for collecting community health data. AB - BACKGROUND: Community-based participatory research (CBPR) approaches are increasingly used in behavioral studies but also may allow public health and health services researchers to study determinants of health in hard-to-reach communities for whom existing data are missing. OBJECTIVES: We describe our experience with a CBPR project in diverse communities of limited English proficient minorities. METHODS: The process included relationship building, recognition of community needs, resource investment by community and academic partners, and shared decision-making. Community-driven implementation, academic driven analysis, and joint reporting took advantage of diverse layers of expertise. RESULTS/LESSONS LEARNED: We mobilized eighteen community interviewers, involved researchers from three institutions, and collected public health/health services data from 525 adults in seven weeks using a 117-item survey in nine languages. CONCLUSION: A CBPR approach can make the process of collecting public health and health services data in hard-to-reach communities not only viable, but also highly successful. PMID- 20543487 TI - Engaging participants in design of a Native Hawaiian worksite wellness program. AB - BACKGROUND: Native Hawaiians today face a disproportionately high rate of obesity. The Designing Healthy Worksites (DHW) project investigated existing administrative policies and supports for healthy eating and physical activity at eight Native Hawaiian-serving organizations in Hawai'i, along with employee preferences for worksite wellness programming. OBJECTIVES: We describe the process by which Native Hawaiian researchers and community members worked together to gather formative data to design future worksite wellness programs. METHODS: A Native Hawaiian doctoral student (JHL) and a Native Hawaiian activist (CKH) spearheaded the project, mentored by a Caucasian professor (KLB) who has worked in Hawaii communities for 30 years. Advisors from the worksites supported the use of environmental assessments (n = 36), administrative interviews (n = 33), focus groups (n = 9), and an employee survey (n = 437) to collect data. We used an interactive process of data collection, sharing, and interpretation to assure mutual agreement on conclusions and future directions. RESULTS: Worksites were at different stages of readiness for worksite wellness programming, suggesting that a toolkit be developed from which agencies could create a program that fit. Activities preferred by large proportions of employees included support groups, experiential nutrition education (e.g., cooking demonstrations and field trips for smart food shopping), food buying clubs, and administrative policies supporting healthy lifestyles. High participation in data collection and interpretation suggest that our methods fostered enthusiasm for worksite wellness programming and for Native Hawaiians as researchers. The team continues to work together to develop and test interventions to promote worksite wellness. CONCLUSION: Native-directed research that engages administrators and employees in designing programs heightens program acceptability and applicability. PMID- 20543488 TI - Utilizing community-based participatory research to adapt a mental health intervention for African American emerging adults. AB - BACKGROUND: Adapting mental health interventions to heighten their cultural and contextual appropriateness may be critical for engaging ethnic/racial groups that have been traditionally excluded or marginalized. Community-based participatory research (CBPR) is a collaborative research approach that highlights unique strengths and expertise of those involved. Although intervention adaptations have garnered much attention there is little previous work specifically describing the adaptation process of mental health interventions using CBPR. OBJECTIVE: This article summarizes the use of a CBPR approach to adapt a mental health intervention for urban adolescents and young adults disconnected from school and work, a population at elevated risk for poor mental health owing to the presence of numerous chronic stressors. METHODS: We describe the process undertaken to modify the content and delivery format of an evidence-based intervention. LESSONS LEARNED: Unique challenges of working with urban African American adolescents and young adults in a job training program are highlighted. By incorporating principles of co-learning and shared responsibility, this partnership was able to achieve positive outcomes. CONCLUSION: Our experience suggests that a CBPR approach can be used effectively to adapt a mental health intervention in collaboration with African American adolescents and emerging adults in a job training program. PMID- 20543489 TI - The one-pager: a practical policy advocacy tool for translating community-based participatory research into action. AB - The multiple and diverse perspectives, skills, and experiences inherent in community-academic partnerships make them uniquely positioned to educate policy makers and advocate for health equity. Effective communication tools are critical to successfully engage in the policy-making process. Yet few resources emphasize the development and use of practical tools for translating community-based participatory research (CBPR) findings into action. The purpose of this article is to describe a CBPR process for developing and using a one-page summary, or "one-pager," of research findings and their policy implications. This article draws on the experience of the Healthy Environments Partnership (HEP), a community-academic partnership in Detroit, Michigan. In addition to describing these processes, this article includes a template for a one-pager and an example of a one-pager that was written for and presented to federal policy makers. PMID- 20543490 TI - Interpretations of interpretations: combining community-based participatory research and interpretive inquiry to improve health. AB - BACKGROUND: Latina immigrants from Mexico suffer significantly increased morbidity and mortality from cervical cancer when compared with non-Hispanic White women, largely owing to lack of screening and appropriate treatment. OBJECTIVES: To demonstrate that by combining the tools of community-based participatory research (CBPR) with the tools of interpretive inquiry, it is possible to address explicit community concerns surrounding a particular problem such as cervical cancer while also examining what other, perhaps less immediately visible, matters consume the time and attention of community members. METHODS: We first briefly discuss and compare CBPR as an approach to research and interpretive inquiry as a qualitative research method. We then provide a case study from our own research using a CBPR approach to examine beliefs and attitudes about cervical cancer prevention among Oregon Latinos. Methods in that study included extensive discussions with our community advisory board (CAB) and promotores (community health workers) regarding barriers to cervical cancer screening for Latinas and community health concerns in general, and in-depth interviews with more than 50 Latino immigrants. CONCLUSION: Combining the tools of CBPR with the tools of interpretive qualitative inquiry may allow researchers to address explicit community concerns while also examining what other, less immediately visible, issues consume the time and attention of community members. In our specific case, combining the insights of our community partners with the results of our interpretive analysis helped us shift the focus from cervical cancer alone to a focus on gender relations and family health as we design future interventions. PMID- 20543491 TI - Phases of "pre-engagement" capacity building: discovery, exploration, and trial alliance. AB - BACKGROUND: Academic prevention researchers who engage limited-resource communities may find that organizational or community capacity for prevention is low. Community organizations, neighborhoods, and academic partners may lack shared issue awareness, mutual interests, and interactive skills necessary for collaborative intervention. Existing capacity building models either ignore a 'pre-engagement' phase or acknowledge it without offering strategic detail. An exploratory or developmental phase before active engagement can be achieved through co-located work in a community setting. The construct, "ecology of practice," provides conceptual background for examining how "shared work" introduces and prepares partners for future collaboration consistent with community-based participatory research (CBPR) principles. OBJECTIVE: This paper presents two case studies where pre-engagement capacity building involved partners who were initially unaware, disinterested, or unable to engage in preventive interventions. These cases illustrate how mutual participation in shared "ecologies of practice" enabled an exchange of cultural knowledge, skill, and language that laid the groundwork for future preventive intervention. METHODS: A trajectory of developmental work in each case occurred over 5 years. Historical timelines, interviews, and personal communications between community and academic leaders were reviewed and common themes identified. A model of "pre capacity building" emerged. CONCLUSION: Capacity-building models that detail strategies for developing equitable engagement in under-resourced settings will more effectively move best practices into vulnerable communities. Preventive interventions must be translated equitably if health disparities are to be reduced. PMID- 20543493 TI - Separation of optical isomers in capillary chromatography using a poly(tetrafluoroethylene) capillary tube and an aqueous-organic mixture carrier solution. AB - Capillary chromatography for the separation of optical isomers was developed using an untreated poly(tetrafluoroethylene) capillary tube and a water hydrophilic/hydrophobic organic solvent mixture as a carrier solution. The open tubular capillary was 110 cm in length (90 cm effective length) and 100 microm in inner diameter. The carrier solution was prepared with a water-acetonitrile-ethyl acetate mixture (15:3:2 volume ratio) containing 1 mM beta-cyclodextrin. A model analyte solution of dansyl-DL-methionine was injected into the capillary tube by a gravity method. The analyte solution was subsequently delivered through the capillary tube with the carrier solution by a microsyringe pump; the system worked under laminar-flow conditions. The analytes were separated through the capillary tube with on-capillary detection by an absorption detector. D-Isomer and L-isomer were eluted in this order with the water-acetonitrile-ethyl acetate carrier solution including beta-cyclodextrin. PMID- 20543494 TI - Aptamer-mediated chemiluminescence detection of prion protein on a membrane using trimethoxyphenylglyoxal. AB - Effective recognition and quantitative analysis of the prion protein are important in drug discovery and diagnosis for prion diseases, such as bovine spongiform encephalopathy and Creutzfeldt-Jakob diseases. We have developed a high-throughput method for a specific and sensitive determination of prion protein on a solid-phase membrane, based on a chemiluminescence reaction of aptamer with 3,4,5-trimethoxyphenylglyoxal. This method using aptamer is facile, inexpensive and convenient for the detection of the prion protein on a membrane, indicating a lower detection limit of ca. 4.2 pmol spot(-1). PMID- 20543495 TI - Modification of a porous sheet (MAPS) for the high-performance solid-phase extraction of trace and ultratrace elements by radiation-induced graft polymerization. AB - In this review, the preparation of a novel porous sheet designed for solid-phase extraction (SPE) and a comparison of the preconcentration performance of metal ions with conventional sorbents are described. A porous sheet (MAPS) with an average pore diameter, porosity, and a thickness of 1.0 microm, 75%, and 2 mm, respectively, was modified into an sorbent used for solid-phase extraction, by radiation-induced graft polymerization. Ion-exchange and chelating groups were immobilized onto polymer chains grafted to the MAPS. Also, extractants were impregnated via a hydrophobic interaction with long alkyl chains introduced into the grafted polymer chains of the MAPS. The applicability of the resultant modified MAPSs was demonstrated by adopting them to analyses of real samples. PMID- 20543496 TI - Polydispersity as a parameter for indicating the thermal stability of proteins by dynamic light scattering. AB - A physical parameter for predicting the thermal stability of proteins was provided by a new approach using dynamic light scattering (DLS). The relationship between the melting point measured by differential scanning calorimetry (DSC) and the polydispersity of the hydrodynamic diameter determined by DLS analysis was examined. Calmodulin (CaM) and concanavalin A (ConA) were used as model proteins. The melting point measured by DSC, an indicator for thermal stability, increased and the polydispersity decreased on binding of the proteins to specific ligands, suggesting that the polydispersity could be used an indicator to predict thermal stability. In addition, the increase of thermal stability that resulted from forming a complex could be quantified by polydispersity analysis even when the melting point changed only slightly. PMID- 20543497 TI - A reflectance flow-through thionine sol-gel sensor for the determination of Se(IV). AB - In this work, a reversible sensor to assess the total Se(IV) content in samples is described. Pre-activated glass slides were spin-coated with 100 microL of a 20 h aged sol-gel mixture of 1 mL of tetramethoxysilane, 305 microL of 50 mmol L(-1) HCl and 2.0 mg of thionine. The flow-cell consisted of one of those slides as a window, and was filled with beads of a polystyrene anionic exchange resin to retain Se(IV) in the form of selenite ions. A reflectance transduction scheme at a wavelength of 596 nm was adopted. The cell was coupled to a multicommutation flow system where a programmed volume of a sample solution and 373 microL of 0.4 mmol L(-1) iodide in a 1.6 mol L(-1) HCl solution were sequentially inserted into the cell. The iodine produced from the reaction of retained Se(IV) with iodide bleached the blue color of thionine. Considering a sample volume of 2.30 mL, with which the preconcentration step was minimized, a linear dynamic working range between 1.5 to 20 microg mL(-1) and a detection limit of 0.29 microg mL(-1) were obtained. The sensor enabled us to perform approximately 200 assays, and provided results similar to those of electrothermal atomic absorption spectrometry. PMID- 20543498 TI - Determination of water content in organic solvents by naphthalimide derivative fluorescent probe. AB - A new fluorescence dye, N-amino-4-(2-hydroxyethylamino)-1,8-naphthalimide (AHN), based on 4-bromo-1,8-naphthalic anhydride was synthesized as a fluorescence probe for determining water content in organic solvents. Changing from a non-polar to a polar solvent increases the solvent interaction with excitation spectrum and emission spectrum shifts to longer wavelengths. The fluorescence intensity of the probe decreased with the increasing concentration of water. In the range of 0.00 4.00% (v/v), the AHN fluorescence intensity changed as a linear function of water content. The detection limits were 0.019, 0.038, and 0.060% for dioxane, acetonitrile and ethanol, respectively. PMID- 20543499 TI - Nano-molar level hydrogen peroxide detection by horseradish peroxidase adsorbed cup-stacked carbon nanotube electrodes and applications to L-glutamate detection. AB - We have developed a simple fabrication method of a highly sensitive direct electron transfer-type electrochemical biosensor for hydrogen peroxide by use of cup-stacked carbon nanotubes (CSCNTs). The CSCNTs, formed by stacking of cup shaped carbon units, has larger internal space and more hydrophilic edges, thanks to the presence of functional groups containing oxygen (e.g., -COOH, -OH), than multi-walled carbon nanotubes (MWCNTs). When the CSCNTs suspension was cast, the CSCNTs were dispersed homogeneously onto a glassy carbon (GC) electrode, and horseradish peroxidase (HRP) was immobilized firmly by physical adsorption without any chemical reactions. The flow injection analysis (FIA) system with the HRP/CSCNTs/GC electrode has superior sensitivity and stability to the HRP/MWCNTs/GC electrode. The detection limit was 0.75 nM (S/N = 3) and the activity was maintained over 85% for 21 days. Further, when the glutamate oxidase (GlOD)-immobilized reactor was set into the proposed FIA system, L-glutamate could be detected repeatedly with a detection limit of 1.2 nM (S/N = 3). PMID- 20543500 TI - Determination of iron monosulfide and iron disulfide in suspensions by an electrochemical method using a platinum-silver twin-electrode. AB - New electrochemical technique with a Pt-Ag twin electrode is proposed for the determining the contents of iron sulfides (FeS and FeS(2)) in a suspension. After electrolytic oxidation with a Pt electrode, Fe(2+) was measured by linear sweep voltammetry. From relations of the charge amount from the baseline to the peak in the voltammogram of Fe(2+) with the content of FeS or FeS(2), linear calibration curves (a) and (b) were prepared, respectively. After measurements of Fe(2+), Fe(2+) and S(0) were reduced with a Pt electrode to remove Fe(2+) and to produce S(2-). With an Ag electrode, Ag(2)S was deposited on Ag. A linear curve (c) was prepared from a relation between the charge amount of the Ag(2)S peak part and the FeS content. However, in the suspension of FeS(2), Ag(2)S can not be detected. When this method is applied to a mixed suspension of FeS and FeS(2), the content of FeS can be determined with curve (c), whereas curves (a) and (b) were not effective in the mixed suspension. PMID- 20543501 TI - Rapid temperature-programmed separation and retention prediction on a novel packed-capillary column in gas chromatography. AB - Novel packed-capillary columns for gas chromatography were developed with a thin wall stainless-steel capillary of 1.0 mm i.d.; and rapid temperature-programmed separations have been carried out after a basic evaluation concerning the compatibility of these columns to the temperature program. With a numerical integration method, the retention of several test analytes during temperature programmed elution was successfully estimated. In order to confirm the suitability of the packed-capillary columns to relatively fast temperature programming up to 40 degrees C/min, theoretically predicted retention data were compared with that actually measured. The results suggested a good separation performance of the newly developed packed-capillary columns as a particle-packed column conventionally used. Also, the compatibility to a rapid temperature programmed operation was quite satisfactory for almost all of the separations currently done in typical analytical laboratories. PMID- 20543502 TI - Simultaneous determination of antidepressants by non-aqueous or quasi-non-aqueous capillary electrophoresis. AB - Simultaneous determinations of 20 antidepressants were carried out by non-aqueous capillary electrophoresis using a background electrolyte consisting of an organic solvent. A bubble cell fused silica capillary (112.5 cm x 50 microm i.d., 150 microm i.d. bubble) was used as an electrophoresis tube. The determination was carried out at 215 nm, while the detection wavelength between 190 and 500 nm was selected for qualitative analysis. When an acetonitrile solution alone was used as the background electrolyte, good separation was observed, but it was not sufficient to separate all tested analytes. It was found that better separation was acquired by adding a few other solvents into acetonitrile, such as water and methanol; the best separation was achieved with a mixture of acetonitrile containing 60 mM ammonium acetate and 1 M acetic acid/water/methanol (100:1:0.5, v/v/v). As for the plasma sample, liquid-liquid extraction and solid-phase extraction (SPE) were considered; as a result, SPE with Oasis HLB was found to be most suitable. The present method is very useful as regards to plasma samples. PMID- 20543503 TI - Determination of tricyclic antidepressants in human breast milk by capillary electrophoresis. AB - A method for the determination of several tricyclic antidepressants (imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, norclomipramine, doxepine and nordoxepine) in breast milk has been developed. This assay consists of a common extraction process in an organic phase, which is evaporated until dried and finally reconstituted in the appropriate buffer for injection in a capillary electrophoresis system. The capillary electrophoresis method used is an "acetonitrile stacking" method previously reported for determining these drugs in serum samples. The method developed was applied to the analysis of these compounds in human breast milk at different concentration levels (50, 100 and 200 ppb of the TCAs hydrochlorides). An interference study of some ansiolitic drugs such as lorazepam and alprazolam was made. PMID- 20543504 TI - Analyses of non-steroidal anti-inflammatory drugs in environmental water samples with microemulsion electrokinetic chromatography. AB - In this study, a microemulsion electrokinetic chromatography (MEEKC) was used to analyze ten non-steroidal anti-inflammatory drugs (NSAIDs) in water samples. The type and ratio of organic modifiers were found to be the predominant influences on the NSAIDs separation. Subsequently, field-amplified sample injection was coupled with this MEEKC method in order to enhance the detection sensitivity. When both the acid plug (3 s) and water plug (5 s) were placed at the front of the capillary, and the acetonitrile (ACN) solvent was added to the water plug (10% ACN) and the sample matrix (15% ACN), the separation time was shortened to 15 min, as well as the limit of detection (LOD) of these NSAIDs was reduced to the range of 0.03 to 0.3 microg/L, which provided about a 1400-fold to 6100-fold enhancement in LOD. Finally, the proposed on-line concentration MEEKC method also successfully determined the NSAIDs residues in water samples after solid-phase extraction. PMID- 20543505 TI - Open-cell titration of seawater for alkalinity measurements by colorimetry using bromophenol blue combined with a non-linear least-squares method. AB - The open-cell titration of seawater was studied for alkalinity measurements by colorimetry. 1) The colorimetric pH of free hydrogen ion concentration, pH(F(ind)), was calculated from the ratio of the absorbances at 436 and 590 nm (R = (590nm)A/(436nm)A), along with the molar absorption coefficient ratios (e(1), e(2) and e(3)/e(2)) and a tentative acid dissociation constant value (pK(a(2))). 2) The perturbation of hydrogen ion was evaluated from the change in titration mass (Deltam). The total hydrogen ion concentration at m + Deltam, pH(T(at m+Deltam)), was calculated using pH(F(ind)) for a mass m and constants for sulfate (S(T)) and fluoride (F(T)). 3) The alkalinity (A(T)) was computed from the titrant mass (m + Deltam) and the corresponding pH(T(at m+Deltam)) through a non-linear least-squares approach using the pK(a(2)) value as a variable parameter. Seawater sample at 2000 m depth from the West Pacific was analyzed. The resulting A(T) (2420.92 +/- 3.35 micromol kg(-1)) was in good agreement with the A(T) measured by potentiometric electric force (2420.46 +/- 1.54 micromol kg( 1)). The resulting pK(a(2)) was 3.7037, in close proximity to that reported by King et al. (pK(a(2)) = 3.695). PMID- 20543506 TI - Elimination technique for alkali metal ion adducts from an electrospray ionization process using an on-line ion suppressor. AB - The effects of an on-line ion suppressor device on alkali metal ion adduct formations of the model compound tacrolimus were investigated. The base peak ion in the positive ion ESI-MS spectrum of tacrolimus was a sodium ion adduct, [M+Na](+). On the other hand, an ammonium ion adduct, [M+NH(4)](+), was the base peak ion in the full-scan mass spectrum of tacrolimus with a cation-exchange suppressor resin, and both [M+Na](+) and [M+K](+) were eliminated. These results indicate that the combination of an on-line ion suppressor with ESI-MS is a simple and effective technique that eliminates undesirable alkali metal ion adduct formations in the positive-ion mode. PMID- 20543507 TI - Development of a simple and low-cost device for fluorometric determination of selenium in water samples. AB - A portable spectrofluorometer device comprising an ultraviolet LED (380 nm) as a light source, an LED driver, a microsyringe as a cell, an optical fiber cable, a CCD spectrometer and a personal computer was used on-site. The device works on a battery for 3 h without the need to re-charge. The consumptions of reagents and sample solution can be reduced by using the device. Using fluorescein solution as a standard, the performance of this device was compared with that of a bench-top spectrofluorometer. The device applicability was demonstrated by the determination of selenium content in river water as a model of hazardous elements in the environment. Selenium reacted with 2,3-diaminonaphthalene to form piazselenol, which was then extracted with cyclohexane. The determination was carried out with both the portable device and the spectrofluorometer. The entire process was completed in approximately 15 min. The recovery of selenium in a river-water sample ranged from 104-112% and the detection limit was 0.5 microg L( 1). PMID- 20543508 TI - Determining the Henry's Law constants of THMs in seawater by means of purge-and trap gas chromatography (PT-GC): the influence of seawater as sample matrix. AB - The influence of seawater salts as salting out agents on the purge-and-trap gas chromatography (PT-GC) determination of trihalomethanes (THMs) was studied. This is particularly important since seawater is chlorinated when used as a cooling agent in coastal nuclear power stations. The chlorination produces unwanted THMs as by-products. A PT-GC apparatus was used to determine the Henry's Law constant of each THM, with seawater as the sample matrix. PMID- 20543510 TI - Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome. AB - We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged. PMID- 20543511 TI - [Involvement of dysfunction of glia-neuron network in chronic pain and drug addiction]. PMID- 20543512 TI - [Entrainment of the mammalian circadian clock via the induction of Period genes]. PMID- 20543513 TI - [Expression of the histamine H4 receptor in human tissues and its clinical role]. PMID- 20543514 TI - [Proton-sensing G-protein-coupled receptors and their physiological roles]. PMID- 20543515 TI - [Method and apparatus for studying cell volume regulation]. PMID- 20543516 TI - [Prophylactic and therapeutic vaccines for Japanese cedar pollinosis]. PMID- 20543517 TI - [Pharmacological and clinical profile of rasburicase (Rasuritek)]. PMID- 20543518 TI - Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet. AB - AIM: Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. METHODS: Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by betaVLDL derived from both groups of rabbits was also investigated. RESULTS: Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of betaVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with betaVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with betaVLDL from the control group. CONCLUSION: Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti inflammatory and anti-oxidant actions. PMID- 20543519 TI - Molecular mechanisms of ezetimibe-induced attenuation of postprandial hypertriglyceridemia. AB - AIM: Postprandial hypertriglyceridemia (PHTG) has been shown repeatedly to be associated with metabolic syndrome and atherosclerotic cardiovascular diseases. We have recently reported that ezetimibe inhibits PHTG in patients with type IIb hyperlipidemia. Ezetimibe was also reported to atten-uate PHTG in combination with low-dose statins in patients with obesity or metabolic syndrome. We reported CD36-deficient (CD36KO) mice as a new model for PHTG, in which the synthesis of chylomicron (CM) in the small intestines is enhanced. In the current study, we investigated the effect of ezetimibe on PHTG in this mouse model of metabolic syndrome. METHODS: Wild-type (WT) mice fed a western diet, and CD36KO mice fed a normal chow diet, respectively, were treated for 3 weeks with and without ezetimibe, followed by an evaluation of triglyceride (TG) concentrations by enzymatic method and by high performance liquid chromatogra-phy (HPLC) as well as those of and apolipoprotein (Apo) B-48 in plasma and intestinal lymph after oral fat loading with olive oil. Intestinal mucosa was also harvested to evaluate the transcriptional regulation of the genes involved in the intestinal production of ApoB-containing lipoproteins. RESULTS: Ezetimibe dramatically reduced PHTG in both WT and CD36KO mice. HPLC analysis of plasma showed that the decrease in TG content in CM and CM remnants-sized particles contributed to this suppression, suggesting that CM production in the small intestines might be reduced after ezetimibe treatment. Intestinal lymph was collected after oral fat loading in ezetimibe-treated and non-treated mice. Both TG content and ApoB-48 mass were decreased in ezetimibe-treated mice. The quantitative RT-PCR of intestinal mucosa showed down-regulation of the mRNA expression of FATP4 and ApoB in both groups along with FABP2, DGAT1, DGAT2 and SCD1 in WT mice at postprandial state after ezetimibe treatment. CONCLUSION: Ezetimibe alone reduces PHTG by blocking both the absorption of cholesterol and the intracellular trafficking and metabolism of long-chain fatty acids in enterocytes, resulting in the reduction of the formation of ApoB-48 which is necessary for the ApoB48-containing lipoprotein production in the small intestines. PMID- 20543520 TI - Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism. AB - Sitosterolemia is a rare, autosomal recessive inherited sterol storage disease associated with high tissue and serum plant sterol concentrations, caused by mutations in the adenosine triphosphate-bind-ing cassette (ABC) transporter ABCG5 or ABCG8 genes. Markedly increased serum concentration of plant sterols. such as sitosterol and campesterol, cause premature atherosclerosis and massive xanthomas. Hitherto known treatments for sitosterolemia, including a low-sterol diet, bile-salt binding resins, ileal bypass surgery and low density lipoprotein (LDL) apheresis have not yielded sufficient reduction of serum plant sterol levels and many patients show a sustained elevation of plant sterol levels, subsequently developing premature atherosclerotic cardiovascular diseases. Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1), has been widely used for decreasing serum LDL cholesterol levels in patients with hypercholesterolemia. Ezetimibe also reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia. In the current review, we discuss the current therapy for patients with sitosterolemia and present two Japanese adolescent patients with this disease, one of whom underwent percutaneous coronary intervention for accelerated coronary atherosclerosis. Ezetimibe administration in addition to conventional drug therapy successfully reduced serum sitosterol levels by 51.3% and 48.9%, respectively, in the two patients, demonstrating ezetimibe as a novel and potent treatment agent for sitosterolemia that could work additively with conventional drug therapy. PMID- 20543521 TI - Usefulness of C-reactive protein to high-molecular-weight adiponectin ratio to predict insulin resistance and metabolic syndrome in Japanese men. AB - AIM: We questioned whether the ratio of C-reactive protein to high-molecular weight adiponectin (C/A ratio), compared to each value alone, is more useful to predict insulin resistance and/or metabolic syndrome. METHODS: We measured serum CRP and HMW adiponectin levels in 841 Japanese men who had participated in an annual health checkup. Correlations of the C/A ratio with metabolic parameters were assessed, and its predictive values for insulin resistance and MetS were compared with CRP or HMW adiponectin alone. RESULTS: The C/A ratio was higher in subjects with MetS (n = 114) than in those without MetS (0.46 +/- 0.67 vs. 0.23 +/- 0.39, p<0.0001). The C/A ratio was correlated with a larger number of metabolic parameters than CRP, but the correlation was comparable to HMW adiponectin. Likewise, the area under the curve of the C/A ratio in receiver operator characteristic analysis for MetS was greater than that of CRP, but comparable to that of HMW adiponectin. However, the AUC of the C/A ratio in ROC analysis for insulin resistance (HOMA-IR >2.5) was greater than that of CRP or HMW adiponectin alone. CONCLUSION: While the C/A ratio provided little advantage to predict MetS, it might be more useful to predict insulin resistance than CRP or HMW adiponectin alone. PMID- 20543522 TI - Association between lowering low-density lipoprotein cholesterol with pravastatin and primary prevention of cardiovascular disease in mild to moderate hypercholesterolemic Japanese. AB - AIMS: To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) change and reduction of cardiovascular disease in the Management of Elevated cholesterol in the primary prevention Group of Adult Japanese (MEGA) study. METHODS: Patients in the diet plus pravastatin group were divided into tertiles by their on-treatment LDL-C level, and the hazard ratios (HRs) in each tertile were compared with the diet group at 5 years using the Cox proportional hazards model. In addition, the treatment groups were combined and divided into quintiles according to the on-treatment LDL-C level during follow-up, and the incidence of cardiovascular events was compared among the 5 groups. RESULTS: In the tertiles of the diet plus pravastatin group, HR was lowest in the second tertile against the diet group (HR 0.57, p=0.01) with on-treatment LDL-C range of 119.8-133.4 mg/dL. In the analysis of quintiles of the total population, a significant risk reduction of CVD was found in the fourth quintile (HR 0.48, p=0.0015) with an on-treatment LDL-C range of 120.9-133.3 mg/dL, and in the fifth quintile (HR 0.64, p=0.048) with an on-treatment LDL-C range of 56.7-120.8 mg/dL against tertile 1 with an on-treatment LDL-C range of 157.5-206.2 mg/dL. CONCLUSIONS: The usual Japanese dose of pravastatin therapy is sufficient in this low-risk patient population to reduce cardiovascular risk, with an achieved LDL-C level <133.4 mg/dL. Further risk reduction was not found with an achieved LDL <120 mg/dL. PMID- 20543523 TI - Serum fetuin-A is an independent marker of insulin resistance in Japanese men. AB - AIM: Fetuin-A, also known as alpha2-Heremans Schmid glycoprotein, is an abundant plasma protein synthesized predominantly in the liver. Fetuin-A inhibits insulin receptor autophosphorylation, which is mediated by its intrinsic tyrosine kinase activity. In this study, we examined the association between the serum fetuin-A level and insulin resistance in Japanese men. METHODS: We recruited 300 unrelated Japanese men without known chronic diseases, such as diabetes mellitus, or a history of regular drug use, and who underwent health examinations. From a 75-g oral glucose tolerance test, the study population included 194 individuals with normal glucose tolerance, 91 with impaired glucose tolerance and/or impaired fasting glucose, and 15 with diabetes mellitus. Serum fetuin-A concentrations were measured using an ELISA kit. RESULTS: Serum fetuin-A concentrations were positively correlated with fasting insulin levels (r = 0.269, p<0.001), HOMA-IR (r = 0.274, p<0.001) and LDL-cholesterol (r = 0.172, p<0.01), and negatively correlated with HDL-cholesterol concentrations (r = -0.191, p<0.001). Fetuin-A concentrations were also positively correlated with serum leptin (r = 0.150, p<0.01) and negatively with adiponectin concentrations (r = -0.208, p<0.001). Stepwise regression analyses confirmed that the fetuin-A concentration was independently associated with the fasting insulin level and HOMA-IR, as were body mass index, triglyceride, LDL-cholesterol, leptin and adiponectin concentrations. CONCLUSION: Our data suggest that increased serum fetuin-A levels constitute an independent marker of insulin resistance and an atherogenic lipid profile in Japanese men. PMID- 20543524 TI - Gambogic acid induces G0/G1 cell cycle arrest and cell migration inhibition via suppressing PDGF receptor beta tyrosine phosphorylation and Rac1 activity in rat aortic smooth muscle cells. AB - AIM: Gambogic acid (GA) is the major active compound of Gamboge, a brownish or orange resin exuded from Garcinia hanburryi tree in Southeast Asia. Previous studies have demonstrated that GA exhibits potent anticancer effects by inducing cell cycle arrest or apoptosis in many types of cancer cell lines and blocking angiogenesis via inhibition of vascular endothelial cell proliferation and migration. Proliferation and migration of vascular smooth muscle cells (VSMCs) are critical steps in the progress of atherosclerosis and restenosis after angioplasty. In the present study, we investigated whether GA has an inhibitory effect on the proliferation and migration of VSMCs and its possible mechanism. METHODS: The inhibitory effect of GA on the proliferation induced by PDGF-BB and EGF was measured by using Cell number counting assay and [(3)H]-thymidine incorporation. The effects of GA on the cell cycle progression and viability stimulated by PDGF-BB and EGF were also analyzed by flow cytometry analysis. The inhibitory effect of GA on the migration stimulated by PDGF-BB was measured by transwell chamber assay. The effect of GA on the Cell cycle regulatory molecules (cyclinD1, cyclinE, CDK2, CDK4), PDGFR and its downstream signaling molecules including ERK1/2, PLCgamma1, AKT and JNK was measured by western blotting. The effect of GA on the Rac1 activity was measured by using GST-pulldown assay. The effects of GA on the tyrosine phosphorylation stimulated by PDGF-BB and EGF and the capacity of GA binding with PDGF-BB and EGF were also measured. RESULTS: We found that GA significantly inhibited proliferation, migration and DNA synthesis in primary cultured rat aortic VSMCs at concentrations of 0.25, 0.5, 1.0 and 2.0 umol/L after stimulation of 50 ug/L platelet-derived growth factor-BB (PDGF-BB). GA induced G0/G1 phase arrest in the cell cycle progression of VSMCs. No obvious necrosis or apoptosis was found with GA treatment. The expressions of CDK2, CDK4, cyclin D1 and cyclin E, cell cycle regulatory molecules, were significantly suppressed by GA treatment in a concentration-dependent manner. The phosphorylation of PDGF receptor beta (PDGFR-beta) and the activities of downstream intracellular signaling molecules including phospho-ERK, phospho PLCgamma1, phospho-AKT, phospho-JNK and GTP-Rac1 were also inhibited by GA pretreatment. GA inhibited PDGFR-beta phosphorylation through inhibiting the activity of tyrosine directly, rather than indirectly via binding PDGF-BB. CONCLUSIONS: The results of this study provide preliminary evidence that the inhibitory effects of GA on VSMCs proliferation and migration may be mediated through multiple signal pathways controlled by PDGF-Rbeta activation and its downstream intracelluar signaling. PMID- 20543525 TI - Hazard Assessments of Manufactured Nanomaterials. AB - Background: It has been difficult to make reliable hazard assessments of manufactured nanomaterials, because the nanomaterials form large agglomerations in both in vitro and in vivo studies. Objective: A project by the New Energy and Industrial Technology Development Organization (NEDO) of Japan has succeeded in ensuring the stability of dispersion (nanoscale <100 nm) of manufactured nanomaterials, and is developing hazard assessments of manufactured nanomaterials. Results and Conclusion: Focusing on titanium dioxide, fullerenes and carbon nanotubes, we introduce findings made in inhalation and intratracheal installation studies overseas, and together with the findings made in the NEDO project, and also assess the hazards presented by manufactured nanoparticles. PMID- 20543526 TI - Functions and regulation of Artemis: a goddess in the maintenance of genome integrity. AB - Artemis is a structure-specific endonuclease when associated with and phosphorylated by DNA-dependent protein kinase catalytic subunit. This structure specific endonuclease is responsible for the resolution of hairpin coding ends in V(D)J recombination. In DNA double-strand break repair, Artemis is implicated in the end-processing step of the non-homologous end-joining (NHEJ) pathway. Recently, we have demonstrated that the involvement of Artemis in NHEJ depends on the type of DNA damage. Interestingly, recent evidence suggests that the end processing activity is not the only function of Artemis. Indeed, Artemis is rapidly phosphorylated by ataxia telangiectasia mutated in response to DNA damage, and such phosphorylation of Artemis appears to be involved in the regulation of cell cycle checkpoints. These findings suggest that Artemis is a multifunctional protein participating in the maintenance of genome integrity at two distinct levels; one at the end processing step of NHEJ, and the other at the signaling pathway of cell cycle regulation. Therefore, understanding Artemis function may give us profound insights into the DNA repair network. In this review, we summarize the functions and regulation of Artemis. PMID- 20543527 TI - Longitudinal trends of total white blood cell and differential white blood cell counts of atomic bomb survivors. AB - In studying the late health effects of atomic-bomb (A-bomb) survivors, earlier findings were that white blood cell (WBC) count increased with radiation dose in cross-sectional studies. However, a persistent effect of radiation on WBC count and other risk factors has yet to be confirmed. The objectives of the present study were 1) to examine the longitudinal relationship between A-bomb radiation dose and WBC and differential WBC counts among A-bomb survivors and 2) to investigate the potential confounding risk factors (such as age at exposure and smoking status) as well as modification of the radiation dose-response. A total of 7,562 A-bomb survivors in Hiroshima and Nagasaki were included in this study from 1964-2004. A linear mixed model was applied using the repeated WBC measurements. During the study period, a secular downward trend of WBC count was observed. Radiation exposure was a significant risk factor for elevated WBC and differential WBC counts over time. A significant increase of WBC counts among survivors with high radiation dose (> 2 Gy) was detected in men exposed below the age of 20 and in women regardless of age at exposure. Effects on WBC of low dose radiation remain unclear, however. Cigarette smoking produced the most pronounced effect on WBC counts and its impact was much larger than that of radiation exposure. PMID- 20543528 TI - Intracranial cholesterol granuloma in a cat. AB - A case of intracranial cholesterol granuloma is described in a 4-year-old neutered European male cat presented with a 5-month history of progressive weakness, ataxia and depression. On clinical evaluation, haematological and biochemical profiles revealed only mild hypercholesterolemia and magnetic resonance imaging showed a large space-occupying extra-axial mass in the area of the falx, not homogeneous after contrast enhancement. At post-mortem examination, an orange-yellowish mass of 22 mm in diameter extended from the right frontal lobe to the temporo-parietal region, causing atrophy of the prosencephalic region of the brain. The site of origin of the mass was within the subarachnoid space of the supracallosum sulcus of the right cerebral hemisphere. Histological examination of the lesion revealed abundant deposits of cholesterol clefts, surrounded by clusters of macrophages and multinucleated giant cells. Neither inflammatory lesions, nor cholesterol deposits were detected in other areas of the brain and in other organs. On the basis of the histological examination, a diagnosis of intracranial cholesterol granuloma was made. PMID- 20543529 TI - Effect of sugar supplementation on rumen protozoa profile and papillae development in retarded growth calves. AB - The effect of sugar supplementation with 1 g/kg BW twice a week for eight weeks on rumen protozoa was determined in ten retarded growth calves. Rumen juice was sampled by abdominal paracentesis during the experiment. Papillae development of rumens excised by experimental laparotomy was macro- and micromorphologically determined before and after sugar supplementation in a selected calf. The numbers of Entodinium, Isotricha, Dasytricha and Epidinium protozoa increased by 3 to 12 folds after 1-3 wk of supplementation and subsequently decreased. The heights of the rumen papillae after sugar supplementation showed marked development compared with before supplementation (Post vs. Pre: 4.44 +/- 0.43 vs. 1.36 +/- 0.24 mm). Sugar supplementation accommodates the rumen protozoa profile and stimulates papillae development in retarded growth calves. PMID- 20543530 TI - An atypical porcine proliferative enteropathy of malgrowth piglets. AB - Two 60-day-old pigs showing clinical signs of malgrowth and diarrhea were diagnosed as atypical porcine proliferative enteropathy (PPE). The intestinal mucosal lesions in the piglets were characterized by the adenomatous proliferation of the crypt epithelium together with growth of small curved bacteria within the enterocytes. The lesions could be seen in the ileum and other portions of the intestine histologically, although no significant thickening of the gut wall could be observed grossly in the present case. The macroscopic findings are extremely important for the diagnosis of PPE, however, this paper shows that the histopathological and/or immunohistochemical findings were also critical to identify the disease. PMID- 20543531 TI - Gastrointestinal and hematologic adverse events after administration of vincristine, cyclophosphamide, and doxorubicin in dogs with lymphoma that underwent a combination multidrug chemotherapy protocol. AB - The present study aimed to objectively evaluate the adverse events after the administration of chemotherapeutic agents used in the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25) for canine lymphoma, using the Veterinary Co-operative Oncology Group common terminology criteria for adverse events (VCOG-CTCAE). The medical records of 40 dogs with multicentric high-grade lymphoma that underwent UW-25 were reviewed. Gastrointestinal adverse events of grade 2 and above and blood/bone marrow adverse events of all grades were evaluated. Gastrointestinal adverse events occurring at least once during the entire period of UW-25 were observed in 50% (20/40), 17.9% (7/39), and 8.1% (3/37) of the dogs after the administration of vincristine (VCR), cyclophosphamide (CPA), and doxorubicin (DXR), respectively. Blood/bone marrow adverse events occurring at least once during UW-25 were observed in 57.5% (23/40), 41% (16/39), and 8.1% (3/37) of the dogs after the administration of VCR, CPA, and DXR, respectively. The rate of patients that experienced gastrointestinal adverse events was higher after the first administration of VCR than after the first administration of DXR. Findings obtained in this study will be helpful in predicting the adverse events that could occur when dogs with lymphoma are treated with UW-25. PMID- 20543532 TI - Expression analysis of desmosomal components of the novel canine epidermal keratinocyte cell line (MSCEK). AB - A novel canine epidermal keratinocyte cell line, MSCEK, was developed from skin of a healthy dog. The aim of this study was to determine its expression of desmosomal components and to evaluate its use as a detection tool for circulating autoantibodies in canine pemphigus. Immunofluorescence and western blotting analyses revealed that MSCEK expresses desmoglein (Dsg) 1, Dsg2, Dsg3, desmoplakin, plakoglobin and cytokeratins. Moreover, positive fluorescent reactions on the surface of MSCEK cells were observed when the cells were incubated with sera obtained from four dogs diagnosed with pemphigus complex. These findings indicate that MSCEK should be a useful tool for future research to characterize circulating autoantibodies that recognize desmosomal components in dogs with pemphigus. PMID- 20543533 TI - [The present situation and future perspectives of the management of chemicals in Japan]. AB - OBJECTIVES: During the scientific revolution era, many chemicals have been used in the work places and released into the environment. In this review, we intend to summarize the legislation for the management of chemicals in Japan and discuss the future perspectives with regard to precautionary principles for hazardous chemicals. METHODS: We searched the articles related to the management and legislation of the chemicals. We also obtained the various documents which have been published from the Japanese Government. RESULTS AND CONCLUSIONS: In Japan, the annual quantity of discharge of certain chemicals has been reported based on the Pollutant Release and Transfer Register (PRTR) law. The European Commission has proposed a new system called REACH (Registration, Evaluation and Authorization of Chemicals) to achieve the overriding goal of risk reduction. In the light of occupational health, risk assessment of chemical toxicity and exposure should be promoted in order to preserve workers' health. Due to the ever increasing use of synthetic chemicals, it is necessary for all parties to clarify their responsibilities to reduce occupational risks. PMID- 20543534 TI - Carnitine palmitoyltransferase 2 deficiency: the time-course of blood and urinary acylcarnitine levels during initial L-carnitine supplementation. AB - Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 micromol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as C16, C18, C18:1 and C18:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients. PMID- 20543535 TI - Phenotypic variability of the homozygous IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene in patients with chronic pancreatitis. AB - Chronic pancreatitis (CP) is a progressive inflammatory disease that eventually results in the impairment of exocrine and endocrine functions of the pancreas. Recent studies have shown an association between mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene and CP. SPINK1 provides the first line of defense against prematurely activated trypsinogen by physically blocking the active site of trypsin. The IVS3+2T>C (c.194+2T>C) mutation is a loss-of-function splicing mutation; it affects the consensus splicing donor site in intron 3 and may cause the skipping of the entire exon 3, where the trypsin-binding site is located. We report here three CP patients carrying this mutation in a homozygous form, with no noticeable family history of pancreatitis. The first patient is a 25-year-old male with juvenile-onset idiopathic CP. He suffered from repeated attacks of pancreatitis since 5 years old and underwent pancreatico-jejunostomy. He complained of epigastralgia, and was diagnosed as obstructive pancreatitis in the area of the accessory pancreatic duct. The second patient is a 75-year-old male with alcoholic CP. He did not have apparent attacks of pancreatitis, but had numerous calcifications throughout the pancreas and confirmed exocrine failure and diabetes mellitus. The last patient is a 44-year-old female with late-onset idiopathic CP. She suffered from repeated attacks of pancreatitis since 32 years old. She had numerous stones in the main pancreatic duct in the pancreas head and confirmed exocrine failure. The clinical courses of these patients are apparently different, indicating the phenotypic variability of the SPINK1 IVS3+2T>C mutation associated CP. PMID- 20543536 TI - MicroRNA profiling in mid- and late-gestational fetal skin: implication for scarless wound healing. AB - Mid-gestational mammalian skin has unique capacity to heal without scar. Fetal skin undergoes phenotypic transition from scarless healing to scar repairing during embryonic development. However, the molecular mechanisms underlying the scarless phenotype and phenotypic transition remain largely unknown. MicroRNAs (miRNAs) are a novel class of small regulatory RNAs emerged as post transcriptional gene repressors and play essential roles in diverse pathophysiological processes including skin morphogenesis and pathogenesis. Here, we performed a genome-wide miRNA profiling to identify the differentially expressed miRNAs between mid-gestational (E16 day) and late-gestational (E19 day) mouse skin, corresponding to scarless and scarring phenotype, respectively. Two miRNAs (miR-29b and miR-29c) with highest fold changes were further validated independently by real-time RT-PCR. Functional annotations of putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets, including Smads, beta-catenin and Ras, were significantly enriched and involved in several signaling pathways important for scarless wound healing. In addition, Dicer, one of the key RNase III responsible for miRNA biogenesis and functions, was found to be up-regulated in the E19 fetal skin as compared with the E16 counterpart. Taken together, our results identified differentially expressed miRNAs between mid-and late-gestational fetal skin that correlated with phenotypic transition from scarless to scarring repair during skin development. Our bioinformatics' analysis suggests that miRNAs might contribute to this phenotypic transition probably by affecting multiple target genes and signaling pathways. PMID- 20543537 TI - Feasibility study of docetaxel, oxaliplatin and capecitabine combination regimen in advanced gastric or gastroesophageal adenocarcinoma. AB - BACKGROUND AND OBJECTIVES: At present, there is no standard regimen for the treatment of gastroesophageal cancer. Docetaxel, cisplatin and fluorouracil (DCF) has been shown to be an effective regimen; however, toxicity is an area of concern in the palliative case setting. Capecitabine and oxaliplatin have been shown to be as effective as fluorouracil and cisplatin, respectively. To reduce the toxicity of DCF while maintaining efficacy, we conducted this study to evaluate the efficacy of docetaxel, oxaliplatin and capecitabine (DOX) combination in advanced gastroesophageal cancer. METHODS: Patients with histologically confirmed metastatic or locally advanced adenocarcinoma of the stomach or gastroesophageal junction received docetaxel 25 mg/m2 and oxaliplatin 50 mg/m2 on days 1 and 8 with capecitabine 625 mg/m2 twice daily from day 1-14, in 21-day cycles. The primary endpoint was overall response rate (ORR). RESULTS: Of 21 patients, there were 16 males and 5 females with a median age of 57 years, range 37-80 years. The primary tumor was located at the gastroesophageal junction in 7 patients and in other parts of the stomach in the remaining 14 patients. One patient had locally advanced tumor without distant metastases and 20 patients presented with metastatic disease. Grade 3/4 toxicities included diarrhea (24%), hand-foot syndrome (5%) and febrile neutropenia (5%). The ORR was 29%. The median survival was 8.4 months. At the time of analysis, 5 of the 21 patients (24%) were alive. CONCLUSIONS: The DOX combination is tolerable, active and a promising day care regimen for advanced gastroesophageal cancer. PMID- 20543538 TI - Protein C levels in beta-thalassemia major patients in the east Nile delta of Egypt. AB - BACKGROUND AND OBJECTIVES: Thalassemic patients have an increased risk for thromboembolic complications. To determine if this might be due to a deficiency in protein C, we investigated the status of the protein C anticoagulant pathway in thalassemia major patients and its relationship to the hypercoagulable state. PATIENTS AND METHODS: Fifty patients with beta-thalassemia major (30 non splenectomized and 20 splenectomized) and 20 healthy children as a control group were tested for levels of serum ferritin, liver enzymes, serum albumin, fibrinogen, protein C and protein S, thrombin antithrombin complex (TAT) and D dimer. RESULTS: Thalassemic patients had lower levels of protein C and S and higher levels of D-dimer and TAT than the control group. These findings were more obvious in splenectomized patients and in those with infrequent blood transfusion. CONCLUSIONS: Protein C plays a major role in the hypercoagulable state in thalassemic patients. These findings raise the issue as to whether it would be cost-beneficial to recommend prophylactic antithrombotic therapy in high risk thalassemic patients. A wider prospective study is necessary to delineate under which circumstances therapy might be needed, and at what level of protein C deficiency to start prophylactic antithrombotic therapy. PMID- 20543539 TI - Human G-protein gamma 7 in extrahepatic cholangiocarcinoma and its clinicopathological significance. AB - BACKGROUND AND OBJECTIVES: Several studies have found a down-regulated G-gamma 7 gene in gastrointestinal tract cancers. We evaluated the expression and clinicopathological significance of the human G protein gamma 7 (G-gamma 7) in human extra-hepatic cholangiocarcinoma (EHCC). METHODS: The expression of G-gamma 7 expression was studied in 21 patients with EHCC. G-gamma 7 mRNA expression was tested by using RealTime reverse transcription polymerase chain reaction (RT PCR).To visualize the localization of G-gamma 7, an immunohistochemistry study was also performed. The G-gamma 7 expression was compared among cancer tissues, peri-cancerous bile duct tissues and normal bile duct tissues. The clinicopathological significance of G-gamma 7 expression was also studied. RESULTS: Expression of G-gamma 7 mRNA and protein were significantly lower in EHCC tissue than in pericancerous bile duct tissue and normal bile duct tissues. G-gamma 7 mRNA and protein expression were significantly lower in poorly differentiated EHCC tissues than in moderate differentiated and well differentiated EHCC tissues (P<.01). There was no significant correlation between G-gamma 7 expression and host factors such as age, gender, clinical staging or the status of preoperative hepatic function CONCLUSIONS: EHCC has a down regulated expression of G-gamma 7. Reduced expression of G-gamma 7 is associated with the histological grade of EHCC and may prove to be a useful marker for predicting the prognosis of human EHCC. PMID- 20543540 TI - Systemic thromboembolic complications after laparoscopic splenectomy for idiopathic thrombocytopenic purpura in comparison to open surgery in the absence of anticoagulant prophylaxis. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) in adults has a chronic course and may necessitate splenectomy. The current study was undertaken to study the systemic thromboembolic complications of laparoscopic splenectomy (LS) versus open splenectomy (OS) in patients with ITP at two large referral hospitals. PATIENTS AND METHODS: We conducted a retrospective analysis of 49 patients who underwent splenectomy (21 LS and 28 OS) for primary/relapsing refractory ITP between June 1995 and November 2004. Clinically and/or radiologically confirmed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) were assessed within 2 weeks before and after splenectomy. None had prophylactic anticoagulants immediately after surgery. Follow up of those who developed complications continued for at least 2 additional years to assess for contributing factors that may have been masked at the time of occurrence. RESULTS: Two (9.5%) LS group had acute PE within 5 days of LS and their platelet count reached 500A103/I(1/4)L within 4 days and 1000A103/I(1/4)L within 7 days after surgery. Three conversions to OS occurred; none had VTE. DVT occurred in 3 patients (10.7%) in the OS group; none were life threatening. There were no deaths. CONCLUSION: Life-threatening venous thromboembolic events are serious complications after LS and OS for ITP patients if prophylactic anticoagulants are not administered. Patients at risk are those who both have an exponential rise of the platelet count, although factors other than the platelet count may be contributing in OS. Postsplenectomy, ITP should be considered as a thrombophilic condition and studies of additional measures to prevent such events are warranted. PMID- 20543542 TI - Squamous cell carcinoma of the lip after allogeneic hemopoietic stem cell transplantation. AB - Allogeneic hemopoietic stem cell transplantation (HSCT) has been considered a curative treatment option for many hematological and non-hematological disorders. Despite the use of advanced methods of tissue typing and new therapies, graft versus host disease (GVHD) remains a major obstacle. Secondary malignancies are also among the most serious long-term complications after HSCT including leukemia, lymphomas, and to a lesser extent, solid tumors. The most commonly observed solid tumor is squamous cell carcinoma (SCC). We report two cases of SCC of the lower lip diagnosed several years after HSCT. Both cases were complicated with GVHD prior to the development of SCC and had a successful outcome with minimal surgical intervention. PMID- 20543541 TI - The impact of recently published negative erythropoiesis-stimulating agent studies on the clinical management of cancer-related anemia at a single center. AB - BACKGROUND AND OBJECTIVES: Anemia in cancer patients is common, but often under recognized and under-treated. Erythropoiesis stimulating agents (ESAs) are widely used to prevent and treat cancer and chemo- therapy-related anemia, but recent studies suggest a negative impact on disease progression and survival associated with their use. This retrospective study describes the prevalence of anemia in cancer patients and recent trends in its management given the negative studies. PATIENTS AND METHODS: All consecutive adult cancer patients (n=959) admitted to regular medical units over one year were reviewed. Patients with a hemoglobin (Hb) value <12 g/dL on admission were considered anemic. Information on the primary tumor, main reasons for admission and treatment given were collected. RESULTS: At the time of enrollment, anemia was detected in 755 (78.7%) patients. The mean Hb value for anemic patients was 9.5 g/dL. Prevalence and severity of anemia varied according to tumor type and reason for admission. The majority (68.6%) of the anemic patients were not offered treatment. The mean Hb value at which treatment was started was 8.0 g/dL. Anemia treatment was related to its severity; treatment rates were 94.4%, 32.9%, and 5.0% in patients with severe, moderate and mild anemia, respectively (P<.0001). Blood transfusion was used the most while ESAs were rarely used. Length of hospital stay was affected by the presence of anemia (7.2 days in anemic patients vs. 4.85 days in nonanemic patients) (P<.001). CONCLUSIONS: Blood transfusion was used the most for cancer related anemia, while ESAs were rarely used. The majority of patients with moderate anemia were not treated, including patients on active chemotherapy. Better guidelines addressing anemia management in this subgroup of patients are highly needed. PMID- 20543543 TI - Successful treatment of biphasic metaplastic sarcomatoid carcinoma of the breast by evaluation of immunohistochemical markers. AB - Biphasic metaplastic sarcomatoid carcinoma (MSC) of the breast is rare and aggressive. Patients with metaplastic breast carcinomas tend to have poor outcomes with a high risk of recurrence following pri- mary surgery. Most reports have shown that systemic therapy appears to be less effective. We report a case of a 42-year-old female who presented with a large (14 cm) cauliflower breast mass. Biopsy revealed a poorly differentiated sarcoma. Initially, neo-adjuvant concurrent chemoradiotherapy with a sarcoma regimen was prescribed, and the tumor regressed to a large ulcer. Subsequent biopsy showed invasive ductal carcinoma (estrogen receptor, progesterone receptor stained weakly, 5%, Her2:2+) and disappearance of the sarcomatous component. Second-line neoadjuvant therapy was designed according to the histologic features of infiltrating ductal carcinoma, which led to nearly a complete response. A modified radical mastectomy of the right breast and axillary dissection was performed followed by monoclonal antibody (trastuzumab) therapy for 6 months due to the surgical specimen showing Her2:3+. The treatment course went smoothly with a good response. The patient had no evidence of disease at 18 months. PMID- 20543544 TI - Granulocytic sarcoma of the stomach: relapse after hematopoietic stem-cell transplantation for chronic myeloid leukemia. AB - An 18-year-old male underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myeloid leukemia (CML) in the first late chronic phase. On day 132, he was readmitted to the hospital with nausea, vomiting and nodular lesions on endoscopy. A diagnosis of granulocytic sarcoma of the stomach was made. Bone marrow cytogenetic analysis for the Philadelphia chromosome and nested polymerase chain reaction for BCR-ABL1 were both negative. Immunosuppression was abruptly discontinued, and by day 180, all gastric lesions had completely disappeared. However, there were histological signs of graft versus-host disease. The patient developed progressive anorexia and elevated hepatic enzymes, which prompted the reintroduction of cyclosporine. Considering the risk of another relapse, imatinib mesylate (IM) 600 mg/day was started. The patient Is condition improved, and there was no evidence of disease recurrence at 36 months after relapse. Relapse of CML is the commonest cause of treatment failure after allo-HSCT. On rare occasions, a localized extramedullary presentation is seen. Unless properly treated, other extramedullary relapse sites and/or marrow infiltration usually occur. Withdrawal of immunosuppression, along with IM therapy seems to be an acceptable approach in this setting. PMID- 20543545 TI - Fludarabine-induced bradycardia in a patient with refractory leukemia. PMID- 20543546 TI - Bronchiolitis obliterans following hematopoietic stem cell transplantation. PMID- 20543547 TI - Piceatannol-3'-O-beta-D-glucopyranoside as an active component of rhubarb activates endothelial nitric oxide synthase through inhibition of arginase activity. AB - Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. Here, we demonstrate that piceatannol-3'-O-beta-D-glucopyranoside (PG), a potent component of stilbenes, inhibits the activity of arginase I and II prepared from mouse liver and kidney lysates, respectively, in a dose-dependent manner. In human umbilical vein endothelial cells, incubation of PG markedly blocked arginase activity and increased NOx production, as measured by Griess assay. The PG effect was associated with increase of eNOS dimer ratio, although the protein levels of arginase II or eNOS were not changed. Furthermore, isolated mice aortic rings treated with PG showed inhibited arginase activity that resulted in increased nitric oxide (NO) production upto 78%, as measured using 4-amino-5 methylamino-2',7'-difluorescein (DAF-FM) and a decreased superoxide anions up to 63%, as measured using dihydroethidine (DHE) in the intact endothelium. PG showed IC((50)) value of 11.22 microM and 11.06 microM against arginase I and II, respectively. PG as an arginase inhibitor, therefore, represents a novel molecule for the therapy of cardiovascular diseases derived from endothelial dysfunction and may be used for the design of pharmaceutical compounds. PMID- 20543550 TI - American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. AB - American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. PMID- 20543548 TI - A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti angiogenic activity. AB - Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases. PMID- 20543551 TI - American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. AB - American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. PMID- 20543552 TI - Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats. AB - Adult-onset hypothyroidism causes cognitive dysfunctions of learning and memory, in which many synaptic proteins in hippocampus are involved. In our work, we studied the effect of adult-onset hypothyroidism on the expression of synaptotagmin 1 (syt 1) and SNAP-25 in dorsal hippocampus as well as its recovery by levothyroxine (L-T(4)) replacement therapy. Rats were divided into 4 groups: control, hypothyroidism, and hypothyroid rats treated with 5 MUg T(4)/100 g body weight (BW) and 20 MUg L-T(4)/100 g BW, respectively. Protein levels of syt 1 and SNAP-25 in dorsal hippocampus were determined by Western blot and immunohistochemistry. The immunoblot analysis indicated that syt 1 was expressed at a significantly lower level in hypothyroid rats, while the level of SNAP-25 was much higher compared to controls. Furthermore, using immunostaining, we found that on the one hand, expression of syt 1 was significantly down-regulated in the examined layers of CA1 and CA3 subregions but not dentate gyrus (DG); however, on the other hand, expression of SNAP-25 was up-regulated in the layers of CA1, CA3, and DG. Two-week treatment with 20 MUg LT(4)/ 100 g BW fully restored the levels of syt 1 and SNAP-25 to the normal level, which was more effective than 5 MUg LT(4)/ 100 g BW that partially restored the levels of both proteins. These results suggest that adult-onset hypothyroidism caused down-regulation of syt 1 and up-regulation of SNAP- 25 level in dorsal hippocampus, which could be restored by L-T(4) treatment, and the recovery degree is related to the LT(4) dosage. PMID- 20543553 TI - Electric and magnetic fields do not modify the biochemical properties of FRTL-5 cells. AB - BACKGROUND: Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described. AIM: The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL- 5). MATERIAL AND METHODS: The experimental setup was designed in order to expose samples to a radiofrequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800-900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured. RESULTS: The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL- 5 cells with respect to basal conditions. CONCLUSIONS: In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro. PMID- 20543554 TI - The effects of native and synthetic estrogenic compounds as well as vitamin D less-calcemic analogs on adipocytes content in rat bone marrow. AB - BACKGROUND: We demonstrated previously that phytoestrogens and vitamin D analogs like estradiol-17beta (E2) modulate bone morphology in rat female model. AIM: We now analyze the effects of phytoestrogens, E2, selective E2 re ceptor modulators, and the less-calcemic analogs of vitamin D: JKF1624F2-2 (JKF) or QW1624F2-2 (QW) on fat content in bone marrow (BM) from long bones in ovariectomized female rats (OVX). MATERIALS AND METHODS: OVX rats were injected with treatments known to affect bone formation, 5 days per week for 2.5 month for analysis of fat content in BM. RESULTS: In OVX young adults there is a decreased bone formation and a 10 fold increase in fat cells content in BM. Treatment with E2, raloxifene (Ral) or DT56a resulted in almost completely abolishment of fat cells content. Daidzein (D) decreased fat cells content by 80%, genistein (G) or biochainin A (BA) did not change fat cells content and carboxy BA (cBA) had a small but significant effect. JKF or QW did not affect fat cells content, whereas combined treatment of JKF or QW with E2 resulted in complete abolishment of fat cells content. These changes in fat cells content are inversely correlated with changes in bone formation. CONCLUSIONS: Our results demonstrate that adipogenesis induced by OVX is a reversible process which can be corrected by hormonal treatments. The awareness of a relationship between fat and bone at the marrow level might provide a better understanding of the pathophysiology of bone loss as well as a novel approach to diagnosis and treatment of postmenopausal osteoporosis. PMID- 20543555 TI - Long-term auxological and pubertal outcome of patients with hereditary insulin like growth factor-I deficiency (Laron and growth hormone-gene deletion syndrome) treated with recombinant human insulin-like growth factor-I. AB - BACKGROUND: GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic pituitary-gonadal (HPG) function. SUBJECTS: We report some data regarding long term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4+/-5.3 yr (range 19-32). METHODS: All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2-14.2) up to the final height. RESULTS: Final height was very disappointing (<= -5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow- up was 8.3 yr with the longest span of 17.2 yr. CONCLUSION: We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation. PMID- 20543556 TI - Experience with adrenal schwannoma in a Chinese population of six patients. AB - OBJECTIVES: Benign adrenal schwannoma is an extremely uncommon cause of incidentaloma. This article describes our experience with the diagnosis and treatment of adrenal schwannoma in a Chinese population of 6 patients. To our knowledge, this is the largest series of this uncommon adrenal tumor treated in a single center. METHODS: From May 1999 to May 2009, 6 patients with incidentally discovered adrenal schwannoma were operated on at a tertiary referral hospital in Eastern China. Clinical details, radiographic features, laboratory examinations, pathological findings, and follow-up data of these patients were analyzed. RESULTS: Of the 6 patients, 4 were females (F) and 2 were males (M), with a mean age of 40.5 yr (range: 30-47, M:F=2:1). The 6 patients were managed with open unilateral adrenalectomy; 5 patients had schwannomas on the left side, and 1 on right side. Abnormal urine catecholamine was detected in 1 patient. The mean pathological size of these tumors was 4.3 +/- 1.1 cm. The diagnosis of schwannoma was based on classic histological findings, and supported by immunohistochemistry of S-100, vimentin, and ABC positivity. In the follow- up of 47.5 +/- 32.3 months, no recurrence and metastasis were observed. CONCLUSIONS: Although there may be some clues for radiological diagnosis of adrenal schwannoma, preoperative misdiagnosis is not infrequent. Those tumors may occasionally have endocrine function. Histological examination is the key of diagnosis, and surgical resection is the treatment of choice once malignancy cannot be excluded by preoperative analyses. PMID- 20543557 TI - The polycomb group protein BMI1 is a transcriptional target of HDAC inhibitors. AB - Polycomb group (PcG) proteins are overexpressed in several human malignancies including breast cancer. In particular, aberrant expression of BMI1 and EZH2 has been linked to metastasis and poor prognosis in cancer patients. At present, very little is known about the pharmacological inhibitors of PcG proteins. Here we show that histone deacetylase inhibitors (HDACi) downregulate expression of BMI1. Treatment of MCF10A cells, which are immortal non-transformed breast epithelial cells, and breast cancer cells with HDACi led to decreased expression of BMI1. We further show that downregulation of BMI1 by HDACi results due to the transcriptional downregulation of BMI1 gene. Specifically, we show that primary transcription and promoter activity of BMI1 is suppressed upon treatment with HDACi. Furthermore, downregulation of BMI1 was accompanied by a decrease in histone 2A lysine 119 ubiquitination (H2AK119Ub), which is catalyzed by BMI1 containing polycomb repressive complex 1. HDACi treatment also led to derepression of growth inhibitory genes and putative tumor suppressors, which are known to be silenced by PcG proteins and polycomb repressive complexes (PRCs). In summary, our findings suggest that BMI1 is an important therapy target of HDACi, and that HDACi can be used alone or in combination with other therapies to inhibit growth of tumors that overexpress PcG proteins such as BMI1. PMID- 20543558 TI - Dynamics of the PI3K-like protein kinase members ATM and DNA-PKcs at DNA double strand breaks. AB - The protein kinases ATM and DNA-PKcs play critical roles in the cellular response to DNA double strand breaks (DSBs). ATM and DNA-PKcs are activated in response to DSBs and play several important roles in propagation of the damage signal and for the repair of DNA damage. Recent work from several groups, including ours, has focused on studying the dynamics of each of these proteins at DSBs and the requirements and factors which play a role(s) in this process. The use of live cell imaging of fluorescently-tagged ATM and DNA-PKcs has allowed us to study the real-time response of these proteins to laser-generated DNA damage in vivo. Here, we will extensively discuss the behavior of the ATM and DNA-PKcs proteins at DSB sites. PMID- 20543560 TI - Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues. AB - BACKGROUND AND AIM: Widespread applicability of tissue-based mRNA expression screening for Barrett esophagus (BE) is likely to require (1) accurate methods for assaying archival formalin-fixed, paraffin-embedded (FFPE) histopathology specimens taken at endoscopy, and (2) validation studies of promising biomarkers in different patient cohorts. RESULTS: 30 genes were significantly differentially expressed by histopathology tissue type. The direction and magnitude of the differences were very similar to those found in previous studies using fresh frozen tissues. Novel upregulated genes were TSPAN8 (also known as CO-029), TSPAN24 (CD151), EGR1 and TCIRG1. Novel downregulated genes were DPYD, TSPAN29 (CD9) and Ets1. Strong associations between histopathology type and gene expression were observed with the overexpressed genes: cyclo-oxygenase-2 (COX-2), for which histopathology type explained 77.7% of the variation in expression, TSPAN1 (73.5%), TSPAN8 (62.9%), SPARC (62.1%), MMP7 (50.8%); and the under expressed genes ADH7 (53.7%), APC (58.2%), RAR-gamma (51.3%). METHODS: mRNA was isolated from 54 FFPE small endoscopic biopsies from patients with Barrett intestinal metaplasia (BE), esophageal adenocarcinoma (EAC), or control patients with a normal squamous-lined esophagus. Multiplexed tandem PCR (MT-PCR) was used to quantitate 50 selected candidate genes for BE and control genes in duplicate. Principal component analysis (PCA) was conducted to explore the presence of global differences in gene expression profiles. One-way analysis of variance (ANOVA) of the transformed data was used to identify genes that were differentially expressed between different histological subtypes. Differentially expressed genes with a fold change of >=2 (upregulated) or <=-2 (downregulated) are reported with the p value for each comparison (EAC vs. normal, EAC vs. BE and BE vs. normal). The Benjamini-Hochberg method was used to control the false discovery rate at 0.01 for all comparisons. CONCLUSIONS: Alterations in expression of select genes are strongly associated with BE or EAC or both. This study's findings for many highly differentially expressed genes are very similar to those previously reported, suggesting that these genes should be tested further in longitudinal studies for their potential role as biomarkers of progression to more advanced Barrett disease. PMID- 20543561 TI - Multiple facets of the unique histone variant macroH2A: from genomics to cell biology. AB - Histone variants replace canonical histones in nucleosomes to designate regions of chromatin for specific purposes. MacroH2A is a large histone variant distinguished by a ~30 kDa carboxyl-terminal macro domain. The association of macroH2A with the inactive X chromosome in female mammals has led to the hypothesis that macroH2A is involved in heterochromatin-associated transcriptional repression. Here we review data from a number of laboratories that suggest the role of macroH2A in regulating gene expression is, in fact, more complex. For example, macroH2A can play either a positive or negative role in transcriptional regulation in a context-dependent manner. Additionally, macroH2A has been linked to the control of the cell cycle and cell proliferation. We also describe areas where further research is required to extend our knowledge about this enigmatic histone variant. PMID- 20543559 TI - Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye? AB - As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling. PMID- 20543563 TI - Are DNA methylation markers ready for colorectal cancer detection? PMID- 20543562 TI - Leupaxin is similar to paxillin in focal adhesion targeting and tyrosine phosphorylation but has distinct roles in cell adhesion and spreading. AB - Focal adhesion (FA) formation is induced by extracellular matrix-stimulated integrin clustering and activation of receptors for diffusible factors. Leupaxin (LPXN) is a member of the paxillin family of FA proteins expressed in many cancer cell lines. We found activation of gastrin-releasing peptide receptor (GRPr) by bombesin (BN) stimulated LPXN translocation from cytoplasm to FAs. Using mutagenesis, we identified LIM3 as the primary FA targeting domain for LPXN and showed BN-induced LPXN tyrosine phosphorylation on residues 22, 62 and 72. A LIM3 point mutant of LPXN failed to target to FAs and had no BN-stimulated tyrosine phosphorylation. Conversely, a non-phosphorylatable mutant (Y22/62/72F) translocated to FAs after BN addition. Stimulation of FA formation using vinblastine also induced LPXN translocation and tyrosine phosphorylation. Therefore, dynamic LPXN tyrosine phosphorylation requires translocation to FAs. LPXN and paxillin had opposite roles in adhesion to collagen I (CNI) in MDA-MB 231 breast cancer cells. LPXN siRNA stimulated whereas paxillin siRNA inhibited cell adhesion. Knockdown of both LPXN and paxillin behaved similarly to paxillin knockdown alone, suggesting LPXN's function in adhesion might depend on paxillin. Additionally, LPXN regulated cell spreading on CNI but not on fibronectin whereas paxillin knockdown suppressed spreading on both substrates. These results demonstrate that although LPXN and paxillin's FA targeting and tyrosine phosphorylation are similar, each protein has distinct functions. PMID- 20543564 TI - The ubiquitin E3 ligase Nedd4-1 controls neurite development. PMID- 20543566 TI - The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration. AB - Induction of autophagy protects from neurodegeneration in many proteinopathies and is being proposed as a therapeutic option. We generated Drosophila models for Dentatorubro-pallidoluysian Atrophy to dissect the mechanism of neuronal cell degeneration. These flies display severe lysosomal dysfunction caused by the Atrophin protein, as a distinctive feature that modulates polyglutamine toxicity. The autophagic flux is blocked after autophagosome-lysosome fusion, leading to clearance defects, and further induction of autophagy does not rescue neurodegeneration but is instead detrimental. This highlights the importance for the full cycle to be completed to achieve neuroprotection by autophagy, much like waste recycling, more than disposal, benefits society. PMID- 20543567 TI - The retinal dehydrogenase/reductase retSDR1/DHRS3 gene is activated by p53 and p63 but not by mutants derived from tumors or EEC/ADULT malformation syndromes. AB - Retinol and its metabolites have important roles in many processes including embryonic development, cellular differentiation, apoptosis and maintenance of epithelia. Retinal short-chain dehydrogenase/reductase retSDR1, also known as dehydrogenase/reductase member 3 (DHRS3), is involved in maintaining the cellular supply of retinol metabolites. We observe that retSDR1 expression is activated by members of the p53 family. Particularly p53 and TAp63gamma regulate transcription through two separate response elements in the retSDR1 promoter. Both proteins bind the promoter in vitro and in vivo. Induction of DNA damage leads to recruitment of p53 and p63 to the retSDR1 promoter. A tumor-derived p53 mutant is unable to activate retSDR1 transcription. As mutants of p63 in humans exhibit phenotypes that cause several autosomal dominantly inherited syndromes leading to developmental malformations, we tested the transcriptional response of TAp63gamma mutants derived from the EEC, SHFM and ADULT syndromes. EEC syndrome-specific mutations of TAp63gamma fail to transactivate retSDR1 and an ADULT syndrome derived mutant stimulates retSDR1 transcription significantly less than the wild type variant of p63. Taken together, the results suggest a potential role of the p53/p63-mediated retSDR1 activation in tumor suppression as well as in developmental processes. PMID- 20543565 TI - Lung cancer-associated auto-antibodies measured using seven amino acid peptides in a diagnostic blood test for lung cancer. AB - Autoantibody profiling is a developing approach that incorporates immune recognition of myriad aberrant cancer proteins into a single diagnostic assay. We have previously described methodology to screen T7-phage NSCLC-cDNA libraries for phage-expressed proteins recognized by NSCLC-associated antibodies, and developed a multiplex assay that has excellent ability to discriminate NSCLC from control samples. This follow-up report describes the development and testing of a diagnostic autoantibody assay that uses seven amino-acid peptides as capture proteins. A random-peptide M13-phage library was screened for proteins recognized by cancer-associated antibodies. One hundred twenty-one NSCLC case and control samples were divided into two groups for training and validation, or alternately, evaluated sequentially in a leave-one-out analysis. Candidate antibody-markers were ranked by statistical discrimination between cases and controls. Receiver Operating-Characteristic (ROC-AUC) suggested the predictive potential of various marker combinations. A five-marker combination (AUC = 0.982) afforded 90% sensitivity and 73% specificity in a training-and-testing strategy. Leave-one-out validation provided similar class prediction. Data confirm the potential of antibody profiling to provide high levels of cancer prediction. Random peptide libraries offer a universal source of capture proteins for antibody profiling that obviates the need for tumor-specific library construction and abrogates inherent problems with tumor heterogeneity during biomarker discovery. PMID- 20543568 TI - Apoptosis induction of ZBB-006, a novel synthetic diterpenoid, in the human hepatocellular carcinoma cell line HepG2 in vitro and in vivo. AB - Diterpenes, present in many medicinal plants, have been the focus of continuous studies for the development of new anticancer agents. ZBB-006 is a new synthetic diterpenoid derivative which exhibited significant anti-proliferation activity against various cancer cell lines in our previous study. Here, we investigated the antitumor effect of ZBB-006 and its potential mechanisms in the human hepatocellular carcinoma cell line HepG2, both in vitro and in vivo. We found that oral administration of ZBB-006 effectively suppressed the growth of HepG2 xenograft tumor in nude mice without body weight decline as compared with the control group. Meanwhile, the growth inhibitory effect of ZBB-006 on HepG2 cells was observed with MTT assay. Apoptosis induced by ZBB-006 in HepG2 cells was evidenced by DAPI staining and Annexin V/PI double staining assay. ZBB-006 also dissipated the mitochondrial membrane potential (DeltaPsim) apparently as revealed by JC-1 staining. Furthermore, the cleavage of PARP, activation of caspase-3 and caspase-9 but not caspase-8 was demonstrated by western blot assay both in vitro and in vivo. Additionally, the proapoptotic protein Bax was markedly elevated, while the antiapoptotic protein Bcl-2 was downregulated. Collectively, our data indicated that ZBB-006 exerted a strong antitumor effect on HepG2 cells by initiating the mitochondrial-dependent apoptosis, and it has potential to be explored as a new promising therapeutic agent against human hepatoma. PMID- 20543569 TI - Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. AB - Suberoylanilide hydroxamic acid (SAHA) is a newly emerging histone deacetylase inhibitor (HDACi) and has been approved in phase II clinical trials for treating patients with cutaneous T-cell lymphoma. Autophagy is a conserved self-digestion process that degrades cytoplasmic materials and recycles long-lived proteins and organelles within cells. In this study, we demonstrate that SAHA stimulates autophagy in Jurkat T-leukemia cells, which was evidenced by the appearance of autophagic vacuoles, formation of acidic vesicular organelles, recruitment of LC3 II to the autophagosomes and conversion of LC3-I to LC3-II . Moreover, SAHA treatment upregulated expression of Beclin 1 and Atg7 and promoted formation of the Atg12-Atg5 conjugate. Furthermore, inhibition of autophagy by chloroquine (CQ) enhanced SAHA-induced apoptosis. To determine the underlying mechanism of SAHA-induced autophagy, two complementary proteomic approaches (2-DE and SILAC), coupled with ESI-Q-TOF MS/MS analysis are utilized to profile differentially expressed proteins between control and SAHA-treated Jurkat T-leukemia cells. In total, 72 proteins were identified with significant alterations. Cluster analysis of the changed proteins reveal several groups of enzymes associated with energy metabolism, anti-oxidative stress and cellular redox control, which suggested an abnormal reactive oxygen species (ROS) production in SAHA-treated Jurkat T leukemia cells. These observations were further confirmed by ROS chemiluminescence assay. Mechanistic studies revealed that SAHA-triggered autophagy was mediated by ROS production, which could be attenuated by N-acetyl cysteine (NAC), a ROS inhibitor. Finally, we illustrated that Akt-mTOR signaling, a major suppressive cascade of autophagy, was inactivated by SAHA treatment. Taken together, our study identifies autophagy as a reaction to counter increased ROS and is thus involved as a cellular prosurvival mechanism in response to SAHA treatment. PMID- 20543570 TI - Linking inflammation to tumorigenesis in colon: Stat3, a double-edged sword? PMID- 20543572 TI - "Autophagy suite": Atg9 cycling in the cytoplasm to vacuole targeting pathway. AB - Macroautophagy continues to gather increasing attention because it is connected with a wide range of human pathophysiologies, developmental processes and life span extension. It is also an interesting process from a basic cellular biology standpoint, as it involves dynamic membrane rearrangements and multiple protein protein interactions. Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway. At present, the Cvt pathway is unique in that it is the only example of a biosynthetic use of macroautophagy. Most of the autophagy-related (Atg) proteins are involved in the Cvt pathway, and various types of analyses have placed these proteins at particular stages of the process. For example, Atg9 is the only characterized transmembrane protein that is absolutely required for Cvt vesicle formation, and it is proposed to carry membrane from peripheral donor sites to the phagophore assembly site where the vesicle forms. Additional proteins, including Atg11, Atg23 and Atg27 are involved in this anterograde movement, whereas Atg1-Atg13 and Atg2-Atg18 are required for the retrograde return to the peripheral sites. Even when we illustrate our understanding of these events in a schematic model, however, they are by necessity flat two-dimensional representations, lacking movement and sound. Yet the cell is a living entity that is not well served by this sole method of information display. Accordingly, we decided to present the Cvt pathway as a vibrant, dynamic process by combining science, music and illustration. PMID- 20543571 TI - HtrA2, taming the oncogenic activities of WT1. AB - Wilms' tumour is a paediatric malignancy of the kidneys and is one of the most common solid childhood cancers. The Wilms' tumour 1 protein (WT1) is a transcription factor that can either activate or repress genes involved in growth, apoptosis and differentiation. It is frequently mutated or aberrantly expressed in Wilms' tumour, where the wild type protein would normally act as a tumour suppressor. Several studies, however, have found that wild type WT1 acts as an oncogene in adult tumours, primarily through the inhibition of apoptosis. The expression of WT1 correlates with the aggressiveness of several adult cancers, and its continued expression following treatment is indicative of a poor outcome.We recently found that the treatment of tumour cell lines with cytotoxic drugs leads to the cleavage of WT1 by the serine protease HtrA2. HtrA2 binds to a specific region of WT1, the suppression domain, and then cleaves WT1 at multiple sites. The HtrA2-mediated proteolysis of WT1 leads to its removal from gene promoter regions and changes in gene expression. Cleavage of WT1 by HtrA2 enhances apoptosis. This event is advantageous to the treatment of adult tumours where WT1 acts as an oncogene. However, when WT1 is acting as a tumour suppressor in paediatric malignancies, proteolysis by HtrA2 would be antagonistic to therapy. PMID- 20543573 TI - PERsuading nuclear receptors to dance the circadian rhythm. AB - The recurring light/dark cycle that has a period length of about 24 hours has been internalized in various organisms in the form of a circadian clock. This clock allows a precise orchestration of biochemical and physiological processes in the body thus improving performance. Recently, we found that the clock component PERIOD2 (PER2) can coordinate transcriptional regulation of metabolic, physiological, or behavioral pathways by interacting with nuclear receptors. PER2 appears to act as co-regulator of nuclear receptors linking clock function and transcriptional regulation at the level of protein-protein interactions. Here, we provide additional evidence for modulation of nuclear receptor dependent transcription by PER2 underscoring the broad implication of our finding. Taken together, our findings provide a base for the understanding of various disorders including mood disorders that have their roots in a temporal deregulation of basic metabolic processes. PMID- 20543575 TI - A20 inhibition of NFkappaB and inflammation: targeting E2:E3 ubiquitin enzyme complexes. PMID- 20543574 TI - SWItching on the transcriptional circuitry in melanoma. AB - Melanoma is an aggressive malignancy that is resistant to current therapy, and the most lethal of all human skin cancers. It is characterized by several genetic alterations that lead to changes in gene expression and tumorigenesis by triggering alterations in the normal transcriptional circuitry. Transformation and tumor progression are thought to be promoted by a complex interplay between the accumulation of genetic alterations and epigenetic changes. In this review, we discuss recent studies that have implicated SWI/SNF chromatin remodeling enzymes as epigenetic regulators of a transcriptional circuit that operates within the context the genetic alterations that frequently occur in melanoma. PMID- 20543576 TI - ERK2/Fra1/ZEB pathway induces epithelial-to-mesenchymal transition. PMID- 20543577 TI - Ischemia dysregulates DNA methyltransferases and p16INK4a methylation in human colorectal cancer cells. AB - Epigenetic modifications are involved in the initiation and progression of cancer. Expression patterns and activity of DNA methyltransferases (DNMTs) are strictly controlled in normal cells, however, regulation of these enzymes is lost in cancer cells due to unknown reasons. Cancer therapies which target DNMTs are promising treatments of hematologic cancers, but they lack effectiveness in solid tumors. Solid tumors exhibit areas of hypoxia and hypoglycaemia due to their irregular and dysfunctional vasculature, and we previously showed that hypoxia reduces global DNA methylation. Colorectal carcinoma (CRC) cells (HCT116 and 379.2; p53+/+ and p53-/-, respectively) were subjected to ischemia (hypoxia and hypoglycaemia) in vitro, and levels of DNMTs were assessed. We found a significant decrease in mRNA for DNMT1, DNMT3a and DNMT3b, and similar reductions in DNMT1 and DNMT3a protein levels were detected by western blotting. In addition, total activity levels of DNMTs (as measured by an ELISA-based DNMT activity assay) were reduced in cells exposed to hypoxic and hypoglycaemic conditions. Immunofluorescence of HCT116 tumor xenografts demonstrated an inverse relationship between ischemia (as revealed by carbonic anhydrase IX staining) and DNMT1 protein. Bisulfite sequencing of the proximal promoter region of p16INK4a showed a decrease in 5-methylcytosine following in vitro exposure to ischemia. These studies provide evidence for the down-regulation of DNMTs and modulation of methylation patterns by hypoxia and hypoglycaemia in human CRC cells, both in vitro and in vivo. Our findings suggest that ischemia, either intrinsic or induced through the use of anti-angiogenic drugs, may influence epigenetic patterning and hence tumor progression. PMID- 20543578 TI - When speed matters: leukemogenic transformation by MLL fusion proteins. PMID- 20543580 TI - Tumor suppressor p53 status does not determine the differentiation-associated G1 cell cycle arrest induced in leukemia cells by 1,25-dihydroxyvitamin D3 and antioxidants. AB - Vitamin D derivatives can induce differentiation of human acute myeloid leukemia (AML) cells. Here, we investigated if the G1 cell cycle block associated with monocytic differentiation is modulated by the p53 status of the cells treated with 1,25D, alone or with plant antioxidants carnosic acid (C) or silibinin (S), and a p38 MAPK inhibitor SB202190 (SB), a combination (D-C/S-SB) previously shown to enhance differentiation of AML p53null cells. D-C/S-SB enhanced differentiation of OCI-AML3 (p53wt) and as expected HL60 (p53 null) cells, but not of MOLM-13 (p53wt) cells. Conversely, MOLM-13 (p53wt) cells treated with 1,25D and/or D-C/S-SB, resembled HL60 (p53 null) cells in rapid G1 block, while OCI-AML3 (p53wt) cells showed a delayed G1 block when treated in a similar way, indicating that there is no relationship between the p53 status and G1 block. Western blot analysis revealed that 1,25D and D-C/S-SB increased the inhibitory phosphorylation levels MEK-1 (P-Thr286), but decreased the levels of activated ERK1/2 (Thr202/Tyr204;Thr185/Tyr187), again without any apparent relationship to the p53 status. Interestingly, the increased levels of p21(Waf1/Cip1) were insufficient to promote a G1 block in this system, as only cell lines with increased levels of p27(Kip1) and p35Nck5a, an activator of Cdk5, showed a rapid G1 block. Overall, our data show that the p53-p21 axis is unlikely to have a role in differentiation-associated G1 block in AML cells with wt p53, and that this block is achieved by several, possibly co-operating but redundant pathways, that include inhibition of MEK-1 by p35Nck5a-activated Cdk5. PMID- 20543579 TI - DNA methylation in endometrial cancer. AB - Endometrial cancer is the most commonly diagnosed gynecological cancer, and it has been shown to be a complex disease driven by abnormal genetic, and epigenetic alterations, as well as environmental factors. Epigenetic changes resulting in aberrant gene expression are dynamic and modifiable features of many cancer types. A significant epigenetic change is aberrant DNA methylation. In this review, we review evidence on the role of aberrant DNA methylation, examining changes in relation to endometrial carcinogenesis, and report on recent advances in the understanding of the contribution of aberrant DNA methylation to endometrial cancer with the emphasis on the role of dietary/ lifestyle and environmental factors, as well as opportunities and challenges of DNA methylation in endometrial cancer management and prevention. PMID- 20543581 TI - The SUMO pathway functions in mouse oocyte maturation. AB - Sumoylation is an important post-translational modification in which SUMO (small ubiquitin-related modifier) proteins are bonded covalently to their substrates. Studies on the roles of sumoylation in cell cycle regulation have been emerging in both mitosis from yeast to mammals and meiosis in budding yeast, but the functions of sumoylation in mammalian meiosis, especially in oocyte meiotic maturation are not well known. Here, we examined the localization and expression of SUMO-1 and SUMO-2/3, the two basic proteins in the sumoylation pathway and investigated their roles through over-expression of Senp2 during mouse oocyte maturation. Immunofluorescent staining revealed differential patterns of SUMO-1 and SUMO-2/3 localization: SUMO-1 was localized to the spindle poles in prometaphase I, MI and MII stages, around the separating homologues in anaphase I and telophase I stages of first meiosis, while SUMO-2/3 was mainly concentrated near centromeres during mouse oocyte maturation. Immunoblot analysis uncovered the different expression profiles of SUMO-1 and SUMO-2/3 modified proteins during mouse oocyte maturation. Over-expression of Senp2, a SUMO-specific isopeptidase, caused changes of SUMO-modified proteins and led to defects in MII spindle organization in mature eggs. These results suggest that the SUMO pathway may play an indispensable role during mouse oocyte meiotic maturation. PMID- 20543582 TI - Nutrient regulation of mTORC1 and cell growth. PMID- 20543584 TI - An N-, C-terminally truncated basic fibroblast growth factor and LPD (liposome polycation-DNA) complexes elicits a protective immune response against murine colon carcinoma. AB - Basic fibroblast growth factor (bFGF) is a mitogen for endothelial cells, which participates in tumor angiogenesis. Active immunity against bFGF could be a promising approach for the biotherapy of cancer. Because bFGF is abundant in normal and malignant tissues, it is presumably difficult for normal bFGF to induce immunity due to self-tolerance. In addition, previous studies have shown that a complex consisting of a cationic liposome and a non-coding plasmid DNA can be used to stimulate innate immunity. This stimulation initiates a potent cytokine response, which can inhibit tumor growth. To investigate the effects of immunity against bFGF on murine colon carcinomas, we employed an N-, C-terminally truncated basic fibroblast growth factor (tbFGF, of human origin) as an antigen and a liposome-DNA complex as an adjuvant. After six immunizations, a robust bFGF specific immune response was elicited. Subsequently, inhibition of tumor growth and a significant reduction in tumor vasculature were observed. The antitumor effect was confirmed by adoptive therapy of activated spleen cells from the immunized mice. In vitro, a CTL assay revealed that bFGF-specific cytotoxic T lymphocytes (CTL) resulted in the lysis of mouse microvascular endothelial cells (MS1) rather than that of the CT26 colorectal cancer cells. These results suggest that anti-angiogenesis treatment induced by a bFGF-specific CTLs against microvascular endothelial cells may be a useful method for cancer therapy. PMID- 20543583 TI - Tensegrin in context: Dual role of alpha8 integrin in the migration of different cell types. AB - alpha8beta1 integrin is highly expressed in cells with contractile function, such as mesangial cells of the kidneys and vascular smooth muscle cells (VSMCs). Although it promotes migration of neural crest cells and breast cancer cells, recent studies suggest that alpha8 integrin has a negative regulatory role in VSMC migration. In this review, the question of why alpha8beta1 integrin plays a dual role in cell migration is raised and discussed. It seems that cells require optimum contractility and balanced tensile forces for migration. alpha8beta1 integrin promotes migration of cells that are initially in a less than optimal contractile state (e.g. neural cells) and reduces the migration of cells known as contractile cells. alpha8beta1 integrin can be called "Tensegrin" as it fits perfectly into the tensegrity model (tensional integrity) and seems to play a prominent role in the integration of the tensile forces. PMID- 20543585 TI - Knowledge and attitudes towards vaccines and immunization among adolescents in South Africa. AB - Despite evidence showing their benefits, routine adolescent immunization programmes are still lacking across Africa. In 2008 we conducted a qualitative study of adolescents' knowledge and attitudes towards immunization in a peri urban community in South Africa. Results show that while vaccination as a concept is acceptable amongst adolescents, low levels of knowledge about vaccines, the process of being vaccinated, as well as unfamiliarity with the concept of preventative medicine in general will likely hinder achieving high and equitable routine adolescent immunization coverage. Effective educational programs and integrated adolescent healthcare strategies will be critical to delivering successful immunization services to this group. PMID- 20543586 TI - HIV, mucosal tissues, and T helper 17 cells: where we come from, where we are, and where we go from here. PMID- 20543587 TI - Human and murine Th17. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize the most recent discoveries in the field of phenotypic and functional characterization of human and murine Th17 cells. RECENT FINDINGS: Human Th17 cells express CD161 and exclusively originate from CD161 precursors present in umbilical cord blood and newborn thymus in response to the combined activity of IL-1beta and IL-23. On the contrary, murine Th17 cells do not express CD161 and originate in response to IL 6, IL-1, and TGF-beta, even if the latter has recently been shown to be dispensable. Studies in mice have initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Studies in humans have subsequently demonstrated the capacity of Th17 cells to shift to Th1 cells when activated in the presence of IL-12. The plasticity of Th17 to Th1 cells has been now confirmed in mice, where it was found that Th17 cells become pathogenic in some models of autoimmune diseases only when they shift to Th1 cells. SUMMARY: The issue of Th17 plasticity is of fundamental importance for those researchers directed to manipulate immune responses in therapeutically useful manner. PMID- 20543588 TI - Th17 cytokines in mucosal immunity and inflammation. AB - PURPOSE OF REVIEW: Compelling evidence suggests that the Th17 lineage and other IL-17-producing cells play critical roles in host defense against pathogens at mucosal sites. However, IL-17 can also contribute to inflammatory responses at mucosal sites. In this review, we will discuss the recent progress in our understanding of the role of Th17 and other IL-17-producing cells in defining the fine balance between immunity and inflammation at different mucosal sites. RECENT FNDINGS: Recent findings have highlighted that Th17 cytokines are important for the induction of innate and adaptive host responses and contribute to host defense against pathogens at mucosal sites. More recent developments have probed how the Th17 responses are generated in vivo in response to infections and their requirement in maintaining barrier function at mucosal sites. Most importantly, it is becoming apparent that there is a fine balance between protective and pathological manifestation of Th17 responses at mucosal sites that defines immunity or inflammation. SUMMARY: In this review, we have summarized the recent advances in our understanding of Th17 cytokines and how they contribute to immunity versus inflammation at mucosal sites. PMID- 20543589 TI - Immune responses to HIV and SIV in mucosal tissues: 'location, location, location'. AB - PURPOSE OF REVIEW: This review summarizes research literature regarding mucosal immunity to HIV and simian immunodeficiency virus (SIV), with an emphasis on work published within the past 18 months. RECENT FINDINGS: Notable recent studies have focused on the pivotal events occurring within mucosal tissues during acute HIV/SIV infection that serve to establish a balance between detrimental immune activation and beneficial adaptive responses. In cervicovaginal mucosa, an early inflammatory response leads to recruitment of susceptible target cells. At this acute stage, the in-vivo ratio between CD8 effector cells and infected CD4 T cells may be critical for limiting viral dissemination. Acute infection is also accompanied by loss of germinal center architecture and T/B cell apoptosis in Peyer's patches of the gastrointestinal tract. During chronic infection, mucosal CD8 T-cells may play a role in immune control, as suggested by studies of elite controllers. SUMMARY: Mucosal tissues serve as the major portal of entry for HIV, and house a majority of the body's lymphocytes, including CD4 T-cells that are targets for infection. Recent studies have focused renewed attention on events occurring immediately after transmission, and underscore the concept that the balance between inflammation and protective immunity is established by host responses in mucosal tissues. PMID- 20543590 TI - Th17 cell dynamics in HIV infection. AB - PURPOSE OF REVIEW: Th17 cells are a newly identified subtype of CD4 T cells that respond to bacterial and fungal antigens and are important in mucosal immunology. Because HIV infection results in loss of CD4 T cells as well as disruption to the gastrointestinal tract that causes microbial translocation and immune activation, Th17 cells potentially play an important role in HIV pathogenesis. Here we examine the relationship between Th17 cells and HIV disease pathogenesis. RECENT FINDINGS: Th17 cells are preferentially lost from the gastrointestinal tract of HIV-infected individuals, which is not entirely due to direct infection, as Th17 cells can be infected in vivo, but are not preferentially infected. Long-term highly active antiretroviral therapy (HAART) can result in restoration of Th17 cells in the gastrointestinal, which may be associated with better disease prognosis. Furthermore, other cells, such as Vdelta1 T cells, can make IL-17 in vivo during HIV infection and may contribute to antibacterial immunity after loss of Th17 cells. SUMMARY: Recent studies have improved our understanding of the role for Th17 cells during HIV infection; however, more studies are needed to discern better the detrimental consequences of loss of Th17 cells during HIV infection. PMID- 20543591 TI - Th17 cells in pathogenic simian immunodeficiency virus infection of macaques. AB - PURPOSE OF REVIEW: We discuss studies on a subset of CD4T cells, designated Th17, and their role in the pathogenesis of human and simian acquired immune deficiency, caused by infection with HIV and simian immunodeficiency virus (SIV), respectively. Most of the Th17 cells are lost within 2 weeks from infection at mucosal sites of SIV-infected macaques and are not replenished over time. Comparison of simian pathogenic and nonpathogenic models of SIV infection suggests that Th17 cells contribute to the pathogenesis of AIDS. RECENT FINDINGS: Th17 cells, a recently identified subset of T helper cells, play a major role in both inducing autoimmune disorders and fencing off extracellular pathogens. Several groups have reported that the number of Th17 cells is decreased in the gut of HIV-infected and SIV-infected hosts. The loss of Th17 cells from the mucosal compartment has been associated with the dissemination of Salmonella typhimurium that is normally contained locally by the host immune system. It is believed that microbial translocation sustains immune activation in HIV infection and contributes to AIDS. SUMMARY: Understanding the mechanisms that lead to disruption of mucosal integrity, viral spread, and chronic immune activation is of crucial importance for the design of efficient vaccines and therapeutic intervention for HIV. PMID- 20543592 TI - Th17 cells and HIV infection. AB - PURPOSE OF REVIEW: This review summarizes the recent literature about the potential perturbation and role of Th17 cells in HIV pathogenesis. We discuss the recent findings on Th17 deficiency in HIV/simian immunodeficiency virus (SIV) infection and how this deficiency may impact the mucosal host defenses, potentially contributing to chronic immune activation. RECENT FINDINGS: Th17 cells have been implicated in host defense against a variety of pathogens and are involved in the pathogenesis of autoimmune diseases. Recently, Th17 cells were shown to be perturbed during HIV infection in humans and SIV infection in nonhuman primates. Th17 cells were found to be infected in vitro by HIV and SIV and are significantly depleted in the gastrointestinal tract of HIV-infected individuals. In monkeys, Th17 cells are only depleted in the pathogenic SIV infection of rhesus macaques, which correlates with the progression to AIDS in these primates, whereas they remain intact in the nonpathogenic SIV infection of African green monkeys or sooty mangabeys. SUMMARY: Th17 cells appear to be perturbed during HIV and SIV infection. This finding could have important implications in understanding the disruption of mucosal defenses in the gastrointestinal tract and potentially in predicting opportunistic infections during the course of HIV disease. PMID- 20543594 TI - Th17 lineage commitment and HIV-1 pathogenesis. AB - PURPOSE OF REVIEW: The present review emphasizes the requirement for functional genomic studies and studies in human immunology toward the identification of tissue-specific regulators of human Th17 lineage commitment and molecular determinants for HIV permissiveness in Th17 cells. RECENT FINDINGS: Th17 cells play a beneficial role in immunity against bacteria and fungi and a deleterious role in autoimmune diseases. Commensal microbiota control Th17 differentiation in the gut. Th17 cells are depleted from the gut of HIV-infected individuals and their depletion is associated with microbial translocation, which is a cause for chronic immune activation and disease progression. Th17 cells are permissive to HIV infection and therefore play a dual role in HIV pathogenesis. SUMMARY: The discovery of human Th17 lineage revised our thinking about CD4 T-cell heterogeneity and plasticity in the context of HIV pathogenesis. The present review highlights unsolved mysteries around the genetic control of differentiation and tissue-specific specialization of human Th17 cells. Systems biology studies are now required to provide a global view of transcriptional changes in Th17 subsets and mucosal tissues and to shed light on molecular mechanisms of Th17 depletion in HIV infection, with the final goal to identify new strategies to improve mucosal immunity in infected individuals. PMID- 20543595 TI - Th17 cells in natural SIV hosts. AB - PURPOSE OF REVIEW: To summarize our current understanding of the regulation of Th17 cells in pathogenic and nonpathogenic lentiviral infections. RECENT FINDINGS: It has been shown that Th17 cells, a recently identified T helper-cell subset deemed critical for antimicrobial mucosal immunity, are preferentially depleted in the gastrointestinal tracts of human immunodeficiency virus (HIV) infected humans and simian immunodeficiency virus (SIV)-infected rhesus and pigtailed (PTMs) macaques. In contrast, Th17 cells are preserved at healthy levels in monkey species that are natural hosts for SIV, such as sooty mangabeys or African green monkeys (AGMs), which maintain mucosal immunity and remain AIDS free. These findings suggest that preservation of Th17 cells (or lack thereof) may be central in determining the pathogenic or nonpathogenic outcome of HIV/SIV infection. SUMMARY: A preferential depletion of mucosal Th17 cells is a feature that distinguishes pathogenic HIV infection of humans from nonprogressive SIV infection of sooty mangabeys and AGMs. The exact mechanism accounting for this different phenotype is still unclear. To understand how natural hosts for SIV preserve Th17 cells and mucosal immunity might be central to the development of therapeutic interventions aimed at improving mucosal immunity in HIV-infected individuals. PMID- 20543593 TI - Th17 and regulatory T cells: implications for AIDS pathogenesis. AB - PURPOSE OF REVIEW: The present review discusses recent reports showing that reciprocal changes in T helper interleukin-17-secreting CD4 Th17 cells and CD4CD25FoxP3 regulatory T cells (Tregs) may play a role in the progressive disease caused by the HIV and by simian immunodeficiency virus. RECENT FINDINGS: Studies in nonhuman primate models of lentiviral infection and in HIV-infected human individuals have shown that pathogenic infection is associated with loss of Th17 cells and an increase in the frequency of Tregs. Because interleukin-17 serves to maintain the integrity of the mucosal barrier, loss of Th17 cells may permit the increase in microbial translocation across the gastrointestinal mucosa that is observed in pathogenic lentiviral disease. It remains unclear, however, whether Th17 cells are preferentially infected or if, instead, their loss is induced by bystander effects of lentiviral infection, for example, the induction of indoleamine 2,3-dioxygenase. SUMMARY: Progressive lentiviral disease is associated with preferential depletion of Th17 cells and loss of Th17/Treg balance. Further analysis of such changes in the composition of subset CD4 T helper and Tregs may shed new light on the immunopathology of HIV disease and suggest new strategies for therapeutic and preventive interventions. PMID- 20543596 TI - Th17 cells, HIV and the gut mucosal barrier. AB - PURPOSE OF REVIEW: We will present recent studies on a subset of CD4 T helper cells, Th17 cells, that appears to be critical for regulating gut mucosal immune responses against extracellular microbial pathogens and may serve as a link between innate and adaptive immune responses. Implications of the loss of Th17 CD4 T cells in HIV infection will be discussed in relation to the chronic immune activation and HIV pathogenesis. RECENT FINDINGS: Severe depletion of CD4 T cells occurs in the gut mucosa during primary HIV and simian immunodeficiency virus infections. A pronounced loss of mucosal Th17 CD4 T cells in the simian immunodeficiency virus-infected rhesus macaque model of AIDS is linked to impaired immune responses in the gut mucosa to an enteric pathogen, Salmonella typhimurium, leading to the lack of local control of the pathogen and its translocation. Recovery of the gut mucosal immune system during highly active antiretroviral therapy is slow and incomplete compared with the peripheral blood compartment. Recent studies suggest that the replenishment of Th17 CD4 T cells in the gut mucosa during highly active antiretroviral therapy, or during nonpathogenic simian immunodeficiency virus infections in the nonhuman primate models, correlates with better restoration and function of the gut mucosal immune system. SUMMARY: A better understanding of the role of Th17 CD4 cells in the generation of mucosal immune responses to enteric pathogens and maintenance of the intestinal epithelial integrity in HIV-infected patients will help in the development of novel strategies to modulate and enhance mucosal immune system and its function. PMID- 20543598 TI - Beyond IL-17: new cytokines in the pathogenesis of HIV infection. AB - PURPOSE OF THE REVIEW: Alterations in cytokine production have been described since the dawn of HIV research. Cytokinology is rapidly evolving because the cytokine-like functions of arrays of proteins are being recognized. Thus, new cytokines are being investigated within the context of HIV pathogenesis. This review describes novel functions of 'old' cytokines and summarizes the potential role of 'new' cytokines in this disease. RECENT FINDINGS: Old cytokines, such as the common gamma (gamma) chain cytokines, were shown to have previously unsuspected biological roles; new cytokines, for example, IL-18, IL-27, IL-32, were recognized as important players in the immunopathogenesis of HIV infection. Finally, hepatocytes were demonstrated to be the main producers of IL-7 in response to various inflammatory signals, transforming overnight the liver in one of the tissues primarily involved in the modulation of immune responses. SUMMARY: Data summarized herein underline the intricacies of cytokine networks. The concept of modulating the immune response using single cytokines is unlikely to succeed. Future therapeutic uses of cytokines will not be effective unless a 'cytokinomics' approach to the study of these important immune modulators is employed. Systematic analyses of cytokine production and of their effects in a biological system will be required. PMID- 20543597 TI - Th17 cells, Job's syndrome and HIV: opportunities for bacterial and fungal infections. AB - PURPOSE OF REVIEW: Patients with hyper IgE syndrome (HIES) share with HIV patients a predisposition to infections, including candidiasis in autosomal dominant HIES (AD-HIES) and molluscum contagiosum and other viral infections in other disorders of elevated IgE with infectious predilections. This review highlights the underlying pathogenesis of these diseases and their relevance to HIV infection. RECENT FINDINGS: Patients with mutations in STAT3, who lack Th17 cells, develop AD-HIES, whereas other disorders of elevated IgE may be caused by mutations in Tyk2 or DOCK8, the latter of which is associated with decreased expansion of CD8 more so than CD4 T cells. Recent studies on patients with recurrent mucocutaneous candidiasis have led to the discovery of mutations in CARD9 and DECTIN-1, genes key to the production of the Th17-driving cytokines IL 1beta, IL-6, and IL-23. Studies of the peripheral blood of HIV-positive patients have shown a decreased Th17:Th1 ratio, and Th17 cells were preferentially depleted from the gastrointestinal tract within weeks of simian immunodeficiency virus infection in rhesus macaques. SUMMARY: The consequences of inadequate Th17 production in primary immunodeficiency syndromes illustrate the role of Th17 cells in controlling pathogens to which HIV-positive individuals are susceptible. Further understanding of the pathogenesis of opportunistic disease in HIV infection will probably require exploring the role of Th17 cells. PMID- 20543599 TI - Th17, gut, and HIV: therapeutic implications. AB - PURPOSE OF REVIEW: The purpose of this review is to discuss the apparent impact of persistent-immune activation and inflammation on morbidity and mortality among treated HIV-infected individuals, to explore the potential role of Th17 T-cell depletion in this process, and to discuss potential-therapeutic implications. RECENT FINDINGS: Although the vast majority of HIV-infected individuals can now achieve and maintain viral suppression with modern-antiretroviral therapy (ART), their life expectancy remains much shorter than the general population and they continue to be at much higher risk for non-AIDS-associated diseases commonly associated with aging (non-AIDS-associated cancer, cardiovascular disease, etc). Abnormal levels of immune activation and inflammation persist despite sustained viral suppression and may drive these clinical events. Although the causes of persistent-immune activation remain incompletely characterized, persistent low level HIV replication and/or release from latently infected cells in gut associated lymphoid tissue (GALT) and microbial translocation probably play a major role. Failure to restore Th17 cells in GALT during ART might impair both the recovery of the gut mucosal barrier and the clearance of microbial products. SUMMARY: Insights from recent-pathogenesis studies might suggest novel therapeutic approaches designed to restore Th17 cells in GALT, thereby decreasing microbial translocation, immune activation, and ultimately morbidity and mortality during treated HIV infection. PMID- 20543600 TI - Modelling sexual transmission of HIV: testing the assumptions, validating the predictions. AB - PURPOSE OF REVIEW: To discuss the role of mathematical models of sexual transmission of HIV: the methods used and their impact. RECENT FINDINGS: We use mathematical modelling of 'universal test and treat' as a case study to illustrate wider issues relevant to all modelling of sexual HIV transmission. SUMMARY: Mathematical models are used extensively in HIV epidemiology to deduce the logical conclusions arising from one or more sets of assumptions. Simple models lead to broad qualitative understanding, whereas complex models can encode more realistic assumptions and, thus, be used for predictive or operational purposes. An overreliance on model analysis in which assumptions are untested and input parameters cannot be estimated should be avoided. Simple models providing bold assertions have provided compelling arguments in recent public health policy, but may not adequately reflect the uncertainty inherent in the analysis. PMID- 20543601 TI - Role of acute and early HIV infection in the sexual transmission of HIV. AB - PURPOSE OF REVIEW: Acute HIV infection (AHI), the earliest period after HIV acquisition, is only a few weeks in duration. In this brief period, the concentration of HIV in blood and genital secretions is extremely high, increasing the probability of HIV transmission. Although a substantial role of AHI in the sexual transmission of HIV is biologically plausible, the significance of AHI in the epidemiological spread of HIV remains uncertain. RECENT FINDINGS: AHI is diagnosed by detecting viral RNA or antigen in the blood of persons who are HIV seronegative. Depending on the setting, persons with AHI represent between 1 and 10% of persons with newly diagnosed HIV infection. The high concentration of virus during AHI leads to increased infectiousness, possibly as much as 26 times greater than during chronic infection. In mathematical models, the estimated proportion of transmission attributed to AHI has varied considerably, depending on model structure, model parameters, and the population. Key determinants include the stage of the HIV epidemic and the sexual risk profile of the population. SUMMARY: Despite its brief duration, AHI plays a disproportionate role in the sexual transmission of HIV infection. Detection of persons with AHI may provide an important opportunity for transmission prevention. PMID- 20543602 TI - Antiretroviral treatment of primary HIV infection to reduce onward transmission. AB - PURPOSE OF REVIEW: This review will discuss the role of antiretroviral therapy to treat primary HIV infection (PHI) as a strategy to prevent onward viral transmission. RECENT FINDINGS: Novel technology has greatly enhanced the appreciation of the characteristics of recently transmitted HIV-1 variants. Recent primate data demonstrate marked enhanced infectiousness of viral variants isolated from acutely infected macaques compared with viruses isolated from animals in the chronic phase of disease. These data are supported by phylogenetic analyses of recently transmitted cases in humans, implying that individuals with PHI may contribute disproportionately to onward transmission at a population level. SUMMARY: In the absence of randomized clinical trial data supporting individual benefit of antiretroviral therapy, targeting and treating individuals with PHI as a public health intervention strategy represent a paradigm shift from current treatment strategies based around proven individual benefit alone. However, there is increasing evidence that PHI contributes disproportionately to viral transmission at a population level and failure to incorporate the potential role PHI plays, particularly in focused epidemics, maybe a naive omission of many of the current mathematical models evaluating the impact of universal test and treat on population-level HIV incidence. PMID- 20543603 TI - An overview of the relative risks of different sexual behaviours on HIV transmission. AB - PURPOSE OF REVIEW: Sexual intercourse represents the majority of HIV transmission and is preventable. Overall, the risk of HIV transmission following a single sexual exposure is low especially in comparison with other sexually transmitted infections (STIs), with estimates of the average probability of male-to-female HIV transmission only 0.0005-0.0026 per coital act. The risk of acquiring HIV from a single contact varies enormously and is dependant upon the infectiousness of the HIV-positive individual and the susceptibility to HIV of their sexual partner. RECENT FINDINGS: Of concern, unprotected sex among men who have sex with men (MSM) has increased in recent years and HIV incidence in both MSM and heterosexuals remains a considerable public health concern. Sexual practices and health optimism about HIV have changed, which have significantly impacted HIV risk behaviour. SUMMARY: In this review article we summarize the current evidence regarding the observed relative risks of HIV transmission for each different types of sex act, relationship type and the strategies that have been tested to interrupt transmission. PMID- 20543604 TI - Highly active antiretroviral treatment as prevention of HIV transmission: review of scientific evidence and update. AB - PURPOSE OF REVIEW: An estimated 33 million people are living with HIV and universal access remains a dream for millions of people. By the end of year 2008, four million people were on treatment; however, over five million needed treatment, and in 2007, there were 2.7 million new infections. Without significant improvement in prevention, we are unlikely to meet universal access targets including the growing demand for highly active antiretroviral treatment (HAART). This review examines HAART as a potential tool for preventing HIV transmission. RECENT FINDINGS: We discuss recent scientific evidence regarding the treatment and prevention gap, importance viral load and HIV transmission, HAART and HIV transmission, when to start, HIV counseling and testing, modeling results and next steps. SUMMARY: HAART has considerable treatment and prevention benefits and it needs to be considered as a key element of combination prevention. To explore HAART as an effective prevention strategy, we recommend further evaluation of human rights and ethical considerations, clarification of research priorities and exploration of feasibility and acceptability issues. PMID- 20543605 TI - Contribution of sexually transmitted infections to the sexual transmission of HIV. AB - PURPOSE OF REVIEW: We review recent evidence about the link between sexually transmitted infections (STI) and HIV transmission and consider implications for control programmes. RECENT FINDINGS: New studies and meta-analyses confirm the association of HIV acquisition and transmission with recent STIs, although there is considerable heterogeneity between organisms and populations. Much of the recent evidence relates to herpes simplex virus type 2 (HSV-2), for which the population-attributable risk percentage (PAR%) for HSV-2 is between 25 and 35 in Africa. Mathematical models show how transmission attributable to STI varies with HIV epidemic phase, and HSV-2 becomes increasingly important as the epidemic matures. HSV-2 suppressive therapy reduces HIV concentrations in plasma and the genital tract in people coinfected with HSV-2, in part due to direct inhibition of HIV reverse transcriptase. Recent trials of HSV-2 suppressive therapy have not shown an impact on the risk of HIV acquisition, nor in controlling transmission from dually infected people to their serodiscordant heterosexual partners. SUMMARY: Although there is a plausible link between STI and HIV risk, intervention studies continue to be disappointing. This fact does not disprove a causal link, but mechanisms of action and the design and implementation of interventions need to be better understood. PMID- 20543606 TI - Sexual risk behaviour for transmission of HIV in men who have sex with men: recent findings and potential interventions. AB - PURPOSE OF REVIEW: Men who have sex with men (MSM) remain one of the groups most at risk of HIV, particularly in countries with concentrated epidemics. Here, we review findings from behavioural research with MSM and discuss the potential of behavioural interventions. RECENT FINDINGS: Increasing sexual risk behaviour and HIV transmission among MSM is apparent. Although risk reduction strategies, including serosorting and strategic positioning, are being widely reported, these appear to offer limited protection to HIV-negative MSM. There are emerging HIV epidemics among MSM in low-income and middle-income countries, with reported high levels of HIV and sexual risk behaviour. Studies of African MSM report higher HIV prevalence than that in the adult male general population. Evidence of effective behavioural interventions is growing. However, further trials, incorporating biological endpoints, are required. SUMMARY: Reducing HIV transmission among MSM remains a significant challenge. Risk reduction strategies, other than condom use, could reduce the risk, but their efficacy is questionable, particularly when knowledge of HIV status may be inaccurate. Behaviour change alone is unlikely to produce the sustained reductions in HIV transmission necessary to change the course of the epidemic. 'Combination prevention', which incorporates biomedical, behavioural, social and structural interventions, should be explored further. PMID- 20543607 TI - Microbicide research: current and future directions. AB - PURPOSE OF REVIEW: Microbicide research has been in the forefront of scientific literature in recent months. Results of large-scale clinical trials have been announced with resultant investigations into the factors that may have contributed to the disappointing outcomes of the most promising candidates. This review takes into consideration clinical, basic scientific and behavioural research published on microbicides in the past 12-18 months. RECENT FINDINGS: Two trials testing PRO 2000, a sulphated polymer, suggested that it has no effect on HIV. Basic science research revealed several facts such as the loss of antiviral activity of microbicides in the presence of seminal plasma. Methodological models suggested that dilution factors might impact on measures of efficacy. Advancement into safety testing of highly specific antiretroviral products such as tenofovir and UC781 for both rectal and vaginal use shows promise. Development of drug delivery systems such as intravaginal rings may alleviate some of the adherence challenges faced when using coitally dependant products. SUMMARY: In the recent past, microbicide research has had disappointing outcomes. However, it has also provided a better understanding of factors that may reduce effectiveness of promising products, enabling the field to be better equipped to select and test new products. PMID- 20543608 TI - Postexposure prophylaxis for HIV following sexual exposure. AB - PURPOSE OF REVIEW: Postexposure prophylaxis (PEP) has become an important part of combined approaches to the prevention of onward HIV transmission. As PEP becomes more widely available after sexual as well as occupational exposure, there are ongoing debates about cost-effectiveness and utility. Different regions have adopted different PEP strategies and the availability of new antiretroviral drugs and classes means that options for PEP regimens are increasing. This review is timely and of importance as it summarizes the evidence supporting current PEP usage and discusses potential future strategies for PEP prescribing. RECENT FINDINGS: This review covers the biology and risk of HIV transmission and evidence supporting the use of PEP. It gives a summary of current guidelines including which agents to use, the potential for drug-drug interactions, possible alternative and potential novel PEP regimens, cost-effectiveness and research on effects of PEP on sexual behaviour. SUMMARY: While reinforcing current practice around PEP prescribing, this review discusses possible future developments including the use of new antiretroviral drugs, new classes of antiretroviral drugs or novel strategies for PEP which are likely to be areas of research in the near future. PMID- 20543610 TI - Antiretroviral drug concentrations in the male and female genital tract: implications for the sexual transmission of HIV. AB - PURPOSE OF REVIEW: To summarize the recent literature (2008-2010) on antiretroviral (ARV) drug disposition into the male and female genital tract. RECENT FINDINGS: Recent studies have confirmed that penetration of antiretroviral agents into the male and female genital tracts are both drug and sex specific. Concentrations achieved vary considerably depending on the class of drug studied, the sampling techniques used and the times samples are obtained. SUMMARY: There appear to be several patterns of drug penetration into the male and female genital tract. In addition there appear to be different patterns of genital shedding under the influence of antiretroviral therapy. What effect these factors will have on the sexual transmission of HIV or the evolution and transmission of resistant HIV remains to be seen. PMID- 20543611 TI - Male circumcision to reduce sexual transmission of HIV. AB - PURPOSE OF REVIEW: Three large trials among African heterosexual men in the last decade have confirmed that male circumcision reduces HIV acquisition. This review summarizes recent data regarding circumcision performed primarily to reduce HIV in high-prevalence settings. RECENT FINDINGS: Male circumcision more than halved the acquisition of HIV in the trials, and was associated with few adverse events and high levels of satisfaction. An additional trial found no direct reduction in HIV risk for female partners of circumcised men. Evidence for an HIV-protective effect of circumcision in men who have sex with men is weak and inconclusive. Acquisition of HSV-2 and high-risk human papillomavirus are both reduced in circumcised heterosexual men, whereas acquisition of common male urethral pathogens are not. Concerns exist that behavioural disinhibition could offset benefits of this intervention, and it remains to be seen whether the low rate of adverse events and adoption of safer sexual practices observed in the trials will be maintained in circumcision programmes outside trial settings. SUMMARY: The evidence that circumcision reduces HIV in African heterosexual men is clear. The impedance of political, cultural and logistic factors on expansion of much-needed African circumcision services requires urgent attention. PMID- 20543609 TI - Identifying and characterizing recently transmitted viruses. AB - PURPOSE OF REVIEW: Improvements in sequencing approaches and robust mathematical modeling have dramatically increased information on viral genetics during acute infection with HIV and simian immunodeficiency virus, providing unprecedented insight into viral transmission and viral/immune interactions. RECENT FINDINGS: Overall viral genetic diversity is reduced significantly during mucosal transmission. Remarkably, in the vast majority of sexual transmissions, this diversity is reduced to a single viral variant that establishes the initial productive clinical infection. By identifying and enumerating transmitted/founder viruses, researchers can begin to define the characteristics that are necessary and sufficient for successful viral replication within a new host. SUMMARY: Acute HIV infection is a critical window of opportunity for vaccine and therapeutic intervention. New sequencing technologies and mathematical modeling of transmission and early evolution have provided a clearer understanding of the number of founder viruses that establish infection, the rapid generation of diversity in these viruses and the subsequent evasion of host immunity. The information gained by identifying transmitted viruses, monitoring the initial host responses to these viruses and then identifying mechanisms of viral escape could provide better strategies for vaccine development, preexposure prophylaxis, microbicides, or other therapeutic interventions. PMID- 20543614 TI - Post-pancreatic resection: general overview and unique complications. AB - Pancreatic cancer is one of the most silently lethal forms of malignancy. With a lack of evidence-based research regarding pancreatic cancer, the evidence-based treatment options are limited. Currently, the best chance for a curative treatment is a pancreatic resection that typically is combined with chemotherapy and/or radiation therapy. The long-term treatment course and overall survival of the patient depend largely on the pathology report generated from the expurgated tissue analysis. After pancreatic resection, patients may experience both general and unique complications that, if not treated appropriately and assessed correctly, can be lethal. Provided here is a general overview of pancreatic resections and their unique postoperative complications for critical-care nurses. As the first-line provider, critical-care nurses assess and manage acute complications, in addition to educating patients to the long-term complications and how to manage them. PMID- 20543616 TI - Safety and satisfaction provided by patient-controlled analgesia. AB - Patient-controlled analgesia (PCA) therapy has become an accepted intervention for delivering pain management in a wide variety of patient populations. The principle of patient-controlled analgesia is to provide patient control over medication delivery. Unfortunately, PCA has come under great scrutiny since its introduction almost 40 years ago. This article focuses on the benefits and safety concerns of PCA and focuses on points that prescribers and nurses should keep in mind. PMID- 20543619 TI - One institution's experience in implementing protocols for glycemic management. AB - The objective for monitoring blood glucose is to determine the need for intervention. This article describes an institution's comprehensive program of protocols and education initiated to manage inpatient hyperglycemia. PMID- 20543620 TI - A brief review of the Belmont report. AB - The Belmont Report is one of the leading works concerning ethics and health care research. Its primary purpose is to protect subjects and participants in clinical trials or research studies. This report consists of 3 principles: beneficence, justice, and respect for persons. This article reviews the Belmont Report and these 3 principles as well as its importance to nurse researchers. PMID- 20543621 TI - Introducing nursing students to pediatric end-of-life issues using simulation. AB - This article describes the first pediatric death experienced by a 20-year-old nurse. This was a disturbing experience that led to the development of strategies as a faculty member to use when teaching nursing students about pediatric end-of life issues using simulation. This article describes those strategies. PMID- 20543624 TI - Who is the emergency room patient? An evolutionary concept analysis. AB - There is an absence of concept analysis discussing: "Who is the emergency room patient?" in the literature. This study aims to clarify and conceptually develop these concepts as they are contextually mediated. Using the evolutionary method of Rodgers (Concept Development in Nursing: Foundations, Techniques, and Applications. 2000:77-127), the findings clearly identified the references, contextual basis, attributes, antecedents, and consequences of the concepts. Clarity of the concepts is important as they could greatly influence future developments in practice, theory, and research. PMID- 20543630 TI - Goldmann applanation tonometry and dynamic contour tonometry after treatment with prostaglandin analog/prostamide. PMID- 20543631 TI - Spontaneous venous pulsation as a barometer for translaminar pressure fluctuation. PMID- 20543633 TI - Documentation--it is a changing. PMID- 20543634 TI - Nurses: great to be needed! PMID- 20543636 TI - Not what I expected: informational needs of women undergoing breast surgery. AB - In 2008, approximately 500,000 women in the United States underwent breast surgery, either cosmetic surgery or reconstruction following mastectomy for breast cancer. There is a growing body of literature on women's motivations to have these types of surgical procedures and on satisfaction with the aesthetic outcomes, but little is known about the information needs and expectations of women who choose to undergo these procedures. Therefore, the purpose of this qualitative study was to gain a better understanding of the informational needs of women who underwent breast augmentation, breast reduction, or breast reconstruction following breast cancer surgery. PMID- 20543638 TI - Nonsurgical body contouring with focused ultrasound. AB - UltraShape is an exciting, clinically proven, nonsurgical and noninvasive body contouring solution for both men and women. It offers an alternative to patients seeking effective reduction of localized areas of fat deposits without surgery. The procedure uses ultrasound technology to deliver focused ultrasound waves to target and break down fat cells without any effect on surrounding tissues or organs. PMID- 20543640 TI - Compression garment sizing: challenges, issues, and a solution. AB - This article explores the issues that nurses and physicians face when trying to properly fit their patients into a correctly sized compression garment. It examines and links the history of compression and the history of sizing to define guidelines that nurses can follow when dealing with the challenges of sizing. Recent research into sizing and measuring is discussed, with further recommendation for research proposed. PMID- 20543642 TI - Silver: an age-old treatment modality in modern times. AB - The use of silver as an antimicrobial for infection spans hundreds of years. The ancient Greeks and Romans used silver to disinfect their water and food supplies. Silver was also used in ancient times to treat burns and wounds as a wound dressing. Silver solutions were approved by the U.S. Food and Drug Administration in the 1920s. Since that time, silver has established itself as an effective and well-known treatment modality for and in the prevention of high-risk infection in clinical wound care (http://int.hansaplast.com/med-info/wound-care-beautiful healing/silver-tech.html). PMID- 20543643 TI - Rhytidectomy (face-lift). PMID- 20543644 TI - "Neither a borrower nor a lender be ...": when it comes to procuring medications for individual plastic surgical practices. PMID- 20543645 TI - Revamping end-user training. PMID- 20543646 TI - Increasing nursing student communication skills through electronic health record system documentation. PMID- 20543648 TI - "Ladies & gentlemen of the jury, I present... the nursing documentation". AB - You wake up in a cold sweat after dreaming that you're the defendant in a medical malpractice case. The plaintiff's lawyer was about to point out the flaws and gaps in your documentation. Thankful it was only a dream, you vow to make sure your charting is up to snuff. No matter how skilled a nurse you are, poor nursing documentation will undermine your credibility if you're ever involved in a lawsuit. Read this article for practical guidelines that will not only improve patient care, but also help shield you from legal fallout if something goes wrong despite your best efforts. PMID- 20543649 TI - Patient safety: Sidestepping unsafe abbreviations. PMID- 20543650 TI - Communicating with physicians, protecting yourself from legal harm. AB - When a patient's condition changes, you as a physical therapist (PT) must quickly consider when, how, and what to communicate to the physician. As you do, remember that these questions have not only clinical implications, but also legal implications. PMID- 20543651 TI - Clinical rounds: Nursing activities: how paperwork eats up your time. PMID- 20543652 TI - Teaching quality improvement and patient safety to trainees: a systematic review. AB - PURPOSE: To systematically review published quality improvement (QI) and patient safety (PS) curricula for medical students and/or residents to (1) determine educational content and teaching methods, (2) assess learning outcomes achieved, and (3) identify factors promoting or hindering curricular implementation. METHOD: Data sources included Medline (to January 2009), EMBASE, HealthSTAR, and article bibliographies. Studies selected reported curricula outlining specific educational content and teaching format. For articles with an evaluative component, the authors abstracted methodological features, such as study design. For all articles, they conducted a thematic analysis to identify factors influencing successful implementation of the included curricula. RESULTS: Of 41 curricula that met the authors' criteria, 14 targeted medical students, 24 targeted residents, and 3 targeted both. Common educational content included continuous QI, root cause analysis, and systems thinking. Among 27 reports that included an evaluation, curricula were generally well accepted. Most curricula demonstrated improved knowledge. Thirteen studies (32%) successfully implemented local changes in care delivery, and seven (17%) significantly improved target processes of care. Factors that affected the successful curricular implementation included having sufficient numbers of faculty familiar with QI and PS content, addressing competing educational demands, and ensuring learners' buy-in and enthusiasm. Participants in some curricula also commented on discrepancies between curricular material and local institutional practice or culture. CONCLUSIONS: QI and PS curricula that target trainees usually improve learners' knowledge and frequently result in changes in clinical processes. However, successfully implementing such curricula requires attention to a number of learner, faculty, and organizational factors. PMID- 20543653 TI - Contemporary HIV diagnoses trends in Australia can be predicted by trends in unprotected anal intercourse among gay men. AB - Data from HIV and behavioural surveillance among gay men in Eastern Australian states in 1994-2008 showed a close relationship between trends in reported unprotected anal intercourse with casual partners (UAIC; measured in behavioural surveys) and routinely reported HIV diagnoses. Increasing UAIC was strongly associated with increasing numbers of HIV diagnoses 2 years later (P = 0.001). This suggests an important public health role of UAIC as a predictor of changes in HIV diagnoses in Australia. PMID- 20543654 TI - Initiation of antiretroviral therapy at higher nadir CD4+ T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals. AB - OBJECTIVE: HIV infection is associated with increased rates of cardiovascular disease. We sought to evaluate whether initiation of HIV therapy at higher nadir CD4(+) T-cell counts might reduce cardiovascular risk, as measured by arterial stiffness. DESIGN: We conducted a cross-sectional study of 80 HIV-infected men who were antiretroviral-treated with undetectable plasma HIV RNA levels. METHODS: Participants underwent noninvasive assessment of arterial stiffness by pulse wave analysis (augmentation index normalized for heart rate of 75 bpm) and carotid femoral pulse wave velocity, both sensitive measures of cardiovascular risk. A generalized linear model was used to determine the relationship between cardiovascular and HIV-related predictors, and arterial stiffness. RESULTS: In unadjusted analyses, predictors of arterial stiffness included age, blood pressure, antihypertensive medication use, and nadir CD4(+) T-cell count below 350 cells/microl (all P < 0.05). After adjusting for both cardiovascular risk factors (age, blood pressure, antihypertensive medication use, diabetes, hypercholesterolemia, and smoking) and HIV-related covariates, nadir CD4(+) T cell count below 350 cells/microl was independently associated with a 0.41 m/s increase in pulse wave velocity (95% confidence interval 0.03-0.79, P = 0.03) and a 7.3% increase in augmentation index (augmentation index normalized for heart rate of 75 bpm; 95% confidence interval 2.6-11.9, P = 0.003). Neither duration of antiretroviral therapy nor exposure to protease inhibitors was associated with arterial stiffness. CONCLUSION: Among treated HIV-infected individuals, arterial stiffness is independently associated with both traditional cardiovascular risk factors as well as a low nadir CD4(+) T-cell count. Our data suggest that cardiovascular risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4 T-cell counts are depressed, a concept that should be tested prospectively in future studies. PMID- 20543655 TI - HIV among Haitian-born persons in the United States, 1985-2007. AB - OBJECTIVE: Haitian-born persons have been historically stigmatized for introducing HIV to North America; however, no previous study has reported on the national HIV surveillance trends among this foreign-born group. METHODS: Annual AIDS cases were estimated for adults and adolescents (aged >12 years) from all 50 US states and the District of Columbia who were diagnosed between 1985 and 2007, and who reported 'Haiti' as country of birth to the Centers for Disease Control and Prevention. HIV data (with or without AIDS) for Haitian-born adults and adolescents diagnosed between 2004 and 2007 were obtained from 34 US states. Denominators for AIDS rates by race/ethnicity are from postcensal estimates, the American Community Survey of the US Census Bureau and the Haitian Consulates. RESULTS: In 2007, Haitian-born persons constituted 1.2% of US AIDS cases, yet accounted for 0.18% of the total US population based on the American Community Survey estimates, which suggests a seven-fold overrepresentation in the CDC AIDS surveillance data. However, when using population estimates from the Haitian Consulate, the overrepresentation ranges from three-to-four-fold, which is similar to the AIDS rate for blacks/African-Americans. CONCLUSION: The importance of having accurate denominators to estimate the AIDS rate for the Haitian population is paramount. PMID- 20543656 TI - Acute HIV-1 infection is highly prevalent in Ugandan adults with suspected malaria. AB - OBJECTIVES: Acute febrile illnesses consistent with malaria are the most common presentation at health clinics in sub-Saharan Africa, accounting for 30-50% of outpatient visits. The symptoms of acute HIV infection can mimic acute malaria. We investigated whether acute HIV infections could be identified among adults with suspected malaria at rural health centers in Uganda. DESIGN: A cross sectional study of 1000 consecutive patients referred for malaria blood smears at each of seven government health centers, of which 2893 (41%) were 13 years or older and tested for HIV. METHODS: HIV enzyme immunoassay antibody testing was performed on dried blood spots and confirmed by western blot. Enzyme immunoassay nonreactive and enzyme immunoassay-reactive, western blot-unconfirmed samples were pooled (10/pool) and tested for HIV RNA by nucleic acid amplification testing. We defined acute HIV infection as HIV-1 RNA positive with a negative or indeterminate HIV-1 western blot pattern and early HIV infection as HIV-1 RNA positive with a positive western blot pattern, but with a BED-corrected optical density of below 0.8. RESULTS: Of 2893 patients evaluated, 324 (11%) had test results indicating HIV infection. Overall, 30 patients (1.0%) had acute HIV infection, 56 (1.8%) had early HIV infection, and 238 (8%) had established HIV infection. Acute HIV infections were more prevalent at sites with higher HIV prevalence and lower malaria endemicity. CONCLUSION: At multiple sites in Uganda, 1-3% of adults with suspected malaria had acute or early HIV infection. These findings highlight a major opportunity for expanding recognition of acute and early HIV infection in Africa. PMID- 20543657 TI - Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia. AB - OBJECTIVE: To evaluate the relationship between early CD4(+) lymphocyte recovery on antiretroviral therapy (ART) and subsequent survival among low body mass index (BMI) HIV-1-infected adults. DESIGN: Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: We evaluated ART-treated adults enrolled in care for more than 6 months. We stratified this study population according to World Health Organization (WHO) malnutrition criteria: normal (BMI >or=18.5 kg/m(2)), mild (17.00-18.49), moderate (16.00-16.99), and severe (<16.0). We used Cox proportional hazards regression to estimate the subsequent risk of death associated with absolute CD4(+) cell count change over the first 6 months on ART. To account for effect modification associated with baseline CD4(+) cell count, a weighted summary measure was calculated. RESULTS: From May 2004 to February 2009, 56,612 patients initiated ART at Lusaka district clinics; of these, 33 097 (58%) were included in this analysis. The median change in 0-6 month CD4(+) cell count in each baseline BMI strata varied from 127 to 131 cells/microl. There was a statistically significant, inverse association between baseline BMI and the post 6-month hazard for mortality only among those patients with less than 100 cells/microl increase in the first 6 months of ART. A CD4(+) cell count increase of at least 100 cells/microl over the first 6 months of ART was not associated with a higher hazard for mortality, regardless of baseline BMI. CONCLUSIONS: Low baseline BMI and attenuated CD4(+) cell count response at 6 months had a compounding, negative impact on post 6-month survival. Specific guidelines for monitoring ART response using immunologic criteria may be warranted for low BMI patients. PMID- 20543658 TI - Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study. AB - OBJECTIVE: To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM. DESIGN: A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study. METHODS: For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated. RESULTS: At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up. CONCLUSION: HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma. PMID- 20543659 TI - Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection. AB - OBJECTIVE: Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population. DESIGN: A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals. METHODS: NK cells were analyzed by flow cytometry. Degranulation was assessed by measuring their expression of CD107a after stimulation with K562 cells, interleukin-12 and interleukin-15. RESULTS: CD56(-)/CD16(+) NK cells are heterogeneous and composed of two populations, namely CD122(-)/CCR7(+) cells and CD122(-)/CCR7(+) cells. We show that expanded CD122(+) but not CCR7(+) cells in HIV-seropositive individuals are characterized by expression of senescence marker CD57 similarly to CD56(dim)/CD16(+) NK cells along with expression of KIRs, CD8, perforin and granzyme B. Despite expression of perforin and granzyme B, CD57 expressing cells exhibited less numbers of degranulating cells as measured by CD107a, indicating their functional impairment. However, there was no correlation between expansion of total CD56(-)/CD16(+) NK cells or the distinct subpopulations and viral load or CD4 cell count. CONCLUSION: These data indicate that expansion of CD56( )/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells. PMID- 20543660 TI - Steady increase in cellular HIV-1 load during the asymptomatic phase of untreated infection despite stable plasma viremia. AB - OBJECTIVE: To compare the dynamics of HIV-1 molecular markers in peripheral blood mononuclear cells (PBMCs) and in plasma during the asymptomatic phase of untreated HIV-1 infection. DESIGN AND METHODS: Using seminested real-time PCR assays, we measured the levels of HIV-1 proviral (pr) DNA, unspliced (us) RNA, and multiply spliced RNA in the PBMCs of 10 untreated HIV-1-infected men at multiple time points during the asymptomatic phase of infection and compared the longitudinal trends of these markers with those of viral RNA in plasma. RESULTS: Whereas plasma RNA levels did not significantly change in any of the individuals, levels of usRNA significantly increased with time in six out of 10 persons, and levels of prDNA in four. Slopes, changes, and time-weighted changes from baseline of usRNA, prDNA, and CD4 cell count, but not of plasma RNA, were significantly different from zero (P < 0.01). No significant longitudinal trend of plasma RNA was observed in the study group using linear mixed models, whereas the trends of usRNA, prDNA, and CD4 cell count were highly significant (P < 0.001). usRNA levels increased significantly faster than those of plasma RNA or prDNA, suggesting a temporal increase in viral replication rates in PBMCs. Finally, CD4 cell count inversely correlated with levels of usRNA and prDNA, but not with plasma RNA level. CONCLUSION: During the asymptomatic phase of untreated HIV-1 infection, when virion production and clearance are balanced, resulting in stable plasma viremia, viral load in PBMCs steadily increases and is a sensitive and direct longitudinal virological marker of infection progression. PMID- 20543661 TI - Cost-effectiveness of routine and low-cost CD4 T-cell count compared with WHO clinical staging of HIV to guide initiation of antiretroviral therapy in resource limited settings. AB - BACKGROUND: HIV is a major cause of disease and death in sub-Saharan Africa. Provision and scale-up of antiretroviral therapy (ART) in resource-limited settings is feasible and cost-effective. Initiation of ART is guided by WHO stage or CD4 cell count; the latter may not be available and up to 70% of eligible individuals are not identified. Low-cost CD4 cell count tests are comparable to conventional methods. We compared the direct healthcare costs and benefits using routine and low-cost CD4 cell count versus WHO staging to initiate ART. METHODS: Using a Markov state transition model, we incorporated costs, survival and quality of life. We compared the direct healthcare costs and benefits in quality adjusted life years gained using routine and low-cost CD4 cell count versus WHO staging to initiate ART. We estimated an incremental cost-effectiveness ratio in US$ per quality-adjusted life year gained and compared with threshold of gross domestic product per capita. Uncertainty was assessed by sensitivity analysis. RESULTS: Routine and low-cost CD4 cell counts compared to WHO staging to guide initiation of ART improved quantity and quality of life and appears to be very cost-effective. The base case estimated an incremental cost-effectiveness ratio of US$939 and US$85 per quality-adjusted life years gained, respectively, and well below the cost effectiveness thresholds of gross domestic product per capita. CONCLUSION: Routine or low-cost CD4 cell count compared to WHO staging, to guide initiation of ART, is a very cost-effective intervention for sub-Saharan Africa and should be an integral part of the scale-up of ART programs. PMID- 20543662 TI - Stress and increased HIV infection risk among gay and bisexual men. AB - OBJECTIVE: Our principal objective was to determine whether psychosocial stress raises the risk of HIV infection among gay and bisexual men. If so, we also aimed to evaluate the evidence for the underlying mechanism, specifically whether stress has an intermediate effect on sexual risk behaviour or an independent, cofactor effect. METHODS: Participants were recruited through the provincial HIV diagnostic laboratory, physicians and community organizations in Ontario, Canada, 1998-2006. Confirmed recent seroconverters (n = 123 cases) were asked about stressful life events and behaviour during the likely period of infection (median 8, range 3-33 months). HIV-negative controls (n = 240) were asked about an equivalent time period. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Cases reported more stressful life events (median = 3, 33% 5 or more) than controls (median = 2, 20% 5 or more). Compared to men who reported no events, risk of HIV infection increased with the number of events, to a 2.5-fold increase in risk among men reporting 5 or more (95% CI 1.3, 4.7). The association weakened when adjusted for sexual risk behaviour (OR = 1.7, 95% CI 0.82, 3.6) and when restricted to men who engaged in unprotected receptive anal sex with an HIV-positive or status unknown partner (OR = 1.3, 95% CI 0.50, 3.6). CONCLUSIONS: Gay and bisexual men experiencing stressful life events were at increased risk of HIV infection. This effect was mediated by sexual risk behaviour. We recommend that coping strategies in response to stress be considered in prevention research and health policy. PMID- 20543664 TI - Severe extrapiramidal symptoms after nonintentional risperidone exposure in a child: case report and review of the literature. AB - Increase in use of atypical antipsychotics has been paralleled by an increase in the incidence of intentional and nonintentional overdose. Pediatric cases are uncommon, but may be severe. We describe a case of a child presenting with severe extrapiramidal symptoms, initially interpreted as seizures, caused by a nonintentional intoxication with risperidone, and review management options and the literature. PMID- 20543665 TI - The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine breathing frequency. AB - OBJECTIVE: The Finometer records the beat-to-beat finger pulse contour and has been recommended for research studies assessing short-term changes of blood pressure and its variability. Variability measured in the frequency domain using spectral analysis requires the impact of breathing be restricted to high frequency spectra (>0.15 Hz) so that the data from participants need to be excluded when the breathing impact occurs in the low frequency spectra (0.04-0.15 Hz). This study tested whether breathing frequency can be estimated from standard Finometer recordings using either stroke volume oscillation frequency or spectral stroke volume variability maximum scores. METHODS: Twenty-two healthy volunteers were tested for 270 s in the supine and upright positions. Finometer recorded the finger pulse contour and a respiratory transducer recorded breathing. Stoke volume oscillation frequency was calculated manually whereas the stroke volume spectral maximums were obtained using the software Cardiovascular Parameter Analysis. These estimates were compared with the breathing frequency using the Bland-Altman procedures. RESULTS: Stroke volume oscillation frequency estimated breathing frequency to less than +/-10% and 95% levels of agreement in both supine (-7.7 to 7.0%) and upright (-6.7 to 5.4%) postures. Stroke volume variability maximum scores did not accurately estimate breathing frequency. CONCLUSION: Breathing frequency can be accurately derived from standard Finometer recordings using stroke volume oscillations for healthy individuals in both supine and upright postures. The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine the breathing frequency. PMID- 20543666 TI - Use of automated blood pressure measurements in clinical trials and registration studies: data from the VALTOP Study. AB - BACKGROUND: Auscultatory measurement of office blood pressure (BP) by mercury sphygmomanometers (AuscBPM) is still the gold standard in clinical trials and registration studies for antihypertensive drugs. The increasing availability of accurate automated oscillometric BP measuring devices has offered new perspectives in this field, although their usefulness in drug studies has not been systematically tested yet. METHODS: During the course of Valsartan 320 mg EU Registration Study we used an electronic automated oscillometric BP measuring device (eBPM) as an alternative to conventional AuscBPM. Altogether 3776 patients were randomized into a double-blinded actively controlled parallel group study in 303 centers, and 54 422 BP readings were recorded by the validated, electronic, automated oscillometric device OMRON 705IT with digital printouts. Terminal digit preference and preference at therapeutic cutoff points were evaluated. The data were compared with the results of an earlier valsartan study similar in design but based on conventional AuscBPM. Furthermore, based on a simulation, four strategies for automated BP measurement with varying number of office readings (3 5) were analyzed to define an optimal method to collect BP at office visits. RESULTS: eBPM eliminated terminal digit preference and dramatically reduced preferences for therapeutic cutoff points as compared with earlier valsartan trials with conventional AuscBPM. However, even with eBPM a minor bias with the therapeutic cutoff value was observed probably because of an observer bias during data documentation. The within-patient variability of three measurements sequentially taken at each visit was similar to other strategies including more measurements. CONCLUSION: On the basis of our data, we suggest that eBPM is a suitable alternative to AuscBPM in clinical trials and registration studies, and may carry specific advantages. Automatic data transfer of recorded values to electronic patient files may further minimize observer bias. Manufacturers should consider such findings for the development of professional devices. PMID- 20543667 TI - Endothelial cell damage in descemet stripping automated endothelial keratoplasty with the underfold technique: 6- and 12-month results. AB - PURPOSE: To evaluate the endothelial cell loss at 6 and 12 months after Descemet stripping automated endothelial keratoplasty (DSAEK) using a modified 40/60 underfolding technique and to compare this to the literature on other commonly used implantation techniques, such as the conventional 60/40-fold, gliding, and hitch suture techniques. METHODS: Endothelial cell density was measured prospectively, and cell loss was calculated at 6 and 12 months after endothelial keratoplasty using a recently described underfolding implantation technique. RESULTS: In this study, 305 eyes undergoing DSAEK were evaluated. Average endothelial cell loss was 26% at 6 months and 27% at 12 months, all statistically significant reductions from preoperative values (P < 0.01). The decrease in cell count from 6 months to 12 months was not statistically significant. CONCLUSIONS: This study demonstrates reduction in endothelial cell loss after DSAEK using the underfold technique when compared with previous reports on conventional folding techniques and similarity to previous reports on glide techniques at 6 and 12 months postoperatively (26% vs. 34% vs. 23% at 6 months). This offers an easy modification to a commonly used existing technique and improves endothelial cell survival after DSAEK. PMID- 20543668 TI - Blunt chest trauma induces mediator-dependent monocyte migration to the lung. AB - OBJECTIVE: This study was designed to determine whether lung contusion induces an increased pulmonary recruitment of monocytes as a source of alveolar macrophages and which mediators are involved. SETTING AND DESIGN: Prospective animal study. SUBJECTS AND INTERVENTIONS: Male Sprague-Dawley rats were subjected to chest trauma by a single blast wave. MEASUREMENTS: Chemokine concentrations in bronchoalveolar lavage fluids and supernatants of alveolar macrophages, chemokine and chemokine receptor mRNA expressions in monocytes, pulmonary interstitial macrophages, and alveolar macrophages isolated after trauma or sham procedure were evaluated. Immigration of monocytes was determined by staining alveolar macrophages with the fluorescent marker PKH26 before chest trauma. Chemotaxis of naive monocytes in response to bronchoalveolar lavage or supernatants from alveolar macrophages isolated after trauma or sham procedure and the migratory response of monocytes isolated after trauma/sham to recombinant chemokines were measured. MAIN RESULTS: Chemokine levels in bronchoalveolar lavage and alveolar macrophage supernatants and the percentage of monocytes migrated to the lungs were increased after chest trauma. Lung contusion enhanced the mRNA expression for CCR2 in monocytes and interstitial macrophages and for monocyte chemotactic protein-1 in alveolar macrophages. Migration of naive monocytes vs. bronchoalveolar lavage or alveolar macrophage supernatants from traumatized animals was increased when compared with samples from shams. Monocytes isolated 2 hrs after trauma showed a reduced migration to CINC-1 or monocyte chemotactic protein-1 compared with sham. CONCLUSIONS: Alveolar macrophages seem to contribute to increased chemokine concentrations in alveoli of animals subjected to blunt chest trauma. Mediators released by alveolar macrophage are potent stimuli for monocyte migration. Monocytes alter their chemokine receptor expression and are recruited to the lungs. PMID- 20543669 TI - Early extracorporeal membrane oxygenator-assisted primary percutaneous coronary intervention improved 30-day clinical outcomes in patients with ST-segment elevation myocardial infarction complicated with profound cardiogenic shock. AB - OBJECTIVES: This study tested the hypothesis that early extracorporeal membrane oxygenator offered additional benefits in improving 30-day outcomes in patients with acute ST-segment elevation myocardial infarction complicated with profound cardiogenic shock undergoing primary percutaneous coronary intervention. METHODS: Between May 1993 and July 2002, 920 patients with acute ST-segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 12.5% (115) with cardiogenic shock were enrolled in this study (group 1). Between August 2002 and December 2009, 1650 patients with acute ST segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 13.3% (219) complicated with cardiogenic shock were enrolled (group 2). RESULTS: The incidence of profound shock (defined as systolic blood pressure remaining < or =75 mm Hg after intra-aortic balloon pump and inotropic agent supports) was similar in both groups (21.7% vs. 21.0%, p > .5). Extracorporeal membrane oxygenator support, which was available only for patients in group 2, was performed in the catheterization room. The results demonstrated that final thrombolysis in myocardial infarction grade 3 flow in infarct-related artery was similar between the two groups (p = .678). However, total 30-day mortality and the mortality of patients with profound shock were lower in group 2 than in group 1 (all p < .04). Additionally, the hospital survival time was remarkably longer in patients in group 2 than in patients in group 1 (p = .0005). Furthermore, multivariate analysis demonstrated that unsuccessful reperfusion, presence of advanced congestive heart failure, profound shock, and age were independent predictors of 30-day mortality (all p < .02). CONCLUSION: Early extracorporeal membrane oxygenator-assisted primary percutaneous coronary intervention improved 30-day outcomes in patients with ST segment elevation myocardial infarction with complicated with profound cardiogenic shock. PMID- 20543670 TI - Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis. AB - OBJECTIVE: To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not well understood. DESIGN: Prospective experimental study. SETTING: University research laboratory. INTERVENTIONS: Wild-type mice underwent cecal ligation and puncture and were treated with antibiotic during 3 days after surgery. On days 1, 7, or 15 after cecal ligation and puncture, the frequency of regulatory T cells, proliferation of CD4 T cells and bacterial counts were evaluated. Fifteen days after cecal ligation and puncture, surviving mice underwent secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella pneumophila. Some mice received agonistic glucocorticoid induced tumor necrosis factor receptor antibody (DTA-1) before induction of secondary infection. MEASUREMENTS AND MAIN RESULTS: Mice surviving cecal ligation and puncture showed a markedly increased frequency of regulatory T cells in thymus and spleen, which was associated with reduced proliferation of CD4 T cells. Fifteen days after cecal ligation and puncture, all sepsis-surviving mice succumbed to nonlethal injection of L. pneumophila. Treatment of mice with DTA-1 antibody reduced frequency of regulatory T cells, restored CD4 T cell proliferation, reduced the levels of bacteria in spleen, and markedly improved survival of L. pneumophila infection. CONCLUSION: These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis. PMID- 20543671 TI - Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs. AB - OBJECTIVE: The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: : Twenty-four female, large, white breed pigs (27-37 kg). INTERVENTIONS: Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). MEASUREMENTS AND MAIN RESULTS: Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/ 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). CONCLUSIONS: Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome. PMID- 20543672 TI - Diagnosis and treatment of allergy to hymenoptera venoms. AB - PURPOSE OF REVIEW: This review overviews select advances reported in the literature from mid-2008 to the present in the diagnosis and management of individuals with immediate-type hypersensitivity to hymenoptera venom(s). RECENT FINDINGS: Skin testing remains the principal confirmatory test for sensitization to hymenoptera venoms. Use of dialyzed extracts in North America could enhance the sensitivity of intradermal skin testing. Hymenoptera venom components are overviewed with focus on their use in IgE antibody microarray assays to distinguish true dual sensitization to yellow jacket venom (YJV) and honeybee venom (HBV) proteins from carbohydrate-related cross-reactivity. Mechanisms on how venom induces vascular permeability in the skin following intradermal testing are elucidated and how tolerance is induced following high-dose venom exposure. For management, venom immunotherapy remains the most effective treatment. Use of immunotherapy in large local reactors to reduce morbidity is discussed. Baseline serum tryptase levels have been identified as one potential marker for severe systemic reactions to a subsequent sting. SUMMARY: Minor enhancements involving dialyzed venoms, component allergens, and microarray systems are poised to improve diagnostic confirmatory assays. Use of venom immunotherapy in large local reactors and tryptase as a predictor of a future severe venom-induced systemic reaction may enhance management programs for stinging insect allergic individuals. PMID- 20543673 TI - Epinephrine and its use in anaphylaxis: current issues. AB - PURPOSE OF REVIEW: Epinephrine is a life-saving medication in the treatment of anaphylaxis, in which it has multiple beneficial pharmacologic effects. Here, we examine the evidence base for its primary role in the treatment of anaphylaxis episodes in community settings. RECENT FINDINGS: We review the practical pharmacology of epinephrine in anaphylaxis, its intrinsic limitations, and the pros and cons of different routes of administration. We provide a new perspective on the adverse effects of epinephrine, including its cardiac effects. We describe the evidence base for the use of epinephrine in anaphylaxis. We discuss the role of epinephrine auto-injectors for treatment of anaphylaxis in community settings, including identification of patients who need an auto-injector prescription, current use of auto-injectors, and advances in auto-injector design. We list reasons why physicians fail to prescribe epinephrine auto-injectors for patients with anaphylaxis, and reasons why patients fail to self-inject epinephrine in anaphylaxis. We emphasize the primary role of epinephrine in the context of emergency preparedness for anaphylaxis in the community. SUMMARY: Epinephrine is the medication of choice in the first-aid treatment of anaphylaxis in the community. For ethical reasons, it is not possible to conduct randomized, placebo controlled trials of epinephrine in anaphylaxis; however, continued efforts are needed towards improving the evidence base for epinephrine injection in this potentially fatal disease. PMID- 20543674 TI - Pathophysiology, diagnosis and management of exercise-induced anaphylaxis. AB - PURPOSE OF REVIEW: The aim of this review is to challenge the current opinions of the pathophysiological mechanisms that give rise to food dependent exercise induced anaphylaxis (FDEIA) and to consider these mechanisms within the wider context of exercise physiology to further inform our understanding and treatment of this condition. RECENT FINDINGS: Exercise-induced anaphylaxis (food dependent and nonfood dependent) is a clinical syndrome in which anaphylaxis occurs in conjunction with exercise. Given the rarity of the condition, our current understanding relies on the many case studies and reviews of the topic. The pathophysiology of FDEIA remains to be fully elucidated with well constructed trials but current working hypotheses to date involve alterations in plasma osmolaltiy and pH, tissue enzyme activity, blood flow redistribution, altered gastrointestinal permeability and facilitated epitope recognition/allergen binding. SUMMARY: Implications for future research are the physiological changes that occur during exercise need deeper consideration to ensure that proposed mechanisms are realistic and actually occur within the time frame and exercise intensity domain during which the reported FDEIA occurred. These theories must be tested rigorously with sufficiently powered studies if progress is to be made in determining the perplexing pathophysiology of FDEIA. PMID- 20543675 TI - Anaphylaxis and insect allergy. AB - PURPOSE OF REVIEW: Anaphylaxis is an acute-onset and potentially life-threatening allergic reaction that can be caused by numerous allergic triggers including stinging insects. This review focuses on recent advances, natural history, risk factors and therapeutic considerations. RECENT FINDINGS: Recent work suggests that concerns over insect allergy diagnosis continue to exist. This is especially true with individuals who have a convincing history of a serious life-threatening anaphylactic event, but lack the necessary diagnostic criteria of venom-specific IgE by skin test or in-vitro diagnostic methods to confirm the diagnosis. The role of occult mastocytosis or increased basophile reactivity may play a role in this subset population. Additionally, epinephrine continues to be underutilized as the primary acute intervention for an anaphylactic reaction in the emergent setting. SUMMARY: The incidence of anaphylaxis continues to rise across all demographic groups, especially those less than 20 years of age. Fortunately, the fatalities related to anaphylaxis appear to have decreased over the past decades. Our understanding of various triggers, associated risk factors, as well as an improved understanding and utilization of biological markers such as serum tryptase have improved. Our ability to treat insect anaphylaxis by venom immunotherapy is highly effective. Unfortunately, anaphylaxis continues to be underappreciated and undertreated especially in regard to insect sting anaphylaxis. This includes the appropriate use of injectable epinephrine as the primary acute management tool. These findings suggest that continued education of the general population, primary care healthcare providers and emergency departments is required. PMID- 20543676 TI - Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. AB - PURPOSE OF REVIEW: There is a growing body of knowledge on pain modulation in various disease states. This article reviews the state of the art regarding the clinical relevance of pain inhibition as revealed by 'pain inhibits pain' test paradigms, trying to organize the clinically relevant data, and emphasizing the pathophysiology of pain. In line with recent experts' recommendations, the term conditioned pain modulation (CPM) will be used, replacing the previous terms 'diffuse noxious inhibitory control (DNIC)' or 'DNIC-like' effects. RECENT FINDINGS: Most of the work in this context was done on the idiopathic pain syndromes, such as irritable bowel syndrome, temporomandibular disorders, fibromyalgia, and tension type headache. The pattern of reduced CPM efficiency seems common to these syndromes and an assertion is made that low CPM efficiency, reflecting low pain inhibitory capacity, is a pathogenetic factor in the development of the idiopathic pain syndromes. Low CPM efficiency was shown to be predictive of acute and chronic postoperative pain, and, in some reports, to be associated with neuropathic pain levels. SUMMARY: Low CPM efficiency is associated with higher pain morbidity and vice versa. Further work is awaited on clarifying plasticity of CPM and its relevance to selection and efficacy of pain therapy. PMID- 20543677 TI - Opioid antagonists for prevention and treatment of opioid-induced gastrointestinal effects. AB - PURPOSE OF REVIEW: The therapeutic action of opioid analgesics is compromised by peripheral adverse effects, among which constipation is the most disabling as laxatives often fail to provide satisfactory relief. This review highlights recent advances in the specific control of opioid-induced constipation by opioid receptor antagonists with limited systemic bioavailability or a peripherally restricted site of action. RECENT FINDINGS: The specific management of opioid induced bowel dysfunction is currently based on three drug entities: oral alvimopan for the shortening of postoperative ileus associated with opioid induced pain control after bowel resection, subcutaneous methylnaltrexone for the reduction of opioid-induced constipation in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the treatment of noncancer and cancer pain. All three drug entities have been shown to attenuate opioid-induced motor stasis in the gut with a favorable adverse effect profile, while the analgesic effect of opioids remains unabated. SUMMARY: The availability of opioid receptor antagonists with restricted access to the central nervous system provides a novel opportunity to specifically control opioid-induced constipation and other peripheral adverse effects of opioid analgesics. Further studies are needed to evaluate the long term efficacy, safety and cost-effectiveness of this approach. PMID- 20543678 TI - The clinical (ir)relevance of opioid-induced immune suppression. AB - PURPOSE OF REVIEW: Opioid-induced immune suppression has been demonstrated in cell culture experiments and in animal models. This review examines whether opioids also increase the risk of infections in the perioperative setting or on the ICU. RECENT FINDINGS: Only a few studies are available. Patients receiving higher doses of systemic opioids had an increased risk of developing a pneumonia perioperatively. However, these results only occurred if laparoscopic vs. open surgery or epidural vs. systemic opioid therapy were compared. These differences are thought to reflect the better quality of analgesia and the improved ability to clear secretions. Alternatively, systemic opioids could induce an immune suppression leading to infectious complications. In intensive care patients, opioid use correlated with infectious complications in patients with burn injuries but did not increase the rate of sepsis in neonates. One retrospective study indicated that opioid withdrawal might be an important risk factor. At present, it remains unclear whether the choice of an opioid, its dose, and mode of withdrawal influence infectious complications. SUMMARY: In contrast to in vitro studies and to animal models, conclusive evidence is currently lacking that opioids induce clinically relevant infectious complications in patients. However, these findings should be interpreted with great caution, as almost no adequately designed trials have been performed. Peripherally selective opioid receptor antagonists might be useful if opioid-induced immune suppression should prove to be clinically relevant. PMID- 20543679 TI - Anesthesia in prehospital emergencies and in the emergency department. AB - PURPOSE OF REVIEW: Recently, notable progress has been made in the field of anesthesia drugs and airway management. RECENT FINDINGS: Anesthesia in prehospital emergencies and in the emergency department is reviewed and guidelines are discussed. SUMMARY: Preoxygenation should be performed with high flow oxygen delivered through a tight-fitting face mask with a reservoir. Ketamine may be the induction agent of choice in hemodynamically unstable patients. The rocuronium antagonist sugammadex may have the potential to make rocuronium a first-line neuromuscular blocking agent in emergency induction. Experienced healthcare providers may consider prehospital anesthesia induction. Moderately experienced healthcare providers should optimize oxygenation, hasten hospital transfer and only try to intubate a patient whose life is threatened. When intubation fails twice, ventilation should be performed with an alternative supraglottic airway or a bag-valve-mask device. Lesser experienced healthcare providers should completely refrain from intubation, optimize oxygenation, hasten hospital transfer and ventilate patients only in life-threatening circumstances with a supraglottic airway or a bag-valve-mask device. Senior help should be sought early. In a 'cannot ventilate-cannot intubate' situation, a supraglottic airway should be employed and, if ventilation is still unsuccessful, a surgical airway should be performed. Capnography should be used in every ventilated patient. Clinical practice is essential to retain anesthesia and airway management skills. PMID- 20543680 TI - Anesthesia for balloon dilatation of esophageal strictures in children with epidermolysis bullosa dystrophica: from intubation to sedation. AB - PURPOSE OF REVIEW: Dystrophic epidermolysis bullosa is a rare disease mainly affecting small children. They often have to undergo different surgical procedures, for example balloon dilatation following esophageal strictures to maintain oral intake and prevent malnutrition. RECENT FINDINGS: So far, no specific treatment is available for patients with any forms of epidermolysis bullosa. However, more and more minimal invasive surgical techniques are used to manage symptoms of the disease, for example endoscopic balloon dilatation for severe esophageal strictures. SUMMARY: In this article implications for the anesthetic management of children with dystrophic epidermolysis bullosa are described. General anesthesia and sedation techniques are feasible if specific prerequisites are fulfilled. The team providing anesthesia and endoscopy must be familiar with the nature and disabilities of this disease. Coordinated care of the involved disciplines is crucial for all planned procedures regarding perioperative management. PMID- 20543681 TI - Right ventricular function by MRI. AB - PURPOSE OF REVIEW: For years, the right ventricle (RV) has been deemed 'unnecessary', as shown by procedures such as Fontan surgery. More recently, right ventricular dysfunction has been recognized as a prognostic factor in many cardiovascular diseases. Supported by advances in echocardiography and MRI, assessment of right ventricular function and morphology has gained interest. The goal of this review is to offer a current clinical perspective on right ventricular function as assessed by MRI. RECENT FINDINGS: MRI has progressed towards a fast and reliable technique for assessing right ventricular morphology, volumes and function. Strain-encoded techniques and single breath-hold four dimensional acquisition techniques are promising, but need to be confirmed in patient studies. Continuous improvement in postprocessing software has further reduced analysis time and effort. SUMMARY: Our understanding of right ventricular behavior even in complex heart disease has taken substantial benefit from modern cardiac MRI techniques. MRI imaging of the RV is patient-tailored, integrating right ventricular volumetric and functional analysis in a comprehensive approach, including assessment of cardiac morphology, myocardial tissue characteristics, flow patterns and great vessel anatomy. This approach provides the clinician a complete view, not only of the RV as such, but also of the RV being an essential part of the cardiopulmonary system. PMID- 20543682 TI - Therapeutic implications of oxidative stress in acute and chronic pancreatitis. AB - PURPOSE OF REVIEW: This review presents new evidence on the role of oxidative stress and antioxidant status in acute and chronic pancreatitis published in the last year. RECENT FINDINGS: In-vitro studies showed that protein phosphatases may play an important role in the interaction between reactive oxygen species and proinflammatory cytokines in acute pancreatitis. In-vivo studies found that several natural compounds ameliorate oxidative stress and, therefore, have therapeutic potential. In the domain of clinical studies, the major development is the first double-blind placebo-controlled randomized trial that showed effectiveness of oral antioxidant supplementation (organic selenium, ascorbic acid, alpha-tocopherol, beta-carotene, and methionine) in relieving pain in patients with chronic pancreatitis. The developments in clinical studies on acute pancreatitis are less spectacular and mainly limited to evaluation of different markers of oxidative stress and antioxidant status in the course of disease. SUMMARY: A significant advance has been made in the arena of research in chronic, but not acute, pancreatitis. There is now solid evidence to justify the use of oral antioxidants in the treatment of patients with chronic pancreatitis. The progress in clinical research on antioxidants in acute pancreatitis is hampered by several factors, including suboptimal classification of acute pancreatitis and route of administration used in previous studies. PMID- 20543683 TI - Fluid administration and the kidney. AB - PURPOSE OF REVIEW: Intravenous fluids are widely administered in the ICU with the intention of preventing or ameliorating acute kidney injury (AKI). This review focuses on recent studies examining fluid administration and renal function in critical illness to critically examine conventional justifications for fluid administration. RECENT FINDINGS: Early, targeted, resuscitation of inadequate cardiac output in shock may have a beneficial effect on organ function and patient outcome. However, experimental evidence suggests the relationship between fluid administration and an increase in renal oxygen delivery is weak, whereas any beneficial effects from fluid administration can be short lived. Conversely, evidence associating fluid overload and adverse outcomes is strengthening, whereas more restrictive fluid administration does not seem to predispose to clinically significant AKI in many situations. Furthermore, concerns persist that some colloid or high chloride concentration solutions may directly impair renal function independent of volume overload. SUMMARY: Adequate volume resuscitation remains a cornerstone to the emergent treatment of critical illness. However, continued fluid administration and positive fluid balances have not been shown to improve renal outcomes and may worsen overall prognosis in AKI. Concerns about renal dysfunction should not deter clinicians from adopting more restrictive approaches to fluid administration. PMID- 20543684 TI - Blood product transfusion in the critical care setting. AB - PURPOSE OF REVIEW: The past two decades have witnessed an extensive re-evaluation of transfusion therapy in the intensive care unit (ICU). The purpose of this review is to present the current state of knowledge regarding blood transfusion in the critically ill and to identify gaps in our current understanding for future research. RECENT FINDINGS: Accumulating evidence suggests a lack of efficacy with red blood cell (RBC), plasma, and platelet transfusion in the majority of critically ill patients. Evidence has also increasingly exposed previously under-recognized transfusion risks. The result is a growing number of recommendations for more restrictive RBC, plasma, and platelet transfusion strategies. An important exception to a more conservative transfusion practice occurs in patients with major trauma and life-threatening bleeding. Delaying RBCs, plasma and platelet component therapies in this population can promote the lethal triad of coagulopathy, acidosis, and hypothermia with a resultant increase in bleeding, greater transfusion requirements, and higher mortality. SUMMARY: Although we have made substantial progress in understanding the role of blood transfusion in the ICU, multiple important knowledge gaps persist. Future studies are needed to better define and characterize the impact of RBC storage, male-only plasma and platelet donor procurement procedures, and transfusion strategies in those requiring massive transfusion and with acute local or global tissue ischemia. PMID- 20543685 TI - Fluid status and fluid responsiveness. AB - PURPOSE OF REVIEW: Fluid boluses are a key element of hemodynamic resuscitation, but overuse of fluids also can be harmful. It is thus important to understand how fluids actually improve clinical problems and how one can predict fluid responsiveness. It is also important to understand potential limitations of fluid therapy. RECENT FINDINGS: Currently there is a lot of attention being paid to the assessment of fluid responsiveness, but there is a lack of studies evaluating indications for fluid treatment and the potential harm from excess fluid use. This review emphasizes the physiological factors that determine the response to fluids, the limitations of these responses, and the predictors of fluid responsiveness. A key principle is that fluid resuscitation improves clinical indicators by increasing cardiac output, and if the volume infusion does not increase cardiac output there will be no benefit. SUMMARY: Assessment of changes in cardiac output, either directly or indirectly, is a key component of managing fluid therapy. Avoiding harm with the use of fluids requires understanding what is physiologically possible. PMID- 20543686 TI - Secrets of the perioptome: new tools for a new concept. AB - PURPOSE OF REVIEW: The field of perioperative genomics is developing rapidly, and by now most practitioners are familiar with the idea that the host response to surgery and trauma is at least in part genetically determined. The precise way in which genetic variation affects outcomes after injury and surgical treatment is not known however. This review considers recent advances in thinking in the domain of perioperative genomics. RECENT FINDINGS: Genome wide association studies (GWAS) have been conducted in tens of thousands of patients at enormous cost, using phenotypes of varying complexity and clarity. Despite this massive investment, we are still unable to explain a majority of the observed heritability of most complex traits, such as the response to surgery. Recently, attention has turned to deep resequencing of candidate genes, as a precursor to the era of the individual genome. SUMMARY: GWAS have not delivered the expected answers to the question 'how does our genome determine our response to illness and its treatment?' There is a new, postgenomic, era dawning, and perioperative scientists are now well positioned to further explore the perioptome--the space where the genome, the operating room, and the ICU intersect. PMID- 20543687 TI - Laparoscopic versus vaginal hysterectomy for benign pathology. AB - PURPOSE OF REVIEW: The following review is an attempt to clarify the current role of vaginal and laparoscopic approaches in case of hysterectomy for benign pathologies. RECENT FINDINGS: Recent researches establish that vaginal hysterectomy seems to be the gold standard in case of benign pathologies and should be performed in preference to abdominal hysterectomy wherever possible. When vaginal hysterectomy is not technically possible, laparoscopic hysterectomy is to be preferred to abdominal hysterectomy. No advantages of laparoscopic hysterectomy could be found over vaginal hysterectomy, in particular, because laparoscopic hysterectomy is associated with a higher rate of complications (especially bladder and ureteral injuries). Other authors, instead, show that laparoscopic hysterectomy permits a safe bilateral salpingo-oophorectomy (BSO), the treatment of additional pathologies at the time of surgery, a reduction of intraoperative bleeding, postoperative pelvic pain and length of stay compared with vaginal hysterectomy. Moreover, laparoscopic approach, in experienced hands, is not associated with any increase in major complication rate. SUMMARY: It's time to reduce abdominal hysterectomy in favour of mini-invasive approaches. To do so a suitable training and supervision are paramount before embarking on total laparoscopic hysterectomy (so that complications are minimized) or on vaginal hysterectomy (so to perform a planned BSO). It is also essential, particularly for total laparoscopic hysterectomy, to share the techniques used by different surgeons, the results and the complications concerning this approach. PMID- 20543688 TI - The outcomes of hysteroscopy in women with implantation failures after in-vitro fertilization: findings and effect on subsequent pregnancy rates. AB - PURPOSE OF REVIEW: To update information on the findings of hysteroscopy in women with implantation failures after in-vitro fertilization (IVF) as well as on the effect of the procedure on subsequent pregnancy rates. RECENT FINDINGS: Information from three review publications indicates that the incidence of abnormal hysteroscopic findings in women with repeated implantation failures (RIFs) varies between 25 and 50%, whereas by pooling data from randomized studies, hysteroscopy significantly increases the clinical pregnancy rate (CPR) on the subsequent IVF cycle (pooled RR = 1.57, 95% CI: 1.29-1.92, P < 0.00001). Two recent clinical articles reported that the incidence of abnormal hysteroscopic findings in RIF patients was approximately 37%: the one study reported no differences in CPR between RIF patients with abnormal versus normal hysteroscopy; the second study reported significantly increased CPR in RIF patients with abnormal or treated hysteroscopic findings compared to those with a normal hysteroscopy, as well as in RIF patients having a hysteroscopy compared to controls not having the procedure. SUMMARY: There is accumulated evidence that hysteroscopy is beneficial for women experiencing implantation failures after IVF. Not only the correction of hysteroscopic findings improves the pregnancy rates, at least when compared to controls not having a hysteroscopy, but also the procedure itself may have a positive prognostic value for achieving a subsequent pregnancy. PMID- 20543689 TI - The outcomes of repeat surgery for recurrent symptomatic endometriosis. AB - PURPOSE OF REVIEW: To evaluate the efficacy of second-line surgery in the management of recurrent endometriosis. RECENT FINDINGS: Long-term probability of pain recurrence after repeat conservative surgery for recurrent endometriosis varies between 20 and 40%. The association of presacral neurectomy to the treatment of endometriosis might be effective in reducing midline pain; however, no studies have evaluated this procedure among patients with recurrent disease. The medium-term outcome of hysterectomy for endometriosis-associated pain is quite satisfactory; nevertheless, probability of pain persistence after hysterectomy is 15% and risk of pain worsening 3-5%, with a six times higher risk of further surgery in patients with ovarian preservation as compared to ovarian removal. The conception rate among women undergoing repetitive surgery for recurrent endometriosis associated with infertility is 26%, whereas the overall crude pregnancy rate after a primary procedure is 41%. SUMMARY: Repeat conservative surgery for pelvic pain associated with recurrent endometriosis has the same efficacy and limitations as primary surgery. Conversely, after repeat conservative surgery for infertility, the pregnancy rate is almost half the rate obtained after primary surgery. More data are needed to define the best therapeutic option in women with recurrent endometriosis, in terms of pain relief, pregnancy rate and patient compliance. PMID- 20543690 TI - Molecular causes of hypogonadotropic hypogonadism. AB - PURPOSE OF REVIEW: What controls puberty remains largely unknown and current gene mutations account for only about one-third of the apparently genetic cases of idiopathic hypogonadotropic hypogonadism. Lately important developments have occurred in this field. RECENT FINDINGS: Substantial variation in clinical expression, from complete anosmia and hypogonadotropic hypogonadism to delayed puberty and normosmia, of the same Kallmann syndrome gene defects including in newer ones (FGF8 and CHD7) continues to be repeatedly observed. Digenic or oligogenic inheritance becomes another feature of Kallmann syndrome. Recent reports of mutations in TAC3 or TACR3 [encoding neurokinin B (NKB) and its receptor, NK3R, respectively] provided compelling evidence for the involvement of NKB signaling in puberty. This energized the field to understand the exact mechanism through which NKB signaling exerts its effects. With the important findings from these recent studies in association with the substantial data from kisspeptin studies in the last 6 years a sketch of GnRH pulse generator has emerged in which NKB signaling appears to play a key role. SUMMARY: Autozygosity mapping may continue helping identify the other genes including those upstream to the GnRH pulse generator in this complex and elusive developmental process. PMID- 20543691 TI - Primary ovarian insufficiency: autoimmune causes. AB - PURPOSE OF REVIEW: To review the pathogenesis of premature ovarian insufficiency due to steroid cell autoimmunity (SCA-POI). RECENT FINDINGS: Autoimmune oophoritis is characterized by a selective mononuclear cell infiltration into the theca layer of large, antral follicles, with earlier stage follicles consistently free of lymphocytic infiltration. SCA-POI is caused by the selective autoimmune destruction of theca cells with preservation of granulosa cells that produce low amounts of estradiol because of lack of substrates. Typically, serum concentrations of inhibins are increased in women with SCA-POI, as compared to both healthy fertile women and women with other forms of ovarian insufficiency. Normal serum antimullerian hormone (AMH) concentrations were detected in two thirds of women with recently diagnosed SCA-POI, which demonstrates that this form of ovarian insufficiency is associated with a preserved pool of functioning follicles. SUMMARY: The combined measurement of autoantibodies and markers of ovarian reserve (as inhibin B and AMH) may permit to identify women with POI due to steroid cell autoimmunity with a preserved proportion of primordial and primary follicles. In the future the development of techniques of in-vitro folliculogenesis may permit new treatment strategies for women with SCA-POI related infertility. PMID- 20543692 TI - Tests for ovarian reserve: reliability and utility. AB - PURPOSE OF REVIEW: This review discusses ovarian reserve tests for ovulation induction and their application in determining fertility capacity, and their current applications to assess risk of natural ovarian failure and to estimate ovarian function after cancer treatment. RECENT FINDINGS: The current arsenal of ovarian reserve tests comprises hormonal markers [basal follicle stimulating hormone, estradiol, inhibin-B, antimullerian hormone (AMH)] and ultrasonographic markers [ovarian volume, antral follicle counts (AFCs)]. These markers have limitations in terms of which test(s) should be used to reliably predict ovarian reserve with regard to accuracy, invasiveness, cost, convenience, and utility. Several studies have correlated sonographic AFCs with serum AMH levels for predicting the ovarian response to ovulation induction protocols during assisted reproduction treatments. SUMMARY: Serum AMH levels and AFC are reliable tests for predicting the ovarian response to ovulation induction. However, none of the currently employed tests of ovarian reserve can reliably predict pregnancy after assisted conception. Further, ovarian reserve tests cannot predict the onset of reproductive and hormonal menopause; thus, they should be used with caution for reproductive life-programming counseling. Moreover, there is no evidence to support the use of ovarian reserve tests to estimate the risk of ovarian sufficiency after cancer treatments. PMID- 20543693 TI - The role of technology in facial prosthetics. AB - PURPOSE OF REVIEW: Technology has the potential to transform the fabrication process of facial prosthetics. The purpose of this review is to highlight the pertinent technological advances in computerized shade selection, three dimensional digital photography, virtual surgical planning, surface scanning, and three-dimensional imaging to obtain the wax pattern. RECENT FINDINGS: There have been a few reported studies documenting the effect of computerized color formulations for facial prosthesis. The technology is still in its infancy and may serve as a tool to manage metamerism and to complement the subjective clinical assessment of the clinician. Three-dimensional photography, surface scanning, and three-dimensional imaging have been used successfully in the fabrication of facial prostheses. Software programs which allow the clinician to plan virtually implant placement allows the treatment planning process to be much more prosthetically driven. Even with the technological advances, it is perhaps most important to remember the basics of proper preparation of the defect to accept the prosthesis. SUMMARY: The incorporation of technology into the fabrication process of facial prostheses can potentially transform the treatment process from a time-consuming artistically driven process to being a reconstructive biotechnology process. PMID- 20543694 TI - Current concepts in the management of the aging forehead in facial plastic surgery. AB - PURPOSE OF REVIEW: This article reviews the significant recent literature on the constantly evolving approach to surgical rejuvenation of the forehead and brow. RECENT FINDINGS: Recent literature describes a variety of modifications to traditional endoscopic approaches, particularly regarding new permanent and temporary fixation techniques. There is continued effort to deepen our understanding of upper facial anatomy and its relationship to the aging process. As interest and research in this area continue to grow, improved quantification of surgical results becomes important. SUMMARY: There has been significant development and refinement of endoscopic approaches to foreheadplasty. Nonetheless, debate regarding the durability, quality of results, and complications of endoscopic versus open approaches continues. Ultimately, optimal results may be achieved through a variety of surgical techniques, but require a thorough understanding of the anatomic basis of aging, attention to detail, and adequate brow fixation. PMID- 20543695 TI - The psychological aspects of rhinoplasty. AB - PURPOSE OF REVIEW: Literature on the psychological aspects of rhinoplasty is sparse compared with publications on methods and instrumentation. Understanding the psychological aspects of rhinoplasty and, more importantly, recognizing the patient who may have an unfavorable postoperative course regardless of the objective outcome is of fundamental importance to the surgeon. RECENT FINDINGS: Several profiles of patients with a high risk of postoperative dissatisfaction have been described and the important role of body dysmorphic disorder and its treatment has been stressed. Still, these criteria can be insufficient when facing the individual patient, as reliable screening instruments for clinical practice have not been developed and the question when not to operate is subject to controversy. The role of computer imaging as a safeguard in preoperative counseling has been highlighted. SUMMARY: The surgeon must rely on instinct and experience to avoid overlooking any signs of psychological imbalance in the patient that may herald adversity. Archetypes described in the literature should be recognized and computer imaging should be used during the preoperative consultation. PMID- 20543696 TI - A review of dermal fillers in facial plastic surgery. AB - PURPOSE OF REVIEW: Over the last decade, injectable soft tissue fillers have become an integral part of facial plastic surgery practice. The vast choice of new products being brought to the market, improved safety profile, lower costs in the current economic climate and high street availability mean that demand for nonsurgical rejuvenation treatments are increasing at an exponential rate and are no longer the preserve of the affluent. RECENT FINDINGS: Recent published work has focused on the addition of local anaesthetic into fillers, widening their indications, reporting longer term results, avoidance of complications, regulation and future directions. SUMMARY IMPLICATIONS: The refinement of techniques to restore facial volume with dermal fillers, and widely available botulinum (BTX) injections to treat dynamic facial rhytids, fuelled by widespread mainstream advertising, has led to a surge in demand for nonsurgical rejuvenation procedures. An increasingly well informed and discerning patient population now seek better value procedures that require minimal downtime and have instant results. A thorough knowledge of the dermal fillers available for soft tissue facial augmentation is therefore essential to any clinician involved in facial plastic surgery. PMID- 20543697 TI - Reconstruction of the midface and maxilla. AB - PURPOSE OF REVIEW: To review all pertinent topics related to midface and maxillary reconstruction including current classification schemes and reconstructive techniques. RECENT FINDINGS: The maxilla represents the functional and aesthetic cornerstone of the midface region. Defects in this area represent a unique challenge to the reconstructive surgeon as the complex anatomy of this area can be challenging to repair and reconstruct. The current indications as well as advantages and disadvantages of different reconstructive approaches are reviewed here in order to provide reconstructive surgeons with optimal information for surgical and clinical decision making in this challenging patient population. Recent developments in midface reconstruction options including near total facial transplant as well as tissue engineering techniques are also reviewed. SUMMARY: Multiple reconstructive pathways can be followed in restoring maxillary and midface defects. The surgeon and rest of the reconstructive team must make individualized decisions based on the nature of the defect as well as the specific needs and concerns of the patient when selecting the optimal reconstructive approach for each patient. PMID- 20543698 TI - Advances in temporomandibular joint reconstruction. AB - PURPOSE OF REVIEW: This article reviews the reconstructive techniques commonly employed in temporomandibular joint (TMJ) surgery with an emphasis on recent developments in the field. RECENT FINDINGS: TMJ reconstruction remains one of the most challenging tasks faced by surgeons who operate in the head and neck, with a variety of autogenous and alloplastic techniques available. The role of alloplastic TMJ reconstruction needs to be reassessed in light of recent literature showing excellent long-term functional outcomes, which reflect advances in prosthetic materials and surgical technique. More recently, transport distraction osteogenesis has been applied to reconstruction of the ramus-condyle unit with promising early results suggesting it may ultimately become the standard of care in selected patients providing a cost-effective approach with low morbidity and excellent functional outcomes. SUMMARY: The myriad of available TMJ reconstructive options reflect the fact that it remains an evolving field. Although no gold standard currently exists, the various techniques each have their own proponents and potential advantages and drawbacks. Ultimately, the reconstructive surgeon must consider the ablative defect and underlying pathology, the needs of the individual patient, the resources of the providing institution and the capabilities of the surgical team. PMID- 20543699 TI - Anterior skull base reconstruction: a review of current techniques. AB - PURPOSE OF REVIEW: The purpose of this review is to discuss current reconstructive options in anterior skull base reconstruction. RECENT FINDINGS: Free tissue transfer has superseded regional myocutaneous flaps in the reconstruction of large anterior skull base defects. Local flaps remain the mainstay for smaller defects. A host of nonautologous biomaterials are also used in the setting of small-to-moderate-sized defects requiring rigid support. They should not be used in the setting of radiation owing to the high extrusion rate. Lastly, the advent of endoscopic tumor resection has introduced a variety of local flaps amenable to endoscopic reconstruction. SUMMARY: The last decade has experienced a growth in anterior skull base reconstructive options owing to improvements in microvascular technique, endoscopic equipment, image guidance, and biomaterials. As a result, the choices in reconstructive technique have expanded, allowing for more radical tumor extirpations. PMID- 20543700 TI - Microvascular reconstruction in the vessel-depleted neck. AB - PURPOSE OF REVIEW: Microvascular reconstruction for head and neck cancers has improved both cosmesis and functionality of patients undergoing treatment. Many patients have had prior surgery (neck dissection), radiation and/or chemotherapy as part of their management. When microvascular reconstruction is required after previous treatment, finding appropriate vessels for anastomosis can be difficult. In this paper we explore the options for microvascular reconstruction in the vessel-depleted neck. RECENT FINDINGS: Arterial options that exist when the neck is depleted of vessels include the superficial temporal, transverse cervical, thoracoacromial, and the internal mammary artery. Venous options include the cephalic vein and vein grafts. SUMMARY: The external carotid artery and the internal jugular vein are the most commonly utilized vessels in microvascular reconstruction when available. However, prior chemotherapy and/or radiation can cause significant scarring and damage to these vessels. Also in patients who have had previous surgery, these vessels can be resected or altered in a way that they are deemed unusable. In these situations several vascular options exist outside the neck. PMID- 20543701 TI - Cycling and sports, but not walking, are associated with 10-year cardiovascular disease incidence: the MORGEN Study. AB - BACKGROUND: Physical activity is inversely related to cardiovascular diseases. However, the type of activities that contribute most to these beneficial effects remain unclear. For this reason, we investigated self-reported leisure time physical activities in relation to fatal/nonfatal cardiovascular disease incidence. DESIGN: The Dutch Monitoring Project on Risk Factors for Chronic Diseases Study, carried out between 1993 and 1997, is a prospective cohort study of over 23000 men and women aged 20-65 years from the general Dutch population. METHODS: From 1994 till 1997 physical activity was assessed with a questionnaire in 7451 men and 8991 women who were followed for an average of 9.8 years. Cox proportional hazards models were used adjusting for age, sex, other physical activities, smoking, alcohol consumption, and educational level. RESULTS: Almost the entire study population (97%) was engaged in walking, about 75% in regular cycling, and about half the population in sports or gardening. Cycling [hazard ratio (HR): 0.82, 95% confidence interval (CI): 0.71-0.95] and sports (HR: 0.74, 95% CI: 0.64-0.87) were both inversely related to cardiovascular disease incidence, whereas walking and gardening were not. For sports (P < 0.001), but not for cycling (P = 0.06), we found a dose - response relationship with respect to cardiovascular disease incidence. Engaging in both cycling and sports resulted in an even greater risk reduction (HR: 0.64, 95% CI: 0.52-0.77). CONCLUSION: In this relatively active population, types of activities of at least moderate intensity, such as cycling and sports were associated with lower CVD incidence, whereas activities of lower intensity, such as walking and gardening, were not. PMID- 20543703 TI - Variations in hemoglobin before colorectal cancer diagnosis. AB - We have conducted the present case-control study to examine whether long-term variations in blood hemoglobin (Hb) levels within the normal range could detect subtle gastrointestinal bleeding in the early development of colorectal cancer (CRC). A total of 1074 CRC cases aged 45-75 years that have been diagnosed with CRC and had normal Hb levels were frequency matched for age and sex with cancer free individuals at a ratio of 10 controls per case. Our retrospective analysis indicates that starting from 4 years prior to cancer diagnosis, a progressive significant (P<0.001) decrement in Hb levels (0.28 g/dl per 6 months) was found among cases but not among controls. CRC patients were characterized in an on going, long-term, logarithmic decrement in Hb levels. Such small changes within the normal Hb range could be missed by health providers, but automatically detected by computerized alert algorithms.. PMID- 20543704 TI - Visual acuity and ocular aberrations with different rigid gas permeable lens fittings in keratoconus. AB - OBJECTIVES: The aim of this case report is to investigate the effect of rigid gas permeable (RGP) lens fitting on visual acuity and ocular higher-order aberrations by systematically applying RGP lenses with different back optic zone radii (BOZR) to a keratoconic eye. METHODS: Eight Menicon-EX RGP lenses (Menicon Co., Nagoya, Japan), which ranged from a BOZR of 7.40 to 8.10 mm in 0.10-mm steps, were fitted to a moderate keratoconic eye. All the trial lenses fitted had a total diameter of 9.60 mm, centre thickness of 0.15 mm, and a back vertex power of -3.00 diopter sphere. Measurements of the higher-order aberrations were made with the RGP lenses in place using a Shack-Hartmann aberrometer (IRX-3; Imagine Eyes, Paris, France). Visual acuities with the lenses were recorded using a high-contrast Early Treatment Diabetic Retinopathy Study letter chart at a distance of 4 m. RESULTS: As the lens BOZR value changed from 7.40 to 8.10 mm, the vertical coma component was found to reduce from +0.34 to +0.21 microm; third-order root mean square error also reduced from +0.34 to +0.23 microm and total higher-order root mean square aberrations decreased from +0.35 to +0.23 microm. More over, changes in the lens BOZR from 7.40 to 8.10 mm led to a substantial change in best corrected LogMAR acuity from +0.58 to -0.30 log units. CONCLUSIONS: The results showed that a flatter RGP lens fit lead to a reduction in higher-order aberrations and improvement in visual acuity in this moderate keratoconic patient. Further investigations into the changes in aberrations with different RGP lens fittings and BOZR values in keratoconic eyes will help to improve our current understanding of how contact lens fitting impacts on optical performance. PMID- 20543705 TI - Comfort-enhanced daily disposable contact lens reduces symptoms among weekly/monthly wear patients. AB - OBJECTIVES: The primary objective of this trial was to explore the extent to which common contact lens-related symptoms may be improved among symptomatic daily wear contact lens wearers who habitually replaced their lenses at intervals of 1 to 4 weeks when fitted with DAILIES AquaComfort Plus for daily disposable, daily wear. Primary variables were frequency and severity of tired eyes, irritated eyes, lens awareness, blurred vision, redness, discomfort, deposits, and dryness. METHODS: Eight sites, investigators enrolled 83 subjects who reported two or more of the symptoms with frequency of often or always. A sample size estimate required 60 subjects for 80% power, two-sided alpha = 0.05. Subjects were dispensed for 4 weeks of bilateral lens wear. Follow-up visits were at 2 and 4 weeks; data were collected by telephone surveys at 1 and 3 weeks. RESULTS: Eighty-one subjects completed the trial. Statistically significant improvements in symptom frequency were found for the symptoms of tired eyes (P<0.001), irritated eyes (P<0.001), blurred vision (P<0.001), redness (P<0.001), discomfort (P=0.024), deposits/lens needs cleaning (P<0.001), and dryness (P<0.001). Statistically significant improvements in symptom severity were found for tired eyes (P<0.001), irritated eyes (P<0.001), blurred vision (P<0.001), redness (P<0.001), discomfort (P=0.037), deposits/lens needs cleaning (P<0.001), and dryness (P<0.001). Biomicroscopy signs of limbal redness, bulbar redness, and conjunctival staining showed statistically significant improvements at 2 weeks (P=0.02, 0.01, and 0.035) and 4 weeks (P< or =0.001, 0.012, and 0.008). CONCLUSIONS: A range of common symptoms can be reduced and biomicroscopy signs can be improved with a comfort-enhanced daily disposable, daily wear lens, thus providing benefits that patients can experience and eye care practitioners can appreciate. PMID- 20543706 TI - Eighteen-month follow-up of HIV-1-infected mothers and their children enrolled in the Kesho Bora study observational cohorts. AB - OBJECTIVE: To assess the effectiveness and safety of antiretrovirals (ARVs) used for treatment or prophylaxis in a breastfeeding population of HIV-1-infected women (Burkina-Faso, Kenya, South Africa). METHODS: HIV-1-infected pregnant women with <200 CD4 cells per cubic millimeter or with World Health Organization stage 4 disease (cohort A) and asymptomatic women with >500 CD4 cells per cubic millimeter (cohort B) were enrolled into 2 prospective cohorts. Women with 200 500 CD4 cells per cubic millimeter were enrolled in a parallel randomized trial. Women in cohort A initiated antiretroviral therapy. Women in cohort B received zidovudine from 34 to 36 weeks gestation until delivery, with single-dose nevirapine in labor (cohort B). All children received single-dose nevirapine. RESULTS: Of 248 women enrolled, 111 (cohort A) and 125 (cohort B) infants alive at 24 hours after birth were analyzed. Sixty-nine percent and 42% of women had undetectable viral load at delivery, respectively. Ten children in each cohort died. The 18-month cumulative incidences of HIV-1 infection were 7.5% (95% confidence interval: 3.8% to 14.5%) (cohort A) and 5.8% (2.8% to 11.8%) (cohort B). Sixty-one percent (cohort A) and 78% (cohort B) were breastfed for a median duration of 20 weeks. Four children in cohort A and only 1 in cohort B became HIV 1 infected after 6 weeks of age. CONCLUSIONS: Antiretroviral therapy initiated a median of 7 weeks before delivery in women with advanced HIV-1 disease was associated with a significant residual risk of HIV-1 transmission due to insufficient decrease in viral load by the time of delivery. Among women with >500 CD4 cells per cubic millimeter, the risk of breast-milk transmission was very low despite lack of postnatal prophylaxis. PMID- 20543707 TI - Epileptic patients who survived sudden cardiac death have increased risk of recurrent arrhythmias and death. AB - BACKGROUND: Cardiac arrhythmogenesis and cryptogenic epilepsy can be due to ion channel dysfunction and may coexist in the same patient. Sudden unexplained death in epilepsy (SUDEP) is a known entity with unknown cause, with the possibility of ventricular tachyarrhythmias being one of the causes. However, no prior study has investigated epileptic survivors of sudden cardiac death (SCD), recurrent life threatening ventricular tachyarrhythmia (LTVA) and other outcomes in this patient population. METHODS: The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n = 1016) was a multicenter trial comparing a cardioverter-defibrillator device (ICD) (n = 507) and anti-arrhythmic drugs (AADs) (n = 499) for secondary prevention of LTVAs. Mean follow-up duration was 916 +/- 471 days per patient. Patients with a history of epilepsy (n = 6) in the ICD arm were included in this analysis. End points were recurrence of LTVA, cardiac death and all-cause mortality. RESULTS: History of epilepsy (n = 6) was a significant predictor of recurrent LTVA [hazard ratio 3.53, 95% confidence interval (CI) 1.30-9.56], cardiac death (hazard ratio 4.14, 95% CI 1.30-13.14) and all-cause mortality (hazard ratio 3.82, 95% CI 1.40-10.48) in the ICD arm (n = 498). This relationship remained unchanged on multivariate analysis after controlling for baseline clinical differences. CONCLUSION: This is the first study to investigate the effect of epilepsy on secondary prevention of LTVA. Epileptic survivors of SCD are at significantly greater risk of recurrent arrhythmias and death as compared to other survivors of recurrent LTVA. Role of coexisting channelopathies in both epilepsy and arrhythmogenesis may explain SUDEP and requires further investigation. PMID- 20543708 TI - The fragmented QRS: does it really indicate a ventricular abnormality? AB - OBJECTIVE: Notching of R and S waves in the QRS complex can result from myocardial infarction. As defined in recent studies, the 'fragmented QRS' (fQRS) showed high sensitivity and specificity for the presence of myocardial scar as imaged by myocardial perfusion scanning in participants studied for ischemic heart disease. The present study attempted to determine the significance of the fQRS in electrocardiograms of patients who had myocardial imaging for a variety of reasons by a variety of methods. METHODS: From a series of electrocardiograms, 218 patients were found with fQRS without abnormal Q waves, but with myocardial imaging by myocardial perfusion scanning or echocardiography. Another 214 patients without fQRS but having had one of these imaging methods were also studied. An additional 106 patients with or without fQRS were selected for having undergone cardiac magnetic resonance imaging with studies for late gadolinium enhancement. RESULTS: Myocardial perfusion scanning, echocardiography, or magnetic resonance imaging revealed a ventricular myocardial abnormality in 52.6% of patients with fQRS and in 29.7% without fQRS (P < 0.0001). Ischemic heart disease was present in only 27% of patients showing fQRS. An electrocardiographic point score system was devised that helped to differentiate tracings having an fQRS with a ventricular abnormality from those without the latter. CONCLUSION: The utility of fQRS varies with the incidence of ventricular disease in the population studied. This electrocardiographic sign is commonly associated with ventricular abnormalities with and without demonstrable myocardial scar, but also occurs in the absence of clinical heart disease. PMID- 20543709 TI - Kounis syndrome presenting with cardiogenic shock. PMID- 20543710 TI - Apolipoprotein E genotypes in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. AB - PURPOSE: Pseudoexfoliation (PEX) syndrome, an age-related, systemic, elastic microfibrillopathy, is characterized by fibrillar-granular deposits in the anterior segment of the eye. Although not representing a true amyloidosis, PEX syndrome shares some features with amyloid disorders, such as Alzheimer disease. It has been shown that amyloid-associated proteins also occur in association with PEX fibrils. Apolipoprotein E (Apo-E) is directly involved in these amyloid deposition and fibrils formation. The epsilon4 allele of APOE gene was shown to be associated both with an increased risk for coronary heart disease and late onset Alzheimer disease. In this study, we therefore investigated whether APOE alleles are associated with PEX syndrome and/or PEX glaucoma (PEXG) in 2 large cohorts of German and Italian origin. METHODS: The 3 common APOE alleles epsilon2, epsilon3, and epsilon4 were genotyped in 661 unrelated patients (459 PEXG and 202 PEX patients) and 342 healthy individuals of German origin and furthermore in 209 unrelated patients (133 PEXG and 76 PEX patients) and 190 healthy individuals of Italian origin using TaqMan assays for allelic discrimination. A genetic association study was then performed. RESULTS: The epsilon3 allele was found to be the most common in both populations (80% to 83%), whereas the epsilon2 allele was the rarest (6% to 9%). No significant differences in allele and genotype frequencies between both groups were observed in either population. CONCLUSION: Our data show that APOE genotypes are not associated with PEX and PEXG in either Germans or Italians. PMID- 20543711 TI - Neuropeptide Y receptor Y2 gene polymorphism interacts with plasma neuropeptide Y levels in predicting left ventricular hypertrophy in dialysis patients. AB - BACKGROUND: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors involved in cardiovascular remodelling and angiogenesis. Plasma levels of NPY are increased in patients with end-stage renal disease (ESRD) and are independently related to left ventricular hypertrophy (LVH) and incident cardiovascular events in these patients. OBJECTIVE: To investigate the relationship between NPY receptor Y2 gene polymorphism and left ventricular mass index (LVMI) as well as the interaction between this polymorphism and plasma NPY in determining LVH in 189 ESRD patients. RESULTS: LVMI was significantly higher (+12%, P = 0.03) in patients carrying the C allele than in those without C allele and was linearly associated with plasma NPY (P = 0.01). Interaction analysis showed a significant NPY-LVMI relationship in patients with the C allele, both at univariate (r = 0.27, P = 0.001) and multivariate (r = 0.21, P = 0.01) analyses, whereas no such relationship existed in patients without this allele. In fully adjusted analyses, a 10 pmol/l increase in plasma NPY entailed a 4.9 g/m increase in LVMI in patients with C allele, whereas the same change in NPY levels did not modify the NPY-LVMI link in patients without such allele (P = 0.009). CONCLUSION: NPY receptor Y2 polymorphism is independently associated with LVMI and interacts with plasma levels of NPY in explaining the variability of LVH in ESRD. These results offer a genetic basis to the hypothesis that NPY is causally implicated in the pathogenetic pathway leading to LVH in ESRD patients. PMID- 20543712 TI - Direct renin inhibition improved insulin resistance and adipose tissue dysfunction in type 2 diabetic KK-A(y) mice. AB - OBJECTIVE: The renin-angiotensin system affects insulin sensitivity mainly through the angiotensin II type 1 receptor. In this study, the effects of renin inhibition on insulin resistance and adipose tissue dysfunction were explored in type 2 diabetic KK-A(y) mice. METHODS AND RESULTS: Male KK-A mice were treated with a direct renin inhibitor, aliskiren, administered subcutaneously at a dose of 50 mg/kg per day for 14 days using an osmotic minipump. This dose of aliskiren strongly inhibited plasma renin activity and lowered blood pressure about 17% in KK-A(y) mice. Aliskiren decreased body weight and plasma glucose level, and increased plasma insulin level in a fed condition. Aliskiren also lowered the plasma levels of cholesterol, fatty acids and triglycerides. In the oral glucose tolerant test, the plasma glucose elevation after glucose load was reduced by aliskiren, without a significant change in insulin level. Insulin tolerance test showed that aliskiren enhanced insulin's effect on plasma glucose. Aliskiren also reduced the epididymal adipose tissue mass by 25% and retroperitoneal adipose tissue mass by 35%. In adipose tissue, expression of the insulin receptor was not changed by aliskiren; however, expression of insulin receptor substrate-1, glucose transporter type 4, adiponectin, peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer-binding proteindelta was increased by aliskiren. Moreover, NADPH oxidase activity and expression of inflammatory factors were reduced in adipose tissue. Aliskiren increased the pancreatic beta cell area in KK-A(y) mice. CONCLUSION: These results suggest that renin inhibition by aliskiren improved insulin resistance and adipose tissue dysfunction in type 2 diabetic mice through an increase in insulin sensitivity, insulin secretion and adipocyte differentiation, and a reduction of oxidative stress. PMID- 20543713 TI - Time to re-appraise the role of alpha-1 adrenoceptor antagonists in the management of hypertension? AB - The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects. PMID- 20543714 TI - A new approach to assessing the structural total peripheral resistance amplifier in renal (Page) hypertension in conscious rabbits. AB - BACKGROUND AND AIM: Structural changes in the large resistance vessels in hypertension amplify resistance responses in vitro, but their role in vivo has been controversial. To resolve this matter, we re-examined earlier data in Page hypertension. METHODS: Total peripheral resistance (TPR) and total peripheral conductance (TPC) responsiveness were compared in hypertensive and normotensive rabbits, 5 weeks after bilateral renal cellophane wrapping or sham operation. The rabbits were studied with effectors intact; during ganglionic blockade; during neurohumoral blockade (NHB). For each condition extended scaled dose (ScD)-TPC and TPR curves were derived from individual dose-response curves to two constrictors and two dilators. RESULTS: The ScD-response curves had two major nonlinearities: at high constrictor doses, due to functional (reversible) rarefaction (reduction in microcirculatory density); at high dilator doses, due to impaired autoregulation. The amplifier is best assessed during NHB over the intervening ScD range, by determining the TPR and TPC ratios from hypertensive and normotensive rabbits. Over this range the hypertensive: normotensive (H: N) ratio averaged 1.88 +/- 0.03 TPR units and was the same for constrictor and dilator responses, suggesting a structural basis; the resting H: N TPR ratio was also closely similar. At higher ScDs functional rarefaction developed initially at a greater rate in normotensive than in hypertensive rabbits. We conjecture that this was because some permanent rarefaction had already developed in hypertensive rabbits since the onset of hypertension. CONCLUSION: The systemic structural TPR amplifier is haemodynamically important in vivo and contributes to hypertension. PMID- 20543716 TI - Reduced discontinuation of antihypertensive treatment by two-drug combination as first step. Evidence from daily life practice. AB - OBJECTIVES: To measure persistence with antihypertensive drug therapy in patients initiating treatment with mono or combination therapy. METHODS: Data analysis was based on two cohorts of patients, that is, a cohort derived from the registration of drug prescriptions in all residents of the Lombardy region receiving Public Health Service and a cohort of patients followed by general practitioners throughout the Italian territory. Data were limited to patients aged 40-80 years who received their first antihypertensive drug prescription (n = 433,680 and 41,199, respectively) in whom persistency of treatment was examined over 9 months. A proportional hazards model was fitted to estimate the association between the pattern of initial antihypertensive drug therapy and risk of treatment discontinuation. Data were adjusted for available potential confounders. RESULTS: Taking patients starting with diuretic monotherapy as reference, the adjusted risk of treatment discontinuation was progressively lower in patients starting with monotherapy other than a diuretic, a two-drug combination, including a diuretic and a two-drug combination without a diuretic. No significant difference in the risk of discontinuation was seen between extemporaneous and fixed dose combinations, including a diuretic, that is, the only combination reimbursable by Public Health Service and, thus, available in the database. Data were similar for the two cohorts. CONCLUSION: Initiating treatment with a combination of two drugs is associated with a reduced risk of treatment discontinuation. PMID- 20543715 TI - Ca(2+) channel blocker benidipine promotes coronary angiogenesis and reduces both left-ventricular diastolic stiffness and mortality in hypertensive rats. AB - BACKGROUND: The beneficial cardiac effects of some Ca(2+) channel blockers have been attributed to blood pressure reduction, but these pleiotropic effects require further investigation. We compared the effects of benidipine, which has beneficial cardiac effects, and nitrendipine, which does not, in an animal model of hypertensive diastolic heart failure (DHF). METHODS AND RESULTS: Male Dahl salt-sensitive rats were fed a high-salt diet from age 7 weeks to induce hypertension and were either vehicle or orally administered benidipine (3 mg/kg daily) or nitrendipine (10 mg/kg daily) from age 10 to 18 weeks. Control rats were maintained on a low-salt diet. In vehicle-treated rats, left-ventricular (LV) fractional shortening was preserved but LV end-diastolic pressure was increased, indicative of DHF. Benidipine and nitrendipine had similar antihypertensive effects and reduced both LV weight and cardiomyocyte hypertrophy. Benidipine reduced LV diastolic stiffness and mortality to a greater extent than did nitrendipine. Benidipine, but not nitrendipine, also reduced lung weight. The extent of interstitial fibrosis and the abundance of mRNAs for prohypertrophic, profibrotic, or proinflammatory genes in the left ventricle were reduced by benidipine and nitrendipine. Benidipine, but not nitrendipine, increased capillary density and restored the expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and endothelial nitric oxide synthase in the left ventricle. CONCLUSIONS: Benidipine reduced LV diastolic stiffness and increased survival, effects likely attributable predominantly to promotion of coronary angiogenesis rather than to attenuation of interstitial fibrosis. Benidipine may thus be more effective than purely L-type Ca(2+) channel blockers in preventing hypertensive DHF. PMID- 20543717 TI - Gastric xanthelasma. PMID- 20543702 TI - Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. AB - AIMS: HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. METHODS AND RESULTS: Prospective multinational cohort study. The data set included 22,625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642-0.820) for myocardial infarction, 0.776 (0.670-0.818) for coronary heart disease and 0.769 (0.695 0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. CONCLUSION: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models. PMID- 20543718 TI - Molecular characterization of intestinal microbiota in infants fed with soymilk. AB - BACKGROUND: : Intestinal bacteria play an important role in the postnatal development of the immune system. The composition of gut microbiota is profoundly influenced by the infant's diet, but there is little information about the effects of soymilk on the composition of intestinal biota. The present study was designed to investigate the intestinal ecosystem of the newborn in relation to the consumption of soymilk. MATERIALS AND METHODS: : Twelve infants had their bovine milk-based formula replaced with soymilk. The intestinal microbial composition of the infants was investigated before and after the change by means of polymerase chain reaction-denaturing gradient gel electrophoresis. In addition, species-specific amplification of 10 Bifidobacterium species, 3 Ruminococcus species, and the Bacteroides group was performed. RESULTS: : Denaturing gradient gel electrophoresis analysis revealed bacterial profiles characterized by numerous bands typical for each subject. No variations were detected by species-specific polymerase chain reaction. CONCLUSIONS: : The data demonstrate that soymilk feeding does not alter the intestinal flora of infants and decrease the intestinal bifidobacterial population. PMID- 20543720 TI - Biliary atresia in Canada: the effect of centre caseload experience on outcome. AB - OBJECTIVES: : Biliary atresia (BA) is a leading cause of end-stage paediatric liver disease. Standard BA treatment is sequential surgery with an initial Kasai procedure (KP) followed by liver transplant (LT) for patients who progress to liver failure. A key determinant for the post-KP patient survival with their native liver is patient age at KP (older age, poorer outcome). Recently, European studies have reported that caseload experience influences prognosis with centres managing <5 cases per year (UK) or <2 cases per year (France) having worse survival. Our study investigates the effect of caseload experience on outcomes of Canadian patients with BA. PATIENTS AND METHODS: : A national database of cases with BA, born from 1992 to 2002, was examined. Patients were grouped according to treatment centre size (A: on average <1 case per year; B: 1 to 3 cases per year; and C: >3 cases per year). Overall patient, post-KP native liver, and LT survivals were compared between centres. Outcome parameters were reevaluated for patients grouped by the largest Canadian centre (>5 cases per year) and all other centres (<5 cases per year). RESULTS: : Two-hundred thirty patients were identified among 6 group A, 4 group B, and 2 group C centres. The overall median age at KP was 64 days. There were no significant differences in patient, post-KP native liver, or LT survivals between the sized centres and even the largest centre, with the overall 4-year post-KP native liver survival being 39%. CONCLUSIONS: : Caseload experience does not importantly affect the outcomes for Canadian children with BA. Although outcomes in Canada are comparable to those elsewhere, national policies directed towards timely referral and earlier age at KP rather than centralisation of care are needed. PMID- 20543719 TI - Effect of Bifidobacterium animalis subsp lactis supplementation in preterm infants: a systematic review of randomized controlled trials. AB - OBJECTIVE: To systematically evaluate and update evidence on the efficacy and safety of Bifidobacterium animalis subsp lactis CNCM I-3446 supplementation in preterm infants. MATERIALS AND METHODS: The Cochrane Library and MEDLINE databases and major pediatric conference proceedings were searched in December 2008 for randomized controlled trials (RCTs). The company that manufactures B lactis was contacted for unpublished data. The review was restricted to RCTs performed in preterm infants <37 weeks of gestation and/or with a birth weight <2500 g. RESULTS: Four RCTs involving 324 infants met the inclusion criteria. Compared with controls, B lactis supplementation has the potential to increase fecal bifidobacteria counts and to reduce Enterobacteriaceae and Clostridium spp counts. It also can reduce stool pH and fecal calprotectin concentrations, increase fecal immunoglobulin A and short-chain fatty acid concentrations, and decrease intestinal permeability. Compared with controls, B lactis supplementation had no effect on the risk of necrotizing enterocolitis stage > or = 2 (3 RCTs, n = 293, risk ratio [RR] 0.53, 95% CI 0.16-1.83), risk of sepsis (2 RCTs, 397 cultures, RR 0.6, 95% CI 0.07-5.2), and use of antibiotics (2 RCTs, n = 255, RR 0.67, 95% CI 0.28-1.62). The power of these studies, however, does not allow for a definitive statement regarding a reduced risk of necrotizing enterocolitis. B lactis supplementation did have some effects on anthropometric parameters. No adverse events associated with B lactis supplementation were reported. CONCLUSIONS: Evidence regarding the potential beneficial effects of B lactis supplementation in preterm infants is encouraging. Further studies to assess clinically relevant outcomes are needed. PMID- 20543721 TI - Hepatorenal syndrome: diagnosis and effect of terlipressin therapy in 4 pediatric patients. PMID- 20543722 TI - Hermansky-Pudlak syndrome: severe colitis and good response to infliximab. PMID- 20543724 TI - Predictive value of bile duct dimensions measured by ultrasound in neonates presenting with cholestasis. AB - OBJECTIVES: : The significance of extrahepatic bile duct dilatation on ultrasound examination in jaundiced infants is often uncertain. We wished to clarify the diagnostic and prognostic significance of the present finding in neonatal conjugated hyperbilirubinaemia. PATIENTS AND METHODS: : We retrospectively enrolled all of the infants younger than 3 months with extrahepatic biliary dilatation > or =1.2 mm (nonfasting ultrasound) who presented during the study period. We reviewed clinical, radiological, and laboratory data to determine mode of presentation, diagnosis, interventions, and long-term outcome. RESULTS: Seventy-six infants (41 male) were identified, all of whom were referred with conjugated hyperbilirubinaemia. Median gestational age was 39 weeks (range 24-42 weeks). Inspissated bile was the most common diagnostic category, whereas congenital choledochal malformation was the diagnosis made in 13% infants. Dilatation was an incidental finding in 9% of the infants. Seventeen percent of infants had required either surgical or radiological intervention by the time of follow-up. Overall, 41% infants had spontaneous resolution of bile duct dilatation, including 8% who had "grown into" an unchanged duct size rather than involution of dilatation. The median size of bile duct at presentation for those who required intervention was 4.7 versus 2 mm for the remainder (P < 0.001). Of those who resolved spontaneously, the median size of duct at presentation was 1.8 mm. CONCLUSIONS: : Bile duct dilatation <3 mm (nonfasting ultrasound) with neonatal cholestasis is unlikely to be of significance whereas >4 mm is likely to be associated with choledochal malformation or need for intervention. The intermediate group is likely to be associated with inspissated bile syndrome following resolution of which innocent biliary dilatation may persist. PMID- 20543723 TI - Epidemiology of uninvestigated gastrointestinal symptoms in adolescents: a population-based study applying the Rome II questionnaire. AB - OBJECTIVES: : Gastrointestinal (GI) disorders in early life contribute to a lower quality of life and more persistent GI symptoms during the rest of life. Epidemiologic data on adolescence GI disorders are scarce. We aimed to perform a population-based study to assess the prevalence of GI symptoms in adolescents and their relation to sex, age, and socioeconomic status. MATERIALS AND METHODS: : A multistage random sample of Tehran middle and high school students (ages 14-19 years) was selected. A validated Persian version of the Rome II questionnaire was used to measure the frequency of different GI disorders as well as demographic socioeconomic variables. RESULTS: : A total of 1436 participants were enrolled in the study, 736 (51.3%) of whom were men. Mean (SD) age was 16.9 (1.8) years. The frequency of at least 1 GI symptom was 32.4%. The 4 most prevalent GI symptoms were bloating (16.9%), heartburn (4.9%), incontinence (4.3%), and irritable bowel syndrome (4.1%). Bloating, irritable bowel syndrome, and proctalgia fugax were significantly more common in girls (P < 0.05). Incontinence was significantly more prevalent in lower socioeconomic status levels (P = 0.01). In logistic regression, age was a risk factor for abdominal bloating and dysphagea and a protective factor for incontinence. CONCLUSIONS: : Our study indicates that GI symptoms are common among adolescents. Girls are more prone to these disorders. Special psychological and medical interventions are necessary for high-risk groups. PMID- 20543725 TI - Development of Candida albicans colitis in a child undergoing steroid therapy for ulcerative colitis. PMID- 20543726 TI - Eosinophilic granuloma of the capital femoral epiphysis. AB - Eosinophilic granuloma occurs almost exclusively in the diaphysis or metaphysis, when tubular bones are affected. The investigators present an extremely rare case of eosinophilic granuloma arising at the epiphysis of the femoral head in an 8 year-old boy. Plain radiographs and computed tomography showed a well circumscribed radiolucent lesion, suggesting chondroblastoma or Brodie's abscess. However, the findings on magnetic resonance images were different from typical features of chondroblastoma or Brodie's abscess. The lesion was curetted. Histological diagnosis was eosinophilic granuloma. Differential diagnoses of a radiolucent lesion at the epiphysis in a child should include, though quite rare, eosinophilic granuloma. PMID- 20543727 TI - Efficacy of potentiation of performance through overweight implement throws on male and female high-school weight throwers. AB - The purpose of the investigation was to determine the acute effects of heavy implements on weight throw performance. Ten high-school weight throwers were recruited to participate. A within-subjects design was used to compare the difference between mean and peak distances achieved with the regulation weight after warm-up with regulation weight (control), 1.37-kg overweight (OVRWGHT1) and 2.27-kg overweight implement (OVRWGHT2). Analysis via repeated-measures analysis of variance revealed main effects for Treatment (p = 0.021) and Attempt (p = 0.015). The mean after the OVRWGHT1 treatment was the highest (14.52 +/- 3.54 m) followed by OVRWGHT2 (14.22 +/- 3.15 m) and the competition weight implement (STAND; 13.38 +/- 2.98). Paired samples t-test for peak distance by treatment revealed that both OVRWGHT1 (p = 0.004) and OVRWGHT2 (p = 0.027) were significantly different from STAND. Post hoc testing revealed that both OVRWGHT1 (p = 0.025) and OVRWGHT2 (p = 0.007) resulted in a significant difference in perceived fatigue compared with STAND. The results suggest that using overweight implements as part of the warm-up may improve performance in high-school athletes. PMID- 20543728 TI - Short-duration massage at the hamstrings musculotendinous junction induces greater range of motion. AB - Massage for the purpose of health dates back to early civilization and more recently has been used in the management and prevention of sport injuries. Massage has also been used as part of a warm-up to help increase acute flexibility. However, the physiological benefits and mechanisms of massage are not well known. The purpose of the present study was to investigate the effectiveness of 3 massage conditions on hip flexion range of motion (ROM). This experimentation involved a novel massage technique, which focused the massage on the musculotendinous junction for a short duration. Ten recreationally active women ranging from 21 to 36 years in age participated in this study. Participants were subjected to 3 massage conditions (no massage, 10-second massage, and 30 second massage) in a random order on separate days. Hip flexion angle, passive leg tension, and electromyography (EMG) were measured thrice before and within 10 seconds after the intervention. A main effect for conditions was found with the 30-second massage providing a 7.2% increase in hip flexion ROM that was significantly greater than the control condition (p < 0.05). Significant interactions occurred with an increased ROM (p < 0.05) from pre to posttests of 5.9 and 7.2% for the 10- and 30-second massage conditions, respectively. There were no significant differences in passive tension or EMG for any conditions or time. With a significant increase in hip angle and no associated increase in passive tension or EMG, there is a suggestion that 10 and 30 seconds of musculotendinous massage induces greater ROM through a modified stretch perception, increased stretch tolerance, or increased compliance of the hamstrings. Musculotendinous massage may be used as an alternative or a complement to static stretching for increasing ROM. PMID- 20543730 TI - Relationship between body composition, leg strength, anaerobic power, and on-ice skating performance in division I men's hockey athletes. AB - The purpose of this study was to examine relationships between laboratory tests and on-ice skating performance in division I men's hockey athletes. Twenty-one men (age 20.7 +/- 1.6 years) were assessed for body composition, isokinetic force production in the quadriceps and hamstring muscles, and anaerobic muscle power via the Wingate 30-second cycle ergometer test. Air displacement plethysmography was used to determine % body fat (%FAT), fat-free mass (FFM), and fat mass. Peak torque and total work during 10 maximal effort repetitions at 120 degrees .s were measured during concentric muscle actions using an isokinetic dynamometer. Muscle power was measured using a Monark cycle ergometer with resistance set at 7.5% of body mass. On-ice skating performance was measured during 6 timed 89-m sprints with subjects wearing full hockey equipment. First length skate (FLS) was 54 m, and total length skate (TLS) was 89 m with fastest and average skating times used in the analysis. Correlation coefficients were used to determine relationships between laboratory testing and on-ice performance. Subjects had a body mass of 88.8 +/- 7.8 kg and %FAT of 11.9 +/- 4.6. First length skate-Average and TLS Average skating times were moderately correlated to %FAT ([r = 0.53; p = 0.013] and [r = 0.57; p = 0.007]) such that a greater %FAT was related to slower skating speeds. First length skate-Fastest was correlated to Wingate percent fatigue index (r = -0.48; p = 0.027) and FLS-Average was correlated to Wingate peak power per kilogram body mass (r = -0.43; p = 0.05). Laboratory testing of select variables can predict skating performance in ice hockey athletes. This information can be used to develop targeted and effective strength and conditioning programs that will improve on-ice skating speed. PMID- 20543729 TI - The effects of creatine loading and gender on anaerobic running capacity. AB - Creatine (Cr) loading consists of short-term, high-dosage Cr supplementation and has been shown to increase intramuscular total Cr content. Increases in body weight (BW) have been shown to result from Cr loading, with differences by gender, and increased BW may impact weight-bearing exercise. The critical velocity (CV) test is used to quantify the relationship between total running distance and time to exhaustion. The CV test provides the variable, anaerobic running capacity (ARC), which is an estimate of the anaerobic energy reserves in muscle. The purpose of this study was to examine the effects of gender and Cr loading on ARC. Fifty moderately trained men and women volunteered to participate in this randomized, double-blinded, placebo (PL)-controlled, repeated-measures study. After a familiarization session, a 3-day testing procedure was conducted. A maximal oxygen consumption test VO(2)max) on a treadmill was performed on day 1 to establish the maximum velocity (Vmax) at VO(2)max and to record BW. Days 2 and 3 involved treadmill running at varying percentages of Vmax. Participants were randomly assigned to either the Cr or PL group and received 20 packets of the Cr supplement (1 packet = 5 g Cr citrate, 18 g dextrose) or 20 packets of the PL (1 packet = 18 g dextrose). After consuming 4 packets daily for 5 consecutive days, the 3-day testing procedure was repeated. The male Cr loading group exhibited a 23% higher (p = 0.003) ARC compared to the PL group. Nonsignificant BW increases were found for the Cr groups. These findings suggest that Cr loading may be an effective strategy for improving ARC in men, but not in women, and revealed only nonsignificant increases in BW. Creatine loading may be used before competition by athletes to provide improvements in high-intensity, short-duration activities. PMID- 20543731 TI - Standing long-jump performance is enhanced when using an external focus of attention. AB - Several experiments have demonstrated that focusing a performer's attention externally (i.e., on the effects of a movement) rather than internally (i.e., on specific parts of the body) enhances performance when the task requires object manipulation (i.e., throwing a ball to a target). The purpose of this experiment was to investigate if whole-body movements (e.g., standing long jump), without object manipulation, are influenced by an internal or external focus of attention. After participants (n = 120) completed a short warm-up, they were assigned to either an internal (INT) or external (EXT) focus of attention group. All participants completed 5 standing long jumps separated by a 2-minute seated rest. Before each jump, participants in the INT condition were read the following instructions: "When you are attempting to jump as far as possible, I want you to focus your attention on extending your knees as rapidly as possible." Participants in the EXT condition were read the following instructions: "When you are attempting to jump as far as possible, I want you to focus your attention on jumping as far past the start line as possible." An independent samples t-test revealed a significant difference (p = 0.003) in the average distance jumped between the EXT (187.37 +/- 42.66 cm) group and the INT group (177.33 +/- 40.97 cm). The results suggest that providing instructions that focus attention externally enhances standing long-jump performance compared with instructions that focus attention internally. This finding is valuable for strength and conditioning professionals that use jumping tests to evaluate performance. PMID- 20543732 TI - The effect of autoregulatory progressive resistance exercise vs. linear periodization on strength improvement in college athletes. AB - Autoregulatory progressive resistance exercise (APRE) is a method by which athletes increase strength by progressing at their own pace based on daily and weekly variations in performance, unlike traditional linear periodization (LP), where there is a set increase in intensity from week to week. This study examined whether 6 weeks of APRE was more effective at improving strength compared with traditional LP in division I College football players. We compared 23 division 1 collegiate football players (2.65 +/- 0.8 training years) who were trained using either APRE (n = 12) or LP (n = 11) during 6 weeks of preseason training in 2 separate years. After 6 weeks of training, improvements in total bench press 1 repetition maximum (1RM), squat 1RM, and repeated 225-lb bench press repetitions were compared between the APRE and LP protocol groups. Analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were used to determine differences between groups. Statistical significance was accepted at p < or = 0.05. Autoregulatory progressive resistance exercise demonstrated greater improvement in 1RM bench press strength (APRE: 93.4 +/- 103 N vs. LP: -0.40 +/- 49.6 N; ANCOVA: F = 7.1, p = 0.02), estimated 1RM squat strength (APRE: 192.7 +/- 199 N vs. LP: 37.2 +/- 155 N; ANOVA: F = 4.1, p = 0.05) and the number of repetitions performed at a weight of 225 lb (APRE: 3.17 +/- 2.86 vs. LP: -0.09 +/- 2.40 repetitions; ANCOVA: F = 6.8, p = 0.02) compared with the LP group over the 6 week training period. Our findings indicate that the APRE was more effective than the LP means of programming in increasing the bench press and squat over a period of 6 weeks. PMID- 20543733 TI - Short range of motion isokinetic testing of wrist flexor and extensor strength in normal subjects and patients with carpal tunnel syndrome. AB - The purpose of this study was to compare the utility of measuring wrist flexors and extensors strength derived from 'full' range of motion (FRoM): 60 degrees of flexion to 30 degrees of extension, and 3 equally spaced short ranges of motion: SRoM1, 60-30 degrees and SroM2, 30-0 degrees of flexion and SRoM3, 0-30 degrees of wrist extension. Fifteen apparently healthy subjects and 8 patients suffering from unilateral carpal tunnel syndrome (CTS) participated in the study. In all participants, SRoM1 findings closely resembled those obtained from FRoM. In the patient groups, the muscular strength of the uninvolved side was not different from that of the healthy subjects. On the other hand, based on a bilateral comparison (involved vs. uninvolved hand), the mean total weakness (in concentric and eccentric modes) was significantly higher in flexion (56.4 +/- 17.3%) than in extension (39.8 +/- 15.5%) but highly symmetrical between FRoM and SRoM1. Although supporting the interchangeable use of FRoM and SRoM isokinetic testing, this study highlights a hitherto unreported dynamic weakness of the wrist extension-flexion apparatus that may partly account for the general reduction in hand function reported by patients with CTS. PMID- 20543734 TI - Effect of plyometric vs. dynamic weight training on the energy cost of running. AB - The purpose of this study is to compare the effects of 2 strength training methods on the energy cost of running (Cr). Thirty-five moderately to well trained male endurance runners were randomly assigned to either a control group (C) or 2 intervention groups. All groups performed the same endurance-training program during an 8-week period. Intervention groups added a weekly strength training session designed to improve neuromuscular qualities. Sessions were matched for volume and intensity using either plyometric training (PT) or purely concentric contractions with added weight (dynamic weight training [DWT]). We found an interaction between time and group (p < 0.05) and an effect of time (p < 0.01) for Cr. Plyometric training induced a larger decrease of Cr (218 +/- 16 to 203 +/- 13 ml.kg.km) than DWT (207 +/- 15 to 199 +/- 12 ml.kg.km), whereas it remained unchanged in C. Pre-post changes in Cr were correlated with initial Cr (r = -0.57, p < 0.05). Peak vertical jump height (VJHpeak) increased significantly (p < 0.01) for both experimental groups (DWT = 33.4 +/- 6.2 to 34.9 +/- 6.1 cm, PT = 33.3 +/- 4.0 to 35.3 +/- 3.6 cm) but not for C. All groups showed improvements (p < 0.05) in Perf3000 (C = 711 +/- 107 to 690 +/- 109 seconds, DWT = 755 +/- 87 to 724 +/- 77 seconds, PT = 748 +/- 81 to 712 +/- 76 seconds). Plyometric training were more effective than DWT in improving Cr in moderately to well-trained male endurance runners showing that athletes and coaches should include explosive strength training in their practices with a particular attention on plyometric exercises. Future research is needed to establish the origin of this adaptation. PMID- 20543735 TI - A longitudinal assessment of running economy and tendon properties in long distance runners. AB - The aim of this study was to investigate longitudinal changes in tendon properties and running economy of long-distance runners (LDRs) in the preparatory periods of track season (TS) and road season (RS). Eleven well-trained LDRs and 6 untrained subjects participated in the present study. In each period, muscle strength, neural activation level, and tendon elongation for both knee extensors and plantar flexors, jump performances, and oxygen consumption during submaximal running velocities were measured. No significant differences observed in any measured variables between the 2 seasons for untrained subjects. For LDRs, the total running distance during 1 month preceding RS (832 +/- 95 km) was significantly longer than that during 1 month preceding TS (718 +/- 80 km). No significant differences in the muscle strength, neural activation level, and jump performances were found between TS and RS. The stiffness of tendon structures in RS was significantly lower than those in TS for both knee extensors (-14.4%, p = 0.023) and plantar flexors (-16.6%, p = 0.040). At 3 running velocities, the oxygen consumptions in RS were significantly lower than those in TS. These results suggested that the lower oxygen consumption during submaximal running velocities observed in the preparatory period of RS may be attributable to the more compliant tendon structures but not in the neuromuscular characteristics. PMID- 20543736 TI - Physical and physiological attributes of female volleyball players--a review. AB - The main objective of this article was to review a series of studies (n = 31) on physical attributes, physiological attributes, and on-court performances of female volleyball players. Empirical and practical knowledge emerging from studies on training-related issues in volleyball, such as body mass, fat-free mass, aerobic profile, strength, and agility and speed, should be integrated and applied when planning annual training programs for volleyball players. Based on our review, it was found that (a) players of a higher skill level are taller, somewhat heavier, and have higher vertical jump values than players of a lower level; (b) the aerobic profile of female volleyball players is similar to that of female basketball players; (c) ballistic resistance training can increase vertical jump values in female volleyball players; and (d) preseason conditioning should be conducted to prevent fatigue and reduced performance at the beginning of the season. Among the research concerns discussed in the article are that there is a lack data for on-court performance and time-motion analysis in female volleyball players and that more experimental/manipulative studies are needed to examine the effectiveness of different training programs on physiological attributes of female volleyball players. Two practical implications are suggested for volleyball and strength and conditioning coaches: (a) functional and nonfunctional overreaching should be carefully monitored when planning strength and conditioning programs, and (b) volleyball programs should include ballistic type training. PMID- 20543737 TI - Evaluation of muscle activity for loaded and unloaded dynamic squats during vertical whole-body vibration. AB - The purpose of this investigation was to examine if the addition of a light external load would enhance whole-body vibration (WBV)-induced increases in muscle activity during dynamic squatting in 4 leg muscles. Thirteen recreationally active male university students performed a series of dynamic squats (unloaded with no WBV, unloaded with WBV, loaded with no WBV, and loaded with WBV). The load was set to 30% of body mass and WBV included 25-, 35-, and 45 Hz frequencies with 4-mm amplitude. Muscle activity was recorded with surface electromyography (EMG) on the vastus lateralis (VL), biceps femoris (BF), tibialis anterior (TA), and gastrocnemius (GC) and is reported as EMGrms (root mean square) normalized to %maximal voluntary exertion. During unloaded dynamic squats, exposure to WBV (45 Hz) significantly (p < 0.05) increased baseline muscle activity in all muscles, except the TA compared with no WBV. Adding a light external load without WBV increased baseline muscle activity of the squat exercise in all muscles but decreased the TA. This loaded level of muscle activity was further increased with WBV (45 Hz) in all muscles. The WBV-induced increases in muscle activity in the loaded condition (approximately 3.5%) were of a similar magnitude to the WBV-induced increases during the unloaded condition (approximately 2.5%) demonstrating the addition of WBV to unloaded or loaded dynamic squatting results in an increase in muscle activity. These results demonstrate the potential effectiveness of using external loads with exposure to WBV. PMID- 20543738 TI - Muscle activity during functional coordination training: implications for strength gain and rehabilitation. AB - The purpose of this study was to evaluate if different types, body positions, and levels of progression of functional coordination exercises can provide sufficiently high levels of muscle activity to improve strength of the neck, shoulder, and trunk muscles. Nine untrained women were familiarized with 7 functional coordination exercises 12 times during 4 weeks before testing. Surface electromyographic (EMG) activity was obtained from rectus abdominus, erector spinae, obliquus externus, and trapezius during the exercises with 2-4 levels of progression. Electromyography was normalized to the maximal EMG activity during maximal voluntary contractions, and a p value < 0.05 was considered significant. All recorded muscles reached sufficiently high levels of activity during the coordination exercises for strength gain (>60% of maximal EMG activity). Type of exercise played a significant role for the attained muscle activity. Body position during the exercises was important for the activity of the erector spinae, and level of progression was important for the activity of the trapezius. The findings indicate that depending on type, body position, and level of progression, functional coordination training can be performed with a muscle activity sufficient for strength gain. Functional coordination training may therefore be a good choice for prevention or rehabilitation of musculoskeletal pain or injury in the neck, shoulder, or trunk muscles. PMID- 20543739 TI - Postactivation potentiation: upper body force development changes after maximal force intervention. AB - The neuromuscular phenomenon postactivation potentiation can possibly be used to increase the rate of force development (RFD) and maximal power (Pmax). Various intervention protocols have been examined with varying results. Maximal intervention protocols using 1 repetition maximum (1RM) have been examined in earlier studies in the lower body with positive results, but no studies have investigated maximal protocols on the upper body. Using maximal protocols would furthermore eliminate the uncertainties when expressing intensity as either numbers of RM or percentage of 1RM and hence emphasize standardization. Thus, the aim of this study was to examine the force development characteristics in the upper body after a maximal bench-press intervention. Eight strength trained male athletes performed an intervention protocol consisting of 5x 1RM in the bench press. Pre and post the intervention, a test consisting of either an isometric maximal voluntary contraction or a bench throw was completed to measure isometric RFD (iRFD) or Pmax, respectively. Statistical significance was accepted at p = 50 yr were included. Heterogeneity between studies was assessed using the Cochran Q and the I statistics, and publication bias was evaluated through physical inspection of funnel plots as well as formal rank-correlation statistics. Mixed-effects meta-regression was incorporated to assess the relationship between RE dosage and changes in LBM. RESULTS: data from 49 studies, representing a total of 1328 participants, were pooled using random effect models. Results demonstrated a positive effect for LBM, and there was no evidence of publication bias. The Cochran Q statistic for heterogeneity was 497.8, which was significant (P < 0.01). Likewise, I was equal to 84%, representing rejection of the null hypothesis of homogeneity. The weighted pooled estimate of mean LBM change was 1.1 kg (95% confidence interval = 0.9-1.2 kg). Meta-regression revealed that higher-volume interventions were associated (beta = 0.05, P < 0.01) with significantly greater increases in LBM, whereas older individuals experienced less increase (beta = -0.03, P = 0.01). CONCLUSIONS: RE is effective for eliciting gains in LBM among aging adults, particularly with higher-volume programs. Findings suggest that RE participation earlier in life may provide superior effectiveness. PMID- 20543752 TI - Functional performance in chronic obstructive pulmonary disease declines with time. AB - PURPOSE: it is well known that people with chronic obstructive pulmonary disease experience declines in functional performance, but little is known about the rate of decline. The purposes of this research were to describe the rate of decline in functional performance and to examine the contribution of disease severity, body composition, symptoms, and functional capacity. Functional performance was defined as the activities that people choose to engage in on a day-to-day basis. METHODS: people (n = 108) with chronic obstructive pulmonary disease were enrolled and followed yearly for 3 yr with self-reported functional performance (Functional Performance Inventory), spirometry, lung volumes, diffusion capacity, body composition (dual-energy x-ray absorptiometry), dyspnea and fatigue (Chronic Respiratory Disease Questionnaire), and functional capacity (6-min walk distance (6MWD), isokinetic strength of knee flexors and extensors, handgrip strength, and maximal inspiratory pressure). A total of 88 subjects completed a (mean +/- SD) of 2.7 +/- 0.9 yr of follow-up. RESULTS: significant negative slopes were observed for functional performance (P = 0.001), spirometry (the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC), P < 0.0001), diffusion capacity (P < 0.0001), and muscle strength (P < 0.0001)). The slopes for dyspnea, fatigue, and functional capacity were not significantly different from zero, but there was a wide individual variation. Hierarchical regression demonstrated that 31% of the variance in the slope of functional performance was accounted for by the hierarchical model, and the primary predictors were the slopes of the FEV1/FVC, 6MWD, and muscle strength (knee flexors/extensor and handgrip). CONCLUSIONS: subjects experienced a slow decline in functional performance, associated with declines in functional capacity and increases in body fat. Symptoms were relatively stable and not associated with declines in functional performance. PMID- 20543753 TI - Physical activity, television viewing time, and retinal vascular caliber. AB - PURPOSE: to examine the associations of physical activity and television (TV) viewing time with retinal vascular caliber in Australian adults. METHODS: a total of 2024 adults aged 25 yr or older without known diabetes in the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab, 1999-2000), a population-based cross-sectional study, were evaluated. Retinal vascular calibers (both arteriolar and venular calibers) were measured from digital retinal photographs using a computer-assisted method and were summarized into central retinal artery and vein equivalents. Self-reported physical activity time and TV viewing time were obtained using interviewer-administered questionnaires. RESULTS: for physical activity, no statistically significant multivariate relationships emerged for men or for women. After adjusting for confounders (age, sex, education, cigarette smoking, diet quality, waist circumference, systolic blood pressure, plasma glucose levels, serum fibrinogen, serum triglyceride, and physical activity time), men who watched TV for at least 2 h.d had a venular caliber that was 4.71 microm (95% confidence interval = 1.37-8.04 microm, P = 0.006) wider compared with those watching <2 h.d of TV. No significant association with venular caliber was noted in women. CONCLUSIONS: these findings provide the first evidence of an association between TV viewing time (a common, leisure time sedentary behavior) and retinal microcirculation. Further research is needed to examine these associations in different populations and by using more comprehensive physical activity and sedentary behavior measures. PMID- 20543754 TI - Stride rate recommendations for moderate-intensity walking. AB - Current physical activity guidelines recommend physical activity of at least moderate intensity to gain health benefits. Previous studies have recommended a moderate-intensity walking cadence of 100 steps per minute for adults, but the influence of height or stride length has not been investigated. PURPOSE: the purpose of the current study was to determine the role of height and stride length in moderate-intensity walking cadence in adults. METHODS: seventy-five adults completed three treadmill walking trials and three overground walking trials at slow, medium, and fast walking speeds while VO2 was measured using indirect calorimetry. Five stride length-related variables were also measured. RESULTS: mixed model regression analysis demonstrated that height explained as much variability in walking intensity at a given cadence as did two different measures of leg length and two different stride length tests. CONCLUSIONS: the previous general recommendations of 100 steps per minute were supported for use where a simple public health message is needed. Depending on height, moderate intensity walking cadence can vary by more than 20 steps per minute, from 90 to 113 steps per minute for adults 198 to 152 cm tall, respectively. Height should therefore be taken into consideration for more precise evaluation or prescription of walking cadence in adults to provide health benefits. PMID- 20543755 TI - Effects of body mass index and step rate on pedometer error in a free-living environment. AB - Pedometers could provide great insights into walking habits if they are found to be accurate for people of all weight categories. PURPOSE: the purposes of this study were to determine whether the New Lifestyles NL-2000 (NL) and the Digi Walker SW-200 (DW) yield similar daily step counts as compared with the StepWatch 3 (SW) in a free-living environment and to determine whether pedometer error is influenced by body mass index (BMI) and speed of walking. The SW served as the criterion because of its accuracy across a range of speeds and BMI categories. Slow walking was defined as <=80 steps per minute. METHODS: fifty-six adults (mean +/- SD: age = 32.7 +/- 14.5 yr) wore the devices for 7 d. There were 20 normal weight, 18 overweight, and 18 obese participants. A two-way repeated measures ANOVA was performed to determine whether BMI and device were related to number of steps counted per day. Stepwise linear regressions were performed to determine what variables contributed to NL and DW error. RESULTS: both the NL and the DW recorded fewer steps than the SW (P < 0.001). In the normal weight and overweight groups, error was similar for the DW and NL. In the obese group, the DW underestimated steps more than the NL (P < 0.01). DW error was positively related to BMI and percentage of slow steps, whereas NL error was linearly related to percentage of slow steps. A surprising finding was that many healthy, community-dwelling adults accumulated a large percentage of steps through slow walking. CONCLUSIONS: the NL is more accurate than the DW for obese individuals, and neither pedometer is accurate for people who walk slowly. Researchers and practitioners must weigh the strengths and limitations of step counters before making an informed decision about which device to use. PMID- 20543756 TI - Serial cardiac 123I-metaiodobenzylguanidine scintigraphic studies are more useful for predicting cardiac death than one-time scan in patients with chronic heart failure: sub-analysis of our previous report. AB - BACKGROUND: Many studies have shown a one-time 123I-metaiodobenzylguanidine (MIBG) scan during a stable period to be useful for determining the prognosis of patients with chronic heart failure (CHF). However, we recently reported that the delta washout rate (WR) determined from serial 123I-MIBG scintigraphic studies is the best prognostic value in patients with CHF. METHODS: A total of 208 patients with CHF (left ventricular ejection fraction <45%), but no cardiac events for at least 5 months, were identified on the basis of a history of decompensated acute heart failure requiring hospitalization. The patients underwent 123I-MIBG scintigraphy and echocardiography just before leaving the hospital and after 6 months of treatment. We evaluated two models for predicting cardiac death using the Cox proportional hazards regression analysis. In addition to clinical characteristics, New York Heart Association functional class and pharmacotherapy, one model included variables of baseline scintigraphic and echocardiographic parameters (model A), and the other model included those of delta (i.e. follow-up minus baseline) scintigraphic and echocardiographic parameters (model B). RESULTS: Of the 208 patients, 56 experienced fatal cardiac events during the study. In model A, a Cox proportional hazards analysis showed baseline WR >=50% to be the only independent predictor of cardiac death (hazard ratio=2.335, 95% confidence interval=1.142-4.774, P=0.020). In model B, delta-WR>=-5% was the only incremental predictor of cardiac death (hazard ratio=4.444, 95% confidence interval=1.511-13.069, P=0.009). The survival rates of patients with a delta-WR of less than -5% were significantly higher for those with a baseline WR of less than 50% (P=0.036). Moreover, high delta-WR was the best predictor compared with single scan, single echocardiography, and their combination evaluated by the global chi2 analysis. CONCLUSION: Baseline WR and delta-WR obtained from 123I MIBG scintigraphy can be used as independent predictors of cardiac death, and two 123I-MIBG scintigraphic studies are more useful than a one-time scan in stabilized patients with CHF. PMID- 20543757 TI - When to image carotid plaque inflammation with FDG PET/CT. AB - OBJECTIVE: Quantification of 18-fluorodeoxyglucose (FDG) uptake in inflamed high risk carotid atherosclerotic plaques is challenged by the spatial resolution of positron emission tomography (PET) and luminal blood activity. Late acquisition protocols have been used to overcome these challenges to enhance the contrast between the plaque and blood-pool FDG activity. However, for prospective studies the late acquisition is inconvenient for the patient and staff, and most retrospective studies of plaque uptake use data from early acquisition protocols. The objective was to evaluate changes in the quantification methods of FDG uptake in carotid artery plaques between early and late PET scans. METHODS: FDG uptake 1 and 3 h after tracer injection was compared in 19 carotid artery plaques. The average plaque maximum standardized uptake value (SUVmax) and a target to background ratio (TBR), using venous blood-pool activity as background, were evaluated at the two time points. These methods have been shown earlier to quantitate the degree of inflammation in late hour scans. RESULTS: A good individual plaque FDG uptake consistency was found between the two time points for SUVmax, r2=0.86. In contrast, the ratio method did not conserve the results between the two time points: TBR r2=0.34. For both methods, absolute values changed over time. TBR values generally increased as blood pool activity decreased, whereas the individual plaque SUVmax values showed both increases and decreases over time. CONCLUSION: Identification of carotid plaque inflammation with PET can be performed 1 h after FDG injection using SUVmax for plaque FDG uptake quantification. PMID- 20543759 TI - Comparison of the effectiveness and safety of two insulin infusion protocols in the management of hyperglycemia in critically ill children. AB - OBJECTIVES: To compare the effectiveness and safety of a paper-based and a computerized algorithm used for tight glycemic control. SETTING: Academic pediatric intensive care unit. DESIGN: Retrospective cohort study. PATIENTS: Two groups of nondiabetic critically ill children with persistent hyperglycemia (blood glucose >=140 mg/dL [ >=7.8 mmol/L] for at least 2 hrs) were included. INTERVENTION: One group of patients' blood glucose was controlled at 90-119 mg/dL (5.0-6.6 mmol/L) using the Yale Insulin Infusion Protocol (YIIP), a paper-based protocol. Another group of patients' blood glucose was controlled at 80-110 mg/dL (4.4-6.1 mmol/L) with eProtocol insulin (ePi), a computerized decision support tool. MEASUREMENTS AND MAIN RESULTS: The effectiveness of the protocols was compared using percentages of blood glucose values within target range and glucose variability index. A safety comparison was made using hypoglycemia rates at <=40 mg/dL (<=2.2 mmol/L), <=50 mg/dL (<=2.8 mmol/L), and <=60 mg/dL (<=3.3 mmol/L). Forty-two patients and 12 patients were included in the YIIP and ePi groups, respectively. The percent of values in range was lower in the YIIP group (33%) compared with the ePi group (41%) (p < .001). Mean glucose variability index was comparable in the two groups (18.7 +/- 8.9 mg/dL/hr [1.0 +/- 0.5 mmol/L/hr] for the YIIP group and 14.4 +/- 7.6 mg/dL/hr [0.8 +/- 0.4 mmol/L/hr] for the ePi group; p = .111). Hypoglycemia rates were statistically similar in both groups. In the YIIP group, 10% of patients and in the ePi group, 25% of patients had blood glucose <=40 mg/dL (<=2.2 mmol/L) (p = .168). CONCLUSION: YIIP is less effective but is as safe as ePi in achieving tight glycemic control. We are awaiting the results of two multicenter trials designed to determine the survival benefit of tight glycemic control in children. Further studies are needed to determine the clinical significance of the different glucose metrics in critically ill patients. PMID- 20543760 TI - An investigation of epidemic enterovirus 71 infection in Taiwan, 2008: clinical, virologic, and serologic features. AB - BACKGROUND: Enterovirus 71 (EV71) is causing life-threatening hand-foot-mouth disease in Asia. In Taiwan, EV71 epidemics with different predominant genotypes occurred in 1998 (C2), 2000-2001 (B4), and 2004-2005 (C4). This genotype replacement may have important implications for vaccine development and prediction of epidemics. A nationwide EV71 outbreak occurred again in 2008, which provided a unique opportunity to characterize clinical, virologic, and serologic features of this epidemic. METHODS: We analyzed clinical and virologic data of 111 EV71 patients hospitalized in 2008 and prospectively conducted follow-ups of healthy children from June 2006 to December 2008. RESULTS: Among the 111 EV71 inpatients, 21 (19%) developed complications. Among the 21 complicated cases, 15 had central nervous system complication only, 2 had acute heart failure, and 4 had central nervous system and pulmonary complications. In the prospective study, 11 symptomatic infections and 4 asymptomatic infections were detected. Twenty-two EV71 isolates were genotyped, and 21 of them belong to genotype B5, which is phylogenetically close to B5 viruses circulating in Southeast Asia. Serologic tests show that children infected with B5 viruses have lower geometric mean titers of neutralizing antibody against genotype C4 than those against genotype B5 (P = 0.004, t test). CONCLUSIONS: The 2008 nationwide EV71 epidemic was caused by genotype B5 that was likely introduced to Taiwan from Southeast Asia. Clinical features of the 2008 epidemic were not different from those observed before in Taiwan. Potential antigenic variations between genotype C4 and B5 viruses could be detected and its long-term epidemiologic significance needs further investigation to clarify. PMID- 20543758 TI - Vision therapy/orthoptics for symptomatic convergence insufficiency in children: treatment kinetics. AB - PURPOSE: To evaluate the kinetics of change in symptoms and signs of convergence insufficiency (CI) during 12 weeks of treatment with commonly prescribed vision therapy/orthoptic treatment regimens. METHODS: In a randomized clinical trial, 221 children aged 9 to 17 years with symptomatic CI were assigned to home-based pencil push-ups (HBPP), home-based computer vergence/accommodative therapy and pencil push-ups (HBCVAT+), office-based vergence/accommodative therapy with home reinforcement (OBVAT), or office-based placebo therapy with home reinforcement (OBPT). Symptoms and signs were measured after 4, 8, and 12 weeks of treatment. The outcome measures were the mean CI Symptom Survey (CISS), near point of convergence (NPC), positive fusional vergence (PFV), and proportions of patients who were classified as successful or improved based on a composite measure of CISS, NPC, and PFV. RESULTS: Only the OBVAT group showed significant improvements in symptoms between each visit (p < 0.001). Between weeks 8 and 12, all groups showed a significant improvement in symptoms. Between-group differences were apparent by week 8 (p = 0.037) with the fewest symptoms in the OBVAT group. For each group, the greatest improvements in NPC and PFV were achieved during the first 4 weeks. Differences between groups became apparent by week 4 (p < 0.001), with the greatest improvements in NPC and PFV in the OBVAT group. Only the OBVAT group continued to show significant improvements in PFV at weeks 8 and 12. The percentage of patients classified as "successful" or "improved" based on our composite measure increased in all groups at each visit. CONCLUSIONS: The rate of improvement is more rapid for clinical signs (NPC and PFV) than for symptoms in children undergoing treatment for CI. OBVAT results in a more rapid improvement in symptoms, NPC and PFV, and a greater percentage of patients reaching pre determined criteria of success when compared with HBPP, HBCVAT+, or OBPT. PMID- 20543761 TI - Hospital-based surveillance to evaluate the impact of rotavirus vaccination in Sao Paulo, Brazil. AB - BACKGROUND: Brazil implemented routine immunization with the human rotavirus vaccine, Rotarix, in 2006 and vaccination coverage reached 81% in 2008 in Sao Paulo. Our aim was to assess the impact of immunization on the incidence of severe rotavirus acute gastroenteritis (AGE). METHODS: We performed a 5-year (2004-2008) prospective surveillance at a sentinel hospital in Sao Paulo, with routine testing for rotavirus in all children less than 5 years of age hospitalized with AGE. Genotypes of positive samples were determined by reverse transcription polymerase chain reaction. RESULTS: During the study, 655 children hospitalized with AGE were enrolled; of whom 169 (25.8%) were positive for rotavirus. In the postvaccine period, a 59% reduction in the number of hospitalizations of rotavirus AGE and a 42.2% (95% confidence interval [CI], 18.6%-59.0%; P = 0.001) reduction in the proportion of rotavirus-positive results among children younger than 5 years were observed, with the greatest decline among infants (69.2%; 95% CI, 24.7%-87.4%; P = 0.004). Furthermore, the number of all-cause hospitalizations for AGE was reduced by 29% among children aged <5 years. The onset and peak incidences of rotavirus AGE occurred 3 months later in the 2007 and 2008 seasons compared with previous years. Genotype G2 accounted for 15%, 70%, and 100% of all cases identified, respectively, in 2006, 2007, and 2008. CONCLUSIONS: After vaccine implementation, a marked decline in rotavirus AGE hospitalizations was demonstrated among children younger than 5 years of age, with the greatest reduction in the age groups targeted for vaccination. The predominance of genotype G2P[4] highlights the need of continued postlicensure surveillance studies. PMID- 20543762 TI - Neonatal exposure to oxidants induces later in life a metabolic response associated to a phenotype of energy deficiency in an animal model of total parenteral nutrition. AB - Failure to protect total parenteral nutrition (TPN) from ambient light exacerbates the generation of peroxides, which affects blood glucose and plasma triacylglyceride (TG) in neonates. Based on the concept that the origin of adult diseases can be traced back to perinatal life, it was hypothesized that neonatal exposure to peroxides may affect energy availability later in life. Three-day-old guinea pigs, fitted with a jugular catheter, were fed regular chow (sham) +/- i.v. 350 microM H2O2 (sham + H2O2) or nourished with light-protected TPN [TPN( )L, 209 +/- 9 microM peroxides] or light-exposed TPN [TPN(+)L, 365 +/- 15 microM peroxides]. After 4 d, infusions were stopped and animals fed chow. Spontaneous ambulatory movements, fasting blood glucose, glucose tolerance, TG, hepatic activities of glucokinase, phosphofructokinase (key enzymes of glycolysis), and acetyl-CoA carboxylase (key enzymes of lipogenesis) were determined at 12-14 wk and compared by ANOVA (p < 0.05). Relative to sham, the animals from sham + H2O2, TPN(-)L and TPN(+)L groups had lower plasma TG explained for 36% by low phosphofructokinase activity; they had lower glucose tolerance, lower body weight, and lower physical activity. In conclusion, neonatal exposure to oxidant molecules such as peroxides has important consequences later in life on lipid and glucose metabolism leading to a phenotype of energy deficiency. PMID- 20543764 TI - Intravitreal bevacizumab in vascular pigment epithelium detachment as a result of subfoveal occult choroidal neovascularization in age-related macular degeneration. AB - PURPOSE: The purpose of this study was to evaluate the effect of intravitreally administered bevacizumab on untreated vascularized pigment epithelium detachment (PED) in sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration. METHODS: In this retrospective study, 28 untreated eyes of 26 patients (4 men, 22 women; mean age, 74.6 +/- 7.2 years) with PED and sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration and additional intra- and/or subretinal fluid were treated with intravitreal injections of 1.25 mg bevacizumab. Baseline and follow-up visits included best-corrected visual acuity, complete ophthalmic examination, and Stratus optical coherence tomography. Fluorescein angiography was performed at baseline. Reinjections were performed if intra- and/or subretinal fluid persisted or recurred or PED increased. RESULTS: Patients received 3.2 +/- 1.8 injections (follow-up 37.9 +/- 18.3 weeks). Mean maximum PED height showed a tendency to decrease (372 +/- 150.5 MUm to 290.3 +/- 189 MUm; P = 0.094). In 14 eyes (53.8%), PED height was reduced at last visit, including complete flattening in 1 eye. Mean visual acuity remained stable (0.58 +/- 0.30 logarithm of the minimum angle of resolution to 0.58 +/- 0.37 logarithm of the minimum angle of resolution; P = 0.905). Pigment epithelium detachment response to treatment did not correlate with baseline PED height or visual acuity at baseline or at the last visit. One patient sustained a retinal pigment epithelium rip, and another patient sustained an extensive subretinal hemorrhage. CONCLUSION: During bevacizumab therapy, mean PED height decreases in 50% of patients. No predictive factors for the response of PED to bevacizumab treatment could be identified. Treatment of PED with bevacizumab might result in a long term functional benefit compared with the natural course. PMID- 20543765 TI - Index and adjacent level kinematics after cervical disc replacement and anterior fusion: in vivo quantitative radiographic analysis. AB - STUDY DESIGN: Prospective, randomized trial. OBJECTIVE: To assess the in vivo kinematics of the cervical spine after cervical fusion and arthroplasty. SUMMARY OF BACKGROUND DATA: Compared with spinal fusion, disc replacement may impede the development of adjacent segment disease. To achieve this goal, any arthroplasty device should achieve desired spinal alignment while maintaining physiologic spinal motion at both the operated and surrounding motion segments. METHODS: As part of a multicenter, prospective, randomized Food and Drug Administration IDE clinical evaluation of the porous coated motion artificial cervical disc, patients underwent either a single-level total disc replacement (TDR; 272 patients) or anterior cervical discectomy and fusion (ACDF; 182 patients) for treatment of cervical radiculopathy or myelopathy. Neutral, flexion, and extension radiographs of the cervical spine obtained before surgery, and at 3, 6, and 12 months after surgery were assessed. Quantitative assessments and comparisons of motion patterns were produced using validated computer-assisted methods. Kinematic parameters, including segmental rotation, translation, center of rotation (COR), disc height, and disc angle were calculated. RESULTS: Cervical TDR preserved angular motion at the operated level, although the range was reduced from 8.0 degrees before surgery to 6.2 degrees at 12 months after surgery (P < 0.001). Significantly after TDR, adjacent-level angular motion was unchanged. In patients treated with fusion, angular motion at the superior adjacent level increased from 9.6 degrees before surgery to 11.0 degrees (P = 0.003) at 12 months, with a trend toward increased postoperative translation (P = 0.07). For the TDR group, the horizontal COR averaged 0.8 mm posterior to the disc center before surgery and 0.2 mm anterior to the center at 12 months after TDR (P < 0.001), and the vertical COR averaged 2.5 mm below the endplate before surgery and 4.0 mm below at 12 months (P = 0.001). COR at the adjacent levels was unaltered by fusion or TDR. Lordotic alignment and disc height at the index level increased after intervention in both groups. CONCLUSION: TDR with the porous coated motion implant is able to restore and maintain lordotic alignment and disc height and maintain angular motion while allowing for similar translation to that seen before surgery. In contrast, after ACDF, the superior adjacent level developed increased angular motion compared with preoperative range of motion. This study provides in vivo data regarding the functioning of TDR and ACDF and their impact on adjacent-level kinematics. PMID- 20543766 TI - Influence of bacteria on spinal implant-centered infection: an in vitro and in vivo experimental comparison between Staphylococcus aureus and mycobacterium tuberculosis. AB - STUDY DESIGN: an in vitro and in vivo experimental study. OBJECTIVE: this study was undertaken to evaluate differences in the capability of inducing an implant centered infection between Staphylococcus aureus and Mycobacterium tuberculosis. SUMMARY OF BACKGROUND DATA: bacterial infection is still one of the most serious and devastating complications after orthopedic implant surgery despite the advent of new antibiotics and treatment methods. METHODS: S. aureus and M. tuberculosis were separately cultured with titanium plates. The bacteria colonized on the plates were isolated and cultured on culture medium. They were evaluated and compared by colony-forming units enumeration. Scanning electron microscopy was used to evaluate the difference in the colonization features of the 2 pathogens. In the in vivo experiment, 22 dogs were used to assess the susceptibility to infection after a local bacterial challenge with either S. aureus or M. tuberculosis. RESULTS: S. aureus showed heavy adhesion and multiplication on the surface of titanium plates in vitro, whereas M. tuberculosis rarely adhered to the surface of the plates. Under scanning electron microscopy, S. aureus colonization was observed: the coccoid was widespread on the surface of the plates but only a few M. tuberculosis cells scattered on the surface of the plates. In in vivo test, the infection rateforthe S. aureus inoculation was higher than that for the M. tuberculosis challenge. The infection rate for the entire test population (n = 44 sites) was 39.58% (19/48). The infection rates were 54.17% (13/24) for the S. aureus challenge and 25% (6/24) for the M. tuberculosis challenge, respectively (P < 0.05). CONCLUSION: it is less likely for M. tuberculosis to adhere and form a biofilm on an implant surface than S. aureus. Under otherwise identical conditions, M. tuberculosis contamination following instrumented spine surgery might lead to less occurrence of infection than S. aureus contamination. PMID- 20543767 TI - Reliability of lumbar lordosis measurement in patients with spondylolisthesis: a case-control study comparing the Cobb, centroid, and posterior tangent methods. AB - STUDY DESIGN: A radiologic analytical study. OBJECTIVE: To compare the reliability of lumbar lordosis (LL) measurement in cases of spondylolisthesis using the Cobb, vertebral centroid, and posterior tangent methods. SUMMARY OF BACKGROUND DATA: Interobserver and intraobserver reliabilities of the several different types of lumbar curvature analysis have been reported using various methods for measurement; however, in patients with spondylolisthesis, it has not been studied till yet. METHODS: A radiologic analytical study was performed in 50 patients who had spondylolisthesis (28 at L4-L5, 22 at L5-S1) with lysis in the lumbar spine. All patients had instability of more than 10 degrees on the lumbar spine flexion and extension radiogram. A total of 26 patients who presented for backache without spondylolisthesis were considered as control group. Three observers measured the global and segmental angle for LL using various methods for measuring the LL using the Cobb, vertebral centroid, and Harrison's posterior tangent methods. All measurements were done by each of the observers on the same computer by keeping at least 2 weeks of interval between 2 sets of measurements. The interobserver and intraobserver reliability was calculated among all the 3 observers' 2 sets of measurements by using the inter- and intraclass correlation coefficient (ICC) test on SPSS program. RESULTS: Five global and 17 segmental angles measured overall. Results showed an excellent ICC (>0.7) while measuring the global LL using any method, the Cobb (T12-S1 or L1-L5), vertebral centroid, and Harrison's posterior tangent (T12-S1 or L1-L5) methods, in both subject and control groups. Similarly measuring the segmental angles, it exhibited excellent intraclass correlation (ICC, >0.7) coefficient by using all 3 methods for all segmental angles in both groups. However, interclass correlation coefficient was excellent (ICCs, >0.7) in both global as well as segmental angles for vertebral centroid and posterior tangent methods in subject and control groups, but it was poor or fair for the Cobb methods in segmental angles and good or excellent in global angles. Measuring the segmental angles, standard error of mean (SEM) was <2 degrees at all the levels by all methods in both subject and control group except the L4-L5-S1 level by centroid method in subject group where SEM >2 degrees was found. CONCLUSION: Posterior tangent method should be used for the global and segmental angle analysis for the LL in cases with spinal instability because of (a) higher correlation coefficient for segmental angle measurements; (b) lower SEM at the instability level than the centroid method despite similar correlation coefficients; and (c) similar to the engineering analysis. PMID- 20543769 TI - Acute central cord syndrome: injury mechanisms and stress features. AB - STUDY DESIGN: Numerical techniques were used to study the mechanisms of acute central cord syndrome. OBJECTIVE: To analyze the features of stress distribution in the cervical cord under different injury conditions using finite element model of the cervical cord and to improve the understanding of the possible pathogenesis of acute central cord syndrome. SUMMARY OF BACKGROUND DATA: Acute central cord spinal injury was initially attributed to hemorrhagic damage to the central portion of the spinal cord, but recent histopathologic studies showed that it was predominantly a white matter injury. The precise anatomic location of neuronal injury and the etiology of the clinical manifestation were poorly understood. METHODS: Cervical cord injury was simulated using a finite element model of the cervical enlargement described previously, with the model loaded under 3 traumatic postures: neutral, flexion, and extension. Five traumatic conditions were simulated and analyzed: hyperextension with the pinch force directed to the anterior (A) or posterior (B); flexion injuries (C), vertical compression with the pinch force directed to the anterior (D) or posterior (E). After simulation, several representative cross-sections of each traumatic pattern were selected. In each cross-section, the average von Mises stress of 9 regions, such as anterior funiculus, lateral part of the lateral funiculus, medial part of the lateral funiculus, lateral part of the posterior funiculus, medial part of the posterior funiculus, anterior horn, the bottom of anterior horn, the cervix cornu posterioris, the caput cornu posterioris, and the apex cornu posterioris was recorded. RESULTS: High localized stress occurred at the portion under compression injury and the level above it. High localized stress tended to occur at the lateral part of the anterior horn motor neurons innervating the hand muscles in traumatic conditions A and D. Under conditions A, D, and E, the average localized stress at the anterior and posterior horn of the gray matter was higher than that at the white matter in all selected cross-sections, and the stress was higher at the anterior funiculus, the medial part of the lateral funiculus, and the lateral part of the posterior funiculus in the white matter. Under conditions B and C, the differences of the localized stress between the gray and the white matter were not as significant as under conditions A, D, and E, and the stress was lower at the medial part of the lateral funiculus than that at the lateral part of the posterior funiculus. Under all traumatic conditions, the average stress at the lateral part was higher than that at the medial part of the posterior funiculus. CONCLUSION: Three common traumatic patterns: hyperextension, flexion, and vertical compression, could be the possibly underlying injury mechanisms of the central cervical cord syndrome according to the results of the current finite element analysis. The stress features under different injury conditions were not in complete accord. High stress mainly occurred at the posterior horn, the anterior horn, and the adjacent white matter. The centermost lesion was not common in mild central cord injuries. The upper extremity weakness should be ascribed to the damage at the corticospinal tract and the motor neurons in the anterior horn. Hyperpathia probably resulted from injuries to the posterior horn, the anterior funiculus, and the fasciculus cuneatus. Just as there are varieties of the localized stress features in central cord injuries, variations in clinical presentations were common. PMID- 20543768 TI - The accuracy of the physical examination for the diagnosis of midlumbar and low lumbar nerve root impingement. AB - STUDY DESIGN: Cross-sectional study with prospective recruitment. OBJECTIVE.: To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement (L2, L3, or L4), low lumbar nerve root impingement (L5 or S1) and level-specific lumbar nerve root impingement on magnetic resonance imaging, using individual tests and combinations of tests. SUMMARY OF BACKGROUND DATA: The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied. METHODS: Sensitivities, specificities, and likelihood ratios (LRs) were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar, low lumbar, and specific nerve root levels. RESULTS: LRs >=5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability. For the diagnosis of midlumbar impingement, the femoral stretch test (FST), crossed FST, medial ankle pinprick sensation, and patellar reflex testing demonstrated LRs >=5.0 (LR infinity). LRs >=5.0 were observed with the combinations of FST and either patellar reflex testing (LR 7.0; 95% confidence interval [CI] 2.3-21) or the sit to-stand test (LR infinity). For the diagnosis of low lumbar impingement, the Achilles reflex test demonstrated an LR >=5.0 (LR 7.1; 95% CI 0.96-53); test combinations did not increase LRs. For the diagnosis of level-specific impingement, LRs >=5.0 were observed for anterior thigh sensation at L2 (LR 13; 95% CI 1.8-87); FST at L3 (LR 5.7; 95% CI 2.3-4.4); patellar reflex testing (LR 7.7; 95% CI 1.7-35), medial ankle sensation (LR infinity), or crossed FST (LR 13; 95% CI 1.8-87) at L4; and hip abductor strength at L5 (LR 11; 95% CI 1.3-84). Test combinations increased LRs for level-specific root impingement at the L4 level only. CONCLUSION: Individual physical examination tests may provide clinical information that substantially alters the likelihood that midlumbar impingement, low lumbar impingement, or level-specific impingement is present. Test combinations improve diagnostic accuracy for midlum-bar impingement. PMID- 20543770 TI - Percutaneous placement of radiopaque markers at the pedicle of interest for preoperative localization of thoracic spine level. AB - STUDY DESIGN: Retrospective review. OBJECTIVE: To describe an accurate method of intraoperative localization of thoracic spine levels with percutaneously placed radiopaque markers at the pedicle of the level of interest. SUMMARY OF BACKGROUND DATA: Intraoperative localization of thoracic spine levels can be difficult in cases without obvious vertebral body deformation (compression fracture, tumor), such as thoracic discectomy, as well as in surgery of the midthoracic spine and in the morbidly obese. Intraoperative fluoroscopy or plain radiographs are useful but can often be difficult to interpret in these cases. METHODS: Fourteen patients requiring anterior thoracic spine surgery for thoracic disc herniations underwent preoperative localization and placement of radiopaque marker. Using standard percutaneous techniques, the radiopaque markers were placed using biplanar fluoroscopy at the pedicle at the level of interest. Eight patients subsequently underwent thoracoscopic discectomy and fusion, and 6 patients underwent mini-open thoracotomy for discectomy and fusion. RESULTS: Placement of radiopaque markers was successfully completed without complications in all 14 patients. Intraoperatively, the markers were easy to identify and assisted in identification of the correct surgical level in all cases. CONCLUSION: Preoperative placement of radiopaque markers at the level of interest before surgery of the thoracic spine is a safe and effective technique for avoiding wrong-level surgery in cases in which standard localization techniques may be difficult. PMID- 20543771 TI - The effect of low back pain on work absenteeism among soldiers on active service. AB - STUDY DESIGN: A prospective longitudinal study. OBJECTIVE: To identify factors that influence absenteeism among soldiers with acute low back pain (ALBP). SUMMARY OF BACKGROUND DATA: Recommendations for the treatment of low back pain include continuing physical activity. Ninety-seven percent of patients return to work within 1 month. METHODS: This was a prospective longitudinal study using a questionnaire to assess morbidity from ALBP and the job being carried out by the soldier at the time of referral to the army clinic and 6 weeks later. Potential associations were investigated between prolonged absenteeism and variables including disease indexes, use of healthcare services, the soldier's army job, and their satisfaction with it. RESULTS.: The study population consisted of 160 soldiers with uncomplicated ALBP. Eighty-six percent of the participants returned to their job within 6 weeks. The rates of improvement in pain, the mental functioning under pain, satisfaction with jobs, and having combat status were higher among soldiers who returned to their jobs as compared with those who did not. Those who did not return to their jobs had higher rates of utilization of healthcare services. CONCLUSION: Nondisease factors are associated with the duration of absenteeism among soldiers with ALBP. Absenteeism is directly related to use of healthcare services. PMID- 20543772 TI - Preparation of Drosophila S2 cells for light microscopy. AB - The ideal experimental system would be cheap and easy to maintain, amenable to a variety of techniques, and would be supported by an extensive literature and genome sequence database. Cultured Drosophila S2 cells, the product of disassociated 20-24 hour old embryos, possess all these properties. Consequently, S2 cells are extremely well-suited for the analysis of cellular processes, including the discovery of the genes encoding the molecular components of the process or mechanism of interest. The features of S2 cells that are most responsible for their utility are the ease with which they are maintained, their exquisite sensitivity to double-stranded (ds)RNA-mediated interference (RNAi), and their tractability to fluorescence microscopy as either live or fixed cells. S2 cells can be grown in a variety of media, including a number of inexpensive, commercially-available, fully-defined, serum-free media. In addition, they grow optimally and quickly at 21-24 degrees C and can be cultured in a variety of containers. Unlike mammalian cells, S2 cells do not require a regulated atmosphere, but instead do well with normal air and can even be maintained in sealed flasks. Complementing the ease of RNAi in S2 cells is the ability to readily analyze experimentally-induced phenotypes by phase or fluorescence microscopy of fixed or live cells. S2 cells grow in culture as a single monolayer but do not display contact inhibition. Instead, cells tend to grow in colonies in dense cultures. At low density, S2 cultures grown on glass or tissue culture treated plastic are round and loosely-attached. However, the cytology of S2 cells can be greatly improved by inducing them to flatten extensively by briefly culturing them on a surface coated with the lectin, concanavalin A (ConA). S2 cells can also be stably transfected with fluorescently-tagged markers to label structures or organelles of interest in live or fixed cells. Therefore, the usual scenario for the microscopic analysis of cells is this: first, S2 cells (which can possess transgenes to express tagged markers) are treated by RNAi to eliminate a target protein(s). RNAi treatment time can be adjusted to allow for differences in protein turn-over kinetics and to minimize cell trauma/death if the target protein is important for viability. Next, the treated cells are transferred to a dish containing a coverslip pre-coated with conA to induce cells to spread and tightly adhere to the glass. Finally, cells are imaged with the researcher's choice of microscopy modes. S2 cells are particularly good for studies requiring extended visualization of live cells since these cells stay healthy at room temperature and normal atmosphere. PMID- 20543773 TI - Electrode fabrication and implantation in Aplysia californica for multi-channel neural and muscular recordings in intact, freely behaving animals. AB - Recording from key nerves and muscles of Aplysia during feeding behavior allows us to study the patterns of neural control in an intact animal. Simultaneously recording from multiple nerves and muscles gives us precise information about the timing of neural activity. Previous recording methods have worked for two electrodes, but the study of additional nerves or muscles required combining and averaging the recordings of multiple animals, which made it difficult to determine fine details of timing and phasing, because of variability from response to response, and from animal to animal. Implanting four individual electrodes has a very low success rate due to the formation of adhesions that prevent animals from performing normal feeding movements. We developed a new method of electrode fabrication that reduces the bulk of the electrodes inside the animal allowing for normal feeding movements. Using a combination of glues to attach the electrodes results in a more reliable insulation of the electrode which lasts longer, making it possible to record for periods as long as a week. The fabrication technique that we describe could be extended to incorporate several additional electrodes, and would be applicable to vertebrate animals. PMID- 20543774 TI - Sedation for dental treatment of children in the primary care sector (UK). AB - OBJECTIVE: To audit the clinical practice of a dental sedation service in the primary care sector and determine which services dentists use to manage unco operative children. DESIGN: Retrospective analysis and prospective audit. SETTING: Sedation clinic in primary care, 2007, England. SUBJECTS: Children attending for dental treatment under sedation. General dental practitioners (GDPs) in the Brighton and West Sussex regions. INTERVENTIONS: Questionnaire. MAIN OUTCOME MEASURES: Clinical service audit, patient satisfaction, referrer satisfaction. RESULTS: Four hundred children (age range 5-12 years) had been referred for caries (78%), with the remainder for orthodontic extractions. The most common treatment carried out on primary and permanent teeth was extractions followed by restorations. A combination of intravenous (IV) midazolam/ketamine/fentanyl was used in 40% of cases, and IV midazolam/ketamine was used in 34% of cases. Seventy-four percent of parents responded to the satisfaction questionnaire; of these 97% rated sedation as excellent/good and 80% would choose sedation or recommend sedation for others. Only 45% of questionnaires to referrers were returned. Fifty-six percent of dentists preferred general anaesthesia (GA) and 66% preferred IV sedation. CONCLUSIONS: Dental treatment for children was provided under IV sedation with most parents satisfied with the procedure. Little difference was seen between referring dentists' perceptions of IV sedation or GA. PMID- 20543777 TI - Insufficient insight. PMID- 20543778 TI - Naive argument. PMID- 20543791 TI - Cracked tooth syndrome. Part 2: restorative options for the management of cracked tooth syndrome. AB - The second of this two part series on 'cracked tooth syndrome' will focus on the available methods for the immediate, intermediate and definitive management of patients affected by this condition. Included in this article is a comprehensive account of the relative merits/drawbacks of various restorative materials and their respective techniques of application for the treatment of symptomatic, incompletely fractured posterior teeth. PMID- 20543792 TI - General medicine and surgery for dental practitioners. Part 4 - skin disorders part B. AB - Skin disorders are potentially important to dentists in diverse ways. The skin disease itself might have oral manifestations, and drugs used to treat skin disorders may impact on dental management. This second paper on skin disorders continues with a consideration of those disorders, and aspects of their treatment, which could have relevance to dental practitioners. PMID- 20543799 TI - Factors influencing the quality of undergraduate clinical restorative dentistry in the UK and ROI: the views of heads of units. AB - In the light of concerns regarding expanded student intakes and reported workforce difficulties, a 2008 survey of heads of departments of restorative dentistry in UK and ROI dental schools sought to clarify the current situation with regard to: workforce configuration; barriers and facilitators of quality undergraduate clinical restorative dentistry; and, implications of the above for programme delivery. The response rate was 100% for the workforce statistics and 65% for the remainder of the survey. Findings were largely consistent across the 14 schools. Workforces were increasingly part-time with a shortage of full-time academics. While resources had generally expanded to meet increased student numbers and outreach teaching had augmented clinical learning, difficulties in recruiting patients and communicating with a fragmented workforce were risking the quality of undergraduate curricula. Issues to be addressed include a pervading sense of teaching being undervalued and staffing being sub-optimal. PMID- 20543817 TI - Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions. AB - The extracellular domains of neuroligins and neurexins interact through Ca(2+) to form flexible trans-synaptic associations characterized by selectivity for neuroligin or neurexin subtypes. This heterophilic interaction, essential for synaptic maturation and differentiation, is regulated by gene selection, alternative mRNA splicing and post-translational modifications. A new, 2.6 A resolution crystal structure of a soluble neurexin-1beta-neuroligin-4 (Nrx1beta NL4) complex permits a detailed description of the Ca(2+)-coordinated interface and unveils concerted positional rearrangements of several residues of NL4, not observed in neuroligin-1, associated with Nrx1beta binding. Surface plasmon resonance analysis of the binding of structure-guided Nrx1beta mutants towards NL4 and neuroligin-1 shows that flexibility of the Nrx1beta-binding site in NL4 is reflected in a greater dissociation constant of the complex and higher sensitivity to ionic strength and pH variations. Analysis of neuroligin mutants points to critical functions for two respective residues in neuroligin-1 and neuroligin-2 in governing the affinity of the complexes. Although neuroligin-1 and neuroligin-2 have pre-determined conformations that respectively promote and prevent Nrx1beta association, unique conformational reshaping of the NL4 surface is required to permit Nrx1beta association. PMID- 20543818 TI - The C-terminal alpha-alpha superhelix of Pat is required for mRNA decapping in metazoa. AB - Pat proteins regulate the transition of mRNAs from a state that is translationally active to one that is repressed, committing targeted mRNAs to degradation. Pat proteins contain a conserved N-terminal sequence, a proline-rich region, a Mid domain and a C-terminal domain (Pat-C). We show that Pat-C is essential for the interaction with mRNA decapping factors (i.e. DCP2, EDC4 and LSm1-7), whereas the P-rich region and Mid domain have distinct functions in modulating these interactions. DCP2 and EDC4 binding is enhanced by the P-rich region and does not require LSm1-7. LSm1-7 binding is assisted by the Mid domain and is reduced by the P-rich region. Structural analysis revealed that Pat-C folds into an alpha-alpha superhelix, exposing conserved and basic residues on one side of the domain. This conserved and basic surface is required for RNA, DCP2, EDC4 and LSm1-7 binding. The multiplicity of interactions mediated by Pat-C suggests that certain of these interactions are mutually exclusive and, therefore, that Pat proteins switch decapping partners allowing transitions between sequential steps in the mRNA decapping pathway. PMID- 20543819 TI - Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP. AB - The rod-shaped cells of the bacterium Myxococcus xanthus move uni-directionally and occasionally undergo reversals during which the leading/lagging polarity axis is inverted. Cellular reversals depend on pole-to-pole relocation of motility proteins that localize to the cell poles between reversals. We show that MglA is a Ras-like G-protein and acts as a nucleotide-dependent molecular switch to regulate motility and that MglB represents a novel GTPase-activating protein (GAP) family and is the cognate GAP of MglA. Between reversals, MglA/GTP is restricted to the leading and MglB to the lagging pole defining the leading/lagging polarity axis. For reversals, the Frz chemosensory system induces the relocation of MglA/GTP to the lagging pole causing an inversion of the leading/lagging polarity axis. MglA/GTP stimulates motility by establishing correct polarity of motility proteins between reversals and reversals by inducing their pole-to-pole relocation. Thus, the function of Ras-like G-proteins and their GAPs in regulating cell polarity is found not only in eukaryotes, but also conserved in bacteria. PMID- 20543820 TI - The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study. AB - Several isolated markers have been proposed to aid in differential diagnostic of difficult melanocytic lesions, albeit none has been shown to be definitive in differentiating Spitz nevus from melanoma. This study proposes a wide panel of 22 markers having important functions in different biological functions (cell cycle, apoptosis, DNA repair proteins and membranous receptors) to provide a combination of proteins associated with either benign or malignant phenotype. Using tissue microarrays, we compared protein expression profiles in 28 typical Spitz nevi and 62 primary vertical growth phase non-spitzoid melanomas. Most of the significant differences were linked to cell-cycle deregulation such as overexpression of cyclin D1 and p21 in Spitz nevi compared with non-spitzoid melanomas (74 vs 16% and 91 vs 27%, respectively) and mitotic rate including Ki-67, highly expressed in deep areas of non-spitzoid melanomas (37%), whereas it is not expressed in Spitz nevi (0%), topoisomerase IIalpha (79% in non-spitzoid melanomas vs 15% in Spitz nevi) and nuclear survivin (69% in melanomas vs 0% in Spitz nevi). A combination of biological markers differentially expressed in Spitz nevi from non spitzoid melanomas is defined, thus providing a potential tool for histopathological differential diagnostic between Spitz nevus and melanoma. Nevertheless, more studies including atypical Spitz nevi and spitzoid melanomas are necessary to further establish a reliable panel to differentiate among difficult cases. PMID- 20543821 TI - PPM1D gene amplification and overexpression in breast cancer: a qRT-PCR and chromogenic in situ hybridization study. AB - PPM1D (protein phosphatase magnesium-dependent 1delta) maps to the 17q23.2 amplicon and is amplified in ~8% of breast cancers. The PPM1D gene encodes a serine threonine phosphatase, which is involved in the regulation of several tumour suppressor pathways, including the p53 pathway. Along with others, we have recently shown that PPM1D is one of the drivers of the 17q23.2 amplicon and a promising therapeutic target. Here we investigate whether PPM1D is overexpressed when amplified in breast cancers and the correlations between PPM1D overexpression and amplification with clinicopathological features and survival of breast cancer patients from a cohort of 245 patients with invasive breast cancer treated with therapeutic surgery followed by adjuvant anthracycline-based chemotherapy. mRNA was extracted from representative sections of tumours containing >50% of tumour cells and subjected to TaqMan quantitative real-time PCR using primers for PPM1D and for two housekeeping genes. PPM1D overexpression was defined as the top quartile of expression levels. Chromogenic in situ hybridization with in-house-generated probes for PPM1D was performed. Amplification was defined as >50% of cancer cells with >5 signals per nucleus/large gene clusters. PPM1D overexpression and amplification were found in 25 and 6% of breast cancers, respectively. All cases harbouring PPM1D amplification displayed PPM1D overexpression. PPM1D overexpression was inversely correlated with expression of TOP2A, EGFR and cytokeratins 5/6 and 17. PPM1D amplification was significantly associated with HER2 overexpression, and HER2, TOP2A and CCND1 amplification. No association between PPM1D gene amplification and PPM1D mRNA overexpression with survival was observed. In conclusion, PPM1D is consistently overexpressed when amplified; however, PPM1D overexpression is more pervasive than gene amplification. PPM1D overexpression and amplification are associated with tumours displaying luminal or HER2 phenotypes. Co-amplification of PPM1D and HER2/TOP2A and CCND1 are not random events and may suggest the presence of a 'firestorm' genetic profile. PMID- 20543822 TI - Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. AB - Although many attempts have been made to predict the occurrence of lymph node metastases from papillary thyroid carcinoma, there are currently no reliable means to accurately predict cervical nodal metastasis. In this study, we present a novel prediction system for the lymph node metastasis based on the histological and cyclin D1 staining features. The frequency of lymph node metastases from a series of 210 papillary thyroid carcinomas was analyzed according to the clinicopathological variables, cyclin D1 staining patterns and BRAF(V600E) mutation in tumor tissue. A total of 113 (54%) patients had lymph node metastasis. Cyclin D1 was constantly expressed at the invasive tumor front and revealed well-defined isolated glands of tumor cells in the extra-tumoral region (isolated glands) and laterally spreading tubular growth along the fibrous septa around the invasive front of the tumor (lateral tubular growth). Upon univariate analysis, an age of less than 45 years (P<0.001), tumor size of 10 mm or more (P<0.001), non-follicular variant (P=0.005), invasive growth pattern (P=0.007), extrathyroid extension (P=0.006), isolated glands (P<0.001), lateral tubular growth (P<0.001) and tumor multiplicity (P=0.005) predicted lymph node metastasis, whereas BRAF(V600E) mutation did not. Upon multivariate analysis, age (P=0.001, odds ratio (OR)=5.146), tumor size (P=0.034, OR=3.119), isolated glands (P<0.001, OR=21.042) and lateral tubular growth (P<0.001, OR=24.652) were found to be strong independent predictors of lymph node metastasis. Cyclin D1 staining of papillary thyroid carcinoma is very useful for identifying the intrathyroidal spreading or multifocality of the tumors. Tumor growth patterns verified by cyclin D1 staining can be used for the identification of papillary thyroid carcinomas with metastatic potential. PMID- 20543823 TI - Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. AB - In neurons, the axon initial segment (AIS) is a specialized region near the start of the axon that is the site of action potential initiation. The precise location of the AIS varies across and within different neuronal types, and has been linked to cells' information-processing capabilities; however, the factors determining AIS position in individual neurons remain unknown. Here we show that changes in electrical activity can alter the location of the AIS. In dissociated hippocampal cultures, chronic depolarization with high extracellular potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 mum away from the soma of excitatory neurons. This movement reverses when neurons are returned to non-depolarized conditions, and depends on the activation of T- and/or L-type voltage-gated calcium channels. The AIS also moved distally when we combined long-term LED (light-emitting diode) photostimulation with sparse neuronal expression of the light-activated cation channel channelrhodopsin-2; here, burst patterning of activity was successful where regular stimulation at the same frequency failed. Furthermore, changes in AIS position correlate with alterations in current thresholds for action potential spiking. Our results show that neurons can regulate the position of an entire subcellular structure according to their ongoing levels and patterns of electrical activity. This novel form of activity-dependent plasticity may fine-tune neuronal excitability during development. PMID- 20543824 TI - Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. AB - Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that regulate heterochromatin formation, developmental timing, defence against parasitic nucleic acids and genome rearrangement. Many small regulatory RNAs are thought to function in nuclei. For instance, in plants and fungi, short interfering RNA (siRNAs) associate with nascent transcripts and direct chromatin and/or DNA modifications. To understand further the biological roles of small regulatory RNAs, we conducted a genetic screen to identify factors required for RNA interference (RNAi) in Caenorhabditis elegans nuclei. Here we show that the gene nuclear RNAi defective-2 (nrde-2) encodes an evolutionarily conserved protein that is required for siRNA-mediated silencing in nuclei. NRDE-2 associates with the Argonaute protein NRDE-3 within nuclei and is recruited by NRDE-3/siRNA complexes to nascent transcripts that have been targeted by RNAi. We find that nuclear-localized siRNAs direct an NRDE-2-dependent silencing of pre messenger RNAs (pre-mRNAs) 3' to sites of RNAi, an NRDE-2-dependent accumulation of RNA polymerase (RNAP) II at genomic loci targeted by RNAi, and NRDE-2 dependent decreases in RNAP II occupancy and RNAP II transcriptional activity 3' to sites of RNAi. These results define NRDE-2 as a component of the nuclear RNAi machinery and demonstrate that metazoan siRNAs can silence nuclear-localized RNAs co-transcriptionally. In addition, these results establish a novel mode of RNAP II regulation: siRNA-directed recruitment of NRDE factors that inhibit RNAP II during the elongation phase of transcription. PMID- 20543825 TI - Presynaptic activity regulates Na(+) channel distribution at the axon initial segment. AB - Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity. The axon initial segment (AIS) is the site at which neural signals arise, and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na(+) channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na(+) current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation. PMID- 20543826 TI - Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. AB - The regulation of mitochondrial DNA (mtDNA) processes is slowly being characterized at a structural level. We present here crystal structures of human mitochondrial regulator mTERF, a transcription termination factor also implicated in replication pausing, in complex with double-stranded DNA oligonucleotides containing the tRNA(Leu)(UUR) gene sequence. mTERF comprises nine left-handed helical tandem repeats that form a left-handed superhelix, the Zurdo domain. PMID- 20543827 TI - A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. AB - In the absence of ligand, some nuclear receptors, including retinoic acid receptor (RAR), act as transcriptional repressors by recruiting corepressor complexes to target genes. This constitutive repression is crucial in metazoan reproduction, development and homeostasis. However, its specific molecular determinants had remained obscure. Using structural, biochemical and cell-based assays, we show that the basal repressive activity of RAR is conferred by an extended beta-strand that forms an antiparallel beta-sheet with specific corepressor residues. Agonist binding induces a beta-strand-to-alpha-helix transition that allows for helix H11 formation, which in turn provokes corepressor release, repositioning of helix H12 and coactivator recruitment. Several lines of evidence suggest that this structural switch could be implicated in the intrinsic repressor function of other nuclear receptors. Finally, we report on the molecular mechanism by which inverse agonists strengthen corepressor interaction and enhance gene silencing by RAR. PMID- 20543828 TI - An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1. AB - Hv1 voltage-gated proton channels mediate rapid and selective transmembrane H(+) flux and are gated by both voltage and pH gradients. Selective H(+) transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H(+) currents. Unexpectedly, charge neutralization was insufficient to abrogate either the Hv1 conductance or coupling of pH gradient and voltage-dependent activation. Molecular dynamics simulations revealed water molecules in the central crevice of Hv1 model structures but not in homologous voltage-sensor domain (VSD) structures. Our results indicate that Hv1 most likely forms an internal water wire for selective proton transfer and that interactions between water molecules and S4 arginines may underlie coupling between voltage- and pH-gradient sensing. PMID- 20543829 TI - Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor. AB - Several lines of evidence point to a role for noncoding RNA in transcriptional repression by Polycomb group (PcG) proteins, but the precise mechanism remains unclear. Here we show that human MOV10, a putative RNA helicase previously implicated in post-transcriptional gene silencing, co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1) from human cells. Endogenous human MOV10 is mostly nuclear, and a proportion associates with chromatin in an RNA-dependent manner. Small hairpin RNA (shRNA)-mediated knockdown of MOV10 in human fibroblasts leads to the upregulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by the dissociation of PRC1 proteins from the locus and a reduction in trimethylation of histone H3 on Lys27 (H3K27me3). As well as prompting reassessment of MOV10's role in other settings, our findings suggest that it is directly involved in transcriptional silencing by PcG complexes. PMID- 20543830 TI - Structural changes in a marine podovirus associated with release of its genome into Prochlorococcus. AB - Podovirus P-SSP7 infects Prochlorococcus marinus, the most abundant oceanic photosynthetic microorganism. Single-particle cryo-electron microscopy yields icosahedral and asymmetrical structures of infectious P-SSP7 with 4.6-A and 9-A resolution, respectively. The asymmetric reconstruction reveals how symmetry mismatches are accommodated among five of the gene products at the portal vertex. Reconstructions of infectious and empty particles show a conformational change of the 'valve' density in the nozzle, an orientation difference in the tail fibers, a disordering of the C terminus of the portal protein and the disappearance of the core proteins. In addition, cryo-electron tomography of P-SSP7 infecting Prochlorococcus showed the same tail-fiber conformation as that in empty particles. Our observations suggest a mechanism whereby, upon binding to the host cell, the tail fibers induce a cascade of structural alterations of the portal vertex complex that triggers DNA release. PMID- 20543831 TI - Protein refolding is required for assembly of the type three secretion needle. AB - Pathogenic Gram-negative bacteria use a type three secretion system (TTSS) to deliver virulence factors into host cells. Although the order in which proteins incorporate into the growing TTSS is well described, the underlying assembly mechanisms are still unclear. Here we show that the TTSS needle protomer refolds spontaneously to extend the needle from the distal end. We developed a functional mutant of the needle protomer from Shigella flexneri and Salmonella typhimurium to study its assembly in vitro. We show that the protomer partially refolds from alpha-helix into beta-strand conformation to form the TTSS needle. Reconstitution experiments show that needle growth does not require ATP. Thus, like the structurally related flagellar systems, the needle elongates by subunit polymerization at the distal end but requires protomer refolding. Our studies provide a starting point to understand the molecular assembly mechanisms and the structure of the TTSS at atomic level. PMID- 20543833 TI - Nanobiotechnology: Nanowires have cells in their sights. PMID- 20543832 TI - Live attenuated influenza virus vaccines by computer-aided rational design. AB - Despite existing vaccines and enormous efforts in biomedical research, influenza annually claims 250,000-500,000 lives worldwide, motivating the search for new, more effective vaccines that can be rapidly designed and easily produced. We applied the previously described synthetic attenuated virus engineering (SAVE) approach to influenza virus strain A/PR/8/34 to rationally design live attenuated influenza virus vaccine candidates through genome-scale changes in codon-pair bias. As attenuation is based on many hundreds of nucleotide changes across the viral genome, reversion of the attenuated variant to a virulent form is unlikely. Immunization of mice by a single intranasal exposure to codon pair-deoptimized virus conferred protection against subsequent challenge with wild-type (WT) influenza virus. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is especially relevant when dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza. PMID- 20543834 TI - Large oscillations of the magnetoresistance in nanopatterned high-temperature superconducting films. AB - Measurements on nanoscale structures constructed from high-temperature superconductors are expected to shed light on the origin of superconductivity in these materials. To date, loops made from these compounds have had sizes of the order of hundreds of nanometres(8-11). Here, we report the results of measurements on loops of La(1.84)Sr(0.16)CuO(4), a high-temperature superconductor that loses its resistance to electric currents when cooled below approximately 38 K, with dimensions down to tens of nanometres. We observe oscillations in the resistance of the loops as a function of the magnetic flux through the loops. The oscillations have a period of h/2e, and their amplitude is much larger than the amplitude of the resistance oscillations expected from the Little-Parks effect. Moreover, unlike Little-Parks oscillations, which are caused by periodic changes in the superconducting transition temperature, the oscillations we observe are caused by periodic changes in the interaction between thermally excited moving vortices and the oscillating persistent current induced in the loops. However, despite the enhanced amplitude of these oscillations, we have not detected oscillations with a period of h/e, as recently predicted for nanoscale loops of superconductors with d-wave symmetry, or with a period of h/4e, as predicted for superconductors that exhibit stripes. PMID- 20543835 TI - Subcellular-resolution delivery of a cytokine through precisely manipulated nanowires. AB - Precise delivery of molecular doses of biologically active chemicals to a pre specified single cell among many, or a specific subcellular location, is still a largely unmet challenge hampering our understanding of cell biology. Overcoming this could allow unprecedented levels of cell manipulation and targeted intervention. Here, we show that gold nanowires conjugated with a cytokine such as tumour-necrosis factor-alpha can be transported along any prescribed trajectory or orientation using electrophoretic and dielectrophoretic forces to a specific location with subcellular resolution. The nanowire, 6 microm long and 300 nm in diameter, delivered the cytokine and activated canonical nuclear factor kappaB signalling in a single cell. Combined computational modelling and experimentation indicated that cell stimulation was highly localized to the nanowire vicinity. This targeted delivery method has profound implications for controlling signalling events on the single cell level. PMID- 20543836 TI - A self-assembly pathway to aligned monodomain gels. AB - Aggregates of charged amphiphilic molecules have been found to access a structure at elevated temperature that templates alignment of supramolecular fibrils over macroscopic scales. The thermal pathway leads to a lamellar plaque structure with fibrous texture that breaks on cooling into large arrays of aligned nanoscale fibres and forms a strongly birefringent liquid. By manually dragging this liquid crystal from a pipette onto salty media, it is possible to extend this alignment over centimetres in noodle-shaped viscoelastic strings. Using this approach, the solution of supramolecular filaments can be mixed with cells at physiological temperatures to form monodomain gels of aligned cells and filaments. The nature of the self-assembly process and its biocompatibility would allow formation of cellular wires in situ that have any length and customized peptide compositions for use in biological applications. PMID- 20543837 TI - A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. AB - It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate. PMID- 20543838 TI - Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. AB - The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model in the mouse has been questioned; however, little is known about the lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of seven progenitor classes from neonatal cord blood and adult bone marrow. Human multilymphoid progenitors, identified as a distinct population of Thy-1(neg lo)CD45RA(+) cells in the CD34(+)CD38(-) stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages and dendritic cells, which indicated that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. PMID- 20543839 TI - Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens. AB - Classic cadherin receptors cooperate with regulators of the actin cytoskeleton to control tissue organization in health and disease. At the apical junctions of epithelial cells, the cadherin ring of the zonula adherens (ZA) couples with a contiguous ring of actin filaments to support morphogenetic processes such as tissue integration and cellular morphology. However, the molecular mechanisms that coordinate adhesion and cytoskeleton at these junctions are poorly understood. Previously we identified non-muscle myosin II as a target of Rho signalling that supports cadherin junctions in mammalian epithelial cells. Myosin II has various cellular functions, which are increasingly attributable to the specific biophysical properties and regulation of its different isoforms. Here we report that myosin II isoforms have distinct and necessary roles at cadherin junctions. Although two of the three mammalian myosin II isoforms are found at the ZA, their localization is regulated by different upstream signalling pathways. Junctional localization of myosin IIA required E-cadherin adhesion, Rho/ROCK and myosin light-chain kinase, whereas junctional myosin IIB depended on Rap1. Further, these myosin II isoforms support E-cadherin junction integrity by different mechanisms. Myosin IIA RNA-mediated interference (RNAi) selectively perturbed the accumulation of E-cadherin in the apical ZA, decreased cadherin homophilic adhesion and disrupted cadherin clustering. In contrast, myosin IIB RNAi decreased filament content, altered dynamics, and increased the lateral movement of the perijunctional actin ring. Myosin IIA and IIB therefore identify two distinct functional modules, with different upstream signals that control junctional localization, and distinct functional effects. We propose that these two isoform-based modules cooperate to coordinate adhesion receptor and F-actin organization to form apical cadherin junctions. PMID- 20543840 TI - Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. AB - Autophagy is characterized by the sequestration of bulk cytoplasm, including damaged proteins and organelles, and delivery of the cargo to lysosomes for degradation. Although the autophagic pathway is also linked to tumour suppression activity, the mechanism is not yet clear. Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation, but this process was independent of the transcriptional activity of FoxO1. In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. This FoxO1-modulated cell death is associated with tumour suppressor activity in human colon tumours and a xenograft mouse model. Our finding links the anti-neoplastic activity of FoxO1 and the process of autophagy. PMID- 20543841 TI - In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. AB - Protein translation has been implicated in different forms of synaptic plasticity, but direct in situ visualization of new proteins is limited to one or two proteins at a time. Here we describe a metabolic labeling approach based on incorporation of noncanonical amino acids into proteins followed by chemoselective fluorescence tagging by means of 'click chemistry'. After a brief incubation with azidohomoalanine or homopropargylglycine, a robust fluorescent signal was detected in somata and dendrites. Pulse-chase application of azidohomoalanine and homopropargylglycine allowed visualization of proteins synthesized in two sequential time periods. This technique can be used to detect changes in protein synthesis and to evaluate the fate of proteins synthesized in different cellular compartments. Moreover, using strain-promoted cycloaddition, we explored the dynamics of newly synthesized membrane proteins using single particle tracking and quantum dots. The newly synthesized proteins showed a broad range of diffusive behaviors, as would be expected for a pool of labeled proteins that is heterogeneous. PMID- 20543842 TI - Neural dynamics of in vitro cortical networks reflects experienced temporal patterns. AB - Learning ultimately relies on changes in the flow of activity in neural microcircuits. The plasticity of neural dynamics is particularly relevant for the processing of temporal information. Chronic stimulation of cultured rat cortical networks revealed experience-dependent plasticity in neural dynamics. We observed changes in the temporal structure of activity that reflected the intervals used during training, suggesting that cortical circuits are inherently capable of temporal processing on short timescales. PMID- 20543843 TI - Na+ imaging reveals little difference in action potential-evoked Na+ influx between axon and soma. AB - In cortical pyramidal neurons, the axon initial segment (AIS) is pivotal in synaptic integration. It has been asserted that this is because there is a high density of Na(+) channels in the AIS. However, we found that action potential associated Na(+) flux, as measured by high-speed fluorescence Na(+) imaging, was about threefold larger in the rat AIS than in the soma. Spike-evoked Na(+) flux in the AIS and the first node of Ranvier was similar and was eightfold lower in basal dendrites. At near-threshold voltages, persistent Na(+) conductance was almost entirely axonal. On a time scale of seconds, passive diffusion, and not pumping, was responsible for maintaining transmembrane Na(+) gradients in thin axons during high-frequency action potential firing. In computer simulations, these data were consistent with the known features of action potential generation in these neurons. PMID- 20543844 TI - Primer-initiated sequence synthesis to detect and assemble structural variants. PMID- 20543845 TI - Imaging plant growth in 4D: robust tissue reconstruction and lineaging at cell resolution. AB - Quantitative information on growing organs is required to better understand morphogenesis in both plants and animals. However, detailed analyses of growth patterns at cellular resolution have remained elusive. We developed an approach, multiangle image acquisition, three-dimensional reconstruction and cell segmentation-automated lineage tracking (MARS-ALT), in which we imaged whole organs from multiple angles, computationally merged and segmented these images to provide accurate cell identification in three dimensions and automatically tracked cell lineages through multiple rounds of cell division during development. Using these methods, we quantitatively analyzed Arabidopsis thaliana flower development at cell resolution, which revealed differential growth patterns of key regions during early stages of floral morphogenesis. Lastly, using rice roots, we demonstrated that this approach is both generic and scalable. PMID- 20543846 TI - Linking promoters to functional transcripts in small samples with nanoCAGE and CAGEscan. AB - Large-scale sequencing projects have revealed an unexpected complexity in the origins, structures and functions of mammalian transcripts. Many loci are known to produce overlapping coding and noncoding RNAs with capped 5' ends that vary in size. Methods to identify the 5' ends of transcripts will facilitate the discovery of new promoters and 5' ends derived from secondary capping events. Such methods often require high input amounts of RNA not obtainable from highly refined samples such as tissue microdissections and subcellular fractions. Therefore, we developed nano-cap analysis of gene expression (nanoCAGE), a method that captures the 5' ends of transcripts from as little as 10 ng of total RNA, and CAGEscan, a mate-pair adaptation of nanoCAGE that captures the transcript 5' ends linked to a downstream region. Both of these methods allow further annotation-agnostic studies of the complex human transcriptome. PMID- 20543847 TI - Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. AB - We conducted a genome-wide association study for testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected individuals and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three new susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5, which has previously been associated with multiple other cancers (rs4635969, OR=1.54, P=1.14x10(-23); rs2736100, OR=1.33, P=7.55x10(-15)). We also identified a locus on chromosome 12 (rs2900333, OR=1.27, P=6.16x10(-10)) that contains ATF7IP, a regulator of TERT expression. Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice. PMID- 20543848 TI - A pair of floral regulators sets critical day length for Hd3a florigen expression in rice. AB - The critical day length triggering photoperiodic flowering is set as an acute, accurate threshold in many short-day plants, including rice. Here, we show that, unlike the Arabidopsis florigen gene FT, the rice florigen gene Hd3a (Heading date 3a) is toggled by only a 30-min day-length reduction. Hd3a expression is induced by Ehd1 (Early heading date 1) expression when blue light coincides with the morning phase set by OsGIGANTEA(OsGI)-dependent circadian clocks. Ehd1 expression is repressed by both night breaks under short-day conditions and morning light signals under long-day conditions. Ghd7 (Grain number, plant height and heading date 7) was acutely induced when phytochrome signals coincided with a photosensitive phase set differently by distinct photoperiods and this induction repressed Ehd1 the next morning. Thus, two distinct gating mechanisms--of the floral promoter Ehd1 and the floral repressor Ghd7--could enable manipulation of slight differences in day length to control Hd3a transcription with a critical day-length threshold. PMID- 20543849 TI - Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. AB - Candida albicans is the most common cause of serious fungal disease in humans. Creation of isogenic null mutants of this diploid organism, which requires sequential gene targeting, allows dissection of virulence mechanisms. Published analyses of such mutants show a near-perfect correlation between C. albicans pathogenicity and the ability to undergo a yeast-to-hypha morphological switch in vitro. However, most studies have used mutants constructed with a marker that is itself a virulence determinant and therefore complicates their interpretation. Using alternative markers, we created approximately 3,000 homozygous deletion strains affecting 674 genes, or roughly 11% of the C. albicans genome. Screening for infectivity in a mouse model and for morphological switching and cell proliferation in vitro, we identified 115 infectivity-attenuated mutants, of which nearly half demonstrated normal morphological switching and proliferation. Analysis of such mutants revealed that virulence requires the glycolipid glucosylceramide. To our knowledge, this is the first C. albicans small molecule that has been found to be required specifically for virulence. PMID- 20543850 TI - Marine antifungal theonellamides target 3beta-hydroxysterol to activate Rho1 signaling. AB - Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Here we report the mode of action of theonellamides, bicyclic peptides derived from marine sponges. We generated a chemical-genomic profile of theonellamide F using a collection of fission yeast strains in which each open reading frame (ORF) is expressed under the control of an inducible promoter. Clustering analysis of the Gene Ontology (GO) terms associated with the genes that alter drug sensitivity suggested a mechanistic link between theonellamide and 1,3-beta-D-glucan synthesis. Indeed, theonellamide F induced overproduction of 1,3-beta-D-glucan in a Rho1-dependent manner. Subcellular localization and in vitro binding assays using a fluorescent theonellamide derivative revealed that theonellamides specifically bind to 3beta-hydroxysterols, including ergosterol, and cause membrane damage. The biological activity of theonellamides was alleviated in mutants defective in ergosterol biosynthesis. Theonellamides thus represent a new class of sterol-binding molecules that induce membrane damage and activate Rho1-mediated 1,3-beta-D-glucan synthesis. PMID- 20543852 TI - Micronutrient deficiency in the aetiology of obesity. PMID- 20543851 TI - Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. AB - Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease. PMID- 20543854 TI - Neurodegenerative diseases: failures in brain connectivity? PMID- 20543855 TI - Insights into semen analysis: a Chinese perspective on the fifth edition of the WHO laboratory manual for the examination and processing of human semen. PMID- 20543856 TI - The role of Dby mRNA in early development of male mouse zygotes. AB - Ejaculated mammalian spermatozoa contain a complex yet specific population of mRNA. However, the possible roles that mRNA has in early zygotic and embryonic development remain unclear. We found that Dby mRNA is selectively retained in capacitated mouse spermatozoa, and is transferred into the oocyte during fertilization by reverse transcription-polymerase chain reaction even though no DBY protein expression is detected. The cellular location of Dby mRNA is seen in the post-acrosome region, and it comprises nearly half of the mouse spermatozoa in in situ hybridization. In contrast, transcripts of the control gene, Smcy, are not detected in capacitated mouse spermatozoa, although the H-Y antigen encoded by Smcy is expressed on the surface of the spermatozoa. In our microinjection experiment, the zygotic development rate of the as-Dby male pronucleus injection group was significantly lower than that of the as-Smcy male pronucleus injection group (35.9% vs. 95%, P = 0.001) and the as-Dby female pronucleus injection group (35.9% vs. 93.8%, P = 0.001). The rate of male-developed zygotes was also lower than that of the as-Smcy male pronucleus injection group (17.4% vs. 57.9%, P = 0.002) and the as-Dby female pronucleus injection group (17.4% vs. 54.1%, P = 0.002). Thus, we conclude that Dby mRNA is selectively retained in capacitated mouse spermatozoa, and it has an important role in the early zygotic development of male mouse zygotes. This might imply that spermatozoa mRNA is involved in early zygotic and embryonic stages of reproduction. PMID- 20543857 TI - The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice. AB - Toll-like receptors (TLRs) are a family of highly conserved germline-encoded pattern-recognition receptors that are essential for host immune responses. TLR ligands represent a promising class of immunotherapeutics or vaccine adjuvants with the potential to generate an effective antitumor immune response. The TLR7/8 agonists have aroused interest because they not only activate antigen-presenting cells but also promote activation of T and natural killer (NK) cells. However, the exact mechanism by which stimulation of these TLRs promotes immune responses remains unclear, and different TLR7/8 agonists have been found to induce different responses. In this study, we demonstrate that both gardiquimod and imiquimod promote the proliferation of murine splenocytes, stimulate the activation of splenic T, NK and natural killer T (NKT) cells, increase the cytolytic activity of splenocytes against B16 and MCA-38 tumor cell lines, and enhance the expression of costimulatory molecules and IL-12 by macrophages and bone marrow-derived dendritic cells (DCs). In a murine model, both agonists improved the antitumor effects of tumor lysate-loaded DCs, resulting in delayed growth of subcutaneous B16 melanoma tumors and suppression of pulmonary metastasis. Further, we found that gardiquimod demonstrated more potent antitumor activity than imiquimod. These results suggest that TLR7/8 agonists may serve as potent innate and adaptive immune response modifiers in tumor therapy. More importantly, they can be used as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy. PMID- 20543858 TI - Recent advances in the molecular pathogenesis of Ewing's sarcoma. AB - Tumor development is a complex process resulting from interplay between mutations in oncogenes and tumor suppressors, host susceptibility factors, and cellular context. Great advances have been made by studying rare tumors with unique clinical, genetic, or molecular features. Ewing's sarcoma serves as an excellent paradigm for understanding tumorigenesis because it exhibits some very useful and important characteristics. For example, nearly all cases of Ewing's sarcoma contain the (11;22)(q24;q12) chromosomal translocation that encodes the EWS/FLI oncoprotein. Besides the t(11;22), however, many cases have otherwise simple karyotypes with no other demonstrable abnormalities. Furthermore, it seems that an underlying genetic susceptibility to Ewing's sarcoma, if it exists, must be rare. These two features suggest that EWS/FLI is the primary mutation that drives the development of this tumor. Finally, Ewing's sarcoma is an aggressive tumor that requires aggressive treatment. Thus, improved understanding of the pathogenesis of this tumor will not only be of academic interest, but may also lead to new therapeutic approaches for individuals afflicted with this disease. The purpose of this review is to highlight recent advances in understanding the molecular pathogenesis of Ewing's sarcoma, while considering the questions surrounding this disease that still remain and how this knowledge may be applied to developing new treatments for patients with this highly aggressive disease. PMID- 20543860 TI - Intermediate filament dynamics and breast cancer: aberrant promoter methylation of the Synemin gene is associated with early tumor relapse. AB - Synemin (SYNM) is a type IV intermediate filament that has recently been shown to interact with the LIM domain protein zyxin, thereby possibly modulating cell adhesion and cell motility. Owing to this multiplicity of potential functions relevant to cancer development, we initiated a study to decipher SYNM expression and regulation in benign human breast tissue and breast cancer. Dot blot array analysis showed significant SYNM mRNA downregulation in 86% (n=100, P<0.001) of breast cancers compared with their normal tissue counterparts, a result that was confirmed by real-time PCR analysis (n=36, P<0.0001). Immunohistochemistry analysis showed abundant SYNM protein expression in healthy myoepithelial breast cells, whereas SYNM expression loss was evident in 57% (n=37, P<0.001) of breast cancer specimens. Next, we analyzed methylation of the SYNM promoter to clarify whether the SYNM gene can be silenced by epigenetic means. Indeed, methylation specific PCR analysis showed tumor-specific SYNM promoter methylation in 27% (n=195) of breast cancers. As expected, SYNM promoter methylation was tightly associated (P<0.0001) with SYNM expression loss. In-depth analysis of the SYNM promoter by pyrosequencing showed extensive CpG methylation of DNA elements supposed to regulate gene transcription. Demethylating treatment of SYNM methylated breast cancer cell lines with 5-aza-2-deoxycytidine clearly reestablished the SYNM expression. Statistical analysis of the patient cohort showed a close association between SYNM promoter methylation and unfavorable recurrence-free survival (hazard ratio=2.941, P=0.0282). Furthermore, SYNM methylation positively correlated with lymph node metastases (P=0.0177) and advanced tumor grade (P=0.0275), suggesting that SYNM methylation is associated with aggressive forms of breast cancer. This is the first study on the epigenetic regulation of the SYNM gene in a cancer entity. We provide first hints that SYNM could represent a novel putative breast tumor suppressor gene that is prone to epigenetic silencing. SYNM promoter methylation may become a useful predictive biomarker to stratify breast cancer patients' risk for tumor relapse. PMID- 20543861 TI - Heterodimerization with Fra-1 cooperates with the ERK pathway to stabilize c-Jun in response to the RAS oncoprotein. AB - Multiple tumorigenic pathways converge on the activating protein-1 (AP-1) family of dimeric transcription complexes by affecting transcription, mRNA decay, posttranslational modifications, as well as stability of its JUN and FOS components. Several mechanisms have been implicated in the phosphorylation- and ubiquitylation-dependent control of c-Jun protein stability. Although its dimer composition has a major role in the regulation of AP-1, little is known about the influence of heterodimerization partners on the half-life of c-Jun. The FOS family member Fra-1 is overexpressed in various tumors and cancer cell lines wherein it controls motility, invasiveness, cell survival and cell division. Oncogene-induced accumulation of Fra-1 results from both increased transcription and phosphorylation-dependent stabilization of the protein. In this report, we describe a novel role of Fra-1 as a posttranslational regulator of c-Jun. By using both constitutively and inducible transformed rat thyroid cell lines, we found that c-Jun is stabilized in response to RAS oncoprotein expression. This stabilization requires the activity of the extracellular signal-related kinase (ERK) pathway, along with c-Jun heterodimerization with Fra-1. In particular, heterodimerization with Fra-1 inhibits c-Jun breakdown by a mechanism dependent on the phosphorylation of the Fra-1 C-terminal domain that positively controls the stability of the protein in response to ERK signaling. Therefore, Fra-1 modulates AP-1 dimer composition by promoting the accumulation of c-Jun in response to oncogenic RAS signaling. PMID- 20543859 TI - The ubiquitous nature of cancer: the role of the SCF(Fbw7) complex in development and transformation. AB - The ubiquitin-proteasome system (UPS) is a multi-subunit pathway that allows for ubiquitin modification of proteins and leads to either degradation or other non proteolytic processes such as trafficking or transcriptional activation. Given its role as a regulator of cellular homeostasis it is not surprising that members of the UPS are frequently aberrantly expressed in a number of disease states including cancer. This review will focus on one member of the UPS, the F-box protein, Fbw7 (also known as Sel-10, Ago, hCDC4) and mechanisms by which Fbw7 interacts with its substrates in the context of development and tumorigenesis will be discussed. In addition, antagonists of this pathway as well as current and future therapeutics for the UPS will be examined. PMID- 20543862 TI - Preneoplastic changes persist after IGF-IR downregulation and tumor regression. AB - Despite our incomplete understanding of the function of the type I insulin-like growth factor receptor (IGF-IR) in tumorigenesis, IGF-IR targeting agents have entered clinical trials for the treatment of human cancers. Previously, we have shown that downregulation of IGF-IR transgene in mammary tumors in MTB-IGFIR transengic mice results in tumor regression in a majority of the mice and most of these mice do not develop recurrent mammary tumors. In this study, we examined mammary tissue of mice that did not develop recurrent tumors. Areas of tumor regression were visible macroscopically and microscopically these lesions contained cell debris, individual cells, lipofuscin and doxycycline crystals. Three of the 12 mice also presented with considerable lobuloalveolar development. The re-expression of the IGF-IR transgene in mammary tissue with stably regressed tumors resulted in the rapid re-emergence of mammary tumors, some of which seemed to originate from the regressed mammary lesions. Thus, despite stable tumor regression after IGF-IR downregulation, mammary tissue contained preneoplastic lesions and tumors rapidly re-appear upon re-overexpression of IGF-IR transgene. Therefore, IGF-IR-targeting agents may be effective at regressing mammary tumors expressing IGF-IR, but these agents will not completely eradicate all tumor cells or restore the mammary stromal environment. PMID- 20543863 TI - L1CAM-integrin interaction induces constitutive NF-kappaB activation in pancreatic adenocarcinoma cells by enhancing IL-1beta expression. AB - L1 cell adhesion molecule (L1CAM) overexpression is often associated with bad prognosis in various human carcinomas. Recent studies also suggest a role of L1CAM in pancreatic ductal adenocarcinomas (PDAC). To further address its contribution, we expressed functional domains of L1CAM in PT45-P1 PDAC cells. We found that L1CAM that is full length (L1-FL), but neither the soluble ectodomain (L1ecto) nor the cytoplasmic part (L1cyt), could enhance cell proliferation or tumour growth in mice. Expression of L1-FL resulted in constitutive activation of NF-kappaB, which was abolished by L1CAM knockdown. We showed that the expression of IL-1beta was selectively upregulated by L1-FL, and increased IL-1beta levels were instrumental for sustained NF-kappaB activation. IL-1beta production and NF kappaB activation were abolished by knockdown of alpha5-integrin and integrin linked kinase, but insensitive to depletion of L1CAM cleavage proteinases. Supporting these data, PT45-P1 cells transduced with an L1CAM mutant deficient in integrin binding (L1-RGE) did not support the described L1-FL functions. Our results suggest that membranous L1CAM interacts with RGD-binding integrins, leading to sustained NF-kappaB activation by IL-1beta production and autocrine/paracrine signalling. The unravelling of this novel mechanism sheds new light on the important role of L1CAM expression in PDAC cells. PMID- 20543864 TI - DEK oncoprotein regulates transcriptional modifiers and sustains tumor initiation activity in high-grade neuroendocrine carcinoma of the lung. AB - Lung cancer shows diverse histological subtypes. Large-cell neuroendocrine cell carcinoma and small-cell lung carcinoma show similar histological features and clinical behaviors, and can be classified as high-grade neuroendocrine carcinoma (HGNEC) of the lung. Here we elucidated the molecular classification of pulmonary endocrine tumors by copy-number profiling. We compared alterations of copy number with the clinical outcome of HGNEC and identified a chromosomal gain of the DEK oncogene locus (6p22.3) that was significantly associated with poor prognosis. We further confirmed that DEK overexpression was associated with poor prognosis in a larger set of HGNEC. Downregulation of DEK by small hairpin RNA led to a marked reduction of in vitro colony formation, in vivo tumorigenicity and chemo resistance, and was associated with loss of lung cancer stem cell markers. Gene expression profiling revealed that DEK downregulation was associated with altered expression of transcriptional regulators, which specifically include known targets of interchromosomal translocations in hematopoietic tumors, and knockdown of these epigenetic modifiers affected colony formation activity. Our study showed that DEK overexpression, partly through an increase in its gene dose, mediates the activity of global transcriptional regulators and is associated with tumor initiation activity and poor prognosis in HGNEC. PMID- 20543865 TI - Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation. AB - Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation. PMID- 20543866 TI - Cell transformation mediated by the Epstein-Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling. AB - Epstein-Barr virus (EBV) open reading frame BILF1 encodes a seven trans-membrane (TM) G protein-coupled receptor that signals with high constitutive activity through Galpha(i) (Beisser et al., 2005; Paulsen et al., 2005). In this paper, the transforming potential of BILF1 is investigated in vitro in a foci formation assay using retrovirally transduced NIH3T3 cells, as well as in vivo by using nude mice. BILF1 revealed a substantial transforming potential that was dependent on constitutive signaling, as a signaling-deficient mutant completely lost its ability to transform cells in vitro, and an intermediately active triple-mutated receptor possessed an intermediate transforming potential. Furthermore, BILF1 expression induced vascular endothelial growth factor secretion in a constitutively active manner. In nude mice, BILF1 promoted tumor formation in 90% of cases, ORF74 (from Kaposi's sarcoma-associated herpes virus) in 100% of cases, whereas the signaling-deficient receptor resulted in tumor establishment in 40% of cases. These data suggest that BILF1, when expressed during EBV infection, could indeed be involved in the pathogenesis of EBV-associated diseases and malignancies. Furthermore, the correlation between receptor activity and the ability to mediate cell transformation in vitro and tumor formation in vivo supports the idea that inverse agonists for BILF1 could inhibit cell transformation and be relevant therapeutic candidates. PMID- 20543868 TI - SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity. AB - SPROUTY-2 (SPRY2) regulates receptor tyrosine kinase signalling and therefore cell growth and differentiation. In this study, we show that SPRY2 expression in colon cancer cells is inhibited by the active vitamin D metabolite 1alpha,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) through E-cadherin-dependent and independent mechanisms. In turn, SPRY2 represses both basal and 1,25(OH)(2)D(3) induced E-cadherin expression. In line with this, SPRY2 induces ZEB1 RNA and protein, but not that of other epithelial-to-mesenchymal transition inducers that repress the CDH1/E-cadherin promoter. Consistently, SPRY2 and E-cadherin protein levels inversely correlate in colon cancer cell lines and xenografted tumours. Moreover, SPRY2 knockdown by small hairpin RNA increases CDH1/E-cadherin expression and, reciprocally, CDH1/E-cadherin knockdown increases that of SPRY2. In colon cancer patients, SPRY2 is upregulated in undifferentiated high-grade tumours and at the invasive front of low-grade carcinomas. Quantification of protein expression in 34 tumours confirmed an inverse correlation between SPRY2 and E-cadherin. Our data demonstrate a tumourigenic action of SPRY2 that is based on the repression of E-cadherin, probably by the induction of ZEB1, and a reciprocal regulation of SPRY2 and E-cadherin that dictates cell phenotype. We propose SPRY2 as a candidate novel marker for high-grade tumours and a target of therapeutic intervention in colon cancer. PMID- 20543867 TI - miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers. AB - Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome. PMID- 20543869 TI - DRR drives brain cancer invasion by regulating cytoskeletal-focal adhesion dynamics. AB - Malignant glioma invasion is a primary cause of brain cancer treatment failure, yet the molecular mechanisms underlying its regulation remain elusive. We developed a novel functional-screening strategy and identified downregulated in renal cell carcinoma (DRR) as a regulator of invasion. We show that DRR drives invasion in vitro and in vivo. We found that while DRR is not expressed in normal glial cells, it is highly expressed in the invasive component of gliomas. Exploring underlying mechanisms, we show that DRR associates with and organizes the actin and microtubular cytoskeletons and that these associations are essential for focal adhesion (FA) disassembly and cell invasion. These findings identify DRR as a new cytoskeletal crosslinker that regulates FA dynamics and cell movement. PMID- 20543870 TI - Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer. AB - Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasis-suppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer. PMID- 20543874 TI - The mathematical review system: does reviewer status play a role in the citation process? AB - This paper revisits an aspect of citation theory (i.e., citer motivation) with respect to the Mathematical Review system and the reviewer's role in mathematics. We focus on a set of journal articles (369) published in Singularity Theory (1974 2003), the mathematicians who wrote editorial reviews for these articles, and the number of citations each reviewed article received within a 5 year period. Our research hypothesis is that the cognitive authority of a high status reviewer plays a positive role in how well a new article is received and cited by others. Bibliometric evidence points to the contrary: Singularity Theorists of lower status (junior researchers) have reviewed slightly more well-cited articles (2-5 citations, excluding author self-citations) than their higher status counterparts (senior researchers). One explanation for this result is that lower status researchers may have been asked to review 'trendy' or more accessible parts of mathematics, which are easier to use and cite. We offer further explanations and discuss a number of implications for a theory of citation in mathematics. This research opens the door for comparisons to other editorial review systems, such as book reviews written in the social sciences or humanities. PMID- 20543875 TI - An Evaluation of the Precision of Measurement of Ryff's Psychological Well-Being Scales in a Population Sample. AB - The aim of this study is to assess the effective measurement range of Ryff's Psychological Well-being scales (PWB). It applies normal ogive item response theory (IRT) methodology using factor analysis procedures for ordinal data based on a limited information estimation approach. The data come from a sample of 1,179 women participating in a midlife follow-up of a national birth cohort study in the UK. The PWB scales incorporate six dimensions: autonomy, positive relations with others, environmental mastery, personal growth, purpose in life and self-acceptance. Scale information functions were calculated to derive standard errors of measurement for estimated scores on each dimension. Construct variance was distinguished from method variance by inclusion of method factors from item wording (positive versus negative). Our IRT analysis revealed that the PWB measures well-being most accurately in the middle range of the score distribution, i.e. for women with average well-being. Score precision diminished at higher levels of well-being, and low well-being was measured more reliably than high well-being. A second-order well-being factor loaded by four of the dimensions achieved higher measurement precision and greater score accuracy across a wider range than any individual dimension. Future development of well being scales should be designed to include items that are able to discriminate at high levels of well-being. PMID- 20543876 TI - "El Sexo no es Malo": Maternal Values Accompanying Contraceptive Use Advice to Young Latina Adolescent Daughters. AB - In this study, we utilized observational methods to identify maternal values and concerns accompanying contraceptive use advice in Latina mother-daughter sexuality conversations. The sample included non-sexually active early adolescents around 12 years of age and their mostly Spanish-speaking Latina mothers. Videotaped conversations were coded for the prevalence of messages related to four sexual values (abstinence, delay sex until older, sex is "normal", sex is "improper") and concerns about pregnancy and STD transmission. We examined whether the duration of time spent conversing about these messages was associated with participant characteristics, general communication openness, and the amount of time the dyads spent discussing contraceptive use. Results indicated that Latina mothers who had fewer years of education and lower family income talked longer to their daughters about the need to delay sex, avoid risky situations that would increase their chances of getting pregnant or acquiring an STD, and engage in self-protective practices. Less perceived openness in general communication as reported by both the mothers and the daughters was associated with increased time discussing that sex is improper. Although the duration of contraceptive use messages was brief, mothers and daughters who discussed the fact that sex is normal, and who communicated more about the importance of delaying sex, talked longer about contraceptive use practices compared to mothers and daughters who engaged in minimal discussion of these sexual values. PMID- 20543877 TI - An epidemiologic review of enteropathogens in Gaborone, Botswana: shifting patterns of resistance in an HIV endemic region. AB - BACKGROUND: The epidemiology of diarrheal disease in Botswana, an HIV endemic region, is largely unknown. Our primary objective was to characterize the prevalent bacterial and parasitic enteropathogens in Gaborone, Botswana. Secondary objectives included determining corresponding antimicrobial resistance patterns and the value of stool white and red blood cells for predicting bacterial and parasitic enteropathogens. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional study examined laboratory records of stool specimens analyzed by the Botswana National Health Laboratory in Gaborone, Botswana from February 2003 through July 2008. In 4485 specimens the median subject age was 23 [interquartile range 1.6-34] years. Overall, 14.4% (644 of 4485) of samples yielded a pathogen. Bacteria alone were isolated in 8.2% (367 of 4485), parasites alone in 5.6% (253 of 4485) and both in 0.5% (24 of 4485) of samples. The most common bacterial pathogens were Shigella spp. and Salmonella spp., isolated from 4.0% (180 of 4485) and 3.9% (175 of 4485) of specimens, respectively. Escherichia coli (22 of 4485) and Campylobacter spp. (22 of 4485) each accounted for 0.5% of pathogens. Comparing antimicrobial resistance among Shigella spp. and Salmonella spp. between two periods, February 2003 to February 2004 and July 2006 to July 2008, revealed an increase in ampicillin resistance among Shigella spp. from 43% to 83% (p<0.001). Among Salmonella spp., resistance to chloramphenicol decreased from 56% to 6% (p<0.001). The absence of stool white and red blood cells correlated with a high specificity and negative predictive value. CONCLUSIONS/SIGNIFICANCE: Most gastroenteritis stools were culture and microscopy negative suggesting that viral pathogens were the majority etiologic agents in this Botswana cohort. Shigella spp. and Salmonella spp. were the most common bacteria; Isospora spp. and Cryptosporidium spp. were the most common parasites. Resistance to commonly used antimicrobials is high and should be closely monitored. PMID- 20543878 TI - Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis. AB - Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment. PMID- 20543879 TI - Structure-function relations in oxaloacetate decarboxylase complex. Fluorescence and infrared approaches to monitor oxomalonate and Na(+) binding effect. AB - BACKGROUND: Oxaloacetate decarboxylase (OAD) is a member of the Na(+) transport decarboxylase enzyme family found exclusively in anaerobic bacteria. OAD of Vibrio cholerae catalyses a key step in citrate fermentation, converting the chemical energy of the decarboxylation reaction into an electrochemical gradient of Na(+) ions across the membrane, which drives endergonic membrane reactions such as ATP synthesis, transport and motility. OAD is a membrane-bound enzyme composed of alpha, beta and gamma subunits. The alpha subunit contains the carboxyltransferase catalytic site. METHODOLOGY/PRINCIPAL FINDINGS: In this report, spectroscopic techniques were used to probe oxomalonate (a competitive inhibitor of OAD with respect to oxaloacetate) and Na(+) effects on the enzyme tryptophan environment and on the secondary structure of the OAD complex, as well as the importance of each subunit in the catalytic mechanism. An intrinsic fluorescence approach, Red Edge Excitation Shift (REES), indicated that solvent molecule mobility in the vicinity of OAD tryptophans was more restricted in the presence of oxomalonate. It also demonstrated that, although the structure of OAD is sensitive to the presence of NaCl, oxomalonate was able to bind to the enzyme even in the absence of Na(+). REES changes due to oxomalonate binding were also observed with the alphagamma and alpha subunits. Infrared spectra showed that OAD, alphagamma and alpha subunits have a main component band centered between 1655 and 1650 cm(-1) characteristic of a high content of alpha helix structures. Addition of oxomalonate induced a shift of the amide-I band of OAD toward higher wavenumbers, interpreted as a slight decrease of beta sheet structures and a concomitant increase of alpha helix structures. Oxomalonate binding to alphagamma and alpha subunits also provoked secondary structure variations, but these effects were negligible compared to OAD complex. CONCLUSION: Oxomalonate binding affects the tryptophan environment of the carboxyltransferase subunit, whereas Na(+) alters the tryptophan environment of the beta subunit, consistent with the function of these subunits within the enzyme complex. Formation of a complex between OAD and its substrates elicits structural changes in the alpha-helical as well as beta-strand secondary structure elements. PMID- 20543881 TI - Domestication Syndrome in Caimito (Chrysophyllum cainito L.): Fruit and Seed Characteristics. AB - Domestication Syndrome in Caimito (Chrysophyllum cainitoL.): Fruit and Seed Characteristics: The process of domestication is understudied and poorly known for many tropical fruit tree crops. The star apple or caimito tree (Chrysophyllum cainito L., Sapotaceae) is cultivated throughout the New World tropics for its edible fruits. We studied this species in central Panama, where it grows wild in tropical moist forests and is also commonly cultivated in backyard gardens. Using fruits collected over two harvest seasons, we tested the hypothesis that cultivated individuals of C. cainito show distinctive fruit and seed characteristics associated with domestication relative to wild types. We found that cultivated fruits were significantly and substantially larger and allocated more to pulp and less to exocarp than wild fruits. The pulp of cultivated fruits was less acidic; also, the pulp had lower concentrations of phenolics and higher concentrations of sugar. The seeds were larger and more numerous and were less defended with phenolics in cultivated than in wild fruits. Discriminant Analysis showed that, among the many significant differences, fruit size and sugar concentration drove the great majority of the variance distinguishing wild from cultivated classes. Variance of pulp phenolics among individuals was significantly higher among wild trees than among cultivated trees, while variance of fruit mass and seed number was significantly higher among cultivated trees. Most traits showed strong correlations between years. Overall, we found a clear signature of a domestication syndrome in the fruits of cultivated caimito in Panama. PMID- 20543880 TI - Trafficking of Sendai virus nucleocapsids is mediated by intracellular vesicles. AB - BACKGROUND: Paramyxoviruses are assembled at the plasma membrane budding sites after synthesis of all the structural components in the cytoplasm. Although viral ribonuclocapsid (vRNP) is an essential component of infectious virions, the process of vRNP translocation to assembly sites is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To analyze real-time trafficking of vRNPs in live infected cells, we created a recombinant Sendai virus (SeV), rSeVLeGFP, which expresses L protein fused to enhanced green fluorescent protein (eGFP). The rSeVLeGFP showed similar growth kinetics compared to wt SeV, and newly synthesized LeGFP could be detected as early as 8 h postinfection. The majority of LeGFP co-localized with other components of vRNPs, NP and P proteins, suggesting the fluorescent signals of LeGFP represent the locations of vRNPs. Analysis of LeGFP movement using time-lapse digital video microscopy revealed directional and saltatory movement of LeGFP along microtubules. Treatment of the cells with nocodazole restricted vRNP movement and reduced progeny virion production without affecting viral protein synthesis, suggesting the role of microtubules in vRNP trafficking and virus assembly. Further study with an electron microscope showed close association of vRNPs with intracellular vesicles present in infected cells. In addition, the vRNPs co-localized with Rab11a protein, which is known to regulate the recycling endocytosis pathway and Golgi to-plasma membrane trafficking. Simultaneous movement between LeGFP and Rab11a was also observed in infected cells, which constitutively express mRFP-tagged Rab11a. Involvement of recycling endosomes in vRNP translocation was also suggested by the fact that vRNPs move concomitantly with recycling transferrin labeled with Alexa 594. CONCLUSIONS/SIGNIFICANCE: Collectively, our results strongly suggest a previously unrecognized involvement of the intracellular vesicular trafficking pathway in vRNP translocation and provide new insights into the transport of viral structural components to the assembly sites of enveloped viruses. PMID- 20543882 TI - Towards Conceptualizing Child Wellbeing in India: The Need for a Paradigm Shift. AB - Globally, there is a vast array of social indicators, many of these specifically oriented to the lives, experience and needs of children. This approach is much more advanced in developed economies and rich countries, where the focus has widened and shifted progressively towards a full recognition of the non-monetary dimensions of child wellbeing. At present, there would appear to be a propitious academic, activist and policy conjuncture for the widening of the discourse on child deprivation in India. This environment is created partly by the emerging reporting requirements and exhortations of the international development regime. But it is also fuelled by dissatisfaction over the inability of the existing methodologies, dominated by the reductionist monetary poverty line approach, to provide a meaningful intellectual or operational frame for contending with issues of child wellbeing in a holistic manner. The basic argument of this paper is that a double paradigm shift is urgently necessary: from mainstream approaches which tend to focus overwhelmingly on the material poverty and deprivation experienced by some children, deemed by definition to be those in households-in-poverty, to one that widens the field of vision to include both material and non-material dimensions of wellbeing of all children. Clearly, fresh epistemological and methodological challenges will have to be met with innovative and creative responses. It is time for India to catch up with best practices in rich countries, and given the impressive dimensions of India's academic and professional infrastructure, this should not be an unrealistic goal. PMID- 20543883 TI - Compact integration factor methods for complex domains and adaptive mesh refinement. AB - Implicit integration factor (IIF) method, a class of efficient semi-implicit temporal scheme, was introduced recently for stiff reaction-diffusion equations. To reduce cost of IIF, compact implicit integration factor (cIIF) method was later developed for efficient storage and calculation of exponential matrices associated with the diffusion operators in two and three spatial dimensions for Cartesian coordinates with regular meshes. Unlike IIF, cIIF cannot be directly extended to other curvilinear coordinates, such as polar and spherical coordinate, due to the compact representation for the diffusion terms in cIIF. In this paper, we present a method to generalize cIIF for other curvilinear coordinates through examples of polar and spherical coordinates. The new cIIF method in polar and spherical coordinates has similar computational efficiency and stability properties as the cIIF in Cartesian coordinate. In addition, we present a method for integrating cIIF with adaptive mesh refinement (AMR) to take advantage of the excellent stability condition for cIIF. Because the second order cIIF is unconditionally stable, it allows large time steps for AMR, unlike a typical explicit temporal scheme whose time step is severely restricted by the smallest mesh size in the entire spatial domain. Finally, we apply those methods to simulating a cell signaling system described by a system of stiff reaction diffusion equations in both two and three spatial dimensions using AMR, curvilinear and Cartesian coordinates. Excellent performance of the new methods is observed. PMID- 20543884 TI - Dually Fluorescent Sensing of pH and Dissolved Oxygen Using a Membrane Made from Polymerizable Sensing Monomers. AB - Using a thermal polymerization approach and polymerizable pH and oxygen sensing monomers with green and red emission spectra, respectively, new pH, oxygen, and their dual sensing membranes were prepared using poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) as a matrix. The sensors were grafted on acrylate-modified quartz glass and characterized under different pH values, oxygen concentrations, ion strengths, temperatures and cell culture media. The pH and oxygen sensors were excited using the same excitation wavelength and exhibited well-separated emission spectra. The pH-sensing films showed good response over the pH range 5.5 to 8.5, corresponding to pK(a) values in the biologically-relevant range between 6.9 and 7.1. The oxygen-sensing films exhibited linear Stern-Volmer quenching responses to dissolved oxygen. As the sensing membranes were prepared using thermally initiated polymerization of sensing moiety-containing monomers, no leaching of the sensors from the membranes to buffers or medium was observed. This advantageous characteristic accounts in part for the sensors' biocompatibility without apparent toxicity to HeLa cells after 40 hours incubation. The dual-sensing membrane was used to measure pH and dissolved oxygen simultaneously. The measured results correlated with the set point values. PMID- 20543885 TI - Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. AB - Darunavir (DRV) is a high affinity (4.5*10(-12) M, DeltaG = -15.2 kcal/mol) HIV-1 protease inhibitor. Two drug-resistant protease variants FLAP+ (L10I, G48V, I54V, V82A) and ACT (V82T, I84V) decrease the binding affinity with DRV by 1.0 kcal/mol and 1.6 kcal/mol respectively. In this study the absolute and relative binding free energies of DRV with wild-type protease, FLAP+ and ACT were calculated with MM-PB/GBSA and thermodynamic integration methods, respectively. Free energy decomposition elucidated that the mutations conferred resistance by distorting the active site of HIV-1 protease so that the residues that lost binding free energy were not limited to the sites of mutation. Specifically the bis tetrahydrofuranylurethane moiety of DRV maintained interactions with the FLAP+ and ACT variants, whereas the 4 - amino phenyl group lost more binding free energy with the protease in the FLAP+ and ACT complexes than in the wild-type protease which could account for the majority of the loss in binding free energy. This suggested that replacement of the 4 - amino phenyl group might generate new inhibitors less susceptible to the drug resistant mutations. PMID- 20543886 TI - Immunotherapy in food allergy. AB - Food allergies are caused by immune responses to food proteins and represent a breakdown of oral tolerance. They can range from mild pruritus to life threatening anaphylaxis. The only current consensus for treatment is food avoidance, which is fraught with compliance issues. For this reason, there has been recent interest in immunotherapy, which may induce desensitization and possibly even tolerance. Through these effects, immunotherapy may decrease the potential for adverse serious reactions with accidental ingestions while potentially leading to an overall health benefit. In this review, we discuss the mechanisms of food allergy and give an overview of the various immunotherapeutic options and current supporting evidence, as well as look towards the future of potential novel therapeutic modalities. PMID- 20543888 TI - Segmented Assimilation Revisited: Types of Acculturation and Socioeconomic Mobility in Young Adulthood. AB - This article examines the debate between key theories of immigrant assimilation by exploring the effect of acculturation types - dissonant, consonant, and selective - on socioeconomic outcomes in young adulthood. Drawing on survey data from the Immigrant Second Generation in Metropolitan New York, we show that while all three types occur, dissonant acculturation is the exception, not the norm, among second generation young adults. Our results also suggest that neither the type of acculturation nor the level of ethnic embeddedness can account for the variation in mobility patterns both across and within second generation groups. These findings lead us to question assumptions about the protective effect of selective acculturation and the negative effect of dissonant acculturation. PMID- 20543889 TI - The ACTive Intervention in Hospice Interdisciplinary Team Meetings: Exploring family caregiver and hospice team communication. AB - This paper presents the theoretical framework and rationale for the ACTive intervention which proposes the use of video technology to facilitate patient and family participation in hospice interdisciplinary team meetings where plans of care are determined. It is surmised that patient and family involvement will improve communication and compliance in hospice care. An analysis of data from a pilot project of the ACTive intervention was conducted to explore active participation among family caregivers and the hospice team. Through the use of videophone technology caregivers participated in video-recorded team meetings. The actual communication behaviors of caregivers and team members were analyzed for active participation. Findings revealed that team-prompted caregiver participation was most common, however, team use of supportive talk in this context was considerably less frequent. The study also found that the team's use of active participation behaviors elicits caregiver active participation behaviors. The results of this study suggest the intervention was an effective way to involve family caregivers as active participants in the designing of care for their loved one. Findings also suggest that hospice staff would benefit from education and training on best practices for communicating with caregivers in the team meeting setting. PMID- 20543887 TI - Thromboxane and the thromboxane receptor in cardiovascular disease. AB - Thromboxane A(2) (TXA(2)), the primary product of COX-1-dependent metabolism of arachidonic acid, mediates its biological actions through the TXA(2) receptor, termed the TP. Irreversible inhibition of platelet COX-1-derived TXA(2) with low dose aspirin affords protection against primary and secondary vascular thrombotic events, underscoring the central role of TXA(2) as a platelet agonist in cardiovascular disease. The limitations associated with aspirin use include significant gastrointestinal toxicity, bleeding complications, potential interindividual response variability and poor efficacy in some disease states. This, together with the broad role of TXA(2) in cardiovascular disease beyond the platelet, has refocused interest towards additional TXA(2)-associated drug targets, in particular TXA(2) synthase and the TP. The superiority of these agents over low-dose aspirin, in terms of clinical efficacy, tolerability and commercial viability, remain open questions that are the focus of ongoing research. PMID- 20543891 TI - On nonparametric comparison of images and regression surfaces. AB - Multivariate local regression is an important tool for image processing and analysis. In many practical biomedical problems, one is often interested in comparing a group of images or regression surfaces. In this paper, we extend the existing method of testing the equality of nonparametric curves by Dette and Neumeyer (2001) and consider a test statistic by means of an Lgrangian (2) distance in the multi-dimensional case under a completely heteroscedastic nonparametric model. The test statistic is also extended to be used in the case of spatial correlated errors. Two bootstrap procedures are described in order to approximate the critical values of the test depending on the nature of random errors. The resulting algorithms and analyses are illustrated from both simulation studies and a real medical example. PMID- 20543892 TI - Organization of Biomedical Data for Collaborative Scientific Research: A Research Information Management System. AB - Biomedical researchers often work with massive, detailed and heterogeneous datasets. These datasets raise new challenges of information organization and management for scientific interpretation, as they demand much of the researchers' time and attention. The current study investigated the nature of the problems that researchers face when dealing with such data. Four major problems identified with existing biomedical scientific information management methods were related to data organization, data sharing, collaboration, and publications. Therefore, there is a compelling need to develop an efficient and user-friendly information management system to handle the biomedical research data. This study evaluated the implementation of an information management system, which was introduced as part of the collaborative research to increase scientific productivity in a research laboratory. Laboratory members seemed to exhibit frustration during the implementation process. However, empirical findings revealed that they gained new knowledge and completed specified tasks while working together with the new system. Hence, researchers are urged to persist and persevere when dealing with any new technology, including an information management system in a research laboratory environment. PMID- 20543890 TI - Synaptic plasticity, a symphony in GEF. AB - Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, the main structural component of dendritic spines. The ability of neurons to alter spine number and size is essential for the expression of neuronal plasticity. Within spines, guanine nucleotide exchange factors (GEFs) act as critical regulators of the actin cytoskeleton by controlling the activity of Rho GTPases. In this review we focus on the Rho-GEFs expressed in the nucleus accumbens and localized to the postsynaptic density, and thus positioned to effect rapid alterations in the structure of dendritic spines. We review literature that ties these GEFs to different receptor systems and intracellular signaling cascades and discuss the effects these interactions are likely to have on synaptic plasticity. PMID- 20543893 TI - Family Structure, Family Processes, and Adolescent Smoking and Drinking. AB - This study examined whether family structure was associated with adolescent risk behaviors, including smoking and drinking. Family living arrangements have become increasingly diverse, yet research on adolescent risk behaviors has typically relied on measures of family structure that do not adequately capture this diversity. Data from the 1994-95 National Longitudinal Study of Adolescent Health were used to conduct logistic regression analyses that revealed adolescents in two biological married parent families were least likely to smoke or drink, whereas adolescents in cohabiting stepfamilies were most likely. Those in single mother families and married stepfamilies were in between. Maternal socialization was related to reduced odds of smoking and drinking. Maternal modeling was positively associated with smoking and drinking. Family structure is indicative of distinct family processes that are linked to risky behaviors among adolescents. PMID- 20543894 TI - Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat. AB - Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material's bio-compatibility and safety. Ultra-small particles may adversely affect living cells and organisms since they can easily penetrate the body through skin contact, inhalation and ingestion. Retrograde transport of copper nanoparticles from nerve endings on the skin can reach the somatosensory neurons in dorsal root ganglion (DRG). Since copper nanoparticles have industrial and healthcare applications, we determined the concentration and size-dependant effects of their exposure on survival of DRG neurons of rat in cell culture. The neurons were exposed to copper nanoparticles of increasing concentrations (10-100 muM) and sizes (40, 60 and 80 nm) for 24 h. Light microscopy, histochemical staining for copper, lactate dehydrogenase (LDH) assay for cell death, and MTS [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay for cell viability were performed to measure the resultant toxicity and cell survival. DRG neurons exposed to copper nanoparticles displayed vacuoles and detachment of some neurons from the substratum. Neurons also exhibited disrupted neurite network. LDH and MTS assays revealed that exposure to copper nanoparticles had significant toxic effect with all the sizes tested when compared to unexposed control cultures. Further analysis of the results showed that copper nanoparticles of smaller size and higher concentration exerted the maximum toxic effects. Rubeanic acid staining showed intracellular deposition of copper. These results demonstrate that copper nanoparticles are toxic in a size- and concentration-dependent manner to DRG neurons. PMID- 20543895 TI - Targeted Nanodelivery of Drugs and Diagnostics. AB - Nanomaterials for targeted delivery are uniquely capable of localizing delivery of therapeutics and diagnostics to diseased tissues. The ability to achieve high, local concentrations of drugs or image contrast agents at a target site provides the opportunity for improved system performance and patient outcomes along with reduced systemic dosing. In this review, the design of targeted nanodelivery systems is discussed with an emphasis on in vivo performance, the physicochemical properties that affect localization at the target site, and the incorporation of therapeutic drugs into these systems. PMID- 20543896 TI - Acetonide Protection of Dopamine for the Synthesis of Highly Pure N docosahexaenoyldopamine. AB - Direct acetonide protection of the catechol of dopamine has proven to be problematic due to formation of Pictet-Spengler isoquinolines. Here we report an efficient method for acetonide protection of dopamine, allowing preparation of a dopamine prodrug without complications from the Pictet-Spengler reaction. Acetonide-protected dopamine was first synthesized by pre-protecting the amino group with phthaloyl followed by refluxing with 2,2-dimethoxypropane in the presence of TsOH. Further work demonstrated that Fmoc or trifluoroacetyl were also suitable N-protective groups, while Boc-protected dopamine gave an isoquinoline product. Acetonide-protected dopamine was coupled to DHA (all cis 4,7,10,13,16,19-docosahexaenoic acid) to produce the N-DHA-dopamine prodrug in high purity. PMID- 20543897 TI - Prescription opioid use among patients seeking treatment for opioid dependence. AB - OBJECTIVE: This study was designed to assess non-medical prescription opioid use among a sample of opioid dependent participants. METHODS: A cross-sectional survey was conducted with a convenience sample of patients hospitalized for medical management of opioid withdrawal. We collected data related to participant demographics, socio-economic characteristics, the age of first opioid use, types of opioids preferred, and routes of administration. We also asked participants to describe how they first began using opioids and how their use progressed over time. RESULTS: Among the 75 participants, the mean age was 32 years (SD: +/- 11, range: 18-70), 49 (65%) were men, 58 (77%) considered themselves to be "white," 55 (74%) had a high school diploma or equivalent, and 39 (52%) were unemployed. All of these participants considered themselves to be "addicted." Thirty-one (41%) felt that their addiction began with "legitimate prescriptions," 24 (32%) with diverted prescription medications, and 20 (27%) with "street drugs" from illicit sources; however, 69 (92%) had reported purchasing opioids "off the street" at some point in time. Thirty-seven (49%) considered heroin to be their current preferred drug, and 43 (57%) had used drugs intravenously. CONCLUSIONS: We found that many treatment-seeking opioid dependent patients first began using licit prescription drugs before obtaining opioids from illicit sources. Later, they purchased heroin, which they would come to prefer because it was less expensive and more effective than prescription drugs. PMID- 20543898 TI - Could gene therapy be the future for muscular dystrophy? PMID- 20543899 TI - Functional Brain Image Analysis Using Joint Function-Structure Priors. AB - We propose a new method for context-driven analysis of functional magnetic resonance images (fMRI) that incorporates spatial relationships between functional parameter clusters and anatomical structure directly for the first time. We design a parametric scheme that relates functional and structural spatially-compact regions in a single unified manner. Our method is motivated by the fact that the fMRI and anatomical MRI (aMRI) have consistent relations that provide configurations and context that aid in fMRI analysis. We develop a statistical decision-making strategy to estimate new fMRI parameter images (based on a General Linear Model-GLM) and spatially-clustered zones within these images. The analysis is based on the time-series data and contextual information related to appropriate spatial grouping of parameters in the functional data and the relationship of this grouping to relevant gray matter structure from the anatomical data. We introduce a representation for the joint prior of the functional and structural information, and define a joint probability distribution over the variations of functional clusters and the related structure contained in a set of training images. We estimate the Maximum A Posteriori (MAP) functional parameters, formulating the function-structure model in terms of level set functions. Results from 3D fMRI and aMRI show that this context-driven analysis potentially extracts more meaningful information than the standard GLM approach. PMID- 20543901 TI - Herpes simplex virus keratitis: histopathology and corneal allograft outcomes. AB - Molecular biologic studies have elucidated the roles of specific and innate immune responses in the pathogenesis of HSV keratitis. Recent evidence suggests that interference with innate immune mechanisms may reduce the severity of HSV keratitis and its complications. The agents targeting innate immune responses are particularly amenable to translational therapy for patients at risk of complications of HSV keratitis and poor corneal transplant outcomes. Histopathologic evidence of neovascularization or inflammation in tissue removed at the time of corneal transplantation predicts patients who are at risk for allograft rejection or failure. Such patients are prime candidates for close monitoring and intensive therapy. Newer imaging techniques, such as clinical confocal biomicroscopy, might be useful in identifying neovascularization and inflammation that place patients at high risk for poor allograft outcomes prior to corneal transplantation. PMID- 20543902 TI - Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes. AB - Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article, we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. PMID- 20543900 TI - Role of specific microRNAs in regulation of vascular smooth muscle cell differentiation and the response to injury. AB - Vascular smooth muscle cells (VSMCs) exhibit remarkable plasticity during postnatal development. Vascular injury initiates and perpetuates VSMCs dedifferentiation to a synthetic phenotype, which has been increasingly recognized to play a central role in neointimal hyperplasia during the pathogenesis of vascular proliferative diseases. MicroRNAs (miRNAs) are a novel class of regulatory noncoding RNAs that regulate gene expression at the posttranscriptional level by binding to 3' untranslated regions of target mRNAs, leading to either degrading mRNAs or inhibiting their translation. There is emerging evidence that miRNAs are critical regulators of widespread cellular functions such as differentiation, proliferation, and migration. Recent studies have indicated that a number of specific miRNAs play important roles in regulation of vascular cell functions and contribute to neointimal hyperplasia after vascular injury. Here, we review recent advance regarding functions of specific miRNAs in vasculature and discuss possible mechanisms by which miRNAs modulate proliferation and differentiation of VSMCs. PMID- 20543903 TI - Ternary Porphyrinato Hf(IV) and Zr(IV) - Polyoxometalate Complexes. AB - We report a facile, high yield synthesis and characterization of discrete, ternary porphyrin-metal-polyoxometalate (Por-M-POM) complexes where a group (IV) transition metal ion is bound both to the porphyrin core and to the lacunary site of a Keggin POM, PW(11)O(39) (-7). The remarkably robust complexes exploit the fact that Hf(IV) and Zr(IV) are 7-8 coordinate and reside outside the plane of the porphyrin macrocycle, thus enabling the simultaneous coordination to meso tetraphenylporphyrin (TPP) or meso-tetra(4-pyridyl)porphyrin (TPyP) and to the defect site in the Keggin framework. The physical properties of the (TPP)Hf(PW(11)O(39))[TBA](5), (TPyP)Hf(PW(11)O(39))[TBA](5), and (TPP)Zr(PW(11)O(39))[TBA](5) complexes are similar because the metal ions have similar oxidation states, and coordination chemistry.This architecture couples the photonic properties of the porphyrin to the POM because the metal ion is incorporated into both frameworks. Thus the ternary complexes can serve as a basis for the characterization of Hf(IV) and Zr(IV) porphyrins bound to oxide surfaces via the group (IV) metal ions. The Hf(Por) and Zr(Por) bind strongly to TiO(2) nanoparticles and indium tin oxide (ITO) surfaces, but significantly less binds to crystalline SiO(2) or TiO(2) surfaces. Together, the strong binding of the metalloporphyrins to the POM, nanoparticles, and the ITO surfaces, and paucity of binding to crystalline surfaces, suggests that the 3-4 open coordination sites on the Hf(Por) and Zr(Por) are predominantly bound at surface defect sites. PMID- 20543904 TI - Optoelectronic tweezers as a tool for parallel single-cell manipulation and stimulation. AB - Optoelectronic tweezers (OET) is a promising approach for the parallel manipulation of single cells for a variety of biological applications. By combining the manipulation capabilities of OET with other relevant biological techniques (such as cell lysis and electroporation), one can realize a true parallel, single-cell diagnostic and stimulation tool. Here, we demonstrate the utility of the OET device by integrating it onto single-chip systems capable of performing in-situ, electrode-based electroporation/lysis, individual cell, light induced lysis, and light-induced electroporation. PMID- 20543905 TI - Mechanisms of lipase maturation. AB - Lipases are acyl hydrolases that represent a diverse group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding and subunit assembly. This article identifies and discusses mechanisms that direct early and late events in lipase folding and assembly. Lipase maturation employs the two general chaperone systems operating in the endoplasmic reticulum, as well as a recently identified lipase-specific chaperone termed lipase maturation factor 1. We propose that the two general chaperone systems act in a coordinated manner early in lipase maturation in order to help create partially folded monomers; lipase maturation factor 1 then facilitates final monomer folding and subunit assembly into fully functional homodimers. Once maturation is complete, the lipases exit the endoplasmic reticulum and are secreted to extracellular sites, where they carry out a number of functions related to lipoprotein and lipid metabolism. PMID- 20543906 TI - The effect of jasplakinolide on the thermodynamic properties of ADP.BeF(x) bound actin filaments. AB - The effect of BeF(x) and a natural toxin (jasplakinolide) was examined on the thermal stability of actin filaments by using differential scanning calorimetry. The phosphate analogue beryllium fluoride shifted the melting temperature of actin filaments (67.4 degrees C) to 83.7 degrees C indicating that the filaments were thermodynamically more stable in their complex with ADP.BeF(x). A similar tendency was observed when the jasplakinolide was used in the absence of BeF(x). When both the ADP.BeF(x) and the jasplakinolide bound to the actin filaments their collective effect was similar to that observed with ADP.BeF(x) or jasplakinolide alone. These results suggested that ADP.BeF(x) and jasplakinolide probably stabilize the actin filaments by similar molecular mechanisms. PMID- 20543909 TI - The Barcelona declaration on bridging knowledge in long-term care and support. Barcelona (Spain), March 7, 2009. PMID- 20543908 TI - Bacterial 'cosmopolitanism' and importance of local environmental factors for community composition in remote high-altitude lakes. AB - In October 2004, plankton samples were collected from six permanent lakes located between 4960 and 5440 m a.s.l. in the Mount Everest region (Nepal) to assess how spatial and local environmental factors affect natural bacterial community composition. Fingerprinting analysis of the bacterial 16S rRNA gene fragment was done by denaturing gradient gel electrophoresis (DGGE).The number of DGGE bands (range: 12-23) was not correlated with lake area or remoteness, but there was a strong negative correlation with the ratio of catchment to lake area (r = -0.826, P < 0.05), suggesting that hydraulic retention time affects the establishment of the bacterial community in these seepage lakes.Most dominant sequences belonged to Betaproteobacteria except in two lakes where members of Bacteroidetes made the largest relative contribution. Up to 81% of the phylotypes had high similarity (>98 to 100%) in partial 16S rRNA gene sequence to those reported from other alpine lakes and glaciers around the world, suggesting the presence of 'cosmopolitan' bacteria.An analysis based on dissimilarity matrices and the Mantel test revealed the existence of dissimilarities in bacterial community composition related to geographical distance over a small spatial scale (<6 km), but determined by local environmental constraints.Our results suggest that several bacterial phylotypes are ubiquitous in the freshwater aquatic realm, but taxon sorting by local environmental constraints is important. PMID- 20543910 TI - Solid-contact potentiometric polymer membrane microelectrodes for the detection of silver ions at the femtomole level. AB - In recent years, ion-selective electrodes based on polymer membranes have been shown to exhibit detection limits that are often in the nanomolar concentration range, and thus drastically lower than traditionally accepted. Since potentiometry is less dependent on scaling laws that other established analytical techniques, their performance in confined sample volumes is explored here. Solid contact silver-selective microelectrodes, with a sodium-selective microelectrode as a reference, were inserted into a micropipette tip used as a 50-mul sample. The observed potential stabilities, reproducibilities and detection limits were attractive and largely matched that for large 100-ml samples. This should pave the way for further experiments to detecting ultra-small total ion concentrations by potentiometry, especially when used as a transducer after an amplification step in bioanalysis. PMID- 20543907 TI - Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles. AB - Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses. PMID- 20543912 TI - Conservative dentistry and endodontics in India. PMID- 20543913 TI - From here...... where and how? PMID- 20543911 TI - ECM-Aware Cell-Graph Mining for Bone Tissue Modeling and Classification. AB - Pathological examination of a biopsy is the most reliable and widely used technique to diagnose bone cancer. However, it suffers from both inter- and intra observer subjectivity. Techniques for automated tissue modeling and classification can reduce this subjectivity and increases the accuracy of bone cancer diagnosis. This paper presents a graph theoretical method, called extracellular matrix (ECM)-aware cell-graph mining, that combines the ECM formation with the distribution of cells in hematoxylin and eosin (H&E) stained histopathological images of bone tissues samples. This method can identify different types of cells that coexist in the same tissue as a result of its functional state. Thus, it models the structure-function relationships more precisely and classifies bone tissue samples accurately for cancer diagnosis. The tissue images are segmented, using the eigenvalues of the Hessian matrix, to compute spatial coordinates of cell nuclei as the nodes of corresponding cell graph. Upon segmentation a color code is assigned to each node based on the composition of its surrounding ECM. An edge is hypothesized (and established) between a pair of nodes if the corresponding cell membranes are in physical contact and if they share the same color. Hence, multiple colored-cell-graphs coexist in a tissue each modeling a different cell-type organization. Both topological and spectral features of ECM-aware cell-graphs are computed to quantify the structural properties of tissue samples and classify their different functional states as healthy, fractured, or cancerous using support vector machines. Classification accuracy comparison to related work shows that ECM-aware cell-graph approach yields 90.0% whereas Delaunay triangulation and simple cell graph approach achieves 75.0% and 81.1% accuracy, respectively. PMID- 20543914 TI - Dental caries: A complete changeover (Part II)-Changeover in the diagnosis and prognosis. AB - Realization that dental caries is a reversible, dynamic biochemical event at a micron level has changed the way the profession recognizes the caries disease and the caries lesion. The diagnosis of dental caries poses challenges due to the complex interaction of multiple endogenous causal factors. The most appropriate diagnostic aid for this purpose is the risk model of caries risk assessment. The analyses of the biological determinants provide clues to the dominant causal factor. The detection of a carious lesion has undergone a rigorous revision and revolution in order to identify the earliest mineral change so that it can be controlled without resorting to invasive management options. Apart from detection, it became mandatory to assess the extent of the lesion (noncavitated/cavitated), assess the activity status of the lesion (active/arrested), monitor the lesion progress (progression/regression over a period of time), and finally to predict the prognosis of the lesion as well as the disease. The prognosis of the disease can be best assessed by analyzing the predictor factors in caries risk assessment. The ultimate objective of such a meticulous and methodical approach aids in devising a tailor-made treatment plan, using preventing measures precisely and restorative measures minimally. This ensures the best oral health outcome of the patient. PMID- 20543915 TI - A comparative evaluation of the bonding efficacy of two-step vs all-in-one bonding agents - An in-vitro study. AB - AIM: Aim of this in vitro study was to compare the tensile bond strength of UniFil Bond (GC America) vs iBond (Heraeus Kulzer) in conjunction with light cure composite resin (Venus, Heraeus Kulzer). MATERIALS AND METHODS: Sixty mandibular molars were taken and divided into 3 groups which were treated with UniFil Bond, iBond and no adhesive respectively. The tensile test was performed using an Instron machine. RESULTS: The results showed that multibottle systems (UniFil Bond, i.e., two-step)performed 30% better as compared with single bottle systems (all-in-one, i.e., one-step bonding agents). CONCLUSION: It can be concluded that UniFil Bond (Multibottle system - 6(th)generation type I) performed better than iBond (Single Bottle system - 7th generation. PMID- 20543916 TI - A clinical survey of the output intensity of 200 light curing units in dental offices across Maharashtra. AB - AIM: The purpose of this study is to examine the intensity of light curing units and factors affecting it in dental offices. MATERIALS AND METHODS: The output intensity of 200 light curing units in dental offices across Maharashtra were examined. The collection of related information (thenumber of months of use of curing unit, the approximate number of times used in a day, and presence or absence of composite build-ups) and measurement of the intensity was performed by two operators. L.E.D Radiometer (Kerr) was used for measuring the output intensity. The average output intensity was divided into three categories (<200 mW/cm(2), 200-400 mW/ cm(2)and >400 mW/cm(2)). RESULTS: Among the 200 curing units examined, 81 were LED units and 119 were QTH units. Only 10% LED machines and 2% QTH curing units had good intensities (>400 mW/cm( 2)). CONCLUSION: Most of the examined curing lights had low output intensity ranging from 200 to 400 mW/cm(2), and most of the curing units had composite build-ups on them. PMID- 20543917 TI - The effect of cavity disinfectants on the sealing ability of dentin bonding system: An in vitro study. AB - AIM: This study was conducted to determine the effect of three cavity disinfectants (chlorhexidine gluconate based-Consepsis; benzalkonium chloride based Tubulicid Red, iodine-potassium iodide/copper-sulphate based Ora-5) on the microleakage of a dentin bonding system, Clearfil SE Bond. MATERIALS AND METHODS: Class V cavities were prepared on 45 extracted molars. The respective experimentalgroups were treated with cavity disinfectants and Clearfil SE Bond. Preparations without cavity disinfectants served as negative control and those with neither disinfectant nor dentin bonding resin application served as positive controls. After the cavity preparations were restored with resin composite (Clearfil APX), the specimens were subjected to dye penetration. Statistical analysis was performed using ANOVA (Kruskal-Wallis) test. RESULTS: Unlike Conspesis and Tubulicid Red, Ora-5 exhibited significantly higher microleakage and adversely affected the sealing ability of Clearfil SE bond. Only Consepsis and Tubulicid Red could be used as cavity disinfectants with Clearfil SE bond, without its sealing abilities being adversely affected. CONCLUSIONS: 1) Consepsis and Tubulicid Red can be used as cavity disinfectants with Clearfil SE Bond, without the sealing ability of Clearfil SE bond being affected. 2) Ora-5 is not an appropriate disinfectant to be used with this dentin bonding system, because it alters its sealing ability. PMID- 20543918 TI - Effect of sealers on fracture resistance of endodontically treated teeth with and without smear layer removal: An in vitro study. AB - AIM: The present study involved the in vitro comparison of root reinforcing abilities of two sealers, i.e., Ketac-Endo and Acroseal, in endodontically treated teeth in the presence and absence of smear layer. MATERIALS AND METHODS: Fifty teeth were taken and sectioned at the cementoenamel junction. The teeth with faults were discarded and a total of 36 teeth were used for study. The samples were biomechanically prepared using step-back technique. In 10 teeth, the smear layer was preserved using sodium hypochlorite. Smear layers were removed from 10 teeth using 17% EDTA, and in another 10 samples, the smear layers were eliminated using 17% EGTA. The remaining samples served as controls. Samples were obturated with sealers using the lateral condensation technique. Ketac-Endo (3M) is a glass ionomer based root canal sealer, and Acroseal (Septodont) sealers were used. The teeth were then tested by using an Instron testing machine. RESULTS: Ketac-Endo shows higher fracture resistance values in comparison to Acroseal. Other factors as the amount of tooth structure remaining, the agents used for the removal of smear layer and instrumentation techniques may alter the tooth resistance to fracture. CONCLUSION: Ketac-Endo shows higher fracture resistance values in comparison to Acroseal. PMID- 20543919 TI - Chemical analysis of dentin surfaces after Carisolv treatment. AB - AIMS AND OBJECTIVES: This study was done to characterize the surface chemistry after caries excavation with burs and Carisolv 2, by analyzing the relative amounts of organic and inorganic content, and also to analyze the penetration of the adhesive after etching and bonding using Micro Raman spectroscopy. MATERIALS AND METHODS: Twenty extracted molars with caries were distributed into the following groups and treated accordingly. Group 1-excavation with bur (10 teeth), and Group 2-excavation using Carisolv 2 (10 teeth). RESULTS AND CONCLUSION: Spectroscopic analysis showed that there was no significant difference in the chemical composition of the tooth between the groups after excavation (P > 0.05) either with bur or with Carisolv. The penetration of the dentin bonding resin in all samples of the Carisolv group was up to 15mum, whereas, in the bur group it was upto 10mum in few samples. Scanning Electron Microscopic analysis showed the surfaces of the Carisolv-treated dentin to be free of the smear layer, with open tubules, whereas, the dentin surfaces of the bur group showed surfaces covered with a smear layer. In the Carislov group the resin tags were found comparatively deeper than in the bur excavation group. In both the groups the integrity of the remaining dentin surfaces were maintained chemically and morphologically. PMID- 20543920 TI - Restoration of badly broken, endodontically treated posterior teeth. AB - It is generally agreed that the successful treatment of a badly broken tooth with pulpal disease depends not only on good endodontic therapy, but also on good prosthetic reconstruction of the tooth after the endodontic therapy is complete. Often, we come across an endodontically treated tooth with little or no clinical crown in routine clinical cases. In such cases, additional retention and support of the restoration are difficult to achieve. Two case reports are discussed here where structurally compromised, endodontically treated, posterior teeth were restored using the Richmond crown in the first case, and by the use of two nonparallel cast posts in the second case. PMID- 20543921 TI - Stem cell therapy - Hype or hope? A review. AB - While the regeneration of a lost tissue is known to mankind for several years, it is only in the recent past that research on regenerative medicine/dentistry has gained momentum and eluded the dramatic yet scientific advancements in the field of molecular biology. The growing understanding of biological concepts in the regeneration of oral/dental tissues coupled with experiments on stem cells is likely to result in a paradigm shift in the therapeutic armamentarium of dental and oral diseases culminating in an intense search for "biological solutions to biological problems." Stem cells have been successfully isolated from variety of human tissues including orofacial tissues. Initial evidence from pioneering studies has documented the likely breakthrough that stem cells offer for various life-threatening diseases that have so far defeated modern medical care. The evidence gathered so far has propelled many elegant studies exploring the role of stem cells and their manifold dental applications. This review takes you on a sojourn of the origin of stem cells, their properties, characteristics, current research, and their potential applications. It also focuses on the various challenges and barriers that we have to surmount before translating laboratory results to successful clinical applications heralding the dawn of regenerative dentistry. PMID- 20543922 TI - Electrosurgery in aesthetic and restorative dentistry: A literature review and case reports. AB - Electrosurgery has been used in dentistry for more than half a century. There is abundant literature on electrosurgery dating back more than a century. During the past three decades, a substantial increase in minimally invasive surgery and microvascular surgery prompted greater use of electrosurgery. Although this surge in utilization has resulted in new applications, equipment features, problems and solutions, the use of electrosurgery in the field of restorative dentistry has remained relatively unchanged. The presence of conflicting and sometimes confusing information on electrosurgical wound healing in the dental literature is the most likely reason. This article briefly explains the literature review of electrosurgery and clinical application of electrosurgery in aesthetic and restorative dentistry. PMID- 20543923 TI - Comparison of laterally condensed, vertically compacted thermoplasticized, cold free-flow GP obturations - A volumetric analysis using spiral CT. AB - AIM/OBJECTIVE: To compare the laterally condensed gutta-percha, vertically compacted thermoplastized gutta-percha (E and Q Plus system) and cold free-flow gutta-percha (GuttaFlow). This is a volumetric analysis using spiral CT, an in vitro study. MATERIALS AND METHODS: Access cavities were prepared in 60 single rooted anterior teeth; cleaning and shaping was done and obturated with three of the different techniques: group A: cold lateral; group B: vertically compacted thermoplasticized and group C: cold free-flow obturation techniques. Volume analysis was done using spiral computed tomography (CT). The percentage difference was calculated and statistically analyzed using one-way ANOVA and post hoc multiple comparison Tukey HSD tests. RESULTS: There were statistical significant differences between group A (0.183cm(3)) and group B (0.136cm(3)); group A (0.183cm(3)) and group C (0.128cm(3)). But there was no statistical significance between group B (0.136cm(3)) and group C (0.128cm(3)). CONCLUSION: Within the limitations of this in vitro study it can be concluded that cold free flow obturation technique showed the highest volume of obturation, followed by the vertically condensed thermoplasticized technique. The least volume of obturation was observed in cold lateral condensation technique. PMID- 20543924 TI - An in vitro study to determine the sealing ability of sealers with and without smear layer removal. AB - AIMS/OBJECTIVES: The objective of this in vitro study is to compare the sealing ability of Ketac-Endo and Acroseal. MATERIALS AND METHODS: Seventy teeth were selected and sectioned at the cementoenamel junction. The teeth were cleaned and shaped, and they were divided into five different groups. Group1: 20 teeth in which the smear layer was left intact using sodium hypochlorite. Group 2: 20 teeth in which the smear layer was removed using 17% EDTA. Group 3: 20 teeth in which the smear layer was removed using 17% EGTA. These groups (1, 2, and 3) were further subdivided into two subgroups (a and b) by obturation utilizing lateral condensation with Gutta-percha and Acroseal (subgroup "a") or Ketac-Endo (subgroup "b"). The subgroups contained 10 teeth each. Group 4: 5 teeth that were instrumented but not obturated. Group 5:5 teeth that were neither instrumented nor obturated. The specimens were immersed in methylene blue dye, and microleakage was assessed using a stereomicroscope. RESULTS: The data was analyzed using one way analysis of variance and student's t-test. CONCLUSION: 17% EGTA is a better and potent alternative to 17% EDTA for smear layer removal. Acroseal sealer has less microleakage as compared with Ketac-Endo. Sealing ability of Acroseal sealer is better when it is used in conjunction with 17% EGTA. PMID- 20543925 TI - Comparison of fracture resistance of endodontically treated teeth using different coronal restorative materials: An in vitro study. AB - AIM/OBJECTIVE: To evaluate the in vitro effect of bonded restorations on the fracture resistance of root canal-treated teeth. MATERIALS AND METHODS: One hundred twenty extracted, maxillary, permanent premolars were collected. After preparing the access cavity, the teeth were biomechanically prepared and obturated. Samples were divided into six groups based on the type of restorative material used to restore them. Teeth were embedded in acrylic resin and their fracture strength was measured using a Universal Testing Machine. Data were evaluated statistically using one-way ANOVA-F and unpaired t-test. RESULTS: Teeth restored with bonded amalgam and composite resin showed higher fracture resistance than those restored with conventional amalgam. Fracture strengths of bonded restorations and intact teeth were not statistically different. The results suggested that the group restored with conventional amalgam had the lowest fracture resistance. No statistically significant differences were found between the bonded amalgam and composite resin groups. CONCLUSION: Conventional amalgam core showed the least fracture resistance whereas; composite resin and bonded amalgam core showed fracture resistance was similar to that of natural tooth. PMID- 20543926 TI - A comparative evaluation of microleakage of three different newer direct composite resins using a self etching primer in class V cavities: An in vitro study. AB - AIMS/OBJECTIVES: The aim of this in vitro study is to study, measure and compare the microleakage in three different newer direct composite resins using a self etch adhesive bonding system in class V cavities by fluorescent dye penetration technique. MATERIALS AND METHODS: Class V cavities were prepared on 45 human maxillary premolar teeth. On all specimens, one coat of G-Bond (GC Japan) applied and light cured. Teeth are then equally divided into 3 groups of 15 samples each. Filtek Z350 (3M ESPE), Ceram X duo (Dentsply Asia) and Synergy D6 (Coltene/Whaledent) resin composites were placed on samples of Groups I, II and III, respectively, in increments and light cured. After polishing the restorations, the specimens were suspended in Rhodamine 6G fluorescent dye for 48 h. The teeth were then sectioned longitudinally and observed for the extent of microleakage under the florescent microscope. STATISTICAL ANALYSIS USED: The results were subjected to statistical analysis using Kruskal Wallis and Mann Whitney U Test. RESULTS: Results showed no statistically significant difference among three groups tested. CONCLUSIONS: None of the materials tested was able to completely eliminate the microleakage in class V cavities. PMID- 20543927 TI - Smile enhancement the conservative way: Tooth whitening procedures. AB - This article presents clinical cases in which different bleaching modalities have been used to successfully treat unsightly teeth. Depending upon the type and severity of discoloration, in-office vital and nonvital bleaching procedures were carried out. Discoloration of a single tooth has been managed using nonvital bleaching alone or with a combination of other minimally invasive modalities for an acceptable esthetic outcome. The case selection was done by considering the patient's needs and expectations, the type and cause of discoloration and patient economics. Moreover, prime importance was given to the conservation of the existing tooth structure and acquiring a complete change in the shade of teeth, which was comparable to that of the adjacent teeth. The desire to have a bright smile has become an important esthetic need of patients. The article explores various forms of bleaching and their successful usage in day-to-day clinical practice. PMID- 20543928 TI - Nonsurgical management of endodontic mishaps in a case of radix entomolaris. AB - Anatomic variations can significantly contribute to the incidence of endodontic mishaps. Perforations and separated instruments form the bulk of such mishaps. Furcal perforations are undesired complications of endodontic treatment, which result in the loss of integrity of the root and further destruction of the adjacent periodontal tissues. Mineral trioxide aggregate (MTA) is a promising material that has been successfully used to repair perforations. This clinical case demonstrates the use of MTA as a repair material for furcal perforation due to an iatrogenic error in radix entomolaris in the mandibular first molar. It also describes the application of ultrasonic technique in the retrieval of separated instrument from the same. Both clinical and radiographic follow-up showed a stable condition without any probing defect, ongoing root resorption, or furcal pathosis. PMID- 20543929 TI - Our Eye is on the Future. PMID- 20543930 TI - Endothelial Keratoplasty: From DLEK to DMEK. AB - The last decade has heralded a revolutionary shift in the treatment of corneal endothelial disease. Only 15 years ago, the only surgical treatment for pseudophakic bullous keratopathy and Fuchs dystrophy was penetrating keratoplasty (PK). Although used successfully for over a century, PK requires many months of refractive adjustments before the eye achieves visual stability. Starting with the advent of posterior lamellar keratoplasty in the late 1990s, a number of procedures have been developed, refined, and widely adopted, which have given patients faster recoveries and improved globe stability in comparison to traditional corneal transplantation. Each iteration of endothelial keratoplasty (EK) has involved the increasingly selective transplantation of corneal endothelial cells. Preliminary results of the most recent form of EK, Descemet's membrane EK, suggest that pure endothelial cell transplantation is on the horizon. PMID- 20543931 TI - Update on limbal stem cell transplantation. AB - Limbal epithelial stem cells are the primary source of corneal epithelial cell regeneration. Limbal stem cell deficiency (LSCD) can develop in traumatic, immunologic, or genetic diseases that affect the ocular surface. LSCD leads to conjunctivalization, with corneal vascularization and opacification and subsequent loss of vision. Limbal stem cell transplantation is a surgical treatment to address LSCD and restore a corneal epithelial phenotype. Based on the source of cells, limbal transplant can be autologous or allogenic. Many surgical techniques are defined according to the source of the stem cells and the carrier tissues that are used. More recently, ex vivo expanded bioengineered epithelial cells have been used to reconstruct the corneal surface using autologous cells to eliminate the risk of rejection. Before transplantation, a systematic exam of the lids, eyelashes, fornices, and aqueous tears is mandatory and every effort should be made to optimize ocular surface health and control inflammation to enhance the chances of graft survival. Postoperative care is also another major determinant of success. Any factor that destabilizes the ocular surface needs to be addressed. In addition, systemic and topical immunosuppressants are also needed in all allograft recipients. In addition to pre-operative and postoperative care and the surgery itself, the etiology of LSCD also has an impact on the outcome. The prognosis of inflammatory diseases such as Stevens-Johnson syndrome is the worst among disorders causing LSCD. PMID- 20543932 TI - Keratoconus: overview and update on treatment. AB - Keratoconus is a non-inflammatory, progressive thinning process of the cornea. It is a relatively common disorder of unknown etiology that can involve each layer of the cornea and often leads to high myopia and astigmatism. Computer- assisted corneal topography devices are valuable diagnostic tools for the diagnosis of subclinical keratoconus and for tracking the progression of the disease. The traditional conservative management of keratoconus begins with spectacle correction and contact lenses. Several newer, more invasive, treatments are currently available, especially for contact lens-intolerant patients. Intrastromal corneal ring segments can be used to reshape the abnormal cornea to improve the topographic abnormalities and visual acuity. Phakic intraocular lenses such as iris-fixated, angle-supported, posterior chamber implantable collamer and toric lenses are additional valuable options for the correction of refractive error. Corneal cross-linking is a relatively new method of stiffening the cornea to halt the progression of the disease. The future management of keratoconus will most likely incorporate multiple treatment modalities, both simultaneous and sequential, for the prevention and treatment of this disease. PMID- 20543933 TI - Corneal collagen cross-linking. AB - Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation.Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID- 20543934 TI - Deep anterior lamellar keratoplasty: indications, surgical techniques and complications. AB - The concept of lamellar keratoplasty (LK) is not new. However, it had been abandoned and largely replaced by the time-honored technique of penetrating keratoplasty (PK) because LK is technically demanding, time consuming and gives suboptimal visual outcomes due to interface irregularity arising from manual lamellar dissection. Recent improvements in surgical instruments and introduction of new techniques of maximum depth of corneal dissection as well as inherent advantages such as preservation of globe integrity and elimination of endothelial graft rejection have resulted in a re-introduction of LK as an acceptable alternative to conventional PK. This review article describes the indications, different techniques, clinical outcomes and complications of deep anterior LK. PMID- 20543935 TI - The use of glycerol-preserved corneas in the developing world. AB - Corneal opacity is the third leading cause of blindness in the developing world and encompasses a wide variety of infectious, inflammatory and degenerative eye diseases. Most caes of corneal blindness are treatable with partial or full thickness keratoplasty, provided adequate corneal tissue and surgical skill is available. However, access to sightrestoring keratoplasty in developing countries is limited by the lack of developed eye banking networks and a critical shortage of tissue suitable for transplantation. Beyond the developed world, corneal transplantation using fresh corneal tissue (FCT) is further hindered by unreliable storage and transportation facilities, unorganized distribution networks, the cost-prohibitive nature of imported tissue, unreliable compliance with medications and follow-up instructions and inadequate health and education services. Glycerol-preserved corneas overcome many of these limitations inherent to the use of FCT. As surgical innovation in lamellar corneal surgery expands the potential use of acellular corneal tissue, long-term preservation techniques are being revisited as a way to increase availability of corneal tissue to corneal surgeons throughout the developing world. Herein, we discuss the advantages of using and the applications for glycerol-preserved corneal tissue throughout the developing world. PMID- 20543936 TI - Day to Day Clinically Relevant Corneal Elevation, Thickness, and Curvature Parameters Using the Orbscan II Scanning Slit Topographer and the Pentacam Scheimpflug Imaging Device. AB - The introduction of different techniques and computerized devices into clinical ophthalmology has significantly improved our knowledge of the eyes, optics, and eye conditions. Today, corneal topography is performed with a wide range of devices that implement a variety of techniques. Advance computerized analysis systems provide us with simple and quick evaluation procedures, yet the sophisticated data and clinical information that is generated can only be interpreted with adequate knowledge of the system itself as well as the accepted normal ranges of various properties assessed with these systems. Two computerized topography systems that are in common use are the Orbscan (Bausch and Lomb Inc., Rochester, NY, USA) and the Pentacam (Oculus GmBH, Wetzlar, Germany). The Orbscan is a slit-scanning device and the Pentacam is Scheimpflug imaging device. In this review, we present a brief description of both technologies, the techniques implemented in each device and the acquisition process with each. This will be followed by a list of corneal parameters that need to be assessed in screening patients for refractive surgery. We will discuss how these parameters are displayed, how each parameter may serve as clinic criteria, and how data should be interpreted. We will also try to provide evidence regarding the accuracy of different measurements, and the comparability of the two devices. PMID- 20543937 TI - Intraoperative and Postoperative Complications of Laser in situ Keratomileusis Flap Creation Using IntraLase Femtosecond Laser and Mechanical Microkeratomes. AB - An essential step of laser in situ keratomileusis surgery is corneal flap creation, Femtosecond (FS)-assisted or mechanical microkeratome. Each type has rare intraoperative and postoperative complication rates. Several recent studies have identified risk factors and guidelines to help manage these complications. Fortunately, studies have shown no loss of best-corrected visual acuity (BCVA) after the management of intraoperative and postoperative complications in IntraLase FS and mechanical microkeratome. Refractive surgeons need to be aware of the types of complications that can occur, how to avoid them and how to manage them to ensure the best possible outcomes. PMID- 20543938 TI - What is Central Toxic Keratopathy Syndrome if it is not Diffuse lamellar Keratitis Grade IV? AB - The Central Toxic Keratopathy (CTK) syndrome describes a rare, acute, self limited, non-inflammatory process that yields central corneal opacification and significant hyperopic shift after refractive surgery. Despite being exceedingly rare, certain clinical features of CTK give the condition a striking resemblance to other more serious inflammatory conditions, including diffuse lamellar keratitis (DLK). As the authors demonstrate in this article, despite the overlapping clinical features, CTK is a disease process that is distinct from DLK and, therefore, in need of distinct management interventions. PMID- 20543940 TI - Torsional mode phacoemulsification: effective, safe cataract surgery technique of the future. AB - PURPOSE: To compare various outcome measures using torsional mode and longitudinal mode in the phacoemulsification of cataract with different nuclear densities. SETTING: Magrabi Eye Hospitals, Kingdom of Saudi Arabia. DESIGN: A randomized comparative clinical study. MATERIALS AND METHODS: This study includes 200 eyes of 156 patients (100 in the ultrasound longitudinal "US" group and 100 in the torsional group). All eyes received AcrySof((R)) single piece intraocular lens (Alcon Surgical, Fort Worth, TX). The primary outcome measures were ultrasound time (UST), cumulative dissipated energy (CDE), and surgical complications. Postoperative outcome measures were the degree of corneal edema on the first postoperative day and final best corrected visual acuity (BCVA) and CCT (central corneal thickness). RESULTS: The differences in UST and CDE between subgroups of nucleus hardness were statistically significant (P < 0.01). The UST and CDE consistently increased in eyes with higher grades of nucleus density. On day one, the mean BCVA was 0.61 +/- 0.13 decimals in the ultrasound (US) group and 0.67 +/- 0.11 decimals in the torsional group (significant P < 0.05). Corneal edema was significantly less in the torsional group (P < 0.05). At 30 days, the mean BCVA was 0.94 +/- 0.22 decimals in the US group and 1.0 +/- 0.12 decimals in the torsional group but this difference was not statistically different (P > 0.05). CONCLUSIONS: The torsional mode provides an effective and safe method for cataract removal with lower energy usage as compared to longitudinal traditional phacoemulsification. However, the final visual outcome was similar for both study groups. PMID- 20543939 TI - Intraocular lens power calculation after corneal refractive surgery. AB - Cataract surgery after corneal refractive surgery can be challenging for the ocular surgeon due to the difficulty with accurate intraocular lens (IOL) power determination and unexpected refractive surprises. As clinicians have done more work, a number of error sources have been determined. Furthermore, an increasing number of methods to avoid these refractive surprises have been proposed. The combination of this work has resulted in recommendations for the modification of standard IOL power calculations to improve outcomes. The following article includes a brief on, and by no means, inclusive, error sources and ways to compensate for them. PMID- 20543941 TI - Point prevalence of pseudoexfoliation syndrome in patients scheduled for cataract surgery in eye camps in yemen. AB - PURPOSE: To study the point prevalence of pseudoexfoliation syndrome (PXS) among Yemeni patients in different governorates with age-related cataract scheduled for surgery. SETTINGS: Eye camps organized by the Nibras Health Society to perform cataract surgeries during the years 2002-2006. All patients aged 40 years and above were included in the study. MATERIALS AND METHODS: A total of 2535 eyes of 2535 patients from 13 governorates, scheduled for cataract surgery in eye camps, were included. All eyes underwent complete eye examination before the surgery and were evaluated for the signs of pseudoexfoliation material in the pupil, iris and lens capsule on dilated slit lamp examination. RESULTS: The study found 495 of the 2535 eyes (19.53%) with PXS with males more commonly affected than females (55.2 and 44.8%, respectively). The mean age of patients with PXS was 66.2 years while it was 64.6 years in non-PXS patients. The prevalence of pseudoexfoliation syndrome increased with age (10.1% in the age group of 41-50 years that increased to 28.8% in the age group of more than 81 years old). The rate of PXS detection in camps in 13 governorates ranged from 13.33 to 24.22% with an overall rate of 19.53%. The lowest rate was noticed in Sana'a and the highest in Al-Dhale governorate. CONCLUSION: This pilot study confirms that PXS was common in patients undergoing cataract surgery in Yemen with an increased detection rate with age. This study also highlights the prevalence of an ocular disease that is associated with systemic and ocular complications; however, further studies based on population studies are needed. PMID- 20543942 TI - Visual function of egyptian children with low vision and the demographic determinants. AB - AIMS: To determine whether the LV Prasad-Functional Vision Questionnaire (LVP FVQ) could be used to assess self-reported visual function and quality of visual life in Egyptian school aged children. MATERIALS AND METHODS: The LVP-FVQ was used to assess the quality of visual function in school-age children. All subjects were students at the time of assessment. Subjects underwent a visual function assessment that included distance and near visual acuity, contrast sensitivity, color vision and visual field examination where possible. Data analysis were for both descriptive and inference statistics. A P < 0.05 was considered statistically significant. RESULTS: Fifty children aged 11.28 +/- 3.5 years (range, 5 years to 18 years) with moderate-to-severe visual impairment most of their lives were enrolled. Twenty-two subjects (44%) had albinism, 18 (36%) subjects had hereditary retinal dystrophy, 6 (12%) subjects had cone dystrophy, 2 (4%) subjects had bilateral amblyopia and 2 (4%) subjects had congenital coloboma without other disabilities. The four most difficult tasks were related to the following daily activities alluded to in the questionnaire such as reading a textbook at arms length, copying from the blackboard, seeing somebody across the road and identifying colors. There was no statistically significant association between the demographic variables and the level of visual functioning, sex, age, type of school, family history or consanguinity (P > 0.05 for all variables). CONCLUSION: LVP-FVQ can be used to screen Egyptian children with visual impairment. Input and integration of the parents and the school teachers to evaluate the child s behavior at home and the school is essential to developing a balanced questionnaire. PMID- 20543943 TI - Challenges, attitudes and practices of the spectacle wearers in a resource limited economy. AB - PURPOSE: To evaluate challenges, attitudes and practices among spectacle wearers to effect positive change when necessary, and determine positive change in a resource-limited economy. MATERIALS AND METHODS: A multi-hospital descriptive, cross sectional survey of spectacle wearers was conducted between May 2007 and December 2008 in Nigeria. RESULTS: A total of 214 wearers comprising 43.5% males and 56.5% females aged 18-84 years were surveyed. The majority of subjects (92.6%) had at least secondary education. The wearers' challenges included expensive spectacles (43.0%), falling/scratched/broken lenses (29.4%) and fear that spectacles would damage the eyes (23.8%). The wearers' attitudes were comprised of consultations with 'road side dispensers' (7%) and permitting other individuals to select spectacle frames for them (26%). Care and maintaince practices included use of handkerchief, tissue paper, fingers and water to clean spectacles (49.5%) and placing spectacles inside spectacle cases (30.4%). There were no associations (P > 0.05) between gender or literacy levels and who selected the frames for the subjects, caregivers consulted for spectacles, and cleaning materials for spectacles. The placement of spectacles when not in use was significantly associated (P < 0.05) with the wearers' gender and literacy levels but not with the length of spectacle wear. CONCLUSION: Attitudes and practices requiring positive change crossed gender and educational levels among spectacle wearers. The cost of spectacles should be regulated and availability of standard eye care practices would reduce challenges including lens-related defects and quackery. During consultation with a recognized eye care professional, counseling of wearers on positive attitudes/practices as well as allaying fear of spectacle wear is required. PMID- 20543944 TI - Efficacy of Garcinia kola 0.5% Aqueous Eye Drops in Patients with Primary Open Angle Glaucoma or Ocular Hypertension. AB - PURPOSE: To evaluate the intraocular pressure (IOP) lowering efficacy of Garcinia kola 0.5% aqueous solution eye drops in patients with newly diagnosed primary open-angle glaucoma or ocular hypertension (POAG/OH). MATERIALS AND METHODS: A randomized, double-masked, multicenter, active-controlled prospective study. Patients who met the inclusion criteria were randomly assigned in equal numbers to receive Timolol 0.5% eye drops as a control medication (A = Group 1 eyes) or Garcinia kola 0.5% eye drops as the study medication (B = Group 2 eyes). All drops were instilled at 6 am and 6 pm daily. Goldman applanation tonometry was performed at 9 am, 12 pm and 3 pm at baseline, week-6, week-12 and week-24 visits. Voluntary and actively elicited reports of adverse events were documented. The mean change in IOP over 24 weeks was the primary outcome measure. Both groups were compared for statistically significant differences at all visits. A P < 0.05 was considered statistically significant. RESULTS: A total of 178 patients were randomly assigned to G. kola and Timolol groups. At baseline there were no differences in mean IOP between groups, based on age, sex, or diagnosis. At the end of the study period (24(th) week), the mean (+/- SD) reduction in IOP was 12.93 +/- 2.3 mmHg (47.8% +/- 0.8% reduction) in G. Kola group and 13.09 +/- 2.8 mm Hg (48.2% +/- 1.03% reduction) in the Timolol group (P > 0.05). Adverse events were mild in nature with no statistically significant differences between groups (P > 0.05). CONCLUSIONS: Garcinia kola ophthalmic solution significantly reduces IOP as compared to baseline. The IOP lowering effect of both treatments was equivalent. PMID- 20543945 TI - Corneal Optical Quality Following Sub 1.8 mm Micro-Incision Cataract Surgery vs. 2.2 mm Mini-Incision Coaxial Phacoemulsification. AB - PURPOSE: To study and compare the effects of the micro-incision cataract surgery (MICS-sub 1.8 mm) and miniincision coaxial phacoemulsification (2.2 mm) on the optical quality of the cornea characterized in terms of corneal aberrations. MATERIALS AND METHODS: Fifty eyes underwent MICS and 50 mini-incision phacoemulsification, by the same surgeon. Both types of cataract surgery were performed using low ultrasound power and through a clear corneal incision, placed on the steepest corneal meridian ranging from 1.6 to 1.8 in MICS (Group I) and from 2.12 to 2.3 mm in mini-incision coaxial phacoemulsification (Group II). Seidel and Zernike aberration coefficients and RMS values were obtained for a 6 mm pupil preoperatively and one month after surgery. RESULTS: THE CORNEAL ASTIGMATISM DID NOT SHOW STATISTICALLY SIGNIFICANT CHANGES IN EITHER OF THE TWO GROUPS: (MICS: -0.73 +/- 0.63, -0.65 +/- 0.53 D, P = 0.25), (mini-incision phacoemulsification; -1.21 +/- 1.52, -1.00 +/- 1.19 D, P = 0.12). The total RMS remained unchanged after MICS (1.77 +/- 1.7, 1.65 +/- 1.3 mum, P = 0.18) and mini incision phacoemulsification (2.00 +/- 1.87, 2.09 +/- 1.8 mum, P = 0.41). Statistically significant changes were found for coma (P = 0.004) and higher order aberrations (P < 0.001), showing MICS significantly less changes in cornea. CONCLUSIONS: Both MICS and mini-incision phacoemulsification do not degrade the optical quality of the cornea. Both surgeries do not induce a modification of the corneal astigmatism, even in the axis. It seems that 2 mm is the limit around which no optical changes are induced by cataract surgery in the human cornea. PMID- 20543946 TI - Iris depigmentation: an unusual complication of intralesional corticosteroid injection for capillary hemangioma. AB - Intralesional injection of corticosteroids has been used successfully in the treatment of adenexal hemangiomas, with advantages of easy administration, rapid action, repeatability, efficacy and safety. We report a case of an eight-month old female infant who underwent intralesional corticosteroid injection for capillary hemangioma that had resulted in amblyopia of her left eye from ptosis. Two weeks after the injection, the hemangioma showed some regression but at that point iris depigmentation of the affected eye was noted. The iris depigmentation remained unchanged during her follow-up visit with significant regression of the hemangioma, associated ptosis and astigmatism. PMID- 20543947 TI - Circular anterior lens capsule rupture caused by blunt ocular trauma. AB - A 16 year old male experienced blunt ocular trauma causing rupture of the anterior lens capsule and mature cataract development. The trauma was due to a stone that impacted the left eye. In an otherwise clear lens, an anterior lens capsule defect formed post-trauma that progressed to a mature cataract over four months reducing distance vision from 20/125 to hand motion. The patient underwent phacoemulsification with posterior chamber intraocular lens implantation in the left eye. One year postoperatively, the vision in the left eye increased to 20/25 without correction. This is a rare case of cataract formation due to a defect in the anterior lens capsule caused by blunt ocular trauma. PMID- 20543948 TI - Association of carotid plaque Lp-PLA(2) with macrophages and Chlamydia pneumoniae infection among patients at risk for stroke. AB - BACKGROUND: We previously showed that the burden of Chlamydia pneumoniae in carotid plaques was significantly associated with plaque interleukin (IL)-6, and serum IL-6 and C-reactive protein (CRP), suggesting that infected plaques contribute to systemic inflammatory markers in patients with stroke risk. Since lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mediates inflammation in atherosclerosis, we hypothesized that serum Lp-PLA(2) mass and activity levels and plaque Lp-PLA(2) may be influenced by plaque C. pneumoniae infection. METHODOLOGY/PRINCIPAL FINDINGS: Forty-two patients underwent elective carotid endarterectomy. Tissue obtained at surgery was stained by immunohistochemistry for Lp-PLA(2) grade, macrophages, IL-6, C. pneumoniae and CD4+ and CD8+ cells. Serum Lp-PLA(2) activity and mass were measured using the colorimetric activity method (CAM) and ELISA, respectively. Serum homocysteine levels were measured by HPLC. Eleven (26.2%) patients were symptomatic with transient ischemic attacks. There was no correlation between patient risk factors (smoking, coronary artery disease, elevated cholesterol, diabetes, obesity, hypertension and family history of genetic disorders) for atherosclerosis and serum levels or plaque grade for Lp PLA(2). Plaque Lp-PLA(2) correlated with serum homocysteine levels (p = 0.013), plaque macrophages (p<0.01), and plaque C. pneumoniae (p<0.001), which predominantly infected macrophages, co-localizing with Lp-PLA(2). CONCLUSIONS: The significant association of plaque Lp-PLA(2) with plaque macrophages and C. pneumoniae suggests an interactive role in accelerating inflammation in atherosclerosis. A possible mechanism for C. pneumoniae in the atherogenic process may involve infection of macrophages that induce Lp-PLA(2) production leading to upregulation of inflammatory mediators in plaque tissue. Additional in vitro and in vivo research will be needed to advance our understanding of specific C. pneumoniae and Lp-PLA(2) interactions in atherosclerosis. PMID- 20543949 TI - Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. AB - BACKGROUND: In obesity, impaired adipose tissue function may promote secondary disease through ectopic lipid accumulation and excess release of adipokines, resulting in systemic low-grade inflammation, insulin resistance and organ dysfunction. However, several of the genes regulating adipose tissue function in obesity are yet to be identified. METHODOLOGY/PRINCIPAL FINDINGS: In order to identify novel candidate genes that may regulate adipose tissue function, we analyzed global gene expression in abdominal subcutaneous adipose tissue before and one year after bariatric surgery (biliopancreatic diversion with duodenal switch, BPD/DS) (n = 16). Adipose tissue from lean healthy individuals was also analyzed (n = 13). Two different microarray platforms (AB 1700 and Illumina) were used to measure the differential gene expression, and the results were further validated by qPCR. Surgery reduced BMI from 53.3 to 33.1 kg/m(2). The majority of differentially expressed genes were down-regulated after profound fat loss, including transcription factors involved in stress response, inflammation, and immune cell function (e.g., FOS, JUN, ETS, C/EBPB, C/EBPD). Interestingly, a distinct set of genes was up-regulated after fat loss, including homeobox transcription factors (IRX3, IRX5, HOXA5, HOXA9, HOXB5, HOXC6, EMX2, PRRX1) and extracellular matrix structural proteins (COL1A1, COL1A2, COL3A1, COL5A1, COL6A3). CONCLUSIONS/SIGNIFICANCE: The data demonstrate a marked switch of transcription factors in adipose tissue after profound fat loss, providing new molecular insight into a dichotomy between stress response and metabolically favorable tissue development. Our findings implicate homeobox transcription factors as important regulators of adipose tissue function. PMID- 20543950 TI - In vitro vs in silico detected SNPs for the development of a genotyping array: what can we learn from a non-model species? AB - BACKGROUND: There is considerable interest in the high-throughput discovery and genotyping of single nucleotide polymorphisms (SNPs) to accelerate genetic mapping and enable association studies. This study provides an assessment of EST derived and resequencing-derived SNP quality in maritime pine (Pinus pinaster Ait.), a conifer characterized by a huge genome size ( approximately 23.8 Gb/C). METHODOLOGY/PRINCIPAL FINDINGS: A 384-SNPs GoldenGate genotyping array was built from i/ 184 SNPs originally detected in a set of 40 re-sequenced candidate genes (in vitro SNPs), chosen on the basis of functionality scores, presence of neighboring polymorphisms, minor allele frequencies and linkage disequilibrium and ii/ 200 SNPs screened from ESTs (in silico SNPs) selected based on the number of ESTs used for SNP detection, the SNP minor allele frequency and the quality of SNP flanking sequences. The global success rate of the assay was 66.9%, and a conversion rate (considering only polymorphic SNPs) of 51% was achieved. In vitro SNPs showed significantly higher genotyping-success and conversion rates than in silico SNPs (+11.5% and +18.5%, respectively). The reproducibility was 100%, and the genotyping error rate very low (0.54%, dropping down to 0.06% when removing four SNPs showing elevated error rates). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that ESTs provide a resource for SNP identification in non-model species, which do not require any additional bench work and little bio informatics analysis. However, the time and cost benefits of in silico SNPs are counterbalanced by a lower conversion rate than in vitro SNPs. This drawback is acceptable for population-based experiments, but could be dramatic in experiments involving samples from narrow genetic backgrounds. In addition, we showed that both the visual inspection of genotyping clusters and the estimation of a per SNP error rate should help identify markers that are not suitable to the GoldenGate technology in species characterized by a large and complex genome. PMID- 20543951 TI - Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine. AB - BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R) availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT) and G protein coupled receptor associated sorting protein-1 (GASP-1) knock out (KO) mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization. PMID- 20543952 TI - Reticulate evolutionary history of a complex group of grasses: phylogeny of Elymus StStHH allotetraploids based on three nuclear genes. AB - BACKGROUND: Elymus (Poaceae) is a large genus of polyploid species in the wheat tribe Triticeae. It is polyphyletic, exhibiting many distinct allopolyploid genome combinations, and its history might be further complicated by introgression and lineage sorting. We focus on a subset of Elymus species with a tetraploid genome complement derived from Pseudoroegneria (genome St) and Hordeum (H). We confirm the species' allopolyploidy, identify possible genome donors, and pinpoint instances of apparent introgression or incomplete lineage sorting. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced portions of three unlinked nuclear genes-phosphoenolpyruvate carboxylase, beta-amylase, and granule-bound starch synthase I-from 27 individuals, representing 14 Eurasian and North American StStHHElymus species. Elymus sequences were combined with existing data from monogenomic representatives of the tribe, and gene trees were estimated separately for each data set using maximum likelihood. Trees were examined for evidence of allopolyploidy and additional reticulate patterns. All trees confirm the StStHH genome configuration of the Elymus species. They suggest that the StStHH group originated in North America, and do not support separate North American and European origins. Our results point to North American Pseudoroegneria and Hordeum species as potential genome donors to Elymus. Diploid P. spicata is a prospective St-genome donor, though conflict among trees involving P. spicata and the Eurasian P. strigosa suggests either introgression of GBSSI sequences from P. strigosa into North American Elymus and Pseudoroegneria, or incomplete lineage sorting of ancestral GBSSI polymorphism. Diploid H. californicum and/or allotetraploid H. jubatum are possible H-genome donors; direct involvement of an allotetraploid Hordeum species would simultaneously introduce two distinct H genomes to Elymus, consistent with some of the relationships among H-genome sequences in Hordeum and Elymus. CONCLUSIONS/SIGNIFICANCE: Comparisons among molecular phylogenetic trees confirm allopolyploidy, identify potential genome donors, and highlight cases of apparent introgression or incomplete lineage sorting. The complicated history of this group emphasizes an inherent problem with interpreting conflicts among bifurcating trees-identifying introgression and determining its direction depend on which tree is chosen as a starting point of comparison. In spite of difficulties with interpretation, differences among gene trees allow us to identify reticulate species and develop hypotheses about underlying evolutionary processes. PMID- 20543953 TI - A straightforward but not piecewise relationship between age and lymph node status in Chinese breast cancer patients. AB - PURPOSE: To investigate the relationship between age and axillary lymph node (LN) involvement in Chinese breast cancer patients, and to replicate a recently identified piecewise relationship between age and LN involvement. METHODS: A dataset, consisting of 3,715 patients (with complete information on study variables) with operable breast cancer consecutively surgically treated between 1996 and 2006, was derived from the database of Shanghai Cancer Hospital. Univariate and multivariate logistic regression were employed to analyze the relationship between age and LN. We subsequently performed a similar analysis on another dataset including 1,832 consecutive patients treated between 2007 and 2008 to replicate our findings in the first dataset. RESULTS: A U-shaped relationship (previously observed in two European populations) between age and LN status failed to be replicated in our dataset of Chinese patients. Instead, we observed a linear rather than piecewise relationship. After multivariate adjustment, the linear relationship was still present. Moreover, the interaction between age and LN involvement was not modified by tumor size. The odds of LN involvement decreased by 1.5% for each year increase in age (OR 0.985, 95% CI 0.979-0.991, P<0.001). Breast cancer subtypes were also associated with LN status. Proportions of basal-like and ERBB2+ subtypes decreased with increasing age. The observations in the first dataset were successfully replicated in a second independent dataset. CONCLUSION: We confirmed a straightforward but not piecewise relationship between age and LN status in Chinese patients. The different pattern between Chinese and European elderly patients should be considered when making clinical decisions. PMID- 20543954 TI - Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay. AB - BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007) and against pandemic A/H1N1 (A/California/04/2009) were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic. PMID- 20543955 TI - Tracking antigen-specific T-cells during clinical tolerance induction in humans. AB - Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T cells within the first 3-5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4 producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets. PMID- 20543956 TI - Human's cognitive ability to assess facial cues from photographs: a study of sexual selection in the Bolivian Amazon. AB - BACKGROUND: Evolutionary theory suggests that natural selection favors the evolution of cognitive abilities which allow humans to use facial cues to assess traits of others. The use of facial and somatic cues by humans has been studied mainly in western industrialized countries, leaving unanswered whether results are valid across cultures. METHODOLOGY/PRINCIPAL FINDINGS: Our objectives were to test (i) if previous finding about raters' ability to get accurate information about an individual by looking at his facial photograph held in low-income non western rural societies and (ii) whether women and men differ in this ability. To answer the questions we did a study during July-August 2007 among the Tsimane', a native Amazonian society of foragers-farmers in Bolivia. We asked 40 females and 40 males 16-25 years of age to rate four traits in 93 facial photographs of other Tsimane' males. The four traits were based on sexual selection theory, and included health, dominance, knowledge, and sociability. The rating scale for each trait ranged from one (least) to four (most). The average rating for each trait was calculated for each individual in the photograph and regressed against objective measures of the trait from the person in the photograph. We found that (i) female Tsimane' raters were able to assess facial cues related to health, dominance, and knowledge and (ii) male Tsimane' raters were able to assess facial cues related to dominance, knowledge, and sociability. CONCLUSIONS/SIGNIFICANCE: Our results support the existence of a human ability to identify objective traits from facial cues, as suggested by evolutionary theory. PMID- 20543957 TI - In vivo chromatin organization of mouse rod photoreceptors correlates with histone modifications. AB - BACKGROUND: The folding of genetic information into chromatin plays important regulatory roles in many nuclear processes and particularly in gene transcription. Post translational histone modifications are associated with specific chromatin condensation states and with distinct transcriptional activities. The peculiar chromatin organization of rod photoreceptor nuclei, with a large central domain of condensed chromatin surrounded by a thin border of extended chromatin was used as a model to correlate in vivo chromatin structure, histone modifications and transcriptional activity. METHODOLOGY: We investigated the functional relationships between chromatin compaction, distribution of histone modifications and location of RNA polymerase II in intact murine rod photoreceptors using cryo-preparation methods, electron tomography and immunogold labeling. Our results show that the characteristic central heterochromatin of rod nuclei is organized into concentric domains characterized by a progressive loosening of the chromatin architecture from inside towards outside and by specific combinations of silencing histone marks. The peripheral heterochromatin is formed by closely packed 30 nm fibers as revealed by a characteristic optical diffraction signal. Unexpectedly, the still highly condensed most external heterochromatin domain contains acetylated histones, which are usually associated with active transcription and decondensed chromatin. Histone acetylation is thus not sufficient in vivo for complete chromatin decondensation. The euchromatin domain contains several degrees of chromatin compaction and the histone tails are hyperacetylated, enriched in H3K4 monomethylation and hypo trimethylated on H3K9, H3K27 and H4K20. The transcriptionally active RNA polymerases II molecules are confined in the euchromatin domain and are preferentially located at the vicinity of the interface with heterochromatin. CONCLUSIONS: Our results show that transcription is located in the most decondensed and highly acetylated chromatin regions, but since acetylation is found associated with compact chromatin it is not sufficient to decondense chromatin in vivo. We also show that a combination of histone marks defines distinct concentric heterochromatin domains. PMID- 20543958 TI - Endosymbiont DNA in endobacteria-free filarial nematodes indicates ancient horizontal genetic transfer. AB - BACKGROUND: Wolbachia are among the most abundant symbiotic microbes on earth; they are present in about 66% of all insect species, some spiders, mites and crustaceans, and most filarial nematode species. Infected filarial nematodes, including many pathogens of medical and veterinary importance, depend on Wolbachia for proper development and survival. The mechanisms behind this interdependence are not understood. Interestingly, a minority of filarial species examined to date are naturally Wolbachia-free. METHODOLOGY/PRINCIPAL FINDINGS: We used 454 pyrosequencing to survey the genomes of two distantly related Wolbachia free filarial species, Acanthocheilonema viteae and Onchocerca flexuosa. This screen identified 49 Wolbachia-like DNA sequences in A. viteae and 114 in O. flexuosa. qRT-PCR reactions detected expression of 30 Wolbachia-like sequences in A. viteae and 56 in O. flexuosa. Approximately half of these appear to be transcribed from pseudogenes. In situ hybridization showed that two of these pseudogene transcripts were specifically expressed in developing embryos and testes of both species. CONCLUSIONS/SIGNIFICANCE: These results strongly suggest that the last common ancestor of extant filarial nematodes was infected with Wolbachia and that this former endosymbiont contributed to their genome evolution. Horizontally transferred Wolbachia DNA may explain the ability of some filarial species to live and reproduce without the endosymbiont while other species cannot. PMID- 20543959 TI - First direct evidence of chalcolithic footwear from the near eastern highlands. AB - In 2008, a well preserved and complete shoe was recovered at the base of a Chalcolithic pit in the cave of Areni-1, Armenia. Here, we discuss the chronology of this find, its archaeological context and its relevance to the study of the evolution of footwear. Two leather samples and one grass sample from the shoe were dated at the Oxford Radiocarbon Accelerator Unit (ORAU). A third leather sample was dated at the University of California-Irvine Accelerator Mass Spectrometry Facility (UCIAMS). The R_Combine function for the three leather samples provides a date range of 3627-3377 Cal BC (95.4% confidence interval) and the calibrated range for the straw is contemporaneous (3627-3377 Cal BC). The shoe was stuffed with loose, unfastened grass (Poaceae) without clear orientation which was more than likely used to maintain the shape of the shoe and/or prepare it for storage. The shoe is 24.5 cm long (European size 37), 7.6 to 10 cm wide, and was made from a single piece of leather that wrapped around the foot. It was worn and shaped to the wearer's right foot, particularly around the heel and hallux where the highest pressure is exerted in normal gait. The Chalcolithic shoe provides solid evidence for the use of footwear among Old World populations at least since the Chalcolithic. Other 4th millennium discoveries of shoes (Italian and Swiss Alps), and sandals (Southern Israel) indicate that more than one type of footwear existed during the 4th millennium BC, and that we should expect to discover more regional variations in the manufacturing and style of shoes where preservation conditions permit. PMID- 20543960 TI - Proteome-wide profiling of the MCF10AT breast cancer progression model. AB - BACKGROUND: Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer. METHODOLOGY/PRINCIPAL FINDINGS: We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the "Warburg effect"). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions. CONCLUSION/SIGNIFICANCE: The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy. PMID- 20543961 TI - Eu(III) Complexes of Octadentate 1-Hydroxy-2-pyridinones: Stability and Improved Photophysical Performance[]. AB - The luminescence properties of lanthanoid ions can be dramatically enhanced by coupling them to antenna ligands that absorb light in the UV/visible and then efficiently transfer the energy to the lanthanoid center. The synthesis and the complexation of Ln(III) cations (Ln=Eu; Gd) for a ligand based on four 1-hydroxy 2-pyridinone (1,2-HOPO) chelators appended to a ligand backbone derived by linking two L-lysine units (3LI-bis-LYS) is described. This octadentate Eu(III) complex ([Eu(3LI-bis-LYS-1,2-HOPO)](-)) has been evaluated in terms of its thermodynamic stability, UV/visible absorption and luminescence properties. For this complex the conditional stability constant (pM) is 19.9, which is an order of magnitude higher than diethylenetriaminepentacetic acid (DTPA) at pH= 7.4. This Eu(III) complex also shows an almost two-fold increase in its luminescence quantum yield in aqueous solution (pH= 7.4) when compared to other octadentate ligands. Hence, despite a slight decrease of the molar absorption coefficient, a much higher brightness is obtained for [Eu(3LI-bis-LYS-1,2-HOPO)](-). This overall improvement was achieved by saturating the coordination sphere of the Eu(III) cation, yielding an increased metal centered efficiency by excluding solvent water molecules from the metal's inner sphere. PMID- 20543962 TI - Arenechromiumtricarbonyl complexes of silyl(germyl)(stannyl)- and silyl(germyl)(plumbyl)methanes including unexpected formation of arenechromiumtricarbonyldimethylsilanol, (eta-C(6)H(5))Cr(CO)(3)SiMe(2)OH. AB - Treatment of PhMe(2)SiCH(2)GeMe(3) (1) with t-BuLi followed by addition of Me(3)ECl, E = Sn, Pb, results in the formation of phenylsilyl(germyl)stannyl- and phenylsilyl(germyl)plumbyl-methanes, PhMe(2)Si(Me(3)Ge)(EMe(3))CH, E = Sn (2), Pb (3). The thermal reaction of 1, 2 and 3 with Cr(CO)(6) yields the corresponding aryl-Cr(CO)(3) analogs, {(eta(6)-C(6)H(5))Cr(CO)(3)}Me(2)Si(Me(3)Ge)CH(2) (4) and {(eta(6)-C(6)H(5))Cr(CO)(3)}Me(2)Si(Me(3)Ge)(EMe(3))CH, E = Sn (5), Pb (6). The thermal treatment of 2 with Cr(CO)(6) in wet THF/di-n-butyl ether mixture results in the formation of the arenechromiumtricarbonyl silanol {(eta(6) C(6)H(5))Cr(CO)(3)}Me(2)SiOH (7) which exhibits amphiphilic character, forming H bonded chains in the solid state in a head-to-head arrangement of the areneCr(CO)(3) units. PMID- 20543963 TI - Evidence-Based Point-of-Care Device Design for Emergency and Disaster Care. PMID- 20543965 TI - Novel Design for Centrifugal Counter-Current Chromatography: III. Saw Tooth Column. AB - The toroidal coil using an equilateral triangular core and zigzag pattern column have improved both retention of the stationary phase and peak resolution of the conventional toroidal coil in centrifugal counter-current chromatography. To further improve the retention of stationary phase and peak resolution, a novel saw tooth column was designed and the performance of the system was evaluated at various flow rates. The results indicated that both retention of the stationary phase and peak resolution were improved as the flow rate was decreased and at a flow rate of 0.005 ml/min the resolution is remarkably increased. Modification of the tubing called flat-twisted tubing further improved the peak resolution without increasing the column pressure. With a decreased column length at a capacity of about 0.2 ml, resolution of the saw tooth column was 1.02. PMID- 20543966 TI - miRNAs as biomarkers in colorectal cancer diagnosis and prognosis. AB - Since the discovery of noncoding small miRNAs and their function in controlling mRNA translational rate, the small non-coding miRNA world has become a research wonderland for cancer and other human diseases. Due to the critical regulatory function, miRNA can act as an oncogene or a tumor-suppressor gene. This review will cover some of the recent discoveries of the potential of miRNAs as cancer biomarkers in colorectal cancer, future challenges and solutions. PMID- 20543967 TI - Redefining hormone resistance in prostate cancer. AB - Prostate cancer relies on signaling through the androgen receptor (AR) for maintenance and progression; and androgen-deprivation therapy remains a cornerstone of treatment for advanced prostate cancer. An effective clinical classification of prostate cancer should account for the extent of the disease as well as the mechanisms that are driving the growth of the tumor. The previous terms hormone-sensitive and hormone-refractory described response to treatment. It has become clear that these terms do not reflect the mechanism of disease relapse; however over the last decade there has been a better understanding of androgen-receptor mediated signaling effects and incomplete suppression of androgens in prostate cancer. The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) now recommends addressing the spectrum of clinical states based on castration status as this ligand-centered terminology can more accurately describe the patients' disease, and ultimately provides a useful framework for patient management and drug development. Optimized use of androgen-deprivation therapy, low molecular weight inhibitors of adrenal androgen biosynthesis, and new AR antagonists are promising new therapeutics that can further define the meaning of castrate state. As hormone resistance is redefined to include patients that are refractory to treatments that ablate adrenal and in situ tumoral androgens, a meaningful new clinical state in patients will be forged. We propose a model for incorporating these patients into the current PCWG2 conceptualization of the disease. PMID- 20543969 TI - The War on Drugs: Methamphetamine, Public Health, and Crime. AB - In mid-1995, a government effort to reduce the supply of methamphetamine precursors successfully disrupted the methamphetamine market and interrupted a trajectory of increasing usage. The price of methamphetamine tripled and purity declined from 90 percent to 20 percent. Simultaneously, amphetaminerelated hospital and treatment admissions dropped 50 percent and 35 percent, respectively. Methamphetamine use among arrestees declined 55 percent. Although felony methamphetamine arrests fell 50 percent, there is no evidence of substantial reductions in property or violent crime. The impact was largely temporary. The price returned to its original level within four months; purity, hospital admissions, treatment admissions, and arrests approached preintervention levels within eighteen months. (JEL I12, K42). PMID- 20543968 TI - Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities. AB - Inward rectifier potassium (Kir) channels have been postulated as therapeutic targets for several common disorders including hypertension, cardiac arrhythmias and pain. With few exceptions, however, the small-molecule pharmacology of this family is limited to nonselective cardiovascular and neurologic drugs with off target activity toward inward rectifiers. Consequently, the actual therapeutic potential and 'drugability' of most Kir channels has not yet been determined experimentally. The purpose of this review is to provide a comprehensive summary of publicly disclosed Kir channel small-molecule modulators and highlight recent targeted drug-discovery efforts toward Kir1.1 and Kir2.1. The review concludes with a brief speculation on how the field of Kir channel pharmacology will develop over the coming years and a discussion of the increasingly important role academic laboratories will play in this progress. PMID- 20543970 TI - Hydrophilic elastomeric biomaterials based on resilin-like polypeptides. AB - The production of complex, yet well defined materials offers many opportunities in regenerative medicine, in which the mechanical and biological properties of the matrix must meet stringent requirements. Here we report the recombinant production of modular polypeptidic materials, based on the highly resilient protein resilin, which are equipped with multiple biologically active domains. The recombinant materials exhibit useful mechanical and cell adhesion behavior. PMID- 20543971 TI - Research Discoveries After Kubin. AB - This paper will discuss commercializing discoveries made at research organizations, particularly with a view to the In re Kubin case, decided April 3, 2009, by the Federal Circuit. Here, the existence of a general method of isolating DNA molecules was held to be relevant to the question whether the DNA molecules themselves would have been obvious under S 103 of the patent act. How are DNA inventions patented anyway? What does it take for academic research to reach patients? How might the decision of In re Kubin effect research commercialization and technology transfer? PMID- 20543972 TI - Integrated team working: a literature review. AB - INTRODUCTION: This literature review was conducted to provide a background understanding of the literature around integrated health and social care prior to a research project evaluating two integrated health and social care teams in England, UK. METHODS: A systematic literature search of relevant databases was employed to identify all articles relating to integrated health and social care teams produced in the last 10 years in the UK. RESULTS: Sixteen articles were found and reviewed; all were reviewed by the first reviewer and half by the second reviewer. DISCUSSION: KEY THEMES IDENTIFIED WERE: drivers, barriers and benefits of integrated working; staff development; and meeting the needs of service users. CONCLUSION: Recommendations for integrated working include; a focus on the management of integrated teams; a need to invest in resources for the successful integration of teams; a need for the development of clear standards for monitoring the success and failure of integrated teams; and the need for further empirical evidence of the processes used by integrated teams. These findings will be valuable for practitioners who are establishing services or want to improve integrated care in their own practice. PMID- 20543973 TI - Integrate now, create health: perspectives from Singapore. PMID- 20543974 TI - Value of integrated care: revival of the monetary valuation of health care benefits. PMID- 20543977 TI - The Effects of Stress on Job Functioning of Military Men and Women. PMID- 20543976 TI - Shotgun proteomics identifies proteins specific for acute renal transplant rejection. AB - PURPOSE: Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. EXPERIMENTAL DESIGN: We used shotgun proteomics applying LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls. RESULTS: A total of 1446 urinary proteins (UP) were identified along with a number of nonspecific proteinuria-specific, renal transplantation specific and AR-specific proteins. Relative abundance of identified UP was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific UP in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (uromodulin, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these UP in AR. CONCLUSIONS AND CLINICAL RELEVANCE: This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of UP for serial, non-invasive clinical monitoring for graft rejection after kidney transplantation. PMID- 20543975 TI - PET in Cerebrovascular Disease. AB - Investigation of the interplay between the cerebral circulation and brain cellular function is fundamental to understanding both the pathophysiology and treatment of stroke. Currently, PET is the only technique that provides accurate, quantitative in vivo regional measurements of both cerebral circulation and cellular metabolism in human subjects. We review normal human cerebral blood flow and metabolism and human PET studies of ischemic stroke, carotid artery disease, vascular dementia, intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage and discuss how these studies have added to our understanding of the pathophysiology of human cerebrovascular disease. PMID- 20543978 TI - Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression. AB - Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant) block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7) the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs. PMID- 20543979 TI - Drosophila TRPN(=NOMPC) channel localizes to the distal end of mechanosensory cilia. AB - BACKGROUND: A TRPN channel protein is essential for sensory transduction in insect mechanosensory neurons and in vertebrate hair cells. The Drosophila TRPN homolog, NOMPC, is required to generate mechanoreceptor potentials and currents in tactile bristles. NOMPC is also required, together with a TRPV channel, for transduction by chordotonal neurons of the fly's antennal ear, but the TRPN or TRPV channels have distinct roles in transduction and in regulating active antennal mechanics. The evidence suggests that NOMPC is a primary mechanotransducer channel, but its subcellular location-key for understanding its exact role in transduction-has not yet been established. METHODOLOGY/PRINCIPAL FINDINGS: Here, by immunostaining, we locate NOMPC at the tips of mechanosensory cilia in both external and chordotonal sensory neurons, as predicted for a mechanotransducer channel. In chordotonal neurons, the TRPN and TRPV channels are respectively segregated into distal and proximal ciliary zones. This zonal separation is demarcated by and requires the ciliary dilation, an intraciliary assembly of intraflagellar transport (IFT) proteins. CONCLUSIONS: Our results provide a strong evidence for NOMPC as a primary transduction channel in Drosophila mechansensory organs. The data also reveals a structural basis for the model of auditory chordotonal transduction in which the TRPN and TRPV channels play sequential roles in generating and amplifying the receptor potential, but have opposing roles in regulating active ciliary motility. PMID- 20543980 TI - Rapamycin pharmacokinetic and pharmacodynamic relationships in osteosarcoma: a comparative oncology study in dogs. AB - BACKGROUND: Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients. METHODOLOGY/PRINCIPAL FINDINGS: This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30 kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy. CONCLUSIONS/SIGNIFICANCE: Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease. PMID- 20543981 TI - Dkk1 stabilizes Wnt co-receptor LRP6: implication for Wnt ligand-induced LRP6 down-regulation. AB - BACKGROUND: The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts. Previous studies have demonstrated that Dkk1 promotes LRP6 internalization and degradation when it forms a ternary complex with the cell surface receptor Kremen. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found that transfected Dkk1 induces LRP6 accumulation while inhibiting Wnt/LRP6 signaling. Treatment with Dkk1-conditioned medium or recombinant Dkk1 protein stabilized LRP6 with a prolonged half-life and induces LRP6 accumulation both at the cell surface and in endosomes. We also demonstrated that Kremen2 co-expression abrogated the effect of Dkk1 on LRP6 accumulation, indicating that the effect of Kremen2 is dominant over Dkk1 regulation of LRP6. Furthermore, we found that Wnt3A treatment induces LRP6 down-regulation, an effect paralleled with a Wnt/LRP6 signaling decay, and that Dkk1 treatment blocked Wnt3A-induced LRP6 down-regulation. Finally, we found that LRP6 turnover was blocked by an inhibitor of caveolae-mediated endocytosis. CONCLUSIONS/SIGNIFICANCE: Our results reveal a novel role for Dkk1 in preventing Wnt ligand-induced LRP6 down-regulation and contribute significantly to our understanding of Dkk1 function in Wnt/LRP6 signaling. PMID- 20543982 TI - Evaluating the cellular targets of anti-4-1BB agonist antibody during immunotherapy of a pre-established tumor in mice. AB - BACKGROUND: Manipulation of the immune system represents a promising avenue for cancer therapy. Rational advances in immunotherapy of cancer will require an understanding of the precise correlates of protection. Agonistic antibodies against the tumor necrosis factor receptor family member 4-1BB are emerging as a promising tool in cancer therapy, with evidence that these antibodies expand both T cells as well as innate immune cells. Depletion studies have suggested that several cell types can play a role in these immunotherapeutic regimens, but do not reveal which cells must directly receive the 4-1BB signals for effective therapy. METHODOLOGY/PRINCIPAL FINDINGS: We show that re-activated memory T cells are superior to resting memory T cells in control of an 8-day pre-established E.G7 tumor in mice. We find that ex vivo activation of the memory T cells allows the activated effectors to continue to divide and enter the tumor, regardless of antigen-specificity; however, only antigen-specific reactivated memory T cells show any efficacy in tumor control. When agonistic anti-4-1BB antibody is combined with this optimized adoptive T cell therapy, 80% of mice survive and are fully protected from tumor rechallenge. Using 4-1BB-deficient mice and mixed bone marrow chimeras, we find that it is sufficient to have 4-1BB only on the endogenous host alphabeta T cells or only on the transferred T cells for the effects of anti-4-1BB to be realized. Conversely, although multiple immune cell types express 4-1BB and both T cells and APC expand during anti-4-1BB therapy, 4 1BB on cells other than alphabeta T cells is neither necessary nor sufficient for the effect of anti-4-1BB in this adoptive immunotherapy model. CONCLUSIONS/SIGNIFICANCE: This study establishes alphabeta T cells rather than innate immune cells as the critical target in anti-4-1BB therapy of a pre established tumor. The study also demonstrates that ex vivo activation of memory T cells prior to infusion allows antigen-specific tumor control without the need for reactivation of the memory T cells in the tumor. PMID- 20543983 TI - Proinflammatory phenotype and increased caveolin-1 in alveolar macrophages with silenced CFTR mRNA. AB - The inflammatory milieu in the respiratory tract in cystic fibrosis (CF) has been linked to the defective expression of the cystic transmembrane regulator (CFTR) in epithelial cells. Alveolar macrophages (AM), important contibutors to inflammatory responses in the lung, also express CFTR. The present study analyzes the phenotype of human AM with silenced CFTR. Expression of CFTR mRNA and the immature form of the CFTR protein decreased 100-fold and 5.2-fold, respectively, in AM transfected with a CFTR specific siRNA (CFTR-siRNA) compared to controls. Reduction of CFTR expression in AM resulted in increased secretion of IL-8, increased phosphorylation of NF-kappaB, a positive regulator of IL-8 expression, and decreased expression of IkappaB-alpha, the inhibitory protein of NF-kappaB activation. AM with silenced CFTR expression also showed increased apoptosis. We hypothesized that caveolin-1 (Cav1), a membrane protein that is co-localized with CFTR in lipid rafts and that is related to inflammation and apoptosis in macrophages, may be affected by decreased CFTR expression. Messenger RNA and protein levels of Cav1 were increased in AM with silenced CFTR. Expression and transcriptional activity of sterol regulatory element binding protein (SREBP), a negative transcriptional regulator of Cav1, was decreased in AM with silenced CFTR, but total and free cholesterol mass did not change. These findings indicate that silencing of CFTR in human AM results in an inflammatory phenotype and apoptosis, which is associated to SREBP-mediated regulation of Cav1. PMID- 20543984 TI - A switch from a gradient to a threshold mode in the regulation of a transcriptional cascade promotes robust execution of meiosis in budding yeast. AB - Tight regulation of developmental pathways is of critical importance to all organisms, and is achieved by a transcriptional cascade ensuring the coordinated expression of sets of genes. We aimed to explore whether a strong signal is required to enter and complete a developmental pathway, by using meiosis in budding yeast as a model. We demonstrate that meiosis in budding yeast is insensitive to drastic changes in the levels of its consecutive positive regulators (Ime1, Ime2, and Ndt80). Entry into DNA replication is not correlated with the time of transcription of the early genes that regulate this event. Entry into nuclear division is directly regulated by the time of transcription of the middle genes, as premature transcription of their activator NDT80, leads to a premature entry into the first meiotic division, and loss of coordination between DNA replication and nuclear division. We demonstrate that Cdk1/Cln3 functions as a negative regulator of Ime2, and that ectopic expression of Cln3 delays entry into nuclear division as well as NDT80 transcription. Because Ime2 functions as a positive regulator for premeiotic DNA replication and NDT80 transcription, as well as a negative regulator of Cdk/Cln, we suggest that a double negative feedback loop between Ime2 and Cdk1/Cln3 promotes a bistable switch from the cell cycle to meiosis. Moreover, our results suggest a regulatory mode switch that ensures robust meiosis as the transcription of the early meiosis-specific genes responds in a graded mode to Ime1 levels, whereas that of the middle and late genes as well as initiation of DNA replication, are regulated in a threshold mode. PMID- 20543985 TI - Control growth factor release using a self-assembled [polycation:heparin] complex. AB - The importance of growth factors has been recognized for over five decades; however their utilization in medicine has yet to be fully realized. This is because free growth factors have short half-lives in plasma, making direct injection inefficient. Many growth factors are anchored and protected by sulfated glycosaminoglycans in the body. We set out to explore the use of heparin, a well characterized sulfated glycosaminoglycan, for the controlled release of fibroblast growth factor-2 (FGF-2). Heparin binds a multitude of growth factors and maintains their bioactivity for an extended period of time. We used a biocompatible polycation to precipitate out the [heparin:FGF-2] complex from neutral buffer to form a release matrix. We can control the release rate of FGF-2 from the resultant matrix by altering the molecular weight of the polycation. The FGF-2 released from the delivery complex maintained its bioactivity and initiated cellular responses that were at least as potent as fresh bolus FGF-2 and fresh heparin stabilized FGF-2. This new delivery platform is not limited to FGF-2 but applicable to the large family of heparin-binding growth factors. PMID- 20543986 TI - Dissociation of CAK from core TFIIH reveals a functional link between XP-G/CS and the TFIIH disassembly state. AB - Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation. PMID- 20543987 TI - Slip-sliding away: serial changes and homoplasy in repeat number in the Drosophila yakuba homolog of human cancer susceptibility gene BRCA2. AB - Several recent studies have examined the function and evolution of a Drosophila homolog to the human breast cancer susceptibility gene BRCA2, named dmbrca2. We previously identified what appeared to be a recent expansion in the RAD51-binding BRC-repeat array in the ancestor of Drosophila yakuba. In this study, we examine patterns of variation and evolution of the dmbrca2 BRC-repeat array within D. yakuba and its close relatives. We develop a model of how unequal crossing over may have produced the expanded form, but we also observe short repeat forms, typical of other species in the D. melanogaster group, segregating within D. yakuba and D. santomea. These short forms do not appear to be identical-by descent, suggesting that the history of dmbrca2 in the D. melanogaster subgroup has involved repeat unit contractions resulting in homoplasious forms. We conclude that the evolutionary history of dmbrca2 in D. yakuba and perhaps in other Drosophila species may be more complicated than can be inferred from examination of the published single genome sequences per species. PMID- 20543988 TI - Utilizing genotype imputation for the augmentation of sequence data. AB - BACKGROUND: In recent years, capabilities for genotyping large sets of single nucleotide polymorphisms (SNPs) has increased considerably with the ability to genotype over 1 million SNP markers across the genome. This advancement in technology has led to an increase in the number of genome-wide association studies (GWAS) for various complex traits. These GWAS have resulted in the implication of over 1500 SNPs associated with disease traits. However, the SNPs identified from these GWAS are not necessarily the functional variants. Therefore, the next phase in GWAS will involve the refining of these putative loci. METHODOLOGY: A next step for GWAS would be to catalog all variants, especially rarer variants, within the detected loci, followed by the association analysis of the detected variants with the disease trait. However, sequencing a locus in a large number of subjects is still relatively expensive. A more cost effective approach would be to sequence a portion of the individuals, followed by the application of genotype imputation methods for imputing markers in the remaining individuals. A potentially attractive alternative option would be to impute based on the 1000 Genomes Project; however, this has the drawbacks of using a reference population that does not necessarily match the disease status and LD pattern of the study population. We explored a variety of approaches for carrying out the imputation using a reference panel consisting of sequence data for a fraction of the study participants using data from both a candidate gene sequencing study and the 1000 Genomes Project. CONCLUSIONS: Imputation of genetic variation based on a proportion of sequenced samples is feasible. Our results indicate the following sequencing study design guidelines which take advantage of the recent advances in genotype imputation methodology: Select the largest and most diverse reference panel for sequencing and genotype as many "anchor" markers as possible. PMID- 20543990 TI - For group II introns, more heat means more mobility. PMID- 20543989 TI - Mechanisms used for genomic proliferation by thermophilic group II introns. AB - Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelements hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting approximately 1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases. PMID- 20543991 TI - Dysregulation of the norepinephrine transporter sustains cortical hypodopaminergia and schizophrenia-like behaviors in neuronal rictor null mice. AB - The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) is a multimeric signaling unit that phosphorylates protein kinase B/Akt following hormonal and growth factor stimulation. Defective Akt phosphorylation at the mTORC2-catalyzed Ser473 site has been linked to schizophrenia. While human imaging and animal studies implicate a fundamental role for Akt signaling in prefrontal dopaminergic networks, the molecular mechanisms linking Akt phosphorylation to specific schizophrenia-related neurotransmission abnormalities have not yet been described. Importantly, current understanding of schizophrenia suggests that cortical decreases in DA neurotransmission and content, defined here as cortical hypodopaminergia, contribute to both the cognitive deficits and the negative symptoms characteristic of this disorder. We sought to identify a mechanism linking aberrant Akt signaling to these hallmarks of schizophrenia. We used conditional gene targeting in mice to eliminate the mTORC2 regulatory protein rictor in neurons, leading to impairments in neuronal Akt Ser473 phosphorylation. Rictor-null (KO) mice exhibit prepulse inhibition (PPI) deficits, a schizophrenia associated behavior. In addition, they show reduced prefrontal dopamine (DA) content, elevated cortical norepinephrine (NE), unaltered cortical serotonin (5 HT), and enhanced expression of the NE transporter (NET). In the cortex, NET takes up both extracellular NE and DA. Thus, we propose that amplified NET function in rictor KO mice enhances accumulation of both NE and DA within the noradrenergic neuron. This phenomenon leads to conversion of DA to NE and ultimately supports both increased NE tissue content as well as a decrease in DA. In support of this hypothesis, NET blockade in rictor KO mice reversed cortical deficits in DA content and PPI, suggesting that dysregulation of DA homeostasis is driven by alteration in NET expression, which we show is ultimately influenced by Akt phosphorylation status. These data illuminate a molecular link, Akt regulation of NET, between the recognized association of Akt signaling deficits in schizophrenia with a specific mechanism for cortical hypodopaminergia and hypofunction. Additionally, our findings identify Akt as a novel modulator of monoamine homeostasis in the cortex. PMID- 20543993 TI - Where to for sexual health education for adolescents in sub-saharan Africa? PMID- 20543992 TI - Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. PMID- 20543994 TI - Long-term biological and behavioural impact of an adolescent sexual health intervention in Tanzania: follow-up survey of the community-based MEMA kwa Vijana Trial. AB - BACKGROUND: The ability of specific behaviour-change interventions to reduce HIV infection in young people remains questionable. Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in ten randomly chosen intervention communities in rural Tanzania, within a community randomised trial (see below; NCT00248469). The intervention consisted of teacher led, peer-assisted in-school education, youth-friendly health services, community activities, and youth condom promotion and distribution. Process evaluation in 1999-2002 showed high intervention quality and coverage. A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 (HSV-2) seroprevalence but found substantial improvements in SRH knowledge, reported attitudes, and some reported sexual behaviours. It was postulated that the impact on "upstream" knowledge, attitude, and reported behaviour outcomes seen at the 3-year follow-up would, in the longer term, lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes. A further impact evaluation survey in 2007/8 ( approximately 9 years post-intervention) tested this hypothesis. METHODS AND FINDINGS: This is a cross sectional survey (June 2007 through July 2008) of 13,814 young people aged 15-30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial (1999-2002). Prevalences of the primary outcomes HIV and HSV-2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio [aPR] 0.91, 95%CI 0.50-1.65; females aPR 1.07, 95%CI 0.68-1.67) or HSV-2 (males aPR 0.94, 95%CI 0.77-1.15; females aPR 0.96, 95%CI 0.87-1.06). The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime (aPR 0.87, 95%CI 0.78-0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR 1.34, 95%CI 1.07-1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies, or other reported sexual behaviours. The study population was likely to have been, on average, at lower risk of HIV and other sexually transmitted infections compared to other rural populations, as only youth who had reached year five of primary school were eligible. CONCLUSIONS: SRH knowledge can be improved and retained long-term, but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov NCT00248469 PMID- 20543995 TI - Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren. AB - BACKGROUND: Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. METHODS AND FINDINGS: We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37-39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12-1.20; 33-36 wk adjusted OR 1.53, 95% CI 1.43-1.63; 28-32 wk adjusted OR 2.66, 95% CI 2.38-2.97; 24-27 wk adjusted OR 6.92, 95% CI 5.58-8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37-39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. CONCLUSIONS: Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery. PMID- 20543996 TI - JNK signalling controls remodelling of the segment boundary through cell reprogramming during Drosophila morphogenesis. AB - Segments are fundamental units in animal development which are made of distinct cell lineages separated by boundaries. Although boundaries show limited plasticity during their formation for sharpening, cell lineages make compartments that become tightly restricted as development goes on. Here, we characterize a unique case of breaking of the segment boundary in late drosophila embryos. During dorsal closure, specific cells from anterior compartments cross the segment boundary and enter the adjacent posterior compartments. This cell mixing behaviour is driven by an anterior-to-posterior reprogramming mechanism involving de novo expression of the homeodomain protein Engrailed. Mixing is accompanied by stereotyped local cell intercalation, converting the segment boundary into a relaxation compartment important for tension-release during morphogenesis. This process of lineage switching and cell remodelling is controlled by JNK signalling. Our results reveal plasticity of segment boundaries during late morphogenesis and a role for JNK-dependent developmental reprogramming in this process. PMID- 20543998 TI - Synthesis and Evaluation of Estradiol Derivatives as Anti-Breast Cancer Agents. AB - 3-N-alkyloxyestradiol derivatives were synthesized, characterized and tested for activity in MCF-7 human breast cancer cells. Among the compounds, the diisopropyl and piperidinyl derivatives were found to be more active than 4-hydroxytamoxifen (HO-Tam), the active metabolite of tamoxifen based upon IC(50) values. The IC(50)s were correlated with structures using molecular modeling. PMID- 20543997 TI - IMITATE: An intensive computer-based treatment for aphasia based on action observation and imitation. AB - BACKGROUND: Neurophysiological evidence from primates has demonstrated the presence of mirror neurons, with visual and motor properties, that discharge both when an action is performed and during observation of the same action. A similar system for observation-execution matching may also exist in humans. We postulate that behavioral stimulation of this parietal-frontal system may play an important role in motor learning for speech and thereby aid language recovery after stroke. AIMS: The purpose of this article is to describe the development of IMITATE, a computer-assisted system for aphasia therapy based on action observation and imitation. We also describe briefly the randomized controlled clinical trial that is currently underway to evaluate its efficacy and mechanism of action. METHODS AND PROCEDURES: IMITATE therapy consists of silent observation of audio-visually presented words and phrases spoken aloud by six different speakers, followed by a period during which the participant orally repeats the stimuli. We describe the rationale for the therapeutic features, stimulus selection, and delineation of treatment levels. The clinical trial is a randomized single blind controlled trial in which participants receive two pre-treatment baseline assessments, six weeks apart, followed by either IMITATE or a control therapy. Both treatments are provided intensively (90 minutes per day). Treatment is followed by a post treatment assessment, and a six-week follow-up assessment. OUTCOMES #ENTITYSTARTX00026; RESULTS: Thus far, five participants have completed IMITATE. We expect the results of the randomized controlled trial to be available by late 2010. CONCLUSIONS: IMITATE is a novel computer-assisted treatment for aphasia that is supported by theoretical rationales and previous human and primate data from neurobiology. The treatment is feasible, and preliminary behavioral data are emerging. However, the results will not be known until the clinical trial data are available to evaluate fully the efficacy of IMITATE and to inform theoretically about the mechanism of action and the role of a human mirror system in aphasia treatment. PMID- 20543999 TI - Local semi-empirical formulae for the contact values of the singlet distribution functions of a double layer. AB - The electrochemical double layer is an important practical and theoretical problem. Generally speaking, experiment gives valuable information about quantities, such as potential differences, that involve integrals of density and charge profiles but does not provide direct information about the profiles themselves. Computer simulations have given numerical information about these profiles. However, explicit expressions are useful in understanding these data. For some years an exact expression has been known for the contact value of total density profile of the ions in the double layer but, until recently, an expression for the contact value of the more important charge profile has been lacking. A few years ago, a semi-empirical local result for the charge profile, valid at low electrode charge, was proposed and, very recently, extended to higher electrode charge. This expression contains a parameter; the effect of variations in this parameter is explored in this paper and the result is compared with a large set of simulation data for the contact values of various profiles that we have accumulated in the past few years. The agreement of the semi empirical expression with our simulation results is excellent. The best values for this parameter are fairly close to the value suggested by theory. PMID- 20544000 TI - Involvement in Intimate Partner Psychological Abuse and Suicide Proneness in College Women: Alcohol Related Problems as a Potential Mediator. AB - This study examined the relations among involvement in intimate partner psychological abuse, alcohol-related problems, and suicide proneness as measured by the Life Attitudes Schedule - Short Form (LAS-SF) in college women (N = 709). Results revealed that, as expected, being involved in a psychologically abusive relationship was significantly and positively correlated with alcohol-related problems and alcohol-related problems were significantly and positively correlated with suicide proneness. Additionally, the intimate partner psychological abuse involvement-suicide proneness link was significantly mediated by alcohol-related problems. Implications are offered for the improved identification and treatment of young women at risk for suicidal and health diminishing behaviors. PMID- 20544001 TI - Assembly of gold nanowires by sedimentation from suspension: Experiments and simulation. AB - We investigated the ordering of gold nanowires that settled from aqueous suspension onto a glass substrate due to gravity. The nanowires, ca. 300 nm in cross-sectional diameter and ca. 2, 4, or 7 microns in length, were coated with 2 mercaptoethanesulfonic acid to provide electrostatic repulsion and prevent aggregation. The layer of nanowires in direct contact with the substrate was examined from below using optical microscopy and found to exhibit smectic-like ordering. The extent of smectic ordering depended on nanowire length with the shortest (2 MUm) nanowires exhibiting the best ordering. To understand the assembly in this system, we used canonical Monte Carlo simulations to model the two-dimensional ordering of the nanowires on a substrate. We accounted for van der Waals and electrostatic interactions between the nanowires. The simulations reproduced the experimental trends and showed that roughness at the ends of the nanowires, which locally increased electrostatic repulsion, is critical to correctly predicting the experimentally observed smectic ordering. PMID- 20544002 TI - PediaFlowTM Maglev Ventricular Assist Device: A Prescriptive Design Approach. AB - This report describes a multi-disciplinary program to develop a pediatric blood pump, motivated by the critical need to treat infants and young children with congenital and acquired heart diseases. The unique challenges of this patient population require a device with exceptional biocompatibility, miniaturized for implantation up to 6 months. This program implemented a collaborative, prescriptive design process, whereby mathematical models of the governing physics were coupled with numerical optimization to achieve a favorable compromise among several competing design objectives. Computational simulations of fluid dynamics, electromagnetics, and rotordynamics were performed in two stages: first using reduced-order formulations to permit rapid optimization of the key design parameters; followed by rigorous CFD and FEA simulations for calibration, validation, and detailed optimization. Over 20 design configurations were initially considered, leading to three pump topologies, judged on the basis of a multi-component analysis including criteria for anatomic fit, performance, biocompatibility, reliability, and manufacturability. This led to fabrication of a mixed-flow magnetically levitated pump, the PF3, having a displaced volume of 16.6 cc, approximating the size of a AA battery and producing a flow capacity of 0.3-1.5 L/min. Initial in vivo evaluation demonstrated excellent hemocompatibility after 72 days of implantation in an ovine. In summary, combination of prescriptive and heuristic design principles have proven effective in developing a miniature magnetically levitated blood pump with excellent performance and biocompatibility, suitable for integration into chronic circulatory support system for infants and young children; aiming for a clinical trial within 3 years. PMID- 20544004 TI - A statistical dynamics approach to the study of human health data: resolving population scale diurnal variation in laboratory data. AB - Statistical physics and information theory is applied to the clinical chemistry measurements present in a patient database containing 2.5 million patients' data over a 20-year period. Despite the seemingly naive approach of aggregating all patients over all times (with respect to particular clinical chemistry measurements), both a diurnal signal in the decay of the time-delayed mutual information and the presence of two sub-populations with differing health are detected. This provides a proof in principle that the highly fragmented data in electronic health records has potential for being useful in defining disease and human phenotypes. PMID- 20544003 TI - Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. AB - BACKGROUND: Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme that hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anti inflammatory, anxiolytic, and antidepressant phenotypes without showing the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. OBJECTIVES: This review highlights advances in the development of FAAH inhibitors of different mechanistic classes and their in vivo efficacy. Also highlighted are advances in technology for the in vitro and in vivo selectivity assessment of FAAH inhibitors employing activity based protein profiling (ABPP) and click chemistry-ABPP, respectively. Recent reports on structure-based drug design for human FAAH generated by protein engineering using interspecies active site conversion are also discussed. METHODS: The literature searches of Medline and SciFinder databases were used. CONCLUSIONS: There has been tremendous progress in our understanding in FAAH and development of FAAH inhibitors with in vivo efficacy, selectivity, and drug like pharmacokinetic properties. PMID- 20544005 TI - Gene set-based module discovery decodes cis-regulatory codes governing diverse gene expression across human multiple tissues. AB - Decoding transcriptional programs governing transcriptomic diversity across human multiple tissues is a major challenge in bioinformatics. To address this problem, a number of computational methods have focused on cis-regulatory codes driving overexpression or underexpression in a single tissue as compared to others. On the other hand, we recently proposed a different approach to mine cis-regulatory codes: starting from gene sets sharing common cis-regulatory motifs, the method screens for expression modules based on expression coherence. However, both approaches seem to be insufficient to capture transcriptional programs that control gene expression in a subset of all samples. Especially, this limitation would be serious when analyzing multiple tissue data. To overcome this limitation, we developed a new module discovery method termed BEEM (Biclusering based Extraction of Expression Modules) in order to discover expression modules that are functional in a subset of tissues. We showed that, when applied to expression profiles of human multiple tissues, BEEM finds expression modules missed by two existing approaches that are based on the coherent expression and the single tissue-specific differential expression. From the BEEM results, we obtained new insights into transcriptional programs controlling transcriptomic diversity across various types of tissues. This study introduces BEEM as a powerful tool for decoding regulatory programs from a compendium of gene expression profiles. PMID- 20544006 TI - Disambiguating multi-modal scene representations using perceptual grouping constraints. AB - In its early stages, the visual system suffers from a lot of ambiguity and noise that severely limits the performance of early vision algorithms. This article presents feedback mechanisms between early visual processes, such as perceptual grouping, stereopsis and depth reconstruction, that allow the system to reduce this ambiguity and improve early representation of visual information. In the first part, the article proposes a local perceptual grouping algorithm that - in addition to commonly used geometric information - makes use of a novel multi modal measure between local edge/line features. The grouping information is then used to: 1) disambiguate stereopsis by enforcing that stereo matches preserve groups; and 2) correct the reconstruction error due to the image pixel sampling using a linear interpolation over the groups. The integration of mutual feedback between early vision processes is shown to reduce considerably ambiguity and noise without the need for global constraints. PMID- 20544007 TI - Acetaminophen modulates the transcriptional response to recombinant interferon beta. AB - BACKGROUND: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP), interferon-beta (IFN beta) or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. CONCLUSIONS/SIGNIFICANCE: A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment. PMID- 20544008 TI - 'It's Not What You Said, It's How You Said It': Perceptions of Condom Proposers by Gender and Strategy. AB - We examined effects of proposer gender and condom negotiation strategy on perceptions of condom proposers in undergraduates in the southwestern regions of the US. Using a video manipulation (N=150), a female proposer was evaluated no more harshly than a male proposer, and was evaluated more positively in some ways. In a vignette manipulation (N=193) a female proposer using an Eroticization negotiation strategy (compared to Refusal of sex or Explanation of consequences) was seen as more exciting and likely to engage in sex. Surprisingly, women were harsher judges than men of a female condom proposer using an Eroticization strategy. Greater attention should be paid to the nature of condom negotiation within the framework of the sexual script. PMID- 20544009 TI - The Interactive Effects of Marital Conflict and Divorce on Parent-Adult Children's Relationships. AB - This study examines main effect and interactive models of the relations between marital conflict, divorce, and parent-adult child relationships, and gender differences in these relations. Data were drawn from a longitudinal study of a community sample (N = 585). Parental marital conflict and divorce were measured from age 5 through age 17. Mother-child and father-child relationship quality at age 22 was assessed in terms of Closeness-Support and Conflict-Control. Results indicate that both marital conflict and divorce were associated with poorer quality of parent-adult child relationships. Divorce moderated the link between marital conflict and subsequent negativity in mother-child relationships, with the estimated effects being stronger in continuously married families than in divorced families, especially for women. PMID- 20544010 TI - Conformational Propensities of Peptides Mimicking Transmembrane Helix 5 and Motif C in Wild-type and Mutant Vesicular Acetylcholine Transporters. AB - Vesicular acetylcholine transporter (VAChT) is a member of the major facilitator superfamily (MFS). It contains conserved sequence motifs originally defined in the bacterial multidrug resistance transporter family of the MFS. Motif C (GSLV(227) A(228)PPFGGIL) is located at the C-terminal end of transmembrane helix 5 (TM 5) in VAChT. The motif is rich in glycine and proline residues that often have special roles in backbone conformations of TMs. The A228G mutant of VAChT transports > 3-fold faster than wild type does [Chandrasekaran et al. (2006)J. Neurochem. 98, 1551-1559.]. In the current study, the structure of Loop 4/5, TM 5, and Motif C were taken from a three-dimensional homology model for human VAChT. The peptide was immersed in implicit membrane, energy minimized, and molecular dynamics (MD) were simulated. Kinking and wobbling occur in otherwise helical peptide at the hinge residues L226 and V227. MD also were simulated for A228G single-mutant and V227L-A228A double-mutant peptides to investigate the structural roles of the A228G mutation and beta-branching at V227. Mutant peptides exhibit increased wobbling at the hinge residues, but in the double mutant the increase is less. Because Motif C participates in the interface that mediates hypothesized rocker-switch re-orientation of the acetylcholine binding site during transport, dynamics in Motif C might be an important contributor to transport rate. PMID- 20544011 TI - The Motive for Support and the Identification of Responsive Partners. AB - To obtain support from others, a person must first identify responsive partners. One strategy for doing so is to use indicators of responsive partners. We argue that a person with a strong motive for support should rate all indicators highly useful-the "Elevated Motives Effect." Study 1 confirmed this hypothesis by correlating participants' total ratings with existing measures of motive strength. Study 2 applied the Elevated Motives Effect to demonstrate that motive strength (in interaction with knowledge of indicators) predicts performance on a laboratory task in which participants evaluated a person: Superior knowledge led to superior performance only when motive-strength was high. Study 3, an experience-sampling study, showed that in everyday life, motivated people more often seek support from others when distressed. PMID- 20544012 TI - Helminth coinfection does not affect therapeutic effect of a DNA vaccine in mice harboring tuberculosis. AB - BACKGROUND: Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections. PMID- 20544013 TI - Orally co-Infected Aedes albopictus from La Reunion Island, Indian Ocean, can deliver both dengue and chikungunya infectious viral particles in their saliva. AB - BACKGROUND: First described in humans in 1964, reports of co-infections with dengue (DENV) and chikungunya (CHIKV) viruses are increasing, particularly after the emergence of chikungunya (CHIK) in the Indian Ocean in 2005-2006 due to a new variant highly transmitted by Aedes albopictus. In this geographic area, a dengue (DEN) outbreak transmitted by Ae. albopictus took place shortly before the emergence of CHIK and co-infections were reported in patients. A co-infection in humans can occur following the bite of two mosquitoes infected with one virus or to the bite of a mosquito infected with two viruses. Co-infections in mosquitoes have never been demonstrated in the field or in the laboratory. Thus, we question about the ability of a mosquito to deliver infectious particles of two different viruses through the female saliva. METHODOLOGY/PRINCIPAL FINDINGS: We orally exposed Ae. albopictus from La Reunion Island with DENV-1 and CHIKV isolated respectively during the 2004-2005 and the 2005-2006 outbreaks on this same island. We were able to show that Ae. albopictus could disseminate both viruses and deliver both infectious viral particles concomitantly in its saliva. We also succeeded in inducing a secondary infection with CHIKV in mosquitoes previously inoculated with DENV-1. CONCLUSIONS/SIGNIFICANCE: In this study, we underline the ability of Ae. albopictus to be orally co-infected with two different arboviruses and furthermore, its capacity to deliver concomitantly infectious particles of CHIKV and DENV in saliva. This finding is of particular concern as Ae. albopictus is still expanding its geographical range in the tropical as well as in the temperate regions. Further studies are needed to try to elucidate the molecular/cellular basis of this phenomenon. PMID- 20544014 TI - Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe. AB - BACKGROUND: HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. METHODOLOGY/PRINCIPAL FINDINGS: Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log(10) HIV-1 copies/10(6) PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4(+) T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. CONCLUSIONS/SIGNIFICANCE: An improved molecular beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV 1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template. PMID- 20544015 TI - ICP0 dismantles microtubule networks in herpes simplex virus-infected cells. AB - Infected-cell protein 0 (ICP0) is a RING finger E3 ligase that regulates herpes simplex virus (HSV) mRNA synthesis, and strongly influences the balance between latency and replication of HSV. For 25 years, the nuclear functions of ICP0 have been the subject of intense scrutiny. To obtain new clues about ICP0's mechanism of action, we constructed HSV-1 viruses that expressed GFP-tagged ICP0. To our surprise, both GFP-tagged and wild-type ICP0 were predominantly observed in the cytoplasm of HSV-infected cells. Although ICP0 is exclusively nuclear during the immediate-early phase of HSV infection, further analysis revealed that ICP0 translocated to the cytoplasm during the early phase where it triggered a previously unrecognized process; ICP0 dismantled the microtubule network of the host cell. A RING finger mutant of ICP0 efficiently bundled microtubules, but failed to disperse microtubule bundles. Synthesis of ICP0 proved to be necessary and sufficient to disrupt microtubule networks in HSV-infected and transfected cells. Plant and animal viruses encode many proteins that reorganize microtubules. However, this is the first report of a viral E3 ligase that regulates microtubule stability. Intriguingly, several cellular E3 ligases orchestrate microtubule disassembly and reassembly during mitosis. Our results suggest that ICP0 serves a dual role in the HSV life cycle, acting first as a nuclear regulator of viral mRNA synthesis and acting later, in the cytoplasm, to dismantle the host cell's microtubule network in preparation for virion synthesis and/or egress. PMID- 20544016 TI - Light-induced changes within photosystem II protects Microcoleus sp. in biological desert sand crusts against excess light. AB - The filamentous cyanobacterium Microcoleus vaginatus, a major primary producer in desert biological sand crusts, is exposed to frequent hydration (by early morning dew) followed by desiccation during potentially damaging excess light conditions. Nevertheless, its photosynthetic machinery is hardly affected by high light, unlike "model" organisms whereby light-induced oxidative stress leads to photoinactivation of the oxygen-evolving photosystem II (PSII). Field experiments showed a dramatic decline in the fluorescence yield with rising light intensity in both drying and artificially maintained wet plots. Laboratory experiments showed that, contrary to "model" organisms, photosynthesis persists in Microcoleus sp. even at light intensities 2-3 times higher than required to saturate oxygen evolution. This is despite an extensive loss (85-90%) of variable fluorescence and thermoluminescence, representing radiative PSII charge recombination that promotes the generation of damaging singlet oxygen. Light induced loss of variable fluorescence is not inhibited by the electron transfer inhibitors 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 2,5-dibromo-3-methyl-6 isopropylbenzoquinone (DBMIB), nor the uncoupler carbonyl cyanide-p trifluoromethoxyphenylhydrazone (FCCP), thus indicating that reduction of plastoquinone or O(2), or lumen acidification essential for non-photochemical quenching (NPQ) are not involved. The rate of Q(A) (-) re-oxidation in the presence of DCMU is enhanced with time and intensity of illumination. The difference in temperatures required for maximal thermoluminescence emissions from S(2)/Q(A) (-) (Q band, 22 degrees C) and S(2,3)/Q(B) (-) (B band, 25 degrees C) charge recombinations is considerably smaller in Microcoleus as compared to "model" photosynthetic organisms, thus indicating a significant alteration of the S(2)/Q(A) (-) redox potential. We propose that enhancement of non-radiative charge recombination with rising light intensity may reduce harmful radiative recombination events thereby lowering (1)O(2) generation and oxidative photodamage under excess illumination. This effective photo-protective mechanism was apparently lost during the evolution from the ancestor cyanobacteria to the higher plant chloroplast. PMID- 20544017 TI - Safety concern between autologous fat graft, mesenchymal stem cell and osteosarcoma recurrence. AB - BACKGROUND: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. PRINCIPAL FINDINGS: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. SIGNIFICANCE: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID- 20544018 TI - Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis. AB - BACKGROUND: Cellular cholesterol is a vital component of the cell membrane. Its concentration is tightly controlled by mechanisms that remain only partially characterized. In this study, we describe a late endosome/lysosomes-associated protein whose expression level affects cellular free cholesterol content. METHODOLOGY/PRINCIPAL FINDINGS: Using a restricted proteomic analysis of detergent-resistant membranes (DRMs), we have identified a protein encoded by gene C11orf59. It is mainly localized to late endosome/lysosome (LE/LY) compartment through N-terminal myristoylation and palmitoylation. We named it Pdro for protein associated with DRMs and endosomes. Very recently, three studies have reported on the same protein under two other names: the human p27RF-Rho that regulates RhoA activation and actin dynamics, and its rodent orthologue p18 that controls both LE/LY dynamics through the MERK-ERK pathway and the lysosomal activation of mammalian target of rapamycin complex 1 by amino acids. We found that, consistent with the presence of sterol-responsive element consensus sequences in the promoter region of C11orf59, Pdro mRNA and protein expression levels are regulated positively by cellular cholesterol depletion and negatively by cellular cholesterol loading. Conversely, Pdro is involved in the regulation of cholesterol homeostasis, since its depletion by siRNA increases cellular free cholesterol content that is accompanied by an increased cholesterol efflux from cells. On the other hand, cells stably overexpressing Pdro display reduced cellular free cholesterol content. Pdro depletion-mediated excess cholesterol results, at least in part, from a stimulated low-density lipoprotein (LDL) uptake and an increased cholesterol egress from LE/LY. CONCLUSIONS/SIGNIFICANCE: LDL derived cholesterol release involves LE/LY motility that is linked to actin dynamics. Because Pdro regulates these two processes, we propose that modulation of Pdro expression in response to sterol levels regulates LDL-derived cholesterol through both LDL uptake and LE/LY dynamics, to ultimately control free cholesterol homeostasis. PMID- 20544019 TI - De Novo assembly of the complete genome of an enhanced electricity-producing variant of Geobacter sulfurreducens using only short reads. AB - State-of-the-art DNA sequencing technologies are transforming the life sciences due to their ability to generate nucleotide sequence information with a speed and quantity that is unapproachable with traditional Sanger sequencing. Genome sequencing is a principal application of this technology, where the ultimate goal is the full and complete sequence of the organism of interest. Due to the nature of the raw data produced by these technologies, a full genomic sequence attained without the aid of Sanger sequencing has yet to be demonstrated.We have successfully developed a four-phase strategy for using only next-generation sequencing technologies (Illumina and 454) to assemble a complete microbial genome de novo. We applied this approach to completely assemble the 3.7 Mb genome of a rare Geobacter variant (KN400) that is capable of unprecedented current production at an electrode. Two key components of our strategy enabled us to achieve this result. First, we integrated the two data types early in the process to maximally leverage their complementary characteristics. And second, we used the output of different short read assembly programs in such a way so as to leverage the complementary nature of their different underlying algorithms or of their different implementations of the same underlying algorithm.The significance of our result is that it demonstrates a general approach for maximizing the efficiency and success of genome assembly projects as new sequencing technologies and new assembly algorithms are introduced. The general approach is a meta strategy, wherein sequencing data are integrated as early as possible and in particular ways and wherein multiple assembly algorithms are judiciously applied such that the deficiencies in one are complemented by another. PMID- 20544020 TI - Methicillin resistant Staphylococcus aureus ST398 in veal calf farming: human MRSA carriage related with animal antimicrobial usage and farm hygiene. AB - INTRODUCTION: Recently a specific MRSA sequence type, ST398, emerged in food production animals and farmers. Risk factors for carrying MRSA ST398 in both animals and humans have not been fully evaluated. In this cross-sectional study, we investigated factors associated with MRSA colonization in veal calves and humans working and living on these farms. METHODS: A sample of 102 veal calf farms were randomly selected and visited from March 2007-February 2008. Participating farmers were asked to fill in a questionnaire (n = 390) to identify potential risk factors. A nasal swab was taken from each participant. Furthermore, nasal swabs were taken from calves (n = 2151). Swabs were analysed for MRSA by selective enrichment and suspected colonies were confirmed as MRSA by using slide coagulase test and PCR for presence of the mecA-gene. Spa types were identified and a random selection of each spa type was tested with ST398 specific PCR. The Sequence Type of non ST398 strains was determined. Data were analyzed using logistic regression analysis. RESULTS: Human MRSA carriage was strongly associated with intensity of animal contact and with the number of MRSA positive animals on the farm. Calves were more often carrier when treated with antibiotics, while farm hygiene was associated with a lower prevalence of MRSA. CONCLUSION: This is the first study showing direct associations between animal and human carriage of ST398. The direct associations between animal and human MRSA carriage and the association between MRSA and antimicrobial use in calves implicate prudent use of antibiotics in farm animals. PMID- 20544021 TI - High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance. AB - Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs) linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug. PMID- 20544022 TI - Hidden drug resistant HIV to emerge in the era of universal treatment access in Southeast Asia. AB - BACKGROUND: Universal access to first-line antiretroviral therapy (ART) for HIV infection is becoming more of a reality in most low and middle income countries in Asia. However, second-line therapies are relatively scarce. METHODS AND FINDINGS: We developed a mathematical model of an HIV epidemic in a Southeast Asian setting and used it to forecast the impact of treatment plans, without second-line options, on the potential degree of acquisition and transmission of drug resistant HIV strains. We show that after 10 years of universal treatment access, up to 20% of treatment-naive individuals with HIV may have drug-resistant strains but it depends on the relative fitness of viral strains. CONCLUSIONS: If viral load testing of people on ART is carried out on a yearly basis and virological failure leads to effective second-line therapy, then transmitted drug resistance could be reduced by 80%. Greater efforts are required for minimizing first-line failure, to detect virological failure earlier, and to procure access to second-line therapies. PMID- 20544023 TI - Rearrangement of retinogeniculate projection patterns after eye-specific segregation in mice. AB - It has been of interest whether and when the rearrangement of neuronal circuits can be induced after projection patterns are formed during development. Earlier studies using cats reported that the rearrangement of retinogeniculate projections could be induced even after eye-specific segregation has occurred, but detailed and quantitative characterization of this rearrangement has been lacking. Here we delineate the structural changes of retinogeniculate projections in the C57BL/6 mouse in response to monocular enucleation (ME) after eye-specific segregation. When ME was performed after eye-specific segregation, rearrangement of retinogeniculate axons in the dorsal lateral geniculate nucleus (dLGN) was observed within 5 days. Although this rearrangement was observed both along the dorsomedial-ventrolateral and outer-inner axes in the dLGN, it occurred more rapidly along the outer-inner axis. We also examined the critical period for this rearrangement and found that the rearrangement became almost absent by the beginning of the critical period for ocular dominance plasticity in the primary visual cortex. Taken together, our findings serve as a framework for the assessment of phenotypes of genetically altered mouse strains as well as provide insights into the mechanisms underlying the rearrangement of retinogeniculate projections. PMID- 20544024 TI - Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei. AB - BACKGROUND: Trypanosoma brucei is the etiological agent of Human African Trypanosomiasis, an endemic parasitic disease of sub-Saharan Africa. TbCatB and rhodesain are the sole Clan CA papain-like cysteine proteases produced by the parasite during infection of the mammalian host and are implicated in the progression of disease. Of considerable interest is the exploration of these two enzymes as targets for cysteine protease inhibitors that are effective against T. brucei. METHODS AND FINDINGS: We have determined, by X-ray crystallography, the first reported structure of TbCatB in complex with the cathepsin B selective inhibitor CA074. In addition we report the structure of rhodesain in complex with the vinyl-sulfone K11002. CONCLUSIONS: The mature domain of our TbCat*CA074 structure contains unique features for a cathepsin B-like enzyme including an elongated N-terminus extending 16 residues past the predicted maturation cleavage site. N-terminal Edman sequencing reveals an even longer extension than is observed amongst the ordered portions of the crystal structure. The TbCat*CA074 structure confirms that the occluding loop, which is an essential part of the substrate-binding site, creates a larger prime side pocket in the active site cleft than is found in mammalian cathepsin B-small molecule structures. Our data further highlight enhanced flexibility in the occluding loop main chain and structural deviations from mammalian cathepsin B enzymes that may affect activity and inhibitor design. Comparisons with the rhodesain*K11002 structure highlight key differences that may impact the design of cysteine protease inhibitors as anti-trypanosomal drugs. PMID- 20544025 TI - An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. AB - BACKGROUND: Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human beta defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown. METHODOLOGY: The relationship between hBD-3, monocyte chemoattractant protein-1 (MCP-1), TAMs, and CCR2 was examined using immunofluorescence microscopy in normal and oral carcinoma in situ biopsy specimens. The ability of hBD-3 to chemoattract host macrophages in vivo using a nude mouse model and analysis of hBD-3 on monocytic cell migration in vitro, applying a cross desensitization strategy of CCR2 and its pharmacological inhibitor (RS102895), respectively, was also carried out. CONCLUSIONS/FINDINGS: MCP-1, the most frequently expressed tumor cell-associated chemokine, was not produced by tumor cells nor correlated with the recruitment of macrophages in oral carcinoma in situ lesions. However, hBD-3 was associated with macrophage recruitment in these lesions and hBD-3-expressing tumorigenic cells induced massive tumor infiltration of host macrophages in nude mice. HBD-3 stimulated the expression of tumor promoting cytokines, including interleukin-1alpha (IL-1alpha), IL-6, IL-8, CCL18, and tumor necrosis factor-alpha (TNF-alpha) in macrophages derived from human peripheral blood monocytes. Monocytic cell migration in response to hBD-3 was inhibited by cross-desensitization with MCP-1 and the specific CCR2 inhibitor, RS102895, suggesting that CCR2 mediates monocyte/macrophage migration in response to hBD-3. Collectively, these results indicate that hBD-3 utilizes CCR2 to regulate monocyte/macrophage trafficking and may act as a tumor cell-produced chemoattractant to recruit TAMs. This novel mechanism is the first evidence of an hBD molecule orchestrating an in vivo outcome and demonstrates the importance of the innate immune system in the development of tumors. PMID- 20544026 TI - Species used for drug testing reveal different inhibition susceptibility for 17beta-hydroxysteroid dehydrogenase type 1. AB - Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17beta-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17beta-HSD types 1, 2, 4, 5 and 7 but also against 17beta-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17beta-HSDs analyzed were observed. Especially, the rodent 17beta-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17beta-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution. PMID- 20544027 TI - Fusion-activated Ca(2+) entry: an "active zone" of elevated Ca(2+) during the postfusion stage of lamellar body exocytosis in rat type II pneumocytes. AB - BACKGROUND: Ca(2+) is essential for vesicle fusion with the plasma membrane in virtually all types of regulated exocytoses. However, in contrast to the well known effects of a high cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) in the prefusion phase, the occurrence and significance of Ca(2+) signals in the postfusion phase have not been described before. METHODOLOGY/PRINCIPAL FINDINGS: We studied isolated rat alveolar type II cells using previously developed imaging techniques. These cells release pulmonary surfactant, a complex of lipids and proteins, from secretory vesicles (lamellar bodies) in an exceptionally slow, Ca(2+)- and actin-dependent process. Measurements of fusion pore formation by darkfield scattered light intensity decrease or FM 1-43 fluorescence intensity increase were combined with analysis of [Ca(2+)](c) by ratiometric Fura-2 or Fluo 4 fluorescence measurements. We found that the majority of single lamellar body fusion events were followed by a transient (t(1/2) of decay = 3.2 s) rise of localized [Ca(2+)](c) originating at the site of lamellar body fusion. [Ca(2+)](c) increase followed with a delay of approximately 0.2-0.5 s (method dependent) and in the majority of cases this signal propagated throughout the cell (at approximately 10 microm/s). Removal of Ca(2+) from, or addition of Ni(2+) to the extracellular solution, strongly inhibited these [Ca(2+)](c) transients, whereas Ca(2+) store depletion with thapsigargin had no effect. Actin GFP fluorescence around fused LBs increased several seconds after the rise of [Ca(2+)](c). Both effects were reduced by the non-specific Ca(2+) channel blocker SKF96365. CONCLUSIONS/SIGNIFICANCE: Fusion-activated Ca(2+)entry (FACE) is a new mechanism that leads to [Ca(2+)](c) transients at the site of vesicle fusion. Substantial evidence from this and previous studies indicates that fusion activated Ca(2+) entry enhances localized surfactant release from type II cells, but it may also play a role for compensatory endocytosis and other cellular functions. PMID- 20544028 TI - The sudden dominance of blaCTX-M harbouring plasmids in Shigella spp. Circulating in Southern Vietnam. AB - BACKGROUND: Plasmid mediated antimicrobial resistance in the Enterobacteriaceae is a global problem. The rise of CTX-M class extended spectrum beta lactamases (ESBLs) has been well documented in industrialized countries. Vietnam is representative of a typical transitional middle income country where the spectrum of infectious diseases combined with the spread of drug resistance is shifting and bringing new healthcare challenges. METHODOLOGY: We collected hospital admission data from the pediatric population attending the hospital for tropical diseases in Ho Chi Minh City with Shigella infections. Organisms were cultured from all enrolled patients and subjected to antimicrobial susceptibility testing. Those that were ESBL positive were subjected to further investigation. These investigations included PCR amplification for common ESBL genes, plasmid investigation, conjugation, microarray hybridization and DNA sequencing of a bla(CTX-M) encoding plasmid. PRINCIPAL FINDINGS: We show that two different bla(CTX-M) genes are circulating in this bacterial population in this location. Sequence of one of the ESBL plasmids shows that rather than the gene being integrated into a preexisting MDR plasmid, the bla(CTX-M) gene is located on relatively simple conjugative plasmid. The sequenced plasmid (pEG356) carried the bla(CTX-M-24) gene on an ISEcp1 element and demonstrated considerable sequence homology with other IncFI plasmids. SIGNIFICANCE: The rapid dissemination, spread of antimicrobial resistance and changing population of Shigella spp. concurrent with economic growth are pertinent to many other countries undergoing similar development. Third generation cephalosporins are commonly used empiric antibiotics in Ho Chi Minh City. We recommend that these agents should not be considered for therapy of dysentery in this setting. PMID- 20544029 TI - Immunostimulatory properties of dendritic cells after Leishmania donovani infection using an in vitro model of liver microenvironment. AB - BACKGROUND: Recent advances demonstrated that liver dendritic cells (DCs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Although there has been significant work on the phenotypic and functional roles of such DCs, the impact of liver microenvironment on the immune properties of infected DC is still poorly explored, probably because of the limitations of modelization. METHODOLOGY/PRINCIPAL FINDINGS: Here, we hypothesized that DC tolerogenic properties have an impact on the antimicrobial response, particularly during the infection by the protozoan parasite Leishmania donovani. Indeed, a lymphocytic Th2 environment was reported to favour the growth and proliferation of L. donovani. We first modelized an adequate monocyte-differentiated DC model, either in rat liver epithelial cell- or in a human hepatic non-parenchymal cell conditioned medium in order to infect them further. We established that DCs differentiated in a hepatic microenvironment displayed a CD14+/CD16+/CD123+ phenotype, secreted low IL-12p70 and had an impaired capacity to stimulate allogeneic T lymphocyte proliferation and IFNgamma secretion. We then infected DCs with L. donovani in the in vitro-defined hepatic microenvironment. The infection of hepatic DCs restored their capacity to stimulate allogeneic T-cell proliferation and to induce lymphocytic secretion of IFNgamma. Such characteristics were recently shown to favour granuloma formation in mice liver. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the specific immunostimulatory properties of infected hepatic DCs might amplify the granuloma maturation, which warrants the effective control of infection in the liver during visceral leishmaniasis. PMID- 20544030 TI - Internet treatment for depression: a randomized controlled trial comparing clinician vs. technician assistance. AB - BACKGROUND: Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. QUESTION: Would guidance from a technician be as effective as guidance from a clinician? METHOD: Randomized controlled non-inferiority trial comparing three groups: Clinician assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health QUESTIONnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (p<0.001) and PHQ-9 (p<0.001) compared to the delayed treatment group but did not differ from each other. Within group effect sizes on the BDI-II were 1.27 and 1.20 for the clinician- and technician-assisted groups respectively, and on the PHQ-9, were 1.54 and 1.60 respectively. At 4-month follow-up participants in the technician group had made further improvements and had significantly lower scores on the PHQ-9 than those in the clinician group. A total of approximately 60 minutes of clinician or technician time was required per participant during the 8-week treatment program. CONCLUSIONS: Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for depression. This form of treatment has potential to increase the capacity of existing mental health services. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000559213. PMID- 20544031 TI - Screening of Trypanosoma brucei gambiense in domestic livestock and tsetse flies from an insular endemic focus (Luba, Equatorial Guinea). AB - BACKGROUND: Sleeping sickness is spread over 36 Sub-Saharan African countries. In West and Central Africa, the disease is caused by Trypanosoma brucei gambiense, which produces a chronic clinical manifestation. The Luba focus (Bioko Island, Equatorial Guinea) has not reported autochthonous sleeping sickness cases since 1995, but given the complexity of the epidemiological cycle, the elimination of the parasite in the environment is difficult to categorically ensure. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work is to assess, by a molecular approach (Polymerase Chain Reaction, PCR), the possible permanence of T. b. gambiense in the vector (Glossina spp.) and domestic fauna in order to improve our understanding of the epidemiological situation of the disease in an isolated focus considered to be under control. The results obtained show the absence of the parasite in peridomestic livestock but its presence, although at very low rate, in the vector. On the other hand, interesting entomological data highlight that an elevated concentration of tsetse flies was observed in two out of the ten villages considered to be in the focus. CONCLUSIONS: These findings demonstrate that even in conditions of apparent control, a complete parasite clearance is difficult to achieve. Further investigations must be focused on animal reservoirs which could allow the parasites to persist without leading to human cases. In Luba, where domestic livestock are scarcer than other foci in mainland Equatorial Guinea, the epidemiological significance of wild fauna should be assessed to establish their role in the maintenance of the infection. PMID- 20544032 TI - Visceral leishmaniasis relapse in Southern Sudan (1999-2007): a retrospective study of risk factors and trends. AB - BACKGROUND: Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized. METHODS: We investigated patient characteristics and drug regimens associated with VL relapse using data from Medecins Sans Frontieres - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors. RESULTS: We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade >or=3 vs 0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade >or=3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30 day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (-3.4%, 28.5%)) and a downward trend in deaths (APC = -18.1% (-22.5%, -13.4%)). CONCLUSIONS: Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy. PMID- 20544033 TI - Simplified automated image analysis for detection and phenotyping of Mycobacterium tuberculosis on porous supports by monitoring growing microcolonies. AB - BACKGROUND: Even with the advent of nucleic acid (NA) amplification technologies the culture of mycobacteria for diagnostic and other applications remains of critical importance. Notably microscopic observed drug susceptibility testing (MODS), as opposed to traditional culture on solid media or automated liquid culture, has shown potential to both speed up and increase the provision of mycobacterial culture in high burden settings. METHODS: Here we explore the growth of Mycobacterial tuberculosis microcolonies, imaged by automated digital microscopy, cultured on a porous aluminium oxide (PAO) supports. Repeated imaging during colony growth greatly simplifies "computer vision" and presumptive identification of microcolonies was achieved here using existing publically available algorithms. Our system thus allows the growth of individual microcolonies to be monitored and critically, also to change the media during the growth phase without disrupting the microcolonies. Transfer of identified microcolonies onto selective media allowed us, within 1-2 bacterial generations, to rapidly detect the drug susceptibility of individual microcolonies, eliminating the need for time consuming subculturing or the inoculation of multiple parallel cultures. SIGNIFICANCE: Monitoring the phenotype of individual microcolonies as they grow has immense potential for research, screening, and ultimately M. tuberculosis diagnostic applications. The method described is particularly appealing with respect to speed and automation. PMID- 20544034 TI - Role of 4-1BB receptor in the control played by CD8(+) T cells on IFN-gamma production by Mycobacterium tuberculosis antigen-specific CD4(+) T Cells. AB - BACKGROUND: Antigen-specific IFN-gamma producing CD4(+) T cells are the main mediators of protection against Mycobacterium tuberculosis infection both under natural conditions and following vaccination. However these cells are responsible for lung damage and poor vaccine efficacy when not tightly controlled. Discovering new tools to control nonprotective antigen-specific IFN-gamma production without affecting protective IFN-gamma is a challenge in tuberculosis research. METHODS AND FINDINGS: Immunization with DNA encoding Ag85B, a candidate vaccine antigen of Mycobacterium tuberculosis, elicited in mice a low but protective CD4(+) T cell-mediated IFN-gamma response, while in mice primed with DNA and boosted with Ag85B protein a massive increase in IFN-gamma response was associated with loss of protection. Both protective and non-protective Ag85B immunization generated antigen-specific CD8(+) T cells which suppressed IFN-gamma secreting CD4(+) T cells. However, ex vivo ligation of 4-1BB, a member of TNF receptor super-family, reduced the massive, non-protective IFN-gamma responses by CD4(+) T cells in protein-boosted mice without affecting the low protective IFN gamma-secretion in mice immunized with DNA. This selective inhibition was due to the induction of 4-1BB exclusively on CD8(+) T cells of DNA-primed and protein boosted mice following Ag85B protein stimulation. The 4-1BB-mediated IFN-gamma inhibition did not require soluble IL-10, TGF-beta, XCL-1 and MIP-1beta. In vivo Ag85B stimulation induced 4-1BB expression on CD8(+) T cells and in vivo 4-1BB ligation reduced the activation, IFN-gamma production and expansion of Ag85B specific CD4(+) T cells of DNA-primed and protein-boosted mice. CONCLUSION/SIGNIFICANCE: Antigen-specific suppressor CD8(+) T cells are elicited through immunization with the mycobacterial antigen Ag85B. Ligation of 4-1BB receptor further enhanced their suppressive activity on IFN-gamma-secreting CD4(+) T cells. The selective expression of 4-1BB only on CD8(+) T cells in mice developing a massive, non-protective IFN-gamma response opens novel strategies for intervention in tuberculosis pathology and vaccination through T-cell co stimulatory-based molecular targeting. PMID- 20544036 TI - High level of pyrethroid resistance in an Anopheles funestus population of the Chokwe District in Mozambique. AB - BACKGROUND: Although Anopheles funestus is difficult to rear, it is crucial to analyse field populations of this malaria vector in order to successfully characterise mechanisms of insecticide resistance observed in this species in Africa. In this study we carried out a large-scale field collection and rearing of An. funestus from Mozambique in order to analyse its susceptibility status to insecticides and to broadly characterise the main resistance mechanisms involved in natural populations. METHODOLOGY/PRINCIPAL FINDINGS: 3,000 F(1) adults were obtained through larval rearing. WHO susceptibility assays indicated a very high resistance to pyrethroids with no mortality recorded after 1 h 30 min exposure and less than 50% mortality at 3 h 30 min. Resistance to the carbamate, bendiocarb was also noted, with 70% mortality after 1h exposure. In contrast, no DDT resistance was observed, indicating that no kdr-type resistance was involved. The sequencing of the acetylcholinesterase gene indicated the absence of the G119S and F455W mutations associated with carbamate and organophosphate resistance. This could explain the absence of malathion resistance in this population. Both biochemical assays and quantitative PCR implicated up-regulated P450 genes in pyrethroid resistance, with GSTs playing a secondary role. The carbamate resistance observed in this population is probably conferred by the observed altered AChE with esterases also involved. CONCLUSION/SIGNIFICANCE: The high level of pyrethroid resistance in this population despite the cessation of pyrethroid use for IRS in 1999 is a serious concern for resistance management strategies such as rotational use of insecticides. As DDT has now been re introduced for IRS, susceptibility to DDT needs to be closely monitored to prevent the appearance and spread of resistance to this insecticide. PMID- 20544035 TI - GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. AB - BACKGROUND: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. METHODOLOGY/PRINCIPAL FINDINGS: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. CONCLUSIONS/SIGNIFICANCE: These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract. PMID- 20544037 TI - WD40 domain divergence is important for functional differences between the fission yeast Tup11 and Tup12 co-repressor proteins. AB - We have previously demonstrated that subsets of Ssn6/Tup target genes have distinct requirements for the Schizosaccharomyces pombe homologs of the Tup1/Groucho/TLE co-repressor proteins, Tup11 and Tup12. The very high level of divergence in the histone interacting repression domains of the two proteins suggested that determinants distinguishing Tup11 and Tup12 might be located in this domain. Here we have combined phylogenetic and structural analysis as well as phenotypic characterization, under stress conditions that specifically require Tup12, to identify and characterize the domains involved in Tup12-specific action. The results indicate that divergence in the repression domain is not generally relevant for Tup12-specific function. Instead, we show that the more highly conserved C-terminal WD40 repeat domain of Tup12 is important for Tup12 specific function. Surface amino acid residues specific for the WD40 repeat domain of Tup12 proteins in different fission yeasts are clustered in blade 3 of the propeller-like structure that is characteristic of WD40 repeat domains. The Tup11 and Tup12 proteins in fission yeasts thus provide an excellent model system for studying the functional divergence of WD40 repeat domains. PMID- 20544038 TI - Test your skills: a worsening rash. AB - A mother brings her 5-year-old boy in to your office because she is concerned about a rash on his legs that seems to be worsening. She tells you that he had a runny nose and a mild cough a week earlier, but that those symptoms resolved before the rash developed. He has also complained of "belly pain." The boy's mother says he has been less active and more irritable since the onset of the rash, and that he is hardly eating. She also tells you that earlier in the day, her son told her that it hurts to walk. A complete review of systems is otherwise negative. The 5-year-old was born at term without complication. He has met all developmental milestones and his immunizations are up to date. He takes no medications. The boy's vital signs are normal. He has an erythematous maculopapular rash distributed on his legs symmetrically; it is palpable, nontender, and nonblanching. You detect no abnormalities in abdominal, neurologic, or musculoskeletal examinations. A complete blood count (CBC) and basic metabolic panel (BMP) reveal mild leukocytosis with a normal differential. Urinalysis shows moderate blood and trace protein. Laboratory results are otherwise normal. What's your diagnosis? PMID- 20544039 TI - When to consider osteopathic manipulation. AB - Consider osteopathic manipulation for low back pain that has not responded to customary care, and other musculoskeletal pain such as headache or neck pain. PMID- 20544040 TI - A look at the long-term safety of an extended-regimen OC. AB - BACKGROUND: Oral contraceptives (OCs) are the most widely used method of reversible contraception. Recent alterations of the standard 28-day regimen have included shortening the traditional hormone-free interval (HFI), supplementing the HFI with low-dose estrogen, or increasing the number of active pills administered, thus extending the time between withdrawal bleeding episodes by a variable number of months. In light of these changes in regimens, clinicians may be seeking evidence that the new regimens are safe and will not result in unexpected adverse events. METHODS: We initiated a long-term extension trial to evaluate the safety of a 91-day extended-regimen OC containing 150 mcg levonorgestrel/30 mcg ethinyl estradiol (EE) for 84 days, followed by 7 days of 10 mcg EE. After participation in a 1-year, open-label, phase 3 contraceptive program, 320 women qualified for enrollment in a multicenter, nonrandomized study of 91-day extended-regimen OCs for up to 3 additional consecutive years; 116 completed the study. We evaluated incidence of reported adverse events (AEs), rates of study discontinuation, and reported bleeding patterns. RESULTS: Total exposure was equivalent to 8292 28-day cycles. Participants reported no thromboembolic events. Thirty-one (9.7%) women discontinued treatment due to AEs. Unscheduled bleeding and spotting diminished during the course of the trial. Overall rates of study discontinuation and incidence of AEs were consistent with those observed in the phase 3 clinical program. CONCLUSION: This study demonstrated that the AE profile of the 91-day extended-regimen OC over 4 years was similar to that seen in the 1-year clinical trials, with no unexpected adverse events. PMID- 20544041 TI - Playing God (part 2). PMID- 20544042 TI - Time to dispel the mitral valve/anxiety link. PMID- 20544043 TI - Got anxiety? Get moving! PMID- 20544044 TI - Determining suicide risk (hint: a screen is not enough). AB - An individualized assessment is essential to identifying relevant risk factors. Use direct questions, such as, "Have you had any thoughts about killing yourself?" to screen for suicidal ideation. Ask a family member or close friend to ensure that any guns or other lethal means of suicide are inaccessible to the patient at risk. Avoid the use of "no harm" contracts, which are controversial and lack demonstrated effectiveness. PMID- 20544045 TI - Optimize your use of stress tests: a Q&A guide. AB - Order exercise stress testing without imaging for patients with a low to intermediate probability of coronary artery disease (CAD), unless preexisting electrocardiographic (EKG) changes would render such a test nondiagnostic. Order stress testing with imaging for patients with preexisting EKG changes and/or a high probability of CAD. Do not use stress testing to screen asymptomatic patients for CAD. Consider pharmacologic testing for patients who are unable to exercise to an appropriate cardiac workload; it has the same predictive value as a nuclear exercise stress test. PMID- 20544046 TI - PT or cervical collar for cervical radiculopathy? AB - To shorten recovery time for adults with acute cervical radiculopathy, recommend either physical therapy (PT) and a home exercise plan or a cervical collar and rest. Both are more effective than a wait-and-see strategy. PMID- 20544047 TI - Fracture pain relief for kids? Ibuprofen does it better. AB - Use ibuprofen instead of acetaminophen with codeine for pediatric arm fractures. It controls the pain at least as well and is better tolerated. PMID- 20544048 TI - USPSTF recommendations you may have missed amid the breast cancer controversy. AB - The USPSTF recommends aspirin for the prevention of stroke and heart attack for those at risk, and screening for major depression and childhood obesity. PMID- 20544049 TI - Diffuse rash and cough in elderly woman with a UTI. AB - A 66-year-old woman came into the emergency department with a diffuse rash and a cough. She had a rash on the palms of her hands, which had developed the day before, but had improved a bit. She also had a rash on her feet, legs, and lower abdomen, which had developed that morning. She said that over the previous 2 days she had had a fever, dry cough, and some difficulty breathing. Her past medical history was significant for asthma, diabetes, hypertension, and osteoarthritis. Her medications included atenolol, celecoxib, metformin, pioglitazone, and an albuterol inhaler, as needed. In addition, she was on the ninth day of a 10-day course of nitrofurantoin for acute cystitis. She was allergic to ampicillin and erythromycin. On physical exam, she had a fever of 101.5 degrees Fahrenheit. On lung examination, she had diffuse wheezes and mild bibasilar crackles. Examination of her skin revealed a nonpainful, nonpruritic, erythematous, maculopapular rash located on the palms and legs, as well as on her lower abdomen. Chest radiograph showed mild opacification in the bases of the lungs. What is your diagnosis? PMID- 20544050 TI - Clinical inquiries. How should you manage children born to hepatitis C-positive women? AB - For starters, don't be overly concerned with the mode of delivery; it does not influence the rate of transmission of hepatitis C virus (HCV), except in women who are also infected with human immunodeficiency virus (HIV). Avoid internal fetal monitoring and prolonged rupture of membranes. Advise patients that it is OK to breastfeed. Breastfeeding does not affect transmission. Check HCV RNA and serum anti-HCV on 2 occasions between 2 and 6 months of age and 18 and 24 months of age. PMID- 20544051 TI - Clinical inquiries. Does hypercoagulopathy testing benefit patients with DVT? AB - There is no evidence to suggest that testing for hypercoagulopathy benefits most patients with deep venous thrombosis (DVT). Nor has research established that thrombophilia test results improve the ability to predict recurrence better than clinical risk assessment alone. Testing may be warranted in patients younger than 50 years with idiopathic DVT or patients with recurrent episodes of thromboembolism to assess risk in other family members. A theoretical cost benefit analysis demonstrates that testing for antiphospholipid antibody syndrome and homozygous factor V Leiden may be cost effective when comparing quality adjusted life years in patients with idiopathic DVT. PMID- 20544052 TI - Clinical inquiries. What is the best approach to benign paroxysmal positional vertigo in the elderly? AB - A canalith repositioning maneuver (CRM), such as the Epley or Semont maneuver, should be the first-line treatment for benign paroxysmal positional vertigo (BPPV) in the elderly. Following the Epley maneuver with self-treatment at home using a modified Epley procedure improves outcomes. Postural restrictions are not necessary after CRM treatment. Medications do not work as well as a CRM, but studies comparing treatments are limited. PMID- 20544053 TI - Managing diabetic peripheral neuropathic pain in primary care. AB - DPN is a common complication of T2DM that often causes a pain syndrome. The diagnosis of DPNP centers around a careful history and physical examination, aided by the use of diagnostic tools, such as the 128-Hz tuning fork. A reduction in pain severity of 30% to 50% is achievable for most patients but generally requires combination therapy. In addition to duloxetine and pregabalin, which have been approved by the FDA for DPNP, adjuvant analgesics are the mainstay of therapy. Of the adjuvant analgesics, the use of the tricyclic antidepressant and anticonvulsant groups is supported by the most extensive evidence. The selection of an adjuvant analgesic is often based on patient comorbidities and tolerability. Frequent follow-up is needed to optimize therapy. PMID- 20544054 TI - The role of statins in managing diabetic dyslipidemia. AB - The common lipid abnormalities associated with T2DM confer substantial CV risk. Statins are a safe and well-established treatment option for lowering this atherogenic burden and improving outcomes in this patient population. Nonetheless, many patients with T2DM are not receiving a statin, and even those who receive treatment may not be achieving recommended lipid targets. Strategies must be implemented to improve the quality of care for these patients who are at high risk for a primary or secondary CV event. PMID- 20544055 TI - Incorporating practical lifestyle management for obesity. PMID- 20544056 TI - Choosing among the incretin agents and why it matters. PMID- 20544057 TI - The importance and treatment of postprandial hyperglycemia. AB - PPG is an important target to address in the overall management of T2DM. Lifestyle interventions play an important role in PPG control, as well as global diabetes management goals. Oral antihyperglycemic agents lower PPG to varying degrees. Our most powerful treatment option to address PPG is prandial insulin. Collaboration between patient, primary care clinician, diabetes educator, and dietitian is critical to successful initiation of insulin therapy. PMID- 20544058 TI - Postmenopausal osteoporosis: another approach to management. PMID- 20544059 TI - Medicine's dirty little secret. PMID- 20544060 TI - Treat generalized anxiety with CBT. PMID- 20544061 TI - Colorectal screening: don't start too early. PMID- 20544062 TI - Shellfish-iodine nexus is a myth. PMID- 20544063 TI - Venous thrombosis: preventing clots in patients at risk. PMID- 20544064 TI - Avoiding drug interactions: here's help. PMID- 20544065 TI - An algorithm for the treatment of chronic testicular pain. PMID- 20544066 TI - A better future for baby: stemming the tide of fetal alcohol syndrome. PMID- 20544067 TI - A mediastinal mass. PMID- 20544068 TI - Clinical inquiries. Does chocolate have cardiovascular benefits? PMID- 20544069 TI - Clinical inquiries. Does lowering a fever >101 degrees F in children improve clinical outcomes? PMID- 20544070 TI - What do I need to know about gout? AB - Many patients with gout present with an acute attack (flare) of gouty arthritis. In its early stages, gout is a chronic, often silent disorder punctuated by acute, extremely painful arthritic flares. Over time, untreated or insufficiently treated gout may progress, with more frequent flares and formation of urate crystal deposits (tophi) and associated chronic, deforming arthritis (gouty arthropathy). About 20% of patients with gout have urinary tract stones and can develop an interstitial urate nephropathy. Gout (also called urate crystal deposition disease) is characterized by reduced renal clearance or, less frequently, an overproduction of uric acid. When the serum urate acid (sUA) level persistently exceeds 6.8 mg/dL, extracellular fluids become saturated and hyperuricemia occurs. Hyperuricemia is also very common among adult men and postmenopausal women, most of whom remain asymptomatic with respect to gout throughout their lives. Nevertheless, hyperuricemia is the major risk factor for gout because it predisposes to urate crystal formation and deposition, particularly in and around joints and in other soft tissue structures. The symptoms and signs of gout result from acute and chronic inflammatory responses of the body to urate crystal deposits. Although any joint may be affected, the metatarsophalangeal (MTP) joint of the great toe (podagra) is the first joint affected in half of all cases. One major goal in managing gout is to treat the pain of acute flares aggressively with anti-inflammatory agents to reduce flare intensity and duration. In addition, most patients with gout eventually require long-term treatment with urate-lowering therapy (ULT) to reverse the chronic urate crystal deposition and to prevent recurrent flares that can cause permanent joint damage. PMID- 20544071 TI - Multi-layer electron transfer across nanostructured Ag-SAM-Au-SAM junctions probed by surface enhanced Raman spectroscopy. AB - We have developed a new layered Au-Ag electrode for studying interfacial electron transfer processes by surface enhanced resonance Raman (SERR) spectroscopy. The device consists of a nanostructured Ag support which is separated from a Au film via a thin self-assembled monolayer (SAM) of amino-terminated mercaptanes (C(y) NH(2), with y = 6, 8, 11). The Au film is biocompatibly coated to allow for binding of redox-active proteins. We have explored the performance of this device for analysing interfacial electron transfer processes by stationary and time resolved SERR spectroscopy, using the heme protein cytochrome c (Cyt-c) as a benchmark protein. The SERRS intensity of Cyt-c on Ag-(C(y)-NH(2))-Au electrodes and Ag electrodes was comparable when the protein was electrostatically attached to the metal coated by a SAM of carboxyl-terminated mercaptanes (C(x)-COOH) surface but 25 times higher upon covalent attachment via Cys102 to the bare Au surface. In the case of electrostatic adsorption the protein remained exclusively in its native state. Electron transfer between the protein and the Ag electrode occurred in an almost ideal Nernstian behaviour with a number of transferred electrons close to one (n = 0.8-0.9). Conversely, the covalent attached Cyt c showed two broad redox transitions (n = 0.3) and a partial conversion to a non native species which remained redox inactive in the potential range from +0.1 to 0.3 V. For the electrostatically immobilised Cyt, apparent electron transfer rates of 0.8 and 49 s(-1) were obtained for y = 11 and x = 15 and 10, respectively, indicating a fast long-distance electron transfer through the multilayer with the electron tunneling through the C(x)-COOH SAM being the rate limiting step. PMID- 20544072 TI - Dynamic remodeling of subcellular chemical gradients using a multi-directional flow device. AB - Elucidation of the mechanisms by which external chemical cues regulate polarized cellular behaviors requires tools that can rapidly recast chemical landscapes with subcellular resolution. Here, we describe an approach for creating steep microscopic gradients of cellular effectors at any desired position in culture that can be reoriented rapidly to evaluate dynamic responses. In this approach, micrometre pores are ablated in a membrane that supports cell adherence, allowing dosing reagent from an underlying reservoir to enter the cell-culture flow chamber as sharp streams that are directed at subcellular targets by using a system of paired sources and drains to specify flow direction. This tool substantially extends capabilities for chemical interaction with cultured cells, enabling investigations of chemotaxis via precise placement and reorientation of peptide gradients formed at the boundaries of dosing streams. These studies demonstrate that neutrophil precursor cells can repolarize and redirect their migration paths using morphological responses that depend on the subcellular localization of chemoattractant gradients. PMID- 20544073 TI - Photochemically driven intercalation of small molecules into DNA by in situ irradiation. AB - Intercalation of small molecules into DNA is photochemically achieved by in situ irradiation of a tetraaryl-pyridinium species. Such a "DNA intercalation on demand" process could highlight an alternative pathway to anticancer basic research, based on photo-activable DNA binders. PMID- 20544074 TI - Proteome-wide detection of phospholipid-protein interactions in mitochondria by photocrosslinking and click chemistry. AB - Photoactivatable lipid analogues are uniquely suited for the detection of lipid protein interactions in biological membranes. Based on photocrosslinking, new methodology has been developed for the proteome-wide detection of lipid-protein interactions. Bifunctional lipid analogues containing a tag for click chemistry in addition to the photoactivatable moiety enable the enrichment of the crosslinked proteins that is required for subsequent identification by mass spectrometry. In principle the phospholipid interaction-based membrane protein proteomics approach is applicable to any biomembrane and any lipid. Here, we review the background and the development of the new methodology. Results obtained with photocrosslinking in purified mitochondrial membranes from the yeast Saccharomyces cerevisiae are summarized and future perspectives discussed. PMID- 20544076 TI - Radical stability and its role in synthesis and catalysis. AB - The thermodynamic stability of carbon-centered radicals may be defined in quantitative terms using the hydrogen transfer reaction shown in . The stability values obtained in this way for substituted systems may be understood as the stabilizing or destabilizing influence of substituents on the neighboring radical center. This approach can be easily adapted to oxygen- or sulfur-centered radicals as expressed in eqn (b). [Formula: see text] The stability values obtained in this way do not only serve as a quantitative basis for the discussion of substituent effects, but also allow for quantitative estimates of reaction energies for hydrogen transfer reactions. These occur as key steps in a multitude of synthetically useful radical-chain processes in apolar solution, in enzyme mediated non-chain processes in biological systems, and in the oxidative degradation of a variety of biomolecules. The review will highlight the usefulness of radical stability values for the rationalization of successful (and not so successful) synthetic radical reactions as well as the potential design of new radical reactions. PMID- 20544075 TI - Constant pressure molecular dynamics simulations for ellipsoidal, cylindrical and cuboidal nano-objects based on inertia tensor information. AB - We present an extension to a constant-pressure molecular dynamics method for ellipsoidal finite systems that allows one to deal with nano-objects of cylindrical and cuboidal shapes. The method is based on the inclusion of a pressure x volume term in the system Lagrangian, where the volume is defined as a function of the eigenvalues of the inertia tensor. We illustrate how such a method works for selected systems, including CdSe nanocrystals and nanorods, carbon nanotubes and NaCl nanocrystals over a range of pressures. We also assess its performance in comparison with the use of an auxiliary pressure transmitting medium. PMID- 20544077 TI - Two unprecedented 10-connected bct topological metal-organic frameworks constructed from cadmium clusters. AB - By simply modifying the expansion of ligand tether length, two Cd(ii) metal organic frameworks have been constructed from linear tetranuclear and trinuclear cadmium clusters, respectively, which present an unprecedented 10-connected uninodal bct net. PMID- 20544078 TI - TEMPO reacts with oxygen-centered radicals under acidic conditions. AB - In the presence of organic acids in organic media, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) reacts with peroxyl radicals at nearly diffusion-controlled rates by proton-coupled electron transfer from the protonated nitroxide. PMID- 20544080 TI - Melt-induced fluorescent signature in a simple naphthalenediimide. AB - The synthesis and fluorescence properties of a naphthalenediimide ditosylate are presented. The fluorescence is highly solvent and morphology dependent with a dramatic change in fluorescence output occurring following melting from a crystalline form. This observation is attributed to thermal disruption of the crystal structure allowing the formation of emissive dimers within the amorphous melt. PMID- 20544081 TI - Nitrogen dioxide removal and nitrous acid formation on titanium oxide surfaces- an air quality remediation process? AB - The reactivity of NO(2) on irradiated TiO(2)/SiO(2) films was studied, with different TiO(2) contents, as proxies for NO(x) de-polluting materials. The influence of the photocatalyst concentration, the role of molecular oxygen and the effect of nitrate on the reactivity of TiO(2) films were investigated. NO, HONO and nitrate anions are produced as a consequence of the NO(2) loss on UV illuminated TiO(2) films. The photoinduced nitrate conversion into NO(x) and HONO at the TiO(2) surface is discussed as being a renoxification process, which involves the NO(3) radical. The presence of O(2) in the carrier gas modifies the NO and HONO production yields in the heterogeneous reaction between NO(2) and TiO(2) as well as the products of the renoxification process. Depending on the nature of the surface, the interaction between NO(2) and nitrate with TiO(2) may generate HONO that may have a negative impact on air quality. PMID- 20544079 TI - Intrinsic disorder and protein multibinding in domain, terminal, and linker regions. AB - Intrinsic disorder is believed to contribute to the ability of some proteins to interact with multiple partners which is important for protein functional promiscuity and regulation of the cross-talk between pathways. To better understand the mechanisms of molecular recognition through disordered regions, here, we systematically investigate the coupling between disorder and binding within domain families in a structure interaction network and in terminal and inter-domain linker regions. We showed that the canonical domain-domain interaction model should take into account contributions of N- and C-termini and inter-domain linkers, which may form all or part of the binding interfaces. For the majority of proteins, binding interfaces on domain and terminal regions were predicted to be less disordered than non-interface regions. Analysis of all domain families revealed several exceptions, such as kinases, DNA/RNA binding proteins, certain enzymes, and regulatory proteins, which are candidates for disorder-to-order transitions that can occur upon binding. Domain interfaces that bind single or multiple partners do not exhibit significant difference in disorder content if normalized by the number of interactions. In general, protein families with more diverse interactions exhibit less average disorder over all members of the family. Our results shed light on recent controversies regarding the relationship between disorder and binding of multiple partners at common interfaces. In particular, they support the hypothesis that protein domains with many interacting partners should have a pleiotropic effect on functional pathways and consequently might be more constrained in evolution. PMID- 20544082 TI - Electrochemistry and nitric oxide mass transport in cancer: why ingestion of sodium nitrite could be effective in treating vascularized tumors. AB - Nitric oxide concentrations in tumors do not reach apoptosis inducing levels when their excess NO is rapidly depleted. The out-flux of NO from a tumor to air or blood scales with the contacting area and with the concentration gradient; the gradient scales with the tumor-air or tumor-blood concentration difference and scales inversely with the thickness of the boundary layer, i.e. the fluid's flow rate. Air-contacting skin and lung cancers account for approximately 60% of all cancers in part because out-diffusion of NO from nascent tumors to air increases the likelihood of their survival. Out-diffusion of NO also explains their initially 2-D spreading at the air interface. Blood is an NO sink because its proteins are rapidly S-nitrosated; depletion of NO by the blood explains the dormancy of tumors until their vascularization and their virulence after vascularization. Erythrocytes store NO(2)- and their carbonic anhydrase converts it to NO and NO(3)(-). Thus, NaNO(2), a common additive in cured meats, may reduce NO out-diffusion by raising the blood NO concentration. PMID- 20544083 TI - Intracellular magnesium detection: imaging a brighter future. AB - A wide variety of biochemical reactions and physiological functions are known to require magnesium; nonetheless, its regulatory mechanisms (both at the cellular and systemic level) are still poorly characterised. Derangement of magnesium homeostasis is associated with several relevant human pathologies, e.g. diabetes, neuromuscular disorders, hypertension and other cardiovascular diseases. The study of the regulation of magnesium has gained particular interest in the last decades thanks to the molecular characterisation of specific magnesium transporters and the exploitation of molecular biology techniques to clarify their cellular and physiological function(s). In contrast, experimental tools to trace cellular magnesium and to define its homeostasis in living cells have not witnessed a corresponding progress. It was not until recently that efforts were paid to design more appropriate fluorescent indicators that could translate the advances of live imaging techniques into the field of magnesium research. Herein we critically summarise the state of the art in intracellular magnesium detection by fluorescent probes and focus on the need for improving methods and techniques in this area. We highlight the advantages of last-generation fluorescent indicators and discuss a number of challenges and opportunities that the development of novel and better sensors for magnesium still faces. PMID- 20544084 TI - Using bacterial cell growth to template catalytic asymmetry. AB - We report an approach to position gold nanoparticle catalysts for metal reduction asymmetrically on a biological template (E. coli) by exploiting the polarity of the bacterial cell envelope undergoing growth and division. PMID- 20544085 TI - Experimental and computational study of the ring opening of tricyclic oxanorbornenes to polyhydro isoindole phosphonates. AB - Phosphonylated azaheterocycles are an important class of compounds with high biological potential as conformationally restricted bioisosteres of amino acids. Therefore, it is of interest to synthesize conformationally constrained amino phosphonates. We wanted to investigate possible routes via ring opening of alpha amino phosphonates with an oxanorbornene skeleton, as these can be synthesized with high stereoselectivity. This was achieved using different Lewis acids, leading to a range of products. The reaction with TiCl(4) and FeCl(3) was modelled at a DFT level of theory to get insight in the pathways towards the corresponding products. To ease the work up, the Fe(iii) catalyst was coated on montmorillonite clay, but this accelerated aromatization after ring opening. Quenching the FeCl(3) catalyzed reaction mixture on celite caused complete aromatization. PMID- 20544086 TI - Chemical stimulation of the Arabidopsis thaliana root using multi-laminar flow on a microfluidic chip. AB - In this article, we developed a "plant on a chip" microfluidic platform that can control the local chemical environment around live roots of Arabidopsis thaliana with high spatial resolution using multi-laminar flow. We characterized the flow profile around the Arabidopsis root, and verified that the shear forces within the device ( approximately 10 dyne cm(-2)) did not impede growth of the roots. Our platform was able to deliver stimuli to the root at a spatial resolution of 10-800 microm. Further, the platform was validated by exposing desired regions of the root with a synthetic auxin derivative, 2,4-dichlorophenoxyacetic acid (2,4 D), and its inhibitor N-1-naphthylphthalamic acid (NPA). The response to the stimuli was observed using a DR5::GFP Arabidopsis line, where GFP expression is coupled to the auxin response regulator DR5. GFP expression in the root matched the position of the flow-focused stream containing 2,4-D. When the regions around the 2,4-D stimulus were exposed to the auxin transport inhibitor NPA, the active and passive transport mechanisms of auxin could be differentiated, as NPA blocks active cell-to-cell transport of auxin. Finally, we demonstrated that local 2,4-D stimulation in a approximately 10 microm root segment enhanced morphological changes such as epidermal hair growth. These experiments were proof-of-concept and agreed with the results expected based on known root biology, demonstrating that this "root on a chip" platform can be used to test how root development is affected by any chemical component of interest, including nitrogen, phosphate, salts, and other plant hormones. PMID- 20544087 TI - Formation of a cyclic tetrapeptide mimic by thermal azide-alkyne 1,3-dipolar cycloaddition. AB - Cyclodimerisation of an appropriate alpha,omega-difunctionalised precursor via thermal azide-alkyne 1,3-dipolar cycloaddition affords a cyclic pseudotetrapeptide whose conformation closely resembles that of a previously prepared analogue containing L-proline and 6-aminopicolinic acid subunits. PMID- 20544088 TI - The effect of the addition of colloidal iridium oxide into sol-gel obtained titanium and ruthenium oxide coatings on titanium on their electrochemical properties. AB - Electrochemical properties of sol-gel processed Ti(0.6)Ir(0.4)O(2) and Ti(0.6)Ru(0.3)Ir(0.1)O(2) coatings on titanium substrate were investigated using cyclic voltammetry, polarization measurements and electrochemical impedance spectroscopy and compared to the properties of Ti(0.6)Ru(0.4)O(2) coating. The role of iridium oxide in the improvement of the electrocatalytic, capacitive and stability properties of titanium anodes activated by a RuO(2)-TiO(2) coating is discussed. The oxide sols were prepared by forced hydrolysis of the metal chlorides. The characterization by dynamic light scattering and X-ray diffraction showed that polydisperse oxide sols were obtained with the particles tending to form agglomerates. The presence of IrO(2) causes a suppression of the X-ray diffraction peaks of TiO(2) and RuO(2) in the sol-gel prepared Ti(0.6)Ir(0.4)O(2) and Ti(0.6)Ru(0.3)Ir(0.1)O(2) coatings. The IrO(2)-containing coatings had an enhanced charge storage ability and activity for the oxygen evolution reaction (OER) in comparison to Ti(0.6)Ru(0.4)O(2) coating. The voltammogram of the Ti(0.6)Ir(0.4)O(2)/Ti electrode showed well-resolved peaks related to Ir redox transitions, which are responsible for the enhanced charge storage ability of IrO(2)-containing coatings. Redox transitions of Ir were also registered in the high-frequency domain of the ac impedance spectra of the coatings as a semicircle with characteristics insensitive to the electrolyte composition and to the electrode potential prior to OER. However, the semicircle characteristics were different for the two IrO(2)-containing coatings, as well as at potentials outside the OER in comparison to those at which the OER occurs. PMID- 20544089 TI - Thiol-capped CdTe nanocrystals: progress and perspectives of the related research fields. AB - This article analyzes and summarizes recent developments and newly emerging research fields related to thiol-capped CdTe nanocrystals, the most successful example of the colloidal quantum dots directly synthesized in aqueous solution. Progress in the synthesis and design of novel materials and functionalities, sophisticated assemblies of thiol-capped nanocrystals, development and validation of analytical and spectroscopic methods relying on thiol-capped CdTe nanocrystals as a model system, and, finally, applications of thiol-capped semiconductor nanocrystals in various fields ranging from light harvesting and energy transfer to biotechnology are addressed. PMID- 20544090 TI - Isotopic effect and temperature dependent intramolecular excitation energy transfer in a model donor-acceptor dyad. AB - We consider here the non-adiabatic energy transfer dynamics for a model bi chromophore system consisting of a perylenemonoimide unit linked to a ladder-type poly(para-phenylene) oligomer. Starting from a semi-empirical parameterization of a model electron/phonon Hamiltonian, we compute the golden-rule rate for energy transfer from the LPPP5 donor to the PMI acceptor. Our results indicate that the non-adiabatic transfer is promoted by the out-of-plane wagging modes of the C-H bonds even though theses modes give little or no contribution to the Franck Condon factors in this system. We also predict a kinetic isotope effect of k((H))/k((D)) = 1.7-2.5 depending upon the temperature. PMID- 20544091 TI - Conformation specific and charge directed reactivity of radical cation intermediates of alpha-substituted (amino, hydroxy, and keto) bioactive carboxylic acids. AB - The reactivity of radical cation carboxylic acids is investigated on the basis of mass spectrometry, infrared-vacuum ultraviolet (IR-VUV) photoionization spectroscopy, and high level correlated ab initio calculations. Their reactivity is found to be highly conformation specific and is governed by their initial charge distribution following ionization. In the present work, the radical cations of lactic acid, pyruvic acid, glycine, and valine are studied to probe their stability and conformation specific reactivity following single photon, vertical ionization at 10.5 eV. For lactic acid, glycine, and valine, the localization site of the hole following sudden removal of an electron depends on their specific intramolecular hydrogen bonding network. Lactic acid, glycine, and valine undergo complete fragmentation following vertical ionization at 10.5 eV; however, pyruvic acid does not completely dissociate following vertical ionization. Only 45% of the pyruvic acid parent ions undergo C(alpha) C(carboxylic) bond dissociation. If the hole is localized on the COOH moiety of glycine, valine, and lactic acid, a hydrogen transfer is favored from the COOH to the alpha-substituent. If the hole is localized on the alpha-hydroxy or -amine substituent and the singly occupied molecular orbital (SOMO, where the hole resides) is parallel to the C(alpha)-C(carboxylic) bond, C(alpha)-C(carboxylic) bond dissociation occurs through charge transfer from the alpha-substituent to the C(alpha)-C(carboxylic) bond. The present study reveals that the specific conformations of alpha-substituted carboxylic acids govern their radical cationic reactivity. The radical cation of pyruvic acid exhibits a special stability due to enolization of the alpha-keto form on the cationic surface. PMID- 20544092 TI - ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection. AB - A miniature 96 sample ELISA-lab-on-a-chip (ELISA-LOC) was designed, fabricated, and tested for immunological detection of Staphylococcal Enterotoxin B (SEB). The chip integrates a simple microfluidics system into a miniature ninety-six sample plate, allowing the user to carry out an immunological assay without a laboratory. Assay reagents are delivered into the assay plate without the need for separate devices commonly used in immunoassays. The ELISA-LOC was constructed using Laminated Object Manufacturing (LOM) technology to assemble six layers with an acrylic (poly(methyl methacrylate) (PMMA)) core and five polycarbonate layers micromachined by a CO(2) laser. The ELISA-LOC has three main functional elements: reagent loading fluidics, assay and detection wells, and reagent removal fluidics, a simple "surface tension" valve used to control the flow. To enhance assay sensitivity and to perform the assay without a lab, ELISA-LOC detection combines several biosensing elements: (1) carbon nanotube (CNT) technology to enhance primary antibody immobilization, (2) sensitive ECL (electrochemiluminescence) detection, and (3) a charge-coupled device (CCD) detector for measuring the light signal generated by ECL. Using a sandwich ELISA assay, the system detected SEB at concentrations as low as 0.1 ng ml(-1), which is similar to the reported sensitivity of conventional ELISA. The fluidics system can be operated by a syringe and does not require power for operation. This simple point-of-care (POC) system is useful for carrying out various immunological assays and other complex medical assays without a laboratory. PMID- 20544093 TI - Analysis of the interactions of mixtures of two beta-agonists steroids with bovine serum albumin: a fluorescence spectroscopy and chemometrics investigation. AB - Beta-agonists such as ractopamine (RAC) and clenbuterol (CLEN), have similar effects as anabolic steroids i.e. they promote growth of muscular tissue and reduce body fat. They have been used successfully with animals and humans but have also been banned in many countries principally, because of their serious side effects. However, their illegal use persists. Thus, their interaction with biomolecules such as bovine serum albumin (BSA) is of significance, especially the co-operative reaction of mixed ligands with the protein. Fluorescence and UV vis spectra of complex mixtures of individual ligands, binary and ternary complexes with BSA resulted in significantly overlapping spectral profiles. Qualitative and quantitative information about the various complex ligand-protein species formed, was obtained with the resolution of the excitation-emission fluorescence three-way data matrices by chemometrics methods-MCR-ALS and PARAFAC. Individual spectra of the ligands, their binary complexes with BSA and their ternary complexes were extracted, and quantitative concentration profiles for each species in a particular interaction were constructed. Such analyses made it possible to interpret the role and behaviour of each reaction component. It was found that both ligands, RAC and CLEN, bound co-operatively in site I of the BSA. This was confirmed with the use of site markers such as warfarin (site I) and ibuprofen (site II). However, CLEN formed a 1:1 CLEN-BSA complex, while RAC formed a 2:1 RAC(2)-BSA binary species. Interestingly, when CLEN or RAC was added to RAC(2)-BSA or CLEN-BSA, respectively, ternary complexes were produced such as RAC(2)-BSA-CLEN. Significantly, the presence of the second ligand in such an interaction in excess, appeared to increase the affinity of the added ligand for BSA. This may have consequences on the amount of steroid required to achieve a desired tissue growth effect. PMID- 20544094 TI - Long-range ordering or not: magnetic properties modulated by second ligands in flexible three-dimensional metal-organic frameworks. AB - The flexibility of the 3D framework derived from Ni(II) and an aromatic dicarboxylate allows for the incorporation of different second bridges, and the resulting materials can be a metamagnet or a paramagnet depending upon the length of the second bridge. PMID- 20544095 TI - Fabrication of Au(111) nanoparticle-like electrode through a seed-mediated growth. AB - We demonstrate a seed-mediated growth of electrodeposited gold-nanoparticles (GNPs) onto a glassy carbon (GC) electrode from a solution of H[AuCl(4)] containing NH(2)OH at pH 0.5, resulting in a Au(111) facet ratio as high as 97%. PMID- 20544096 TI - Photocatalytic reductive dechlorination of chlorobenzene to benzene in 2-propanol suspension of metal-loaded titanium(IV) oxide nanocrystals in the presence of dissolved sodium hydroxide. AB - Photocatalytic reaction of chlorobenzene in 2-propanol suspension of palladium- and rhodium-loaded titanium(IV) oxide nanocrystals in the presence of dissolved sodium hydroxide under deaerated conditions, in which 2-propanol, metal loaded (palladium and rhodium) and sodium hydroxide effectively acted as hole scavenger, co-catalyst and chloride solidifier, respectively, quantitatively gave benzene and chloride ions with a high stoichiometry. PMID- 20544097 TI - Two-dimensional self-assembly of disulfide functionalized bis-acylurea: a nanosheet template for gold nanoparticle arrays. AB - A new functional bis-acylurea molecule allows a two-stage self-organization process. It self-organizes--at first--into 2D nanosheets with disulfide groups at the surface, which act--in the second stage--as a template for gold nanoparticle arrays. PMID- 20544099 TI - Electronic energy harvesting multi BODIPY-zinc porphyrin dyads accommodating fullerene as photosynthetic composite of antenna-reaction center. AB - Efficient electronic energy transfer (EET) in the newly synthesized dyads comprised of zinc porphyrin covalently linked to one, two or four numbers of boron dipyrrin (BDP) entities is investigated. Both steady-state and time resolved emission as well as transient absorption studies revealed occurrence of efficient singlet-singlet energy transfer from BDP to zinc porphyrin with the time scale ranging between 28 and 48 ps. A decrease in time constants for energy transfer with increasing the number of BDP units is observed revealing better antenna effect of dyads bearing higher number of boron dipyrrin entities. Further, supramolecular triads to mimic the 'antenna-reaction center' functionality of photosynthetic reaction center have been successfully constructed by coordinating fulleropyrrolidine appended with an imidazole ligand to the zinc porphyrin. The structural integrity of the supramolecular triads was arrived by optical, computational and electrochemical studies. Free energy calculations revealed possibility of photoinduced electron transfer from singlet excited zinc porphyrin to fullerene, and the preliminary transient absorption studies involving pump-probe technique are supportive of occurrence of electron transfer from (1)ZnP* to fullerene in the supramolecular triads. PMID- 20544098 TI - The stability of [Zn(NH(3))(4)](2+) in water: A quantum mechanical/molecular mechanical molecular dynamics study. AB - To investigate the structural and dynamical properties of the tetraamminezinc(ii) complex (Zn-tetraamine) in aqueous solution, ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulation was performed for 50 ps at the Hartree-Fock (HF) level of theory. A predominant 4 coordinate solvation structure with a maximum probability of the Zn-N distance at approximately 2.1 A was observed, which seems to be involved in the associative mode of water exchange reactions to produce a short-lived, 5-coordinated trigonal bipyramidal structure. Several sets of structural and dynamical parameters such as radial distribution functions (RDF), coordination number distributions (CND), angular distributions (ADF), ligands' mean residence times (MRT) and ion-ligand stretching frequencies have been evaluated in order to get an in depth knowledge of the physical and chemical properties of the tetraamminezinc(ii) complex in aqueous solution. A comparative study of the tetraamminezinc(ii) complex with previously published mono-, di- and triamminezinc(ii) complexes has been also performed, which yielded significant insights into the complex properties as a function of an increasing number of first-shell ammonia ligands. PMID- 20544100 TI - Coadsorption of hydrogen and CO on well-defined Pt(35)Ru(65)/Ru(0001) surface alloys--site specificity vs. adsorbate-adsorbate interactions. AB - The coadsorption of CO and hydrogen on a structurally well-defined Pt(35)Ru(65)/Ru(0001) monolayer surface alloy and, for comparison, on Ru(0001) were investigated by temperature programmed desorption (TPD) and infrared reflection absorption spectroscopy (IRAS). The data reveal distinct modifications in the hydrogen adsorption behavior and also in the CO adsorption properties compared to adsorption of the individual components both on the mono-metallic and on the bimetallic surface. These modifications are discussed on an atomic scale, in a picture that involves adsorbate-adsorbate interactions and site-specific variations in the (local) adsorption properties of the bimetallic surface, due to electronic ligand and strain effects and geometric ensemble effects. PMID- 20544101 TI - Superexchange-mediated electronic energy transfer in a model dyad. AB - On the basis of time-dependent density functional theory (TD-DFT) calculations coupled to the polarizable continuum model (PCM) and single molecule spectroscopic studies, we provide a detailed investigation of excitation energy transfer within a model bi-chromophoric system where a perylene monoimide (PMI) donor is bridged to a terrylene diimide (TDI) acceptor through a ladder-type pentaphenylene (pPh) spacer. We find that the electronic excitation on the PMI donor significantly extends over the bridge giving rise to a partial charge transfer character and inducing a approximately 3-fold increase in the electronic interaction between the chromophores, which explains the failure of the Forster model in reproducing the observed energy migration rates when treating PMI as the donor. However, despite an increased charge transfer contribution in the effective donor state, the increase in solvent polarity is not accompanied by an enhancement in the electronic coupling between the subunits, which is rationalized from a detailed analysis of the excited-state wavefunctions. PMID- 20544102 TI - Quantum coherence and its interplay with protein environments in photosynthetic electronic energy transfer. AB - Recent experiments suggest that electronic energy transfer in photosynthetic pigment-protein complexes involves long-lived quantum coherence among electronic excitations of pigments. [Engel et al., Nature, 2007, 446, 782-786.] The observation has led to the suggestion that quantum coherence might play a significant role in achieving the remarkable efficiency of photosynthetic light harvesting. At the same time, the observation has raised questions regarding the role of the surrounding protein in protecting the quantum coherence. In this Perspective, we provide an overview of recent experimental and theoretical investigations of photosynthetic electronic energy transfer paying particular attention to the underlying mechanisms of long-lived quantum coherence and its non-Markovian interplay with the protein environment. PMID- 20544103 TI - Hierarchy of reaction dynamics in a thermally fluctuating environment. AB - Nonlinear dynamics in the passage over a rank-one saddle is investigated as a function of temperature in the presence of stochastic, thermal fluctuation. The analyses are based on a framework we developed recently adopting a multidimensional underdamped Langevin equation (without any assumption for the form of the potential of mean force). The framework can in principle provide a single coordinate to enable us to predict the final destination of the reaction in a thermally fluctuating media. At each temperature, the preciseness or the error of the reaction coordinate is evaluated in capturing the true reaction dynamics at different levels of approximations. By using the Muller-Brown potential as an illustrative example, it is found that a hierarchy of dynamical structure exists in the region of a rank-one saddle, in which the crossing dynamics qualitatively changes as the temperature increases. We discuss the mechanism of how the reaction coordinate persists, which provides a boundary of the reaction to divide the phase space into the reactive and the nonreactive regions, even in the presence of thermal fluctuation. PMID- 20544104 TI - Nonlinear dynamical effects on reaction rates in thermally fluctuating environments. AB - A framework to calculate the rate constants of condensed phase chemical reactions of manybody systems is presented without relying on the concept of transition state. The theory is based on a framework we developed recently adopting a multidimensional underdamped Langevin equation in the region of a rank-one saddle. The theory provides a reaction coordinate expressed as an analytical nonlinear functional of the position coordinates and velocities of the system (solute), the friction constants, and the random force of the environment (solvent). Up to moderately high temperature, the sign of the reaction coordinate can determine the final destination of the reaction in a thermally fluctuating media, irrespective of what values the other (nonreactive) coordinates may take. In this paper, it is shown that the reaction probability is analytically derived as the probability of the reaction coordinate being positive, and that the integration with the Boltzmann distribution of the initial conditions leads to the exact reaction rate constant when the local equilibrium holds and the quantum effect is negligible. Because of analytical nature of the theory taking into account all nonlinear effects and their combination with fluctuation and dissipation, the theory naturally provides us with the firm mathematical foundation of the origin of the reactivity of the reaction in a fluctuating media. PMID- 20544105 TI - Fluorescence enhancement of single DNA molecules confined in Si/SiO2 nanochannels. AB - We demonstrate that the detected emission intensity from YOYO-labeled DNA molecules confined in 180 nm deep Si/SiO2 nanofunnels changes significantly and not monotonically with the width of the funnel. This effect may be of importance for quantitative fluorescence microscopy and for experiments with a tight photon budget. PMID- 20544106 TI - Core-shell structured microcapsular-like Ru@SiO2 reactor for efficient generation of CO(x)-free hydrogen through ammonia decomposition. AB - The core-shell structured microcapsular-like Ru@SiO(2) reactor is proved to be the most efficient material known to date for CO(x)-free hydrogen production via ammonia decomposition for fuel cells application. The very active Ru core particles can retain good stability even at high temperatures (up to 650 degrees C) thanks to the protection of the inert SiO(2) nano-shell. PMID- 20544107 TI - Discovery of potent inhibitor for farnesyl pyrophosphate synthase in the mevalonate pathway. AB - The mevalonate pathway is an important drug target for the treatment of cancer and cardiovascular disease. We synthesized and studied a new type of nitrogen containing bisphosphonate analogs and developed a sensitive end point assay method for enzyme FPPS, which was used for inhibitor screening. One potent FPPS inhibitor was discovered, and the structure-activity relationship of bisphosphonates for the enzyme inactivation was studied. PMID- 20544108 TI - Non-invasive analysis in micro-reactors using Raman spectrometry with a specially designed probe. AB - An optical interface has been designed to maximise the sensitivity and spatial resolution required when Raman spectrometry is used to monitor a reaction in a micro-reactor, revealing advantages over a conventional commercial probe. A miniature aspheric lens was shown to be better than microscope objectives to focus the probing laser beam onto the sample. The diameters of the exciting and collection optical fibres were also shown to have a significant influence on sensitivity and the signal-to-background ratio, with 62.5 microm diameter 0.28 numerical aperture (NA) fibres found to be best for analysis of liquids in the 150 microm deep channel in the micro-reactor used. With a spectral measurement time of 2 s, it was shown that the probe could monitor the progress of an esterification reaction in real time and quickly optimise the reagent flow rates. The fast response time revealed features related to short-term pump instabilities and micro-reactor rheology effects that would not have been identified without rapid real-time measurements. PMID- 20544109 TI - Biopolymer-mediated synthesis of anisotropic piezoelectric nanorods. AB - Alginate biopolymer was used to control the crystal growth of the lead-free piezoelectric material langasite. The piezo-response of these nanorods was demonstrated to be equivalent to that of ZnO. This is the first time that templated growth of langasite and its associate phases has been demonstrated. PMID- 20544110 TI - Assembly of two- and three-dimensionally patterned silicate materials using responsive soft templates. AB - We report a soft and straightforward method for synthesizing two- and three dimensionally patterned silicate materials by phase separation using nonionic emulsion templates. Our liquid-state method involves, under controlled atmosphere, the mixing of a condensed silica solution with an oil-in-water emulsion in the presence of a solution of a nonionic emulsifier, Triton X-100. The preparation is stabilized using an organic solvent. The morphology of the silicate materials is significantly modified by changing the reaction conditions or the concentration of the reagents. Three-dimensionally macro and nanoporous continuous films and nanoporous individual spherical particles, both made of amorphous silica, are obtained. The structure of the films and particles is defined by the emulsion template. Films were on average 20 microm thick with a volume-based porosity of approximately 7 x 10(-2) cm(3) g(-1), with pore size correlating well with the size of the oil droplets in the templating emulsion. The siliceous films are bicontinuous leading to large surface areas and openly accessible pores. Individual spheres ranged in size from approximately 1 to 6 microm in diameter with nanoporous openings of 300 nm in diameter. The porosity and integrity of all materials are maintained upon calcination. PMID- 20544111 TI - In search of the elusive amalgam SrHg8: a mercury-rich intermetallic compound with augmented pentagonal prisms. AB - In confirmation of its predicted existence in the Sr-Hg phase diagram, the mercury-rich intermetallic compound SrHg(8) has been prepared by reaction of the elements at 200 degrees C. Single-crystal X-ray diffraction analysis revealed that it adopts a new structure type (Pearson symbol oP72, space group Pnma, a = 13.328(1) A, b = 4.9128(5) A, c = 26.446(3) A). The Sr atoms are centred within two types of 18-vertex Hg polyhedra formed by augmenting pentagonal prisms with octagonal waists. The condensation of these Sr@Hg(18) clusters is associated with the formation of a complex anionic Hg-Hg bonding network, as supported by electronic structure calculations which reveal strong mixing of Hg 6s and 6p states in highly delocalized bands superimposed with a narrower 5d band below the Fermi level. PMID- 20544112 TI - Bright white upconversion emission from Yb(3+), Er(3+), and Tm(3+)-codoped Gd(2)O(3) nanotubes. AB - Yb(3+), Er(3+), and Tm(3+)-codoped Gd(2)O(3) nanotubes were synthesized via a simple wet-chemical route at low temperature and ambient pressure followed by a subsequent heat treatment at 800 degrees C. X-Ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA), upconversion (UC) emission spectra, and kinetic decay were used to characterize the samples. Bright white UC luminescence in the nanotubes was observed under diode laser excitation of 980 nm. The white light consists of the blue ((1)G(4)- >(3)H(6) of Tm(3+)), green ((2)H(11/2)/(4)S(3/2)-->(4)I(15/2) of Er(3+)), and red ((4)F(9/2)-->(4)I(15/2) of Er(3+)) UC emissions. As the excitation power density changed in the range of 20-200 W cm(-2), the calculated CIE color coordinates shift only slightly and fall well within the white region. This material may be a potential candidate for applications of color displays, lighting and photonics. PMID- 20544113 TI - In situ mechanical characterization of mouse oocytes using a cell holding device. AB - This paper presents a cellular force measurement technique that allows for mechanical characterization of mouse oocytes during microinjection (i.e., in situ) without requiring a separate characterization process. The technique employs an elastic cell holding device and a sub-pixel computer vision tracking algorithm to resolve cellular forces in real time with a nanonewton force measurement resolution (2 nN at 30 Hz). Mechanical properties (i.e., stiffness) of both healthy and defective mouse oocytes are characterized. The experimental results suggest that the in situ obtained force-deformation data are useful for distinguishing healthy mouse oocytes from those with aging-induced cellular defects, promising an approach for oocyte quality assessment during microinjection. Biomembrane and cytoskeleton structures of the healthy and defective oocytes are also investigated in an attempt to correlate the measured subtle mechanical difference to cellular structure changes. PMID- 20544114 TI - Suspended nanoparticle crystal (S-NPC): A nanofluidics-based, electrical read-out biosensor. AB - Here we report an approach utilizing a suspended nanoparticle crystal (S-NPC) as an electrical read-out biosensor based on a nanofluidic electrokinetics principle. As a preliminary demonstration, streptavidin-modified S-NPC with a particle diameter of 520 nm was used to detect biotin in a PBS buffer. The present result indicated that the detection range of biotin by this nanofluidics based biosensor was about 1 nM-10 muM (in 10(-4)x PBS) with a sensitivity of 160 nS/nM. Being easy to get established, low-cost, and having large electrical read out signal, the present S-NPC is believed to be a promising biosensing scheme in the micro total analysis system. PMID- 20544115 TI - Facile dihydrogen release from phosphino-borinate ester Lewis pairs. AB - New phosphino-borinate ester Lewis pairs of the type (t)Bu(2)PCH(2)C(R)(2)OB(C(6)F(5))(2) (R = Me or CF(3)) are synthesised from the corresponding phosphino-alcohol and HB(C(6)F(5))(2). Dihydrogen release from the zwitterionic (t)Bu(2)PHCH(2)C(R)(2)OBH(C(6)F(5))(2) is facile. PMID- 20544116 TI - Two-step synthesis of high-quality water-soluble near-infrared emitting quantum dots via amphiphilic polymers. AB - High-quality water-soluble near-infrared emitting quantum dots (QDs) are synthesized using a two-step approach for the first time. The CdS shell efficiently increases the structural stability of PbS QDs during water transfer and leads to good photostability and a significantly enhanced quantum yield as high as 30% in buffer. PMID- 20544117 TI - Total synthesis of antimicrobial and antitumor cyclic depsipeptides. AB - The total synthesis of natural products "has to be viewed as an art and a science that needs to be advanced for its own sake" (K. C. Nicolaou) and indeed, the achievements within this field of chemistry during the last decades are astonishing. However, besides its inherent beauty, total synthesis also opens the gates widely to a better understanding of biological processes and the development of pharmaceutical interesting substances. Cyclic depsipeptides form one of the compound classes that have attracted tremendous attention from synthetic chemists. They often feature non-proteinogenic amino acids and various types of structural unique building blocks, which make them challenging targets for synthetic efforts. Their total synthesis offers the chance to implement the use of newly developed synthetic tools in a complex environment. Synthetic dead ends have shown the limitations of today's chemistry as well as triggering the development of new methodologies to circumvent the observed problems. Cyclic depsipeptides also often possess biological properties, especially antimicrobial and antitumor activity, that make them promising candidates for further pharmaceutical investigations and thus have a value at their own. Furthermore, through construction from scratch, ambiguities regarding the structure of several members of that compound class could be successfully clarified and derivatives for structure-activity-relationship (SAR) studies obtained. PMID- 20544118 TI - Oxime-derived palladacycles as source of palladium nanoparticles. AB - Oxime-derived palladacycles are very efficient and versatile pre-catalysts for a wide range of carbon-carbon bond coupling reactions in air, under very low loading conditions, and employing reagent-grade chemicals. This tutorial review presents the main achievements, advantages and limitations of oxime palladacycles as a source of highly active palladium nanoparticles for high-turnover catalyzed Heck, as well as other homo- and cross-coupling reactions usually carried out employing organic or aqueous solvents. Comparison with other ligandless Pd(II) catalysts is also presented. Recent advances to develop supported oxime-derived palladacycles in order to facilitate precatalyst recovery and reuse in cross coupling reactions, especially under aqueous reaction conditions, are also discussed. PMID- 20544119 TI - The influence of the relative position of the thiophene and pyrrole rings in donor-acceptor thienylpyrrolyl-benzothiazole derivatives. A photophysical and theoretical investigation. AB - A detailed spectroscopic and photophysical study has been carried out on a series of heterocyclic compounds-known to display nonlinear optical properties consisting on a electron donating thienylpyrrolyl pi-conjugated system functionalized with an electron acceptor benzothiazole moiety. The absorption, emission and triplet-triplet absorption together with all relevant quantum yields (fluorescence, intersystem crossing and internal conversion), excited state lifetimes and the overall set of deactivation rate constants (k(F), k(IC) and k(ISC)) were obtained in solution at room (293 K) and low (77 K) temperature. The optimized ground-state molecular geometries for the compounds together with the prediction of the lowest vertical one-electron excitation energy and the relevant molecular orbital contours for the compounds were also determined using density functional theory (DFT) at the B3LYP/3-21G* level. The experimental results showed that the photophysical properties are influenced by the relative position of the pyrrole and thiophene relative to the benzothiazole group. PMID- 20544120 TI - UVA absorption and photostability of coumarins. AB - Various substituted 4-methylcoumarin derivatives were synthesized in order to obtain photostable derivatives with UVA absorption property. It was found that substitution positions affected maximum absorption wavelength, whereas types of substituents, whether hydroxy or alkoxy groups, caused no significant effect. Photostability, however, was affected by both the substitution positions and the types of substituents. An acid-catalyzed mechanism through enolization coupled with pre-organization via hydrogen bonding between two coumarin moieties is proposed as an explanation for the different extents of the [2+2] cycloaddition (dimerization) amongst different derivatives, which results in a different photostability amongst them. Photostable coumarin derivatives with an absorption maximum in the UVA region are reported. PMID- 20544121 TI - The solid state structure and reactivity of NbCl(5) x (N,N'-dicyclohexylurea) in solution: evidence for co-ordinated urea dehydration to the relevant carbodiimide. AB - NbCl(5) x (N,N'-dicyclohexylurea) 1a owns a distorted octahedral structure due to intramolecular NH...Cl bonding. The unit cell contains four units which are intermolecularly NH...Cl and NH...N bonded. An extended intramolecular network of H-bonding (N-H...Cl, CH...Cl, CH...N) causes the 3D self assembling of the units. Upon addition of base, the HCl release from 1a is observed with the transfer to Nb of the O-atom of the carbonylic function of the starting urea which is converted into the relevant carbodiimide CyN=C=NCy 4. The latter is quantitatively released by adding an excess of NEt(3) at 308 K (py and DBU are less efficient) with formation of the known NbOCl(3)(NEt(3))(2), isolated in quantitative yield. Increasing the temperature leads to a loss in selectivity as the formed DCC undergoes further reactions. At 350 K, the isocyanate CyN=C=O has been isolated in 60% yield besides a mixture of Nb-complexes. DFT calculations have been coupled to IR and NMR experiments for characterizing possible reaction intermediates and the behaviour of 1a. Several other MCl(x) species (ScCl(3), YCl(3), LaCl(3), TiCl(4), TaCl(5), AlCl(3), SnCl(4)) have been shown to be able to co-ordinate DCU but not all of them promote the conversion of urea into DCC. PMID- 20544122 TI - Low temperature extraction and upgrading of oil sands and bitumen in supercritical fluid mixtures. AB - Preliminary results are reported for the extraction and catalytic hydrocracking of Alberta bitumen and oil sands using supercritical fluid mixtures; high levels of extraction and upgrading were attained using reaction conditions significantly milder than those previously reported. PMID- 20544123 TI - Method for regio-, chemo- and stereoselective deuterium labeling of sugars based on ruthenium-catalyzed C-H bond activation. AB - An efficient and facile deuterium labeling of sugars has been achieved in a completely regio-, chemo- and stereoselective manner using the Ru/C-H(2)-D(2)O combination via C-H bond activation assisted by the coordination of Ru to the oxygen atom of the sugar-hydroxyl groups. PMID- 20544124 TI - Identifying targets of miR-143 using a SILAC-based proteomic approach. AB - Although the targets of most miRNAs have not been experimentally identified, microRNAs (miRNAs) have begun to be extensively characterized in physiological, developmental and disease-related contexts in recent years. Thus far, mainly computational approaches have been employed to predict potential targets for the large majority of miRNAs. Although miRNAs exert a major influence on the efficiency of translation of their targets in animals, most studies describing experimental identification of miRNA target genes are based on detection of altered mRNA levels. miR-143 is a miRNA involved in tumorigenesis in multiple types of cancer, smooth muscle cell fate and adipocyte differentiation. Only a few miR-143 targets are experimentally verified, so we employed a SILAC-based quantitative proteomic strategy to systematically identify potential targets of miR-143. In total, we identified >1200 proteins from MiaPaCa2 pancreatic cancer cells, of which 93 proteins were downregulated >2-fold in miR-143 mimic transfected cells as compared to controls. Validation of 34 of these candidate targets in luciferase assays showed that 10 of them were likely direct targets of miR-143. Importantly, we also carried out gene expression profiling of the same cells and observed that the majority of the candidate targets identified by proteomics did not show a concomitant decrease in mRNA levels confirming that miRNAs affect the expression of most targets through translational inhibition. Our study clearly demonstrates that quantitative proteomic approaches are important and necessary for identifying miRNA targets. PMID- 20544125 TI - [Gradenigo's syndrome: a case-report]. AB - Acute otitis media is the most common bacterial infection in children. Despite efficient antibiotic therapy, there are still reports of both intratemporal and intracranial complications with potential risk of high morbidity and mortality. Mastoiditis, apical petrositis and labyrinthitis are caused by the extension of purulent middle ear infection into nearby structures. Giuseppe Gradenigo first described the clinical triad of acute otitis media, unilateral pain in the region innervated by the 1 masculine and 2 masculine branches of the trigeminal nerve and ipsilateral abducens nerve paralysis. This is a serious but rare complication of middle ear infection that should be suspected in every patient with unilateral headache and abducens nerve palsy. We report a case of Gradenigo's syndrome in a 6-year-old boy. PMID- 20544126 TI - [Toxic epidermal necrolysis after treatment with oseltamivir: case report]. AB - Toxic epidermal necrolysis is a rare acute and potentially life-threatening drug related reaction. Osetalmivir is one of the drugs responsible for these reaction. We describe the case of a Down syndrome patient with toxic epidermal necrolysis previously treated with oseltamivir. PMID- 20544127 TI - [Childhood cutaneous polyarteritis nodosa]. AB - Cutaneous polyarteritis nodosa is an infrequent necrotizing vasculitis of small and medium-sized arteries, with a recurrent and chronic course, that can be associated with fever, arthralgia, myalgia and neuropathy without visceral involvement. We report a cutaneous polyarteritis nodosa case. PMID- 20544128 TI - [Retrorectal cyst hamartoma: report of a pediatric case]. AB - The retrorectal hamartoma cyst or retrorectal cyst is an uncommon congenital lesion. We present the case of a 7 days-old girl with a retrorectal tumor diagnosed by ultrasound during pregnancy. The histological examination was a cyst lined by squamous and urotelial typical epithelium and a double layer of smooth muscle. The treatment of choice is the complete excision of the lesion, as local recurrences or a malignant transformation have been observed. PMID- 20544129 TI - [Psoas abscess as a chicken pox complication]. AB - Chicken pox is the most frequent exantematic illness; usually its course is self limited and benign. Several bacterial complications are described due to the disruption of the skin as a defensive barrier because of the characteristics of the injuries and the associated inmunodepression. Psoas abscess is a rare illness and it's difficult to diagnose, with a general unspecified clinical presentation. We present the case of a 5-year-old girl, on her fifth day of chicken pox, who consults about a febrile convulsion, from which she recovers without any neurological symptoms, referring to functional impotence of her inferior left limb and pain in the lumbar and gluteal zone, which irradiates to the homolateral hip, making deambulation impossible. The definitive diagnosis was made with a CAT at hospital admission. The germ isolated was community-acquired methricillin resistant Staphilococcus aureus. Treatment consisted in surgical drainage and endovenous antibiotics. PMID- 20544132 TI - [The infant with recurrent wheezing and inhaled corticosteroids therapy]. PMID- 20544133 TI - [Anemia, a complex issue, simple solutions?]. PMID- 20544134 TI - [The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: a randomized, controlled trial]. AB - BACKGROUND: Delayed umbilical cord clamping could increase iron stores and prevent iron deficiency in infants. To test this hypothesis we measured serum ferritin and hemoglobin levels at six months of age in term infants who had participated in a randomized controlled trial, assessing the effect of cord clamping timing on neonatal hematocrit values and clinical outcome. Main outcome measure. Serum ferritin level at six months of age. METHODS: Out of the 276 mothers and their infants that participated in the initial study, 255 (92.4%) were followed up to six months and included in this study. Of these, 86 had their cords clamped within the first 15 seconds (early clamping), 83 at one minute, and 83 at three minutes. The pediatricians in charge of the evaluations during the follow-up period and personnel in charge of the biochemical tests were blinded to the assignment group. In all but 3 infants the ferritin levels and hemoglobin levels were measured at six months of age. RESULTS: Mothers and infants in the three groups had similar baseline characteristics. Serum ferritin levels were significantly higher in the infants of the three minutes group than in the infants of the early group: 33.2 microg/L vs. 20.9 microg/L (geometric mean ratio: 1.6; 95% CI: 1.2 to 2.11) but no difference was observed in one minute group (25.5 microg/L) vs. early group. There were no significant differences in mean hemoglobin values, 10.6 g/dl (SD 1,1); 10.8 g/dl (SD 0.9) and 10.7 g/dl (SD 1.0) between groups early, one minute, and three minutes, respectively. Although there were no significant differences between groups, the prevalence of iron deficiency anemia (hemoglobin < 10.5 g/dl and ferritin < 9 microg/L) was 3 times more frequent in early clampling group (7.2%) than in three minutes group (2.4%) (RR: 0.30; IC 95%: 0.10-1.60). CONCLUSIONS: Delayed umbilical cord clamping at three minutes significantly increases serum ferritin levels in infants at 6 months of age. No significant differences were found between groups in mean hemoglobin levels. PMID- 20544135 TI - [Prevention of catheter-related infection: usefulness and cost-effectiveness of antiseptic catheters in children]. AB - OBJECTIVE: To evaluate the cost-effectiveness of the antiseptic-impregnated catheter compared with conventional catheters in preventing catheter- related blood stream infections (CR-BSI). DESIGN: Cost-effectiveness analysis; clinical trial, experimental, randomized, controlled, prospective, open label. Patients and methods. A 172 patient cohort, under 1-year-old or less than 10 kg, postoperative cardiovascular children with central venous catheters (CVC) admitted to Cardiac Intensive Care Unit (UCI 35) at Hospital Nacional de Pediatria "Prof. Dr. Juan P. Garrahan", since September 2005 to December 2007. Demographic and CVC data were retrieved to compare: age, gender, weight, diagnosis, surgery, CVC days, costs and complications. Intervention. CVC Arrow, double-lumen, > 48 h of duration; intervention group: antiseptic-impregnated CVC vs. control group: CVC without antiseptics (conventional). RESULTS: The incidence of CR-IE (CR-Infected Events: colonization, local infection and/or CRBSI; combined end point) was 27% for antiseptic- impregnated CVC vs. 31% for conventional catheters (p= 0.6) with similar accumulated incidence of CR- BSI: 2.8 vs. 3.3 per 1000 dayscatheter. We found no differences between groups, except in weight: median 4.0 kg (r 2-17) vs. 4.7 kg (r 2-9) p= 0.0002 and age, median 2 months (r 1- 48) vs. 5 months (r 1- 24) p= 0.0019 in antiseptic-impregnated CVC group. These differences, though statistically significant were clinically non relevant. Median cost per patient during intensive care stay in the conventional CVC group was $3.417 (359-9.453) and in the antiseptic-impregnated-CVC group was $4.962 (239-24.532), p= 0.10. CONCLUSIONS: The use of antiseptic-impregnated CVC compared with conventional CVC did not decrease CR-BSI in this population. The cost per patients was higher in the antiseptic impregnated CVC group. These results do not support the routine use of this type of CVC in our population. PMID- 20544136 TI - [Cardiopulmonary resuscitation in nine pediatric intensive care units of the Argentine Republic]. AB - INTRODUCTION: The cardiopulmonary resuscitation (CPR) is a common setting in the pediatric intensive care unit (PICU). There are very few reports or publications that evaluate the form of CPR administered in children. OBJECTIVES: 1) Identify the etiology and epidemiology of the CPR in the PICU. 2) Describe how to conduct CPR. 3) Describe the drugs used. 4) Knowing the patient outcomes. 5) Knowing CPR training of physicians in the PICU. PATIENTS AND METHODS: All children with cardiopulmonary arrest who were resuscitated in the PICU between 01/04/2004- 31/03/2005. A prospective cohort study. RESULTS: There were 2065 admissions in nine 9 PICU and CPR was conducted in 132 patients (6.39%). Most common etiologies of PCR were hypoxia and hypotension (65.9% of total). The initial rates of PCR were 43.94% bradycardia, asystolia 43.18%, 9.85% ventricular arrhythmias. The average beginning of time of CPR was 0.08 minutes (SD 0.25) and the average total duration was 25.91 minutes (SD 18.56). Patients who require drugs were 131. The number (mean) dose of adrenaline was 4.03 (SD 2.78). Increased number of doses of adrenaline was associated with less chance of recovery of spontaneous circulation (ROSC), OR 0.48 95% CI 0.37-0.63. (p= 0.000). The duration of CPR was inversely associated and significantly related to achieve ROSC, OR 0.93 95% CI 0.87-0.99. One hundred and four (78.79%) patients died and 28 survived. All survived were discharged from PICU, but 26 from hospital. In 22 patients there were not evidence of severe neurological damage when discharged home. CONCLUSIONS: Most common etiologies of PCR were hypoxia and shock. Most children received drugs. The drugs most used were the association adrenaline-bicarbonate and adrenaline alone. The chances of recovery were not favorable when CPR was conducted for over sixty minutes or more than six doses of adrenaline were given, without response. CPR in PICU children has a high mortality. Most patients discharged from hospital, had neurological normal state or slight disability. PICU physicians were highly trained in CPR with resuscitation courses. PMID- 20544137 TI - [Obstructive sleep apneas in symptomatic obese children: polisomnographic confirmation and its association with disturbances in carbohydrate metabolism]. AB - INTRODUCTION: It has been shown that obesity is a risk factor for Obstructive Sleep Apneas (OSA) and that it could be related to insulin resistance (IR). OBJECTIVE: To establish the frequency of OSA in obese children and adolescents with suggestive symptoms of sleep disordered breathing (SDB) by polisomnografic study (PSG) and to clinically characterize the groups with and without OSA, and their association with IR. PATIENTS, MATERIAL AND METHODS: Descriptive, retrospective, cross-sectional study in patients with obesity and symptoms of SDB examined in the Hospital Nacional de Pediatria "Prof. Dr. Juan P. Garrahan" between october/2002 and july/2008 to whom PGS had been done. Anthropometric and oral glucose tolerance test data were obtained and indices of insulin resistance derived from the homeostatic model were calculated. We assessed the presence of OSA defined as apnea-hypopnea Index > or = 1 Student's and Chi Square Tests were used, establishing a level of significance of 0.05. RESULTS: A total of 58 children were studied (59%M), average age 8.8 +/- 3.5 and Score Z-IMC 2.8 +/- 0.7. In 55.2% of cases, OSA was confirmed, independently of the degree of obesity. 56.9% presented IR. The patients were divided in groups according to the presence or not of OSA. There were no significant differences in age nor in Score Z-IMC. The patients with OSA presented greater frequency of tonsil hypertrophy (p= 0.01, OR= 6.86) and IR (p= 0.01, OR= 4,44) and less insulin sensitivity (p= 0.04). CONCLUSIONS: Both IR and the presence of tonsil hypertrophy were predictors of OSA. This population seems to be heterogeneous. We underline the importance to look for SDB related signs and symptoms in patients with obesity of any degree. PMID- 20544138 TI - [Comparative measurement of urine specific gravity: reagent strips, refractometry and hydrometry]. AB - INTRODUCTION: The urine specific gravity is commonly used in clinical practice to measure the renal concentration/dilution ability. Measurement can be performed by three methods: hydrometry, refractometry and reagent strips. AIM: To assess the accuracy of different methods to measure urine specific gravity. METHODS: We analyzed 156 consecutive urine samples of pediatric patients during April and May 2007. Urine specific gravity was measured by hydrometry (UD), refractometry (RE) and reagent strips (TR), simultaneously. Urine osmolarity was considered as the gold standard and was measured by freezing point depression. Correlation between different methods was calculated by simple linear regression. RESULTS: A positive and acceptable correlation was found with osmolarity for the RE as for the UD (r= 0.81 and r= 0.86, respectively). The reagent strips presented low correlation (r= 0.46). Also, we found good correlation between measurements obtained by UD and RE (r= 0.89). Measurements obtained by TR, however, had bad correlation when compared to UD (r= 0.46). Higher values of specific gravity were observed when measured with RE with respect to UD. CONCLUSIONS: Reagent strips are not reliable for measuring urine specific gravity and should not be used as an usual test. However, hydrometry and refractometry are acceptable alternatives for measuring urine specific gravity, as long as the same method is used for follow-up. PMID- 20544139 TI - [Portal hypertension in pediatrics. I: pathophysiology and clinical aspects]. AB - Portal hypertension causes serious and life-threatening complications. It is produced by increased resistance to blood flow through the portal axis, with a gradient to inferior vena cava higher than 5 mmHg. When this is 10 to 12 mmHg there is risk of bleeding from esophageal varices. In pediatric patients two different models exist: prehepatic (without liver disease), and intrahepatic (with liver disease), with different etiologies and prognosis. Doppler ultrasound, and liver function tests allow the distinction between them. Pediatricians should learn to recognize accurately the syndrome in order to approach the patients in a timely manner. PMID- 20544140 TI - [Onichocryptosis in pediatrics: conservative treatment and spiculectomy]. AB - Onychocryptosis (onyx: nail and kriptos: hidden) is the main reason for consultation due to nail pain. It is secondary to the penetration of the lateral border of the nail plate into the lateral nail fold causing pain and inflammation in the surrounding tissue. Symptoms range from erythema, edema, and pain when pressure is applied on the nail fold, up to secondary infection and functional impotence. It is a mechanical onicopathy, almost exclusively of the first toe, which recognizes multiple causes. We present the therapeutic management in children by conservative measures and the spiculectomy. PMID- 20544141 TI - [Early hemodynamic support in septic shock]. AB - Sepsis is the most common cause of death in children. Its adequate management has a significant impact on morbidity and mortality. Pediatricians who take initial contact with these patients play a fundamental role in the chain of actions that start at the Emergency Area and finish in the Intensive Care Unit. In recent years, some strategies have been developed to achieve staggered targets: clinical, hemodynamic, biochemical, and oxygenation. The correct interpretation of each affected component will allow the most appropriate intervention. The aggressive management with fluids and the early indication of inotropes are the basis for the management of shock. This paper summarizes primary interventions in the Emergency Department. PMID- 20544142 TI - [Retinoblastoma]. PMID- 20544144 TI - [Allergen immunotherapy for prevention and treatment of respiratory allergy in childhood]. PMID- 20544145 TI - [Guidelines for clinical practice: hymenoptera sting allergy in children]. PMID- 20544147 TI - [Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus]. AB - INTRODUCTION: Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. MATERIALS AND METHODS: The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. RESULTS: The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p less than 0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p less than 0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p less than 0.001). CONCLUSIONS: The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1. PMID- 20544148 TI - Causes of blind certification in an Italian province and comparison with other European countries. AB - PURPOSE: Low vision and blindness are significantly growing in both industrialized and developing countries. In Italy there are few epidemiological studies that provide data on this phenomenon. In this paper we report the main causes of blindness and the characteristics of the subjects who obtained a disability certification due to blindness in an Italian province. MATERIALS AND METHODS: Disability certificates issued by the Civil Blind Provincial Commission of the Viterbo province over a 2-year period (2002-2003) were analysed. The causes of blindness and the age of occurrence were investigated and divided into 12 groups. RESULTS: The four most frequent causes of blindness were age related macular degeneration (19%), cataract (14%), glaucoma (15%) and diabetic retinopathy (15%). The main eye pathology which caused partial blindness was age related macular degeneration (22.3%). Glaucoma (19.6%) was the main cause of total blindness. CONCLUSIONS: The estimates of blindness were based on certification for visual impairment with limited characteristics as our data was exclusively administrative. However, a general appraisal of the magnitude and causes of visual impairment was determined. This is important towards planning appropriate preventive and management measures. PMID- 20544149 TI - [Adhesion molecules and diabetes mellitus]. AB - Adhesion molecules play a significant role in leukocyte migration across the endothelium and are also involved in regulating immune system. It is shown that diabetic patients have an increase of soluble adhesion molecules (sICAM-1, sICAM 2, sVCAM-1, sE-selectin, sL-selectin, sP-selectin) considered an integral part of inflammatory state. This inflammation is responsible for the increased cardiovascular risk of these patients. There is a close link between hyperglycemia, oxidative stress, coagulopathy and inflammation and between these factors and the vascular damage. Various studies have showed the potential role of adhesion molecules in the pathogenesis of diabetic vasculopathy. They promote leukocyte recruitment, which is one of the initial steps in the genesis of atherosclerotic plaque. Adhesion molecules are also involved in the pathogenesis of diabetes mellitus type 1; sICAM-1 would have a particular immunomodulatory role in the process of destroying beta-cells and could be used as a subclinical marker of insulitis. Plasma levels of soluble adhesion molecules correlate with hyperglycemia, insulin resistance, dyslipidemia and obesity; they are associated with the development of nephropathy, retinopathy, myocardial infarction, stroke and obliterant peripheral arterial disease in diabetic type 1 and 2. Given the role of these molecules in endothelial dysfunction genesis and tissue damage associated with diabetes, they could constitute a therapeutic target for the prevention of genesis and progression of chronic complications of diabetic disease. PMID- 20544150 TI - Transferring results of occupational safety and health cost-effectiveness studies from one country to another - a case study. AB - OBJECTIVES: There are a limited number of studies about the cost-effectiveness of occupational health and safety (OSH) interventions. Applying the results of a cost-effectiveness study from one country to another is hampered by differences in the organization of healthcare and social security. In order to find out how these problems can be overcome, we transferred the results of a Dutch occupational cost-effectiveness study to the Finnish situation and vice-versa. METHODS: We recalculated incremental cost-effectiveness ratios (ICER) for the target country based on resource use in the original study and the associated costs in the target country. We also allocated the costs to the employer, the employee, and tax-payers. RESULTS: We found that the ICER did not differ very much from those in the original studies. However, the different healthcare funding structure led to a more unfavorable ICER for employers in the Netherlands. Both interventions represented a cost saving for tax-payers and employees. Employers had to invest euro10-54 to avert one day of sick leave. CONCLUSIONS: We conclude that results of cost-effectiveness studies can be transferred from one country to another, but many adjustments are needed. An extensive description of the intervention, a detailed list of resource use, allocation of costs to various parties, and detailed knowledge of the healthcare systems in the original studies are necessary to enable calculations. PMID- 20544151 TI - European Union of Medical Specialists (UEMS) section of Physical & Rehabilitation Medicine: a position paper on physical and rehabilitation medicine in acute settings. AB - Physical and rehabilitation medicine (PRM) specialists have an important role in the clinical care of patients during the acute phase of a disabling health condition. This phase is defined as once definitive care or resuscitation has taken place and a patient's need to stay in hospital as an inpatient is primarily for PRM services for rehabilitation. This paper describes 4 options for the delivery of services for people, who continue to require to be inpatients and who will benefit from PRM interventions. These are described, along with their clear benefits during the acute phase of a health condition. The first 2 models are the most effective in making best use of the acute facilities and PRM services. The benefits of dedicated PRM beds appear to outweigh those of the other options and may be cheaper, although no cost-effectiveness studies comparing the first 2 options have yet been undertaken. Prospective trials are required to show this benefit, and a number of examples need to be set up to pilot this in order to provide realistic cost-effectiveness data. PMID- 20544152 TI - Prognosis of six-month functioning after moderate to severe traumatic brain injury: a systematic review of prospective cohort studies. AB - OBJECTIVE: To systematically review which determinants, assessed within the first month after a moderate to severe traumatic brain injury, predict 6-month functional outcome. METHODS: Databases were searched for relevant publications between 1995 and August 2008. Selection criteria were: prospective cohort studies; determinants associated with functional outcome 6 months after moderate to severe traumatic brain injury in adult patients; determinants assessed within the first month post-injury. Two reviewers independently performed the selection and quality assessment. A best- evidence synthesis was performed for prognostic factors assessed in 2 or more studies. RESULTS: Twenty-eight studies were included, 27 of which were high quality. Most studies used the Glasgow Outcome Score at 6 months post-injury as outcome measure, sometimes in combination with other outcome measures. Strong evidence for predicting outcome at 6 months was found for the Glasgow Coma Scale (GCS), GCS admission, motor score, midline shift on computed tomography scan, subdural haematoma and pulsatility index. Strong evidence of no association was found for gender and intraventricular haemorrhage. For other determinants, inconclusive or no evidence was found. CONCLUSION: GCS, GCS on admission, motor score, midline shift, subdural haematoma and pulsatility index predicted outcome 6 months after traumatic brain injury. Gender and intraventricular haemorrhage did not have predictive value. PMID- 20544153 TI - A feasibility study using interactive commercial off-the-shelf computer gaming in upper limb rehabilitation in patients after stroke. AB - BACKGROUND: Commercial off-the-shelf computer gaming devices have been making inroads into the rehabilitation arena, with the objective of making therapeutic exercise fun and contextual. One such device is the Nintendo Wii. Published clinical studies evaluating its acceptance, potential benefits and side-effects in the rehabilitation of patients with post-stroke weakness are few in number. OBJECTIVE: The aim of this study is to assess the feasibility of using the Nintendo Wii as an adjunct to conventional rehabilitation of patients with post stroke upper limb weakness. METHODS: Twenty rehabilitation inpatients within 3 months after a stroke with upper limb weakness received 6 sessions of upper limb exercises via a Nintendo Wii over 2 weeks in addition to conventional rehabilitation. Outcome measures include a questionnaire, Fugl-Meyer Assessment of Upper Limb Motor Function and visual analogue scale of upper limb pain. RESULTS: A total of 16 subjects completed the study. All 16 found Nintendo Wii gaming enjoyable and comparable to, if not better than, conventional therapy. There were small but statistically significant improvements in the Fugl-Meyer Assessment and Motricity Index scores. CONCLUSION: Nintendo Wii appears to be a feasible adjunctive device to augment conventional therapy in a cohort of subacute stroke patients with moderate impairments of upper limb strength and function. PMID- 20544154 TI - Voice therapy for laryngeal hemiplegia: the role of timing of initiation of therapy. AB - OBJECTIVE: Laryngeal hemiplegia, also known as vocal fold paralysis, causes severe communicative disability. Although voice therapy is commonly considered to be beneficial for improving the voice quality in several voice disorders, there are only a few papers that present scientific evidence of the effectiveness of voice therapy in treating the disabilities of laryngeal hemiplegia. The aim of this study was to evaluate the outcomes of voice therapy in patients with laryngeal hemiplegia and to evaluate the role of the time gap between onset of laryngeal hemiplegia and initiation of therapy. DESIGN: A prospective study comparing subjects treated either within or more than 3 months after the onset of laryngeal hemiplegia. SUBJECTS: The study involved 30 laryngeal patients with hemiplegia (16 males, 14 females, age range 15-80 years). METHODS: All patients underwent videolaryngostroboscopy, maximum phonation time measurement, GIRBAS perceptual evaluation, Voice Handicap Index self-assessment and Multi-Dimensional Voice Program voice analysis before and after therapy. RESULTS: In all tests, there were significant improvements in voice quality, both in the group treated within 3 months after the onset of laryngeal hemiplegia and in the group treated after this time. CONCLUSION: Voice therapy is effective in treating laryn-geal hemiplegia even if treatment is delayed by more than 3 months from onset of laryngeal hemiplegia. PMID- 20544155 TI - Repetitive transcranial magnetic stimulation to hemispatial neglect in patients after stroke: an open-label pilot study. AB - OBJECTIVE: To test whether multiple sessions of inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left parietal area can improve hemispatial neglect after stroke. DESIGN: An open-label design. PATIENTS: Seven consecutive patients with hemispatial neglect after right hemispheric stroke were compared with 7 retrospectively recruited control patients. METHODS: Seven patients received a session of 1 Hz rTMS to the left parietal area immediately prior to occupational therapy for 10 days. Seven control patients received only behavioural therapy. RESULTS: Baseline values of the line bisection test and the Albert test were comparable in the two groups. The stimulation group showed a greater improvement in the line bisection test than did the control group. However, no differences were found between the two groups according to the Albert test. CONCLUSION: In this pilot study, low frequency rTMS application to the non-affected left parietal area was found to be safe and to improve line bisection test, which suggests that non-invasive cortical stimulation has a potential role as an adjuvant strategy during cognitive rehabilitation training in patients with hemispatial neglect. A prospective randomized, sham-controlled study is required to determine the beneficial role of non-invasive cortical stimulation on hemispatial neglect. PMID- 20544156 TI - Symptomatic upper limb spasticity in patients with chronic stroke attending a rehabilitation clinic: frequency, clinical correlates and predictors. AB - OBJECTIVE: To document the frequency, clinical correlates and predictors of symptomatic upper limb spasticity in patients one year or more after stroke. DESIGN: Cross-sectional study. SUBJECTS: A total of 140 patients after stroke attending a rehabilitation clinic. METHODS: Assessments of spasticity, upper limb function and self-care ability using the Ashworth Scale (AS), Motor Assessment Scale and Modified Barthel Index. We categorized spasticity as: spasticity in general (AS score > or = 1), severe spasticity (AS score > or = 3) and symptomatic spasticity (spasticity affecting upper limb function). RESULTS: The mean age (standard deviation, SD) was 61.0 (SD 13.3) years and patients were evaluated at 41.7 (SD 35.1) months after stroke onset. The observed frequency of spasticity in general, severe spasticity and symptomatic spasticity was 78.6%, 38.6% and 30%, respectively. The total AS score was the most important correlate of symptomatic spasticity; patients with higher scores were likely to be symptomatic (p = 0.001). Severe spasticity was predicted by poor lower extremity power (p = 0.002), high National Institute of Health Stroke Scale score (p = 0.015) and presence of dysphasia (p = 0.046) on admission to rehabilitation. No predictors of symptomatic spasticity could be established. CONCLUSION: Symptomatic spasticity is relatively common in patients with chronic stroke and is significantly correlated with the severity of spasticity. PMID- 20544157 TI - Disease-related knowledge of patients with chronic regional pain syndrome. AB - OBJECTIVE: The aim of this study was to investigate patients' knowledge of the most salient features of complex regional pain syndrome and to identify patient characteristics associated with the patients' level of knowledge. METHODS: Questionnaire interview of 101 patients with complex regional pain syndrome in Switzerland (mean age 54 years, 77% female). A questionnaire about patients' disease-related knowledge was developed and piloted. The level of knowledge was defined by a consensus process among clinical experts and a patient. The questions were based on expert consensus about the minimum knowledge a person affected with complex regional pain syndrome should have. RESULTS: Only 6 patients (6%) reached the minimum medical knowledge. The mean score for all participants was 7.6 points out of a total score of 11 points (range 3-11, SD 2.1). The scores were slightly higher among patients with higher education (apprenticeship, vocational school +0.38 (95% confidence interval (CI); -0.59 to 1.34: p=0.44), university entrance diploma +1.12 (95% CI-0.16 to 2.49: p=0.08), university diploma, advanced technical college +2.36 (95% CI 1.11-3.61: p<0.001)) compared with mandatory school, and among those with professional medical backgrounds +1.13 (95% CI 0.06-2.20: p=0.04). Most patients received information from their caregivers and wanted to know more about therapy or general aspects of the condition. CONCLUSION: Many patients with complex regional pain syndrome do not have the minimum knowledge of their disease as defined by clinical experts. Physicians should be aware that patients expect to receive disease-related information primarily from their caregivers. In particular, patients wanted more information about therapy and general aspects of the illness. PMID- 20544158 TI - Dry needle stimulation of myofascial trigger points evokes segmental anti nociceptive effects. AB - OBJECTIVE: To test the hypothesis that dry needle stimulation of a myofascial trigger point (sensitive locus) evokes segmental anti-nociceptive effects. DESIGN: Double-blind randomized controlled trial. SUBJECTS: Forty subjects (21 males, 19 females). METHODS: Test subjects received intramuscular dry needle puncture to a right supraspinatus trigger point (C4,5); controls received sham intramuscular dry needle puncture. Pain pressure threshold (PPT) readings were recorded from right infraspinatus (C5,6) and right gluteus medius (L4,5S1) trigger points at 0 (pre-needling baseline), 1, 3, 5, 10 and 15 min post-needling and normalized to baseline values. The supraspinatus and infraspinatus trigger points are neurologically linked at C5; the supraspinatus and gluteus medius are segmentally unrelated. The difference between the infraspinatus and gluteus medius PPT values (PPTseg) represents a direct measure of the segmental anti nociceptive effects acting at the infraspinatus trigger point. RESULTS: Significant increases in PPTseg were observed in test subjects at 3 (p = 0.002) and 5 (p = 0.015) min post-needling, compared with controls. CONCLUSION: One intervention of dry needle stimulation to a single trigger point (sensitive locus) evokes short-term segmental anti-nociceptive effects. These results suggest that trigger point (sensitive locus) stimulation may evoke anti nociceptive effects by modulating segmental mechanisms, which may be an important consideration in the management of myofascial pain. PMID- 20544159 TI - Assessment of the effectiveness of a functional splint for osteoarthritis of the trapeziometacarpal joint on the dominant hand: a randomized controlled study. AB - OBJECTIVE: To assess the effectiveness of a functional splint for trapeziometacarpal osteoarthritis. METHODS: Forty patients with a diagnosis of painful trapezio-metacarpal osteoarthritis of the dominant hand were randomized into 2 groups. The study group received the splint at baseline and used it during activities of daily living for 180 days and the control group used the splint only during the evaluations for the first 90 days and during activities of daily living for the following 90 days. Pain, strength, hand function and dexterity (with and without splint) were measured by a blinded assessor at baseline, 45, 90 and 180 days. RESULTS: The groups were homogenous at baseline for all outcomes evaluated. Pain without the splint was significantly different between groups over time; the study group experienced a decrease in pain beginning with the first evaluation (45 days), whereas the control group achieved a lower pain score only at the end of the study, after having used the splint for 90 days. No significant differences between groups were found for the other parameters. CONCLUSION: Splint use during activities of daily living for patients with trapeziometacarpal osteoarthritis reduces pain, but does not alter function, grip strength, pinch strength or dexterity. PMID- 20544160 TI - Take charge: Patients' experiences during participation in a rehabilitation programme for burnout. AB - OBJECTIVE: The aim of this study was to explore the experiences of patients with burnout during a rehabilitation programme. PATIENTS AND METHODS: Eighteen patients with burnout were interviewed at the end of a one-year rehabilitation programme. The programme consisted of 2 groups, one with a focus on cognitively oriented behavioural rehabilitation and Qigong and 1 with a focus on Qigong alone. The interviews were analysed using the grounded theory method. RESULTS: One core category, Take Charge, and 6 categories emerged. The core category represents a beneficial recovery process that helped the patients to take control of their lives. The common starting point for the process is presented in the 3 categories of Good encounters, Affirmation and Group cohesiveness. The categories were basic conditions for continuing development during rehabilitation. In the categories Get to know myself, How can I be the one I want to be? and Choice of track, the more group-specific tools are included, through which the patients adopted a new way of behaving. CONCLUSION: Patients in both groups experienced group participation as being beneficial for recovery and regaining control of their lives, although in somewhat different way. An experience of affirmation and support from health professionals and group participants is of importance for beha-vioural change. PMID- 20544161 TI - Development of a tool for prediction of falls in rehabilitation settings (Predict_FIRST): a prospective cohort study. AB - OBJECTIVE: To develop and internally validate a simple falls prediction tool for rehabilitation settings. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 533 inpatients. METHODS: Possible predictors of falls were collected from medical records, interview and physical assessment. Falls during inpatient stays were monitored. RESULTS: Fourteen percent of participants fell. A multivariate model to predict falls included: male gender (odds ratio (OR) 2.70, 95% confidence interval (CI) 1.57-4.64), central nervous system medications (OR 2.50, 95% CI 1.47-4.25), a fall in the previous 12 months (OR 2.21, 95% CI 1.07-4.56), frequent toileting (OR 2.14, 95% CI 1.27-3.62) and tandem stance inability (OR 2.00, 95% CI 1.11-3.59). The area under the curve for this model was 0.74 (95% CI 0.68-0.80). The Predict_FIRST tool is a unit weighted adaptation of this model (i.e. 1 point allocated for each predictor) and its area under the curve was 0.73 (95% CI 0.68-0.79). Predicted and actual falls risks corresponded closely. CONCLUSION: This tool provides a simple way to quantify the probability with which an individual patient will fall during a rehabilitation stay. PMID- 20544162 TI - Increased cardiovascular disease risk in Swedish persons with paraplegia: The Stockholm spinal cord injury study. AB - OBJECTIVE: Comparison of prevalence of cardiovascular disease risks in persons with chronic traumatic paraplegia with those in the general population. DESIGN: Cross-sectional comparative study. SUBJECTS: A total of 135 individuals, age range 18-79 years, with chronic (> or = 1 year) traumatic paraplegia. METHODS: The prevalences of diabetes mellitus, dyslipidaemia, hypertension, overweight, and smoking, were assessed in the study population and were compared with an age- and gender-matched sample of the general population in the region under study. History of myocardial infarction and medication for dyslipidaemia, hypertension, and diabetes mellitus were also recorded. chi2 tests were used to compare the paraplegic cohort with the general population sample. RESULTS: Significantly more persons with paraplegia reported a history of myocardial infarction (5.9%) than those in the comparison group (0.7%). The prevalences of diabetes mellitus (5.9%), dyslipidaemia (11.1%), and hypertension (14.1%) were also significantly higher in the paraplegic group, as were drug treatment for these disorders. CONCLUSION: Persons with paraplegia report increased prevalences of diabetes mellitus, hypertension, and dyslipidaemia, in particular, compared with the general population. Population-based screening and therapeutic counter-measures for these conditions may therefore be particularly indicated for this patient group. PMID- 20544163 TI - Manual ability and its relationship with daily activities in adolescents with cerebral palsy. AB - OBJECTIVE: To describe the manual ability of adolescents with cerebral palsy and to investigate the relationship of manual ability with daily activities. DESIGN: Cross-sectional study. SUBJECTS: Ninety-four adolescents with cerebral palsy, aged 12-16 years. METHODS: Manual ability was assessed according to the Manual Ability Classification System (MACS) and the ABILHAND-Kids. Daily activities were assessed with the Vineland Adaptive Behavior Scales (VABS) sub-scales for (personal and domestic) daily living skills. The relationship between manual ability and daily activities was investigated with regression analysis: independent variables were manual ability, disease and personal characteristics. RESULTS: MACS and ABILHAND-Kids were both strongly associated with personal daily activities (explained variance 77% and 84%, respectively) and less strongly with domestic daily activities (explained variance 45% and 62%, respectively). Including other disease characteristics and personal characteristics in the model increased the explained variance of personal daily activities to 91% for both models and the explained variance of domestic daily activities to 68% and 73% for the MACS and ABILHAND-Kids models, respectively. CONCLUSION: Manual ability is limited in many adolescents with cerebral palsy, and limitations in manual ability are strongly related to limitations in daily activities. PMID- 20544164 TI - Determinants of the shoulder pain and disability index in patients with subacromial shoulder pain. AB - OBJECTIVE: To examine the influence of determinants on the Shoulder Pain and Disability Index. DESIGN: A cross-sectional study. Baseline registrations were applied. PATIENTS: Two hundred patients with subacromial shoulder pain lasting at least 3 months. METHODS: A questionnaire consisting of possible determinants, 2 independent variables regarding pain and 2 regarding function, and the outcome measurement. Two multiple regression models (one with and one without the independent variables of pain and function) for the Shoulder Pain and Disability Index, the 2 subscales, and the determinants, were performed. RESULTS: The included determinants explained 29% of the variance of the Shoulder Pain and Disability Index (25% for pain and 33% for disability subscale) with pain medication, emotional distress, flexion, and the hand-behind-back range accounting for 26%. When pain and function were included, the final model explained 65% of the variance, with gender, education and range of flexion showing significance. CONCLUSION: The determinants explained 26% of the variance of the Shoulder Pain and Disability Index, but explained only a minor proportion when pain and function were included. This supports the Shoulder Pain and Disability Index as a shoulder pain and disability questionnaire. PMID- 20544165 TI - Prediction of walking disability by disease-related factors in patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate the relationship between disease-related factors and walking disability in different phases of rheumatoid arthritis; and to predict future walking disability in rheumatoid arthritis, using disease-related factors assessed 2 years after diagnosis. METHODS: A cohort of 848 newly diagnosed patients with rheumatoid arthritis was followed up for a maximum of 8 years. Walking disability and several disease-related and demographic factors were recorded during follow-up. A logistic regression model was used to study associations between walking disability and these factors at different time points. A multilevel logistic regression model for longitudinal data was used to predict walking disability during follow-up from potential predictors at year 2. RESULTS: Global pain and disease activity were consistently related to walking disability at almost every time point. Significant predictors of future walking disability were: walking disability, knee pain, global pain, the passage of time during follow-up, and age. CONCLUSION: Global pain and disease activity are related to walking disability during the first 8 years of RA. Walking disability, knee pain, and global pain at 2 years follow-up predict walking disability later in the disease. In addition, the risk for walking disability increases during the disease process and with higher age at diagnosis. PMID- 20544166 TI - [Minimally invasive follicular thyroid carcinoma : Not always total thyroidectomy]. AB - Current treatment guidelines for follicular thyroid carcinoma (FTC) recommend total thyroidectomy, lymphadenectomy and radioiodine ablation. Considering the low malignant potential of minimally invasive follicular thyroid carcinoma (MIFTC), a limited radical therapeutic procedure may be adequate. MIFTC is an intensely discussed group of tumors and a review of the literature reveals disagreement among experts concerning the criteria for a distinct definition. Therefore, in 2005 Rosai proposed a clinically more significant classification of FTC based on the extent of capsular and vascular invasion: MIFTC with capsular invasion only, with limited (< or =3) vascular invasion, encapsulated FTC with extensive (>3) vascular invasion and broadly invasive FTC with extensive invasive growth.For the diagnosis of MIFTC a complete investigation of the encapsulated follicular lesion should be performed by the pathologist and examination of at least 10 tissue blocks is mandatory. Due to the excellent prognosis hemithyroidectomy constitutes an adequate therapeutic approach in MIFTC with capsular invasion only and may also be considered for MIFTC with limited vascular invasion. There are no indications for systematic lymphadenectomy. PMID- 20544167 TI - [Total thyroidectomy for multinodular goiter]. AB - Multinodular goiter is a frequent disease which plays a central role in the daily routine of general and visceral surgeons. Analyses of the national DRG statistics reveal that total thyroidectomy is increasingly replacing partial thyroid resections. This paradigm shift is substantiated by the comprehension of multinodular goiter as a disease affecting the whole organ as well as the fact that total thyroidectomy avoids high risk secondary interventions for incidental thyroid carcinomas and recurrent disease while offering comparable operative risks. However, the available evidence on operative results originates predominantly from thyroid centers and clinical data regarding long-term effects of thyroid hormone substitution following total as well as sub-total thyroidectomy are lacking. Therefore, the preservation of functionally relevant normal thyroid tissue retains its relevancy as an alternative treatment. If a comparably low operative risk can be guaranteed and considering the patient's compliance, life situation and wishes, total thyroidectomy represents the optimal therapy for bilateral multinodular goiter. PMID- 20544169 TI - [Digital volume tomography in ENT medicine]. AB - Digital volume tomography (DVT) is an advancement of panoramic tomography used in dentistry. DVT enables precise display of fine osseous structures without any disturbing artefacts. This makes its application interesting in the field of the lateral, anterior skull base and paranasal sinuses, as well as for the diagnosis of nasal bone fractures. The tomograms can be completed according to need by volume rendering or panoramic slices within a short time. Assuming they have the appropriate technical qualifications in radiation protection, ENT specialists are even able to perform tomography independently using DVT. PMID- 20544168 TI - [Prophylactic and therapeutic vaccines against human papilloma virus]. AB - Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature. PMID- 20544170 TI - [Diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma]. AB - Classical prognostic factors for squamous cell carcinoma of the head and neck (HNSCC) are based on general parameters such as tumor stage or histological grading and only allow for a rough estimation of the clinical course. However, predicting individual responses to treatment remains challenging and diverging clinical courses of same-stage HNSCC stage remain obscure. The need for a better understanding of the individual genomic or proteomic signature of HNSCC resulted in a great number of publications on novel biomarkers. Still, in most cancer centres therapy planning and risk appraisal are solely based on the classical factors with only a few exceptions such as HPV status in oropharyngeal carcinoma. Future improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. This review highlights the criteria for a successful biomarker candidate, gives an overview on the most important new biomarkers, and introduces the principles of genomic and proteomic biomarker chips. PMID- 20544171 TI - [Analysis of spinal stress during surgery in otolaryngology]. AB - BACKGROUND: Back pain is a common cause of sick leave in industrialized countries. Performing surgery is often associated with considerable cervical spine disorders. However, only a few studies have examined to what extent working posture or individual surgical techniques can be seen as stress indicators. MATERIAL AND METHODS: Posture and movement of the spine and trunk were assessed by means of a newly developed analysis system (3-D-SMG). The individual-case study was carried out during six sinus operations using varying techniques (microscope, endoscope or headlamp only). RESULTS: Spine and trunk deviation from neutral position (upright standing) was strongest in the sagittal plane. Awkward distortions were primarily observed in the cervical and lumbar spine. The analysis of work characteristics revealed static postures in 65-90% of sinus operations. Isometric positions were mainly related to microscopic surgery. CONCLUSIONS: The data from this explorative individual-case study indicate that prevalence and magnitude of forced isometric and awkward postures are strongly associated with work-related spinal stress in sinus surgery. The new measurement device enables not only the recommendation of individual preventive strategies but also the objective evaluation of ergonomics. PMID- 20544172 TI - [Adjuvant chemotherapy in older women with breast cancer. CALGB Study (The Cancer and Leukemia Group B Study)]. PMID- 20544173 TI - [Hematopoietic growth factors. Possibilities and limitations]. AB - The production of hematopoietic cells is under the tight control of distinct growth factors. As therapeutic agents, granulocyte colony-stimulating factor (G CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents (TSA) are in routine clinical use. Granulocyte colony-stimulating factor is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite a reduced duration of neutropenia, randomized controlled trials have documented only a modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Clinical practice guidelines recommend the use of G-CSF for patients with a high risk of adverse outcome of febrile neutropenia. Erythropoiesis-stimulating agents (ESAs) are used as an alternative to blood transfusion in patients with chemotherapy-induced anemia. However, recent meta-analyses of clinical studies suggest that their use was associated with an increased risk of all-cause mortality and serious adverse events. Thrombopoiesis-stimulating agents have been introduced recently into the market for patients with immune thrombocytopenic purpura. Prior to the use of TSA in other conditions such as chemotherapy-induced thrombocytopenia the lessons learned with G-CSF and ESAs should be taken into account. PMID- 20544174 TI - [Endo-exo femoral prosthesis: clinical course after primary implantation of an intramedullary percutaneous endo-exo femoral prosthesis following upper leg amputation]. AB - Because of insufficient soft-tissue conditions and variability in the size and mechanical friction of the stump treatment of upper leg amputees with an ordinary prosthesis might be difficult or even impossible. Alternatively, for such patients an endo-exo femoral prosthesis (EEFP) is sometimes the best treatment option. The use of EEFPs will be demonstrated as exemplified by the clinical course in a patient with a primary EEFP implantation including all relevant side effects and associated problems. PMID- 20544176 TI - Child sexual abuse reported by an English national sample: characteristics and demography. AB - AIM: The 2007 adult psychiatric morbidity survey in England provides detailed information of high quality about sexual abuse. Given the major psychiatric implications of child sexual abuse (CSA), we aimed to establish its sociodemographic distribution in the general population. METHOD: The experience of sexual abuse was elicited in a random sample of the English household population (N = 7,353), using computer assisted self-completion interviewing. Respondents were handed a laptop, and entered their responses to detailed questions. The interviewer was blind to their responses. CSA was defined as occurring before the age of 16. RESULTS: 2.9% of women and 0.8% of men reported CSA involving non-consensual intercourse, figures that rose to 11.1 and 5.3% if experiences involving sexual touching were included. CSA was common before puberty, but peaked in adolescence. CSA greatly increased the chance in adulthood both of further sexual abuse (OR 10.6; CI 8.9-12.6), and of prostitution (OR 3.3; CI 1.9-5.5). There was no association with ethnicity or social class, but people over 65 were less likely to report CSA. The odds of CSA were doubled in those not brought up with both biological parents until the age of 16. CONCLUSION: CSA is common, particularly in women, and is not the preserve of any particular social group. Its frequency and its association with psychiatric consequences render it a major public health issue. PMID- 20544178 TI - Calcium and vitamin-D supplementation on bone structural properties in peripubertal female identical twins: a randomised controlled trial. AB - A randomised controlled trial was used in assessing the impact of 6 months of daily calcium and vitamin-D supplementation on trabecular and cortical bone acquisition at distal tibial and radial sites using peripheral quantitative computed tomography (pQCT). Daily supplementation was associated with increased bone density and bone strength at the distal tibia and radius. INTRODUCTION: pQCT has not been used to assess bone responses to calcium and vitamin-D supplementation on peripubertal children. This randomised controlled trial aimed to assess the impact of a 6-month daily calcium and vitamin-D supplementation on trabecular and cortical bone acquisition at distal tibial and radial sites using pQCT. METHODS: Twenty pairs of peripubertal female identical twins, aged 9 to 13 years, were randomly assigned to receive either 800 mg of calcium and 400 IU of vitamin D3, or a matched placebo. Bone structural properties at the distal tibia and distal radius were acquired at baseline and 6 months. RESULTS: The calcium supplemented group showed greater gains in trabecular density, trabecular area and strength strain index at the 4% of distal tibial and radial sites compared with the placebo group (p=0.001). Greater gains in cortical area at the 38% and 66% of tibial sites were also found in twins receiving the calcium supplement (p=0.001). CONCLUSIONS: Daily supplementation for a period of 6 months was associated with increased trabecular area, trabecular density and strength strain index at the ultra-distal tibia and radius and increased cortical area at tibial mid-shaft. PMID- 20544179 TI - Molecular characteristics of community-associated methicillin-resistant Staphylococcus aureus strains for clinical medicine. AB - Infections caused by methicillin-resistant S. aureus strains are mainly associated with a hospital setting. However, nowadays, the MRSA infections of non hospitalized patients are observed more frequently. In order to distinguish them from hospital-associated methicillin-resistant S. aureus (HA-MRSA) strains, given them the name of community-associated methicillin-resistant S. aureus (CA-MRSA). CA-MRSA strains most commonly cause skin infections, but may lead to more severe diseases, and consequently the patient's death. The molecular markers of CA-MRSA strains are the presence of accessory gene regulator (agr) of group I or III, staphylococcal cassette chromosome mec (SCCmec) type IV, V or VII and genes encoding for Panton-Valentine leukocidin (PVL). In addition, CA-MRSA strains show resistance to beta-lactam antibiotics. Studies on the genetic elements of CA-MRSA strains have a key role in the unambiguous identification of strains, monitoring of infections, improving the treatment, work on new antimicrobial agents and understanding the evolution of these pathogens. PMID- 20544180 TI - On-chip photoactivation of heterologously expressed rhodopsin allows kinetic analysis of G-protein signaling by surface plasmon resonance spectroscopy. AB - Surface plasmon resonance spectroscopy allows the study of protein interaction dynamics in real-time. Application of this technique to G-protein coupled receptors, the largest family of receptors involved in signal transduction, has been complicated by their low level of expression and the critical dependence of their native conformation on the hydrophobic transmembrane lipid environment. Here, we investigate and compare three different strategies to immobilize rhodopsin, a prototypical G-protein coupled receptor on a sensor chip surface using antibodies and a lectin for receptor capturing. By further probing of different experimental conditions (pH, detergent type) we identified the optimal factors to maintain rhodopsin in a functional conformation and extended this approach to recombinant rhodopsin that was heterologously expressed in COS cells. Functional operation of rhodopsin on the sensor chip surface was proven by its activation and subsequent light-stimulated G-protein coupling. The influence of these experimental parameters on the association and dissociation kinetics of G protein receptor coupling was determined. Thereby, we found that the kinetics of G(t) interaction were not changed by the strategy of immobilization or the type of detergent. Regeneration of opsin directly on a chip allowed recycling of the immobilized native and recombinant receptor. Thus, the approach provides an experimental framework for choosing the most suitable conditions for the solubilization, immobilization, and for functional tests of rhodopsin on a biosensor surface. PMID- 20544181 TI - Raman spectroscopy. PMID- 20544182 TI - Probing of multidrug ABC membrane transporters of single living cells using single plasmonic nanoparticle optical probes. AB - Currently, molecular mechanisms of multidrug ABC (ATP-binding cassette) membrane transporters remain elusive. In this study, we synthesized and characterized purified spherically shaped silver nanoparticles (Ag NPs) (11.8 +/- 2.6 nm in diameter), which were stable (non-aggregation) in PBS buffer and inside single living cells. We used the size-dependent localized surface plasmon resonance (LSPR) spectra of single Ag NPs to determine their sizes and to probe the size dependent transport kinetics of the ABC (BmrA, BmrA-EGFP) transporters in single living cells (Bacillus subtilis) in real time at nanometer resolution using dark field optical microscopy and spectroscopy (DFOMS). The results show that the smaller NPs stayed longer inside the cells than larger NPs, suggesting size dependent efflux kinetics of the membrane transporter. Notably, accumulation and efflux kinetics of intracellular NPs for single living cells depended upon the cellular expression level of BmrA, NP concentrations, and a pump inhibitor (25 muM, orthovanadate), suggesting that NPs are substrates of BmrA transporters and that passive diffusion driven by concentration gradients is the primary mechanism by which the NPs enter the cells. The accumulation and efflux kinetics of intracellular NPs for given cells are similar to those observed using a substrate (Hoechst dye) of BmrA, demonstrating that NPs are suitable probes for study of multidrug membrane transporters of single living cells in real-time. Unlike fluorescent probes, single Ag NPs exibit size-dependent LSPR spectra and superior photostability, enabling them to probe the size-dependent efflux kinetics of membrane transporters of single living cells in real-time for better understanding of multidrug resistance. PMID- 20544183 TI - Analytical techniques for single-cell metabolomics: state of the art and trends. AB - Single-cell metabolomics is an emerging field that addresses fundamental biological questions and allows one to observe metabolic phenomena in heterogeneous populations of single cells. In this review, we assess the suitability of different detection techniques and present considerations on sample preparation for single-cell metabolomics. Although targeted analysis of single cells can readily be conducted using fluorescent probes and optical instruments (microscopes, fluorescence detectors), a comprehensive metabolomic approach requires a powerful label-free method, such as mass spectrometry (MS). Mass-spectrometric techniques applied to study small molecules in single cells include electrospray MS, matrix-assisted laser desorption/ionization MS, and secondary ion MS. Sample preparation is an important aspect to be taken into account during further development of methods for single-cell metabolomics. PMID- 20544184 TI - Aging does not affect generalized postural motor learning in response to variable amplitude oscillations of the support surface. AB - Postural motor learning for dynamic balance tasks has been demonstrated in healthy older adults (Van Ooteghem et al. in Exp Brain Res 199(2):185-193, 2009). The purpose of this study was to investigate the type of knowledge (general or specific) obtained with balance training in this age group and to examine whether embedding perturbation regularities within a balance task masks specific learning. Two groups of older adults maintained balance on a translating platform that oscillated with variable amplitude and constant frequency. One group was trained using an embedded-sequence (ES) protocol which contained the same 15-s sequence of variable amplitude oscillations in the middle of each trial. A second group was trained using a looped-sequence (LS) protocol which contained a 15-s sequence repeated three times to form each trial. All trials were 45 s. Participants were not informed of any repetition. To examine learning, participants performed a retention test following a 24-h delay. LS participants also completed a transfer task. Specificity of learning was examined by comparing performance for repeated versus random sequences (ES) and training versus transfer sequences (LS). Performance was measured by deriving spatial and temporal measures of whole body center of mass (COM) and trunk orientation. Both groups improved performance with practice as characterized by reduced COM displacement, improved COM-platform phase relationships, and decreased angular trunk motion. Furthermore, improvements reflected general rather than specific postural motor learning regardless of training protocol (ES or LS). This finding is similar to young adults (Van Ooteghem et al. in Exp Brain Res 187(4):603-611, 2008) and indicates that age does not influence the type of learning which occurs for balance control. PMID- 20544186 TI - Continuous transformation learning of translation invariant representations. AB - We show that spatial continuity can enable a network to learn translation invariant representations of objects by self-organization in a hierarchical model of cortical processing in the ventral visual system. During 'continuous transformation learning', the active synapses from each overlapping transform are associatively modified onto the set of postsynaptic neurons. Because other transforms of the same object overlap with previously learned exemplars, a common set of postsynaptic neurons is activated by the new transforms, and learning of the new active inputs onto the same postsynaptic neurons is facilitated. We show that the transforms must be close for this to occur; that the temporal order of presentation of each transformed image during training is not crucial for learning to occur; that relatively large numbers of transforms can be learned; and that such continuous transformation learning can be usefully combined with temporal trace training. PMID- 20544185 TI - Saccade adaptation as a model of learning in voluntary movements. AB - Motor learning ensures the accuracy of our daily movements. However, we know relatively little about its mechanisms, particularly for voluntary movements. Saccadic eye movements serve to bring the image of a visual target precisely onto the fovea. Their accuracy is maintained not by on-line sensory feedback but by a learning mechanism, called saccade adaptation. Recent studies on saccade adaptation have provided valuable additions to our knowledge of motor learning. This review summarizes what we know about the characteristics and neural mechanisms of saccade adaptation, emphasizing recent findings and new ideas. Long term adaptation, distinct from its short-term counterpart, seems to be present in the saccadic system. Accumulating evidence indicates the involvement of the oculomotor cerebellar vermis as a learning site. The superior colliculus is now suggested not only to generate saccade commands but also to issue driving signals for motor learning. These and other significant contributions have advanced our understanding of saccade adaptation and motor learning in general. PMID- 20544187 TI - Bone mineral density and fracture rate in response to intravenous and oral bisphosphonates in adult osteogenesis imperfecta. AB - The effect of bisphosphonate treatment on bone mineral density (BMD) and fracture rates was assessed in adults with osteogenesis imperfecta (OI). This observational nonrandomized study included 90 OI adults treated with intravenous pamidronate (n = 28), oral alendronate (n = 10), or oral residronate (n = 17) or not treated (n = 35). There were 63 type I, 15 type III, and 12 type IV OI patients. BMD results were observed for up to 161 months and an average of 52 months of treatment. For type I and grouped type III/IV patients, treatment with pamidronate showed an increasing rate in L1-L4 BMD from baseline (0.006 [P = 0.03] and 0.016 [P < 0.001] gm/cm(2)/year, respectively); oral bisphosphonate treatment showed a significant increasing rate in L1-L4 BMD (0.004 gm/cm(2)/year [P = 0.047]) for type I patients. Pamidronate-treated type III/IV and oral bisphosphonate-treated type I patients showed significant increases in total-hip BMD (0.006 [P = 0.003] and 0.011 [P = 0.046] gm/cm(2)/year, respectively). Bisphosphonate effect on fracture rate was assessed for 5-year periods before and after treatment in 51 treated and 22 nontreated individuals matched for age at which bisphosphonate was first administered to the treated group. Bisphosphonate treatment did not decrease fracture rate in type I OI patients. Fracture rate decreased in type III/IV patients following pamidronate but not following oral bisphosphonate treatment. These results underscore a need to consider whether bisphosphonate treatment is appropriate for all adults with OI. PMID- 20544188 TI - Anomalous inferior vena cava drainage to the left atrium with successful staged repair in a 32-year-old woman with arthritis. AB - This report describes a case involving anomalous drainage of inferior vena cava (IVC) to the left atrium diagnosed when the patient was 32 years old. The tricuspid valve and the right ventricle were small. Successful surgical repair was performed, with significant improvement of the patient's clinical status. The use of exercise testing with pulse oxymetry monitoring aided in the decision of timing for closure of the iatrogenically created atrial septal defect. PMID- 20544189 TI - Evaluation of a training program for general ultrasound screening for developmental dysplasia of the hip in preventive child health care. AB - BACKGROUND: A research study in the Netherlands showed that general ultrasound (US) screening was cost-effective in the detection of developmental dysplasia of the hip (DDH). This study was followed by a pilot implementation study. Part of this pilot implementation study is to investigate whether professionals of the infant health care (IHC) system, with no previous US experience, would be able to perform US of the hip. OBJECTIVE: This study looks at health care worker ability to classify US images into a modified Graf system. MATERIALS AND METHODS: After theoretical and practical training, seven nurses and physicians of the participating IHC centers reported their findings on sonographic images of 80 children. This was repeated five months later. From the two evaluation moments the intraobserver agreement and the interobserver agreement was determined. RESULTS: The average estimated interobserver Cohen's kappa for both sessions was for nurses 0.6 and for physicians 0.5. The second evaluation showed a decrease from an average of 4.3% missed cases per screener to 2.3% and an increase of an average of 5% false positives per screener to 9.1%. CONCLUSION: The inter- and intra-observer agreement is comparable to similar studies in which the participants had a professional background in US examination. The level of agreement of the trainees in the perspective of the screening process was considered sufficient for the pilot implementation project. PMID- 20544190 TI - Pediatric teleradiology: the benefits. PMID- 20544191 TI - Conflicting interests: real or apparent? PMID- 20544192 TI - The options for the future production of the medical isotope 99Mo. PMID- 20544193 TI - PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature. AB - PURPOSE: To give an up-to-date overview of the potential clinical utility of (18)F-labelled choline derivatives for tumour imaging with positron emission tomography. METHODS: A PubMed search for (18)F-labelled choline analogues was performed. Review articles and reference lists were used to supplement the search findings. RESULTS: (18)F-labelled choline analogues have been investigated as oncological PET probes for many types of cancer on the basis of enhanced cell proliferation. To date, studies have focused on the evaluation of prostate cancer. Available studies have provided preliminary results for detecting local and metastatic disease. Experience with (18)F-fluorocholine PET in other tumour types, including brain and liver tumours, is still limited. In the brain, excellent discrimination between tumour and normal tissue can be achieved due to the low physiological uptake of (18)F-fluorocholine. In the liver, in which there is a moderate to high degree of physiological uptake in normal tissue, malignancy discrimination may be more challenging. CONCLUSION: PET/CT with (18)F fluorocholine can be used to detect (recurrent) local prostate cancer, but seems to have limited value for T (tumour) and N (nodal) staging. In patients presenting with recurrent biochemical prostate cancer, it is a suitable single step examination with the ability to exclude distant metastases when local salvage treatment is intended. In the brain, high-grade gliomas, metastases and benign lesions can be distinguished on the basis of (18)F-fluorocholine uptake. Moreover, PET imaging is able to differentiate between radiation-induced injury and tumour recurrence. In the liver, (18)F-fluorocholine PET/CT seems promising for the detection of hepatocellular carcinoma. PMID- 20544194 TI - Guidelines for paediatric bone scanning with 99mTc-labelled radiopharmaceuticals and 18F-fluoride. AB - The purpose of these guidelines is to offer nuclear medicine teams a framework that could prove helpful in daily practice. The guidelines include information related to the indications, acquisition, processing and interpretation of bone scans in children, focusing primarily on (99m)Tc-labelled diphosphonate scintigraphy, and also recommendations with regard to the emerging use of PET with (18)F-fluoride. PMID- 20544195 TI - Identification and characterization of Ch806 mimotopes. AB - The chimeric antibody 806 (Ch806) is a promising antitumor agent that recognizes both the epidermal growth factor receptor variant III (EGFRvIII) and the overexpressed epidermal growth factor receptor (EGFR) in cancer tissues but does not recognize the wild type EGFR in normal tissues. However, passive antibody immunization could not produce effective antitumor titers unless the immunization was administered repeatedly over long periods. To overcome this limitation, we generated epitope mimics that bind to Ch806 and tested whether the peptide mimics could induce the production of similar antibodies when actively immunizing mice with the peptides. We used the PH.D-12 phage display peptide library to identify peptides that bind to the monoclonal antibody (mAb) 12H23, which also recognizes similar epitopes of Ch806. Two mimotopes (WHTEILKSYPHE and LPAFFVTNQTQD) were shown to mimic the mAb 12H23 and Ch806 epitope using immunoassays. The mimotopes were conjugated to immunogenic carrier proteins and used to intraperitoneally immunize BALB/c mice. Interestingly, sera from the mice immunized with the isolated mimotopes not only recognize the recombinant or synthetic 806 eptitope, but can also recognize EGFR that is overexpressed in A431 cells and EGFRvIII expressed in Huh7-EGFRvIII cells, whereas sera from mice immunized with the control peptide-KLH (keyhole limpet hemocyanin) and carrier KLH alone failed to show a similar reactivity. Furthermore, in an antibody-dependent cellular cytotoxicity assay (ADCC), the mimotope-induced antibodies specifically lysed human Huh-7-EGFRvIII cells. Our data indicate that the isolated mimotopes reported here may potentially be used as new alternative agents for treating cancer with EGFRvIII expression or EGFR overexpression. PMID- 20544196 TI - Cup loosening after cemented Metasul(r) total hip replacement: a retrieval analysis. AB - Small-diameter cemented Metasul(r) cups have been previously identified to be at high risk of early loosening. We asked whether this particular mode of failure was associated with a specific histological feature. Periprosthetic tissues were obtained at the time of revision of two aseptically loose cemented Metasul(r) cups. Each tissue sample was processed for routine histological analysis. A slight metallosis was visible microscopically in all tissue samples. Metallic wear-debris particles were present both extracellularly and within the cytoplasm of macrophages. We noted a perivascular infiltration of lymphocytes accompanied by mature plasma cells. Our observations are compatible with the hypersensitivity like reaction previously reported, described as an aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). Although wear was within normal reported range limits, this tissue reaction appeared as a consequence of continuous release of metallic ions from the prosthetic articulation. We hypothesise that ALVAL was involved in acetabular component failure, although acetabular loosening may have been initiated by high mechanical stress. PMID- 20544197 TI - Kashin Beck Disease: more than just osteoarthrosis: a cross-sectional study regarding the influence of body function-structures and activities on level of participation. AB - The purpose of this study was to investigate the influence of body function, activities and pain on the level of activity in adults with Kashin Beck Disease (KBD). Seventy-five KBD patients with a mean age of 54.8 years (SD 11.3) participated. Anthropometrics, range of joint motion (ROM) and muscle strength were measured as well as the time-up-and-go test and functional tests for the lower and upper extremities. Activity was assessed with the participation scale and the WHO DAS II. In the shoulder, elbow, hip and knee joints, a severe decrease in ROM and bilateral pain was noted. A decrease in muscle strength was observed in almost all muscles. The timed-up-and-go test scores decreased. No or mild restriction in activity was found in 35%, and 33% experienced a moderate restriction whereas 32% had severe to extreme restriction. Activities in the lower extremities were mildly to moderately correlated to ROM and muscle strength, whereas in the upper extremities activities were correlated to range of joint motion. Activity was significantly associated with ROM after correction for muscle strength, gender and age. Participation was borderline significantly associated with ROM after correction for muscle strength, gender, age and the activity time-up-and-go. In KBD adults, a severe decrease in activity is primarily caused by decrease in ROM. These findings have strong influence on rehabilitation and surgical intervention. PMID- 20544198 TI - Quorum sensing in Aeromonas species isolated from patients in Malaysia. AB - Bacterial quorum sensing signal molecules called N-acylhomoserine lactone (AHL) controls the expression of virulence determinants in many Gram-negative bacteria. We determined AHL production in 22 Aeromonas strains isolated from various infected sites from patients (bile, blood, peritoneal fluid, pus, stool and urine). All isolates produced the two principal AHLs, N-butanoylhomoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL). Ten isolates also produced additional AHLs. This report is the first documentation of Aeromonas sobria producing C6-HSL and two additional AHLs with N-acyl side chain longer than C(6). Our data provides a better understanding of the mechanism(s) of this environmental bacterium emerging as a human pathogen. PMID- 20544199 TI - Distribution and diversity of bacteria in a saline meromictic lake as determined by PCR-DGGE of 16S rRNA gene fragments. AB - The variations in vertical distribution and composition of bacteria in the meromictic Lake Faro (Messina, Italy) were analysed by culture-independent methods in two different mixing conditions. Water samples were collected from a central station from the surface to the bottom (30 m depth) on two different sampling dates--the first characterised by a well-mixed water mass and the second by a marked stratification. A 'red-water' layer, caused by a dense growth of photosynthetic sulphur bacteria, was present at a depth of 25 m in December 2005 and at 15 m in August 2006, defining two different zones in terms of their physicochemical properties. The vertical distribution of bacterioplankton showed that the interface zones were more densely populated than others. In both sampling periods, the highest numbers of live cells were observed within 'red water' layers. The dominant phylotypes of the bacterial community were determined by sequencing the Denaturing Gradient Gel Electrophoresis (DGGE) bands resulting from PCR amplification of 16S rRNA gene fragments. The number of DGGE bands, considered indicative of the total species richness, did not vary predictably across the two different sampling periods. Proteobacteria (alpha-, gamma-, delta- and epsilon subclass members), Cytophaga-Flavobacterium-Bacteroides, green sulphur bacteria and Cyanobacteria were retrieved from Lake Faro. Most of the bands showed DNA sequences that did not match with other previously described organisms, suggesting the presence of new indigenous bacterial phylotypes. PMID- 20544200 TI - Glycerol/glucose co-fermentation: one more proficient process to produce propionic acid by Propionibacterium acidipropionici. AB - Cosubstrates fermentation is such an effective strategy for increasing subject metabolic products that it could be available and studied in propionic acid production, using glycerol and glucose as carbon resources. The effects of glycerol, glucose, and their mixtures on the propionic acid production by Propionibacterium acidipropionici CGMCC1.2225 (ATCC4965) were studied, with the aim of improving the efficiency of propionic acid production. The propionic acid yield from substrate was improved from 0.475 and 0.303 g g(-1) with glycerol and glucose alone, respectively, to 0.572 g g(-1) with co-fermentation of a glycerol/glucose mixture of 4/1 (mol/mol). The maximal propionic acid and substrate conversion rate were 21.9 g l(-1) and 57.2% (w/w), respectively, both significantly higher than for a sole carbon source. Under optimized conditions of fed-batch fermentation, the maximal propionic acid yield and substrate conversion efficiency were 29.2 g l(-1) and 54.4% (w/w), respectively. These results showed that glycerol/glucose co-fermentation could serve as an excellent alternative to conventional propionic acid fermentation. PMID- 20544201 TI - [Oncological data elements in histopathology]. AB - In order to cope with increasing demands to supply information to a variety of documentation systems outside pathology, pathologists need to set standards both for the content and the use of the information they generate. Oncological datasets based on a set vocabulary are urgently required for use both in pathology and in further processing. Data elements were defined according to German pathology report guidelines for colorectal cancers in line with ISO 11179 requirements for the relations between data element concepts and value domains, as well as for further formal conditions, which can be exported in XML together with metadata information. Tests on 100 conventionally written diagnoses showed their principal usability and an increasing degree of guideline conformity in diagnoses commensurate with training time. This set of oncological data elements is a valuable checklist tool for pathologists, enabling formatted information export for further use and saving documentation effort. PMID- 20544202 TI - [Pterygium]. PMID- 20544203 TI - Endogenous origin of endo-beta-1,4-glucanase in common woodlouse Porcellio scaber (Crustacea, Isopoda). AB - Because endogenous cellulases have been observed in arthropods, the potential ability to produce cellulose degrading enzymes was examined in the terrestrial isopod Porcellio scaber, an important decomposer of decayed plant material. cDNA fragments encoding portions of two novel endo-beta-1,4-glucanase amino acid sequences were amplified by RT-PCR, and the amino acid sequences predicted were affiliated to endo-beta-1,4-glucanases from other arthropods, where they cluster with endo-beta-1,4-glucanases of decapod crustaceans. Hybridization in situ reveals the hepatopancreas to be the primary site of gene expression and provides direct evidence of the endogenous origin of endo-beta-1,4-glucanase in P. scaber. Conservation of catalytically important amino acid residues suggests that both sequences translate into functional cellulases. Cellulolytic activity was detected in hepatopancreatic extract after separation by SDS-PAGE, which included CMC as substrate. This is the first evidence of endogenous cellulases in peracarid crustaceans and gives strong support for the involvement of isopod endo beta-1,4-glucanases in the degradation of cellulose in their diet. PMID- 20544204 TI - Programming of offspring sex ratios by maternal stress in humans: assessment of physiological mechanisms using a comparative approach. AB - Sex ratio adjustment has become a hot topic in ecology and evolutionary biology, as documentations of sex ratio skews are numerous, and include examples in diverse animal species. Over the past several decades, scientists have repeatedly debated whether human sex ratios also significantly deviate toward one sex or the other based on environmental or social conditions. An increasing number of studies supports the idea that exposure to stressful conditions can influence the sexes of offspring produced by humans, a majority of which document significantly fewer males after exposure to adverse conditions such as severe life events, economic disruption, or natural disasters. From a comparative standpoint, these findings are similar to studies in non-human mammals and other vertebrate species showing a bias toward females during times of stress. However, the mechanisms by which stress-related biases in the offspring sex ratio may occur remain elusive, and the involvement of glucocorticoids indicating a true influence of stress itself remains unstudied. Here, I review the evidence that stressful events induce sex ratio adjustment in humans. Additionally, I discuss the possibility for glucocorticoid mediation of sex ratio adjustment and the potential reproductive stages during which stress-induced sex ratio adjustment may occur in humans and other mammals. PMID- 20544205 TI - Capsule endoscopy in small-bowel surveillance of patients with hereditary polyposis syndromes. AB - PURPOSE: Familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS) are hereditary polyposis syndromes with a high risk for benign small-bowel polyps and cancer. The aim of this study was to assess the prevalence of small-bowel polyps beyond the duodenum in patients with FAP and PJS and to examine the clinical value and the optimal interval of capsule endoscopy (CE) for the surveillance of small-bowel polyps in patients with FAP. METHODS: Between 2002 and 2009, standard gastroscopy, duodenoscopy, and CE were performed on 19 consecutive patients with hereditary polyposis syndromes (FAP n=15; PJS n=4). The number, size, and location of polyps detected by CE were assessed. Five FAP patients had repeated CEs in intervals of 2-7 years. RESULTS: In 13 of the 15 (87%) FAP patients, small-bowel polyps were detected by CE ranging from estimated <5 mm to >10 mm in size. Thereof, in four patients, medium-sized (5-10 mm) or large-sized (>10 mm) polyps were seen-all of them located in the proximal jejunum. In three FAP patients with repeated CEs, the latest CE displayed medium- and large-sized polyps in the proximal jejunum, whereas previous CEs had detected only small-sized (<5 mm) polyps. In three of the four PJS patients, large-sized small-bowel polyps were visualized by CE which could then be removed by double balloon enteroscopy (DBE) or surgical resection. CONCLUSION: CE is an effective and safe method for small-bowel surveillance in FAP and PJS. PMID- 20544206 TI - Drug abuse, personality disorder, and colorectal metastases: when chemotherapy becomes an illusion and surgery cannot help any more. PMID- 20544207 TI - Hemorrhagic colitis as the onset of Wegener's granulomatosis. PMID- 20544208 TI - Adjuvant radiotherapy following total mesorectal excision for stage IIA rectal cancer: is it beneficial? AB - PURPOSE: The benefit of adjuvant radiotherapy in patients with stage IIA (T3N0) rectal cancer following total mesorectal excision (TME) is controversial. We evaluated the effect of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) alone on the local recurrence and survival of patients with stage IIA rectal cancer after TME. METHODS: Between 1996 and 2004, patients with stage IIA rectal cancer who received adjuvant CT (n = 29) or CRT (n = 122) following TME were enrolled. Oncologic outcomes were compared between groups, and risk factors for local recurrence and overall survival rates were analyzed. RESULTS: The median follow-up period was 78 months. No significant differences were observed in the 5 year local recurrence (3.4% versus 9.0%; P = 0.348) or 5-year overall survival rates (86.2% versus 80.3%; P = 0.924) between CT and CRT. However, involvement of the circumferential resection margin and age >60 years were associated with adverse oncologic outcomes. CONCLUSIONS: Additional postoperative radiotherapy did not alter local recurrence or survival after TME in patients with stage IIA rectal cancer. Postoperative radiation may be an overtreatment as an adjuvant therapy in patients with stage IIA rectal cancer if they had no other risk factors. However, randomized controlled trials are warranted to confirm this suggestion. PMID- 20544209 TI - Electromechanical characteristics of the human colon in vitro: is there any difference between the right and left colon? AB - PURPOSE: We examined the electrical and mechanical characteristics of the smooth muscles in the human colon at the muscle cell, the muscle strip, and at the whole tissue levels METHODS: Conventional microelectrode recordings and tension recordings were performed. RESULTS: There was no difference in resting membrane potential, frequency, and amplitude of slow waves between the right and left colon; but there were significant differences in frequency and amplitude of the slow waves between inner circular muscle (CM) and longitudinal muscle (LM), and between inner CM and outer CM, but not between outer CM and LM. On tension recording of CM and LM strip and colonic segment, amplitude, frequency, and area under the curve showed no difference between the right and left colon. In whole colonic segment, high amplitude dominant waves (DW) were found both in CM and LM. Low amplitude non-DWs were detected only in CM, more commonly in right colon and propagated aborally. DWs in the CM were associated with DWs in the LM. In the CM of the left colon, all DWs in the CM propagated aborally ending-up with DW in the LM layer. However, in the right colon, mixed pattern of propagation was detected in adjacent recording sites in 60% of tissues examined. CONCLUSION: Electrophysiologic and mechanical characteristics were similar between the right and left human colon. However, the retrograde propagation of both DWs and non-DWs in the CM was more frequent in the right colon, accounting for mixing function in this region of the human colon. PMID- 20544210 TI - Biosutures improve healing of experimental weak colonic anastomoses. AB - PURPOSE: Use of biosutures in animal models of colonic anastomoses is associated with decreased adhesions without affecting anastomotic strength. This study aimed to evaluate the effect of biosutures on colonic anastomoses kept free of adhesions by peritoneal instillation of icodextrin 4%. METHODS: Three types of colonic anastomoses were compared: group 1, anastomoses without icodextrin 4% and control suture; group 2, anastomoses with icodextrin 4% (adhesion-free anastomoses) and control suture; and group 3, anastomoses with icodextrin 4% (adhesion-free anastomoses) and biosutures. Dehiscence, adhesion formation, and anastomotic strength were evaluated on day 4 after the operation. RESULTS: When peritoneal icodextrin 4% was used in anastomoses with conventional sutures, a decrease in the adhesion index (P = 0.01) and a lower bursting pressure (P = 0.15) were observed. When adhesion-free anastomoses were compared, those performed with biosutures had a higher bursting pressure (P = 0.008) and a similar pattern of adhesion index (P = 0.48). CONCLUSIONS: Biosutures improve the strength of adhesion-free colonic anastomoses. PMID- 20544211 TI - Mutations of CARD11 but not TNFAIP3 may activate the NF-kappaB pathway in primary CNS lymphoma. AB - Primary CNS lymphoma (PCNSL), the intracerebral subgroup of diffuse large B cell lymphoma (DLBCL), shows evidence for aberrant activation of the nuclear factor (NF)-kappaB pathway. In order to identify potential activators of the NF-kappaB complex, we analyzed the CARD11 and TNFAIP3 genes for the presence of somatic mutations and TNFAIP3 for aberrant promoter methylation in PCNSL. We also compared PCNSL to spinal DLBCL, because CARD11 and TNFAIP3 mutations have been described in systemic DLBCL. CARD11 mutations, located in the coiled-coil region, which may activate NF-kappaB, were detected in 16% (5/32) of PCNSL, while TNFAIP3 mutations were detected in 3% (1/32) of PCNSL. In PCNSL, all CARD11 mutations were heterozygous, in-frame, induced amino acid exchanges, and presumably led to activation of this oncogene. Spinal DLBCL harbored mutations of CARD11 and TNFAIP3 in 10% (1/10) and 20% (2/10) of cases, respectively. In both PCNSL and spinal DLBCL, mutations in CARD11 and TNFAIP3 were mutually exclusive. TNFAIP3 was unmethylated in all PCNSLs (30/30) and spinal DLBCLs (10/10). We conclude that mutations of the oncogene CARD11 may contribute to NF-kappaB activation and thereby play a role in the pathogenesis of PCNSL, while, in contrast to systemic DLBCL, inactivation of TNFAIP3 either by mutation or methylation seems to be of minor significance. PMID- 20544212 TI - Etanercept causes regression of endometriotic implants in a rat model. AB - OBJECTIVE: To determine the effects of etanercept (anti-TNF-alpha) on surgically induced endometriosis in a rat model. MATERIALS AND METHODS: This is a prospective, randomized, controlled, experimental study that was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Thirty female nonpregnant, nulligravid Wistar-Hannover albino rats were used. The summary of the technique: surgical induction of endometriosis, administration of estrogen for 2 weeks, and laparotomy; administration of etanercept for 2 weeks following the induction of endometriosis and laparotomy; administration of estrogen for 2 weeks and necropsy. The volume and histopathological scores of the endometriotic foci were evaluated. RESULTS: One-hundred twenty uterine horns were implanted in 30 rats. Endometriosis was completely formatted in 112 lesions (93.3%). No rats were lost. In the etanercept group, the lesions' volumes were 83.9 +/- 13.1, 47.2 +/- 8.4, and 96.7 +/- 34.8 mm(3) at the end of the second week (pretreatment stage), at the end of the fourth week (post-treatment stage), and at the end of the sixth week, respectively (P = 0.007). Histopathologic scores were 2.3 +/- 0.2, 1.7 +/- 0.2, and 1.9 +/- 0.1, respectively (P = 0.08). The changes in the other groups were not statistically significant. CONCLUSIONS: Etanercept, a fusion protein consisting of human recombinant soluble TNF receptor-2, neutralizes TNF activity. Anti-TNF therapy could be a new non-hormonal therapeutic option for the treatment of endometriosis in humans. PMID- 20544213 TI - The effect of tension-free vaginal tape placement on distal anterior vaginal wall support at the time of laparoscopic sacral colpoperineopexy. AB - PURPOSE: The occurrence of stress urinary incontinence and pelvic organ prolapse can often coexist resulting in the need for concomitant surgical procedures to treat both conditions. The purpose of this study was to determine if tension-free vaginal tape (TVT) at the time of laparoscopic sacral colpoperineopexy (LSCP) had an effect on distal anterior vaginal wall support. METHODS: This was a retrospective cohort study of patients that had LSCP between January 2005 and December 2007 (n = 121). These patients were divided according to those with (n = 63) and without TVT (n = 58) at the time of LSCP. Pre- and postoperative information was compared between groups using Student's t tests, ANCOVA, and Fisher's exact tests (P <= 0.05). RESULTS: Preoperatively, there were no significant differences between groups for all demographic and anatomic variables (P > 0.05). Patients were followed-up until 12 months after surgery. Patients with and without TVT had similar postoperative anterior vaginal wall measurements (points Aa and Ba) and stage of prolapse (P > 0.05). There were also no differences between groups with regard to recurrent prolapse symptoms or surgical satisfaction (P > 0.05). CONCLUSIONS: Tension-free vaginal tape at the time of LSCP did not improve postoperative distal anterior vaginal support. PMID- 20544214 TI - Bio-medicolegal guidelines and protocols: survey and future perspectives in Europe. AB - The preservation of uniqueness and the enhancement of the value of evidence in legal medicine is based on the implementation and development of a "quality management system," which includes a continuous education of specialists, the introduction and application of guidelines and protocols, as well as mechanisms of internal quality control. This ongoing process shows differences with regard to various fields of knowledge such as forensic genetics, toxicology, forensic pathology or forensic psychiatry, especially if different European countries are compared. To get an overview on the development of legal medicine in different European countries, a questionnaire was developed and sent to representatives of 42 European countries to verify the existence of bio-medicolegal guidelines and protocols. A National Society of Legal Medicine is established in 27 out of 32 countries (84%) which could be included in the final analyses. In 25 countries (78%), a specialisation is necessary as a prerequisite of inclusion in a national register, and 30 of the countries (94%) have guidelines in at least one field of legal medicine. The most common guidelines concern forensic pathology (in the fields of professional qualification and sudden death), forensic toxicology (driving under the influence of drugs and substance testing) and forensic genetics (paternity testing and personal identification). The findings of this study show that comparison is possible and can be a basis for further consensus in the European medicolegal community. The process of harmonisation of the medicolegal autopsy rules in Europe initiated in 1990 was a first step on this way. Further consensus is necessary and might be gained by developing European guidelines for each field within the subdisciplines, based on a standard European Guideline Format. PMID- 20544215 TI - Trophoblast glycogen cells differentiate early in the mouse ectoplacental cone: putative role during placentation. AB - The role of differentiated trophoblast glycogen cells (GCs) in the ectoplacental cone (EPC) has not been elucidated yet. Recently, GC progenitors have been shown to be present from embryonic day 7.5 (E7.5), but glycogen is found in GC only from E10.5. Herein, we investigated the origin, localization and characterization of mouse GCs in EPC and their relationship with blood cells and trophoblast giant cells (TGCs) during placentation. Implantation sites (E5.5-E12.5) were processed for histological studies, histochemical detection (glycogen) and immunohistochemical staining (Ki67). Three-dimensional reconstruction of the EPC was obtained from suitably oriented embryos at E7.5. Our findings evidence that GCs are present and assembled in clusters from E6.5 to E12.5, and that they exhibit the classic vacuolated appearance and contain PAS-positive glycogen, which is amylase-sensitive and acetylation-resistant. In fact, only GCs were stained after acetylation, confirming unequivocally their presence in tissues. At E6.5, GCs showed numerous mitoses and vacuoles with scattered glycogen particles. At E7.5, GCs showed low numbers of mitoses and abundant vacuoles full of glycogen. During E7.5-E8.5, GCs were in close proximity to TGCs, and cells were intercalated by thin maternal blood spaces; placental GCs lost maternal blood contact during E9.5-E12.5. Our results indicate that GCs are originated and proliferate in the upper portion in the midregion of EPC at E6.5, and that at E7.5-E8.5 they show consistent glycogen deposits, which are likely metabolized to glucose. This compound may be directly transferred to circulating maternal blood, and used as a source of energy by GCs and TGCs during placentation. PMID- 20544216 TI - Integrated preventive care coverage effectiveness in high-risk worksites in Mexico. AB - OBJECTIVES: Worksites have been considered a propitious environment for promoting health. In 2005, an integrated preventive care (IPC) system was implemented in Mexico consisting of health promotion and disease prevention interrelated activities, delivered on a single visit and on location. This project contributes relevant information on IPC coverage and its degree of effectiveness on providing health promotion services to workers at high-risk worksites. METHODS: There were included 68 worksites particularly affected by high fatal and nonfatal injury rates; the target population comprised 45,724 workers. Coverage referred to the completion of IPC actions within the last year, and effectiveness was defined as the extent to which an observed IPC coverage came close to an ideal IPC coverage. Means and 95% confidence intervals (CI) were calculated for given estimates. RESULTS AND CONCLUSIONS: Overall IPC mean coverage effectiveness was 61.2% (95% CI 60.8-61.6), a value below satisfactory range limits. Results broken down by sex and age showed higher mean coverage effectiveness for adult working men than adult working women (p < 0.0001). Promotion of reproductive health was the IPC process with the lowest mean coverage effectiveness (51.8%; 95% CI 50.8-52.7), followed by the disease detection process (59.0%; 95% CI 58.4-59.6) and the disease prevention and control process (61.0%; 95% CI 60.5-61.5). Maintaining the health of the workforce poses a significant challenge for health services. Therefore, analysis of coverage effectiveness represents a useful tool for evaluating and reorganizing preventive medicine care at worksites. PMID- 20544217 TI - Biochemical characterization of the small ubiquitin-like modifiers of Chlamydomonas reinhardtii. AB - Dynamic modification of target proteins by small ubiquitin-like modifier (SUMO) is known to modulate many important cellular processes and is required for cell viability and development in all eukaryotes. However, understanding of SUMO systems in plants, especially in unicellular green algae, remains elusive. In this study, Chlamydomonas reinhardtii CrSUMO96, CrSUMO97 and CrSUMO148 were characterized. We show that the formation of polymeric CrSUMO96 and CrSUMO97 chains can be catalyzed either by the human SAE1/SAE2 and Ubc9 SUMOylation system in vitro or by an Escherichia coli chimeric SUMOylation system in vivo. An exposed C-terminal di-glycine motif of CrSUMO96 or CrSUMO97 is essential for functional SUMOylation. The human SUMO-specific protease, SENP1, demonstrates more processing activity for CrSUMO97 than for CrSUMO96. The CrSUMO148 precursor notably has four repeated di-glycine motifs at the C-terminus. This unique feature is not found in other known SUMO proteins. Interestingly, only 83 residual CrSUMO148(1-83) with the first di-glycine motif can form SAE1/SAE2-SUMO complex and further form polymeric chains with the help of Ubc9. More surprisingly, CrSUMO148 precursor is digested by SENP1, solely at the peptide bond after the first di-glycine motif although there are four theoretically identical processing sites in the primary sequence. This process directly generates 83-residual CrSUMO148(1-83) mature protein, which is exactly the form suitable for activation and conjugation. We also show that SENP1 displays similar isopeptidase activity in the deconjugation of polymeric CrSUMO96, CrSUMO97 or CrSUMO148 chains, revealing that the catalytic mechanisms of processing and deconjugation of CrSUMOs by SENP1 may differ. PMID- 20544218 TI - A proposed conserved role for an avocado FW2.2-like gene as a negative regulator of fruit cell division. AB - Previous studies using 'Hass' avocado and its small fruit (SF) phenotype as a model showed that SF is limited by cell number, not by cell size. In an attempt to explore the molecular mechanisms regulating avocado fruit cell division, we isolated four distinct avocado cell proliferation-related genes and investigated their expression characteristics, comparing normal fruit (NF) and SF developmental patterns. Three cDNAs termed PaCYCA1, PaCYCB1 and PaPCNA, encoding two mitotic cyclins and a proliferating cell nuclear antigen (PCNA), were first isolated from young NF tissues. The accumulation of their transcripts was predominant in mitotically active organs, including young fruitlets, leaves and roots. Furthermore, a fourth full-length cDNA, designated Pafw2.2-like, encoding a FW2.2 (fruit-weight)-like protein, was isolated from SF tissues. FW2.2 is postulated to function as a negative regulator of cell division in tomato fruit. Remarkably, northern analysis revealed that the accumulation of the mitotic cyclins and of PCNA transcripts gradually decreased in NF tissues during growth, whereas in SF, their levels had already decreased at earlier stages of fruit development, concomitant with an earlier arrest of fruit cell division activity. In contrast, parallel sq-RT-PCR analysis showed that Pafw2.2-like mRNA accumulation was considerably higher in SF tissues than in the same NF tissues essentially at all examined stages of fruit growth. Together, our data suggest essential roles for the two mitotic cyclins genes and the PCNA gene in regulating avocado fruit development. Furthermore, the possibility that Pafw2.2-like acts as does fw2.2 in tomato, is discussed. PMID- 20544219 TI - Iron containing anti-tumoral agents: unexpected apoptosis-inducing activity of a ferrocene amino acid derivative. AB - PURPOSE: Due to the severe problems accompanied with multiple drug resistance (MDR), agents that can induce apoptosis independently of death-suppressing proteins are required. Here, we show that the ferrocene derivative HUNI 068 is active against cancer cells and overcomes different mechanisms of multiple drug resistance (MDR). METHODS: Proliferation inhibition was determined by using a CASY((r))CellCounter. DNA fragmentation assay and annexin-V/PI binding assays measured apoptosis, and necrosis was excluded by LDH-release assay. Drug resistant cell lines were generated to test the ability to overcome MDR. By real time PCR, alterations in gene expression of treated cells were analyzed. The apoptosis pathway was investigated by immunoblotting and measurement of mitochondrial membrane permeability transition. RESULTS: HUNI 068 leads to proliferation inhibition and apoptosis mediation, but only minimal necrosis induction. Healthy leukocytes seem to be less affected than cancer cells. The compound overcomes drug resistance to vincristine and daunorubicin. Independence of p-glycoprotein and Bcl-2 overexpression is probable, and upregulation of the anti-Bcl-2 protein harakiri was seen. Combined treatment with vincristine leads to synergistic effects. In different primary tumor cells, HUNI 068 achieved acceptable effects where tolerance to some conventional drugs was shown. Induction of apoptosis is FADD-independent, but associated with a reduced mitochondrial membrane potential and activation of caspase-9, indicating the intrinsic apoptosis pathway via mitochondria. CONCLUSIONS: HUNI 068 is a promising new compound with activity even against MDR tumor cells. Further investigations into the class of ferrocene-derived agents might reveal compounds with improved activity for a more specific and safe anti-cancer therapy. PMID- 20544220 TI - Evaluation of the transmission mode of B. hominis by using PCR method. AB - Blastocystis hominis is a common intestinal parasite observed in fecal examination. On the other hand, the transmission of this parasite is certainly unknown. The transmission of B. hominis can be realized by animal contact and the contamination by water and food with excreted cysts from the reservoir hosts. B. hominis isolated from 25 humans, their pets, and tap water was identified by polymerase chain reaction using sequenced tag site primers in this study. B. hominis isolates obtained from humans and pets were identified as subtype1, subtype2, and subtype3 while B. hominis isolates obtained from tap water were also identified as subtype1. The B. hominis isolates obtained from humans in this study were defined as the same as the subtypes of the B. hominis isolates obtained from the pets, of which these people keep at their homes, and the tap water. These findings reveal that the source of B. hominis infection could be pets and tap water. PMID- 20544221 TI - Survival rate of bat bugs (Cimex pipistrelli, Heteroptera) under different microclimatic conditions. AB - Survival of facultative ectoparasites, e.g. bed bugs (Cimex spp.), is more intensely affected by climatic factors, namely temperature, than that of permanent ectoparasites. The ontogenetic time of the bat bug (Cimex pipistrelli) in bat roosts is limited by different survival rates under different temperatures in particular nymphal stages. This limitation could affect bug densities and cause asynchrony between the ectoparasite and bat reproductive cycle. Therefore, bug survival under different temperatures was tested in the laboratory. Survival success was evaluated by three types of survival analyses: Kaplan-Meier estimation, the Cox proportional hazards model and Weibull parametric regression. The bugs survived for only a few hours at 45 degrees C; however, such a high temperature was never found in natural roosts. Different survival probability among different ontogenetic stages was found at the temperatures of 5-35 degrees C, and it was the highest in adult females and nymphs of fourth and fifth instar. Early instars first to third were found to be the most sensitive with the highest mortality of all stages studied and having their best survival at 5 degrees C. The hazard rate ratio of Weibull regression shows the low daily failure rate of 2.23-4.34% within the span of 5-35 degrees C. C. pipistrelli had the shorter life cycle and the better survival at higher temperature (35 degrees C) than C. lectularius. The ability of the former to survive high temperatures could be the consequence of its long-term coexistence with bats preferring crevice-like roosts or attics which become overheated during the summer months. PMID- 20544222 TI - Genetic mapping of a novel hypotrichosis locus to chromosome 7p21.3-p22.3 in a Pakistani family and screening of the candidate genes. AB - Hereditary hypotrichosis is a heterogeneous group of inherited hair loss disorders characterized by diffused or localized thinning or absence of hair affecting scalp, eyebrows and eyelashes, and other body parts. Over the past few years, at least four autosomal dominant and six autosomal recessive forms of hypotrichosis have been described. All these ten forms of hypotrichosis have been mapped on different human chromosomes and the corresponding genes have been identified in most of these cases. In the present study, we have described a six generation Pakistani consanguineous family with an autosomal recessive transmission of hereditary hypotrichosis. All the five affected individuals of the family showed complete absence of scalp hair and sparse eyebrows and eyelashes. They were born with complete absence of scalp hairs. Facial hair of beard and mustaches were present in all the affected adult male individuals. Papules were observed only on scalp of the affected individuals. A scalp biopsy from an affected individual showed markedly reduced number of hair follicles. Human genome scan using polymorphic microsatellite markers mapped the disease locus on chromosome 7p21.3-p22.3, flanked by markers D7S1532 and D7S3047. A maximum two-point LOD score of 4.74 (theta = 0.00) was obtained at marker D7S481. The linkage interval spans 15.69 cM, which corresponds to 6.59 Mb according to the sequence-based physical map (Build 36.2). Mutation analysis of five potential candidate genes (GNA12, FOXK1, DAGLB, ZNF12, ACTB), located in the linkage interval, did not reveal any functional sequence variant. PMID- 20544223 TI - Carboxymethyl cellulose and Pluronic F68 protect the dinoflagellate Protoceratium reticulatum against shear-associated damage. AB - The red-tide dinoflagellate Protoceratium reticulatum is shown to be protected against turbulence-associated damage by the use of the additives Pluronic F68 (PF68) and carboxymethyl cellulose (CMC) in the culture medium. Relative to agitated controls, these additives had a dose-dependent protective effect at concentrations of up to 0.4 and 0.5 g L(-1) for CMC and F68, respectively. In static cultures, these additives inhibited growth directly or indirectly at a concentration of >0.5 g L(-1). Compared to CMC, PF68 was a better protectant overall. Cell-specific production of yessotoxins was enhanced under elevated shear stress regimens so long as the turbulence intensity was insufficient to damage the cells outright. Shear-induced production of reactive oxygen species and direct effects of turbulence on the cell cycle contributed to the observed shear effects. PMID- 20544224 TI - A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea. AB - PURPOSE: Our aim was to evaluate the literature for the prevalence of and interventions for oral viral infections and, based on scientific evidence, point to effective treatment protocols. Quality of life (QOL) and economic impact were assessed if available in the articles reviewed. METHODS: Our search of the English literature focused on oral viral infections in cancer patients within the timeframe of 1989-2007. Review methods were standardized. Cohort studies were used to determine the weighted prevalence of oral viral infection in cancer patients. The quality of selected articles were assessed and scored with respect to sources of bias, representativeness, scale validity, and sample size. Interventional studies were utilized to determine management guidelines. Literature search included measures of QOL and economic variables. RESULTS: Prevalence of oral herpes simplex virus (HSV) infection in neutropenic patients was higher than in patients treated with radiotherapy for head and neck cancer (49.8% vs. 0%, respectively). In patients treated with radiochemotherapy for head and neck cancer, the prevalence of oral HSV infection increases up to 43.2% (CI, 0-100%). Prevalence of HSV infection was higher when oral ulcers existed. Information about other oral viral infections is sparse. There was a significant benefit of using acyclovir to prevent HSV oral infection (at 800 mg/day). Various dosing protocols of valacyclovir achieved prevention of HSV reactivation (500 or 1,000 mg/day). The prevalence of HSV reactivation was similar for acyclovir and valacyclovir. No information about impact on QOL and economic burden was available. CONCLUSIONS: Acyclovir and valacyclovir are equally effective in preventing oral HSV infection. Neutropenic patients, who were primarily treated for hematological malignancies in the studies reviewed, are at a greater risk for viral infection. PMID- 20544225 TI - A systematic review of orofacial pain in patients receiving cancer therapy. AB - PURPOSE: We present the findings of a structured systematic review of the literature assessing orofacial pain induced by malignant disease and/or its therapy (excluding mucositis). This evaluation of the literature published after the 1989 NIH Development Consensus conference on the oral complications of cancer therapies is an effort to assess the prevalence of pain, quality of life and economic impact, and management strategies for cancer therapy-induced orofacial pain. METHODS: A systematic medical literature search was conducted with assistance from a research librarian in MEDLINE/PubMed and EMBASE databases for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers with expertise in the field of oral oncology. RESULTS: Thirty-nine studies assessed pain in the head and neck region. The measure was commonly embedded in quality of life studies. Most of these studies described pain in head and neck cancer (HNC) patients, which therefore became the focus of the report. Pain is common in patients with HNC and is reported by approximately half of patients prior to cancer therapy, 81% during therapy, 70% at the end of therapy, and by 36% at 6 months after treatment. Pain is experienced beyond the 6-month period by approximately one third of patients and is typically more severe than pre-treatment cancer-induced pain. CONCLUSIONS: This systematic review identified the presence of pain before cancer therapy, likely attributable to the cancer; an increase in pain during therapy and the common persistence of pain following cancer treatment. Continuing research should use validated tools to prospectively assess orofacial pain, its causes and pathophysiology, and its effect on quality of life and economic impact. Clinical trials of pain management in this setting are also warranted. PMID- 20544226 TI - Aprepitant against pruritus in patients with solid tumours. PMID- 20544227 TI - A comparative study of fibroid ablation rates using radio frequency or high intensity focused ultrasound. AB - This study compared the technical success of fibroid devascularization using high intensity focused ultrasound (HIFU) and radio frequency (RF) to provide an experimental basis for the clinical selection of a suitable, minimally invasive method for treating uterine fibroids. Patients were randomly divided into two groups and treated with HIFU or RF accordingly. The two groups of patients were divided again into subgroups A, B, and C based on fibroid diameter and subgroups A', B', and C' based on fibroid blood supply grades. The fibroid diameters in subgroups A, B, and C were 2.0 cm 0.05). In other subgroups, the complete ablation rates of RF were better than those of HIFU (p < 0.05). No severe complications were observed after these two treatments. RF can be applied for the majority of fibroids. As a noninvasive therapy, HIFU could be the preferred method for the treatment of small, hypovascular fibroids. PMID- 20544228 TI - Minimally invasive treatment of small renal tumors: trends in renal cancer diagnosis and management. AB - Renal cell carcinoma is a common malignancy causing significant mortality. In recent years abdominal imaging, often for alternate symptomatology, has led the trend toward the detection and confirmation of smaller renal tumors. This has permitted the greater use of localized and nephron-sparing techniques including partial nephrectomy and image-guided ablation. This article aims to review the current role of image-guided biopsy and ablation in the management of small renal tumors. The natural history of renal cell carcinoma, the role of renal biopsy, the principles and procedural considerations of thermal energy ablation, and the oncological outcomes of these minimally invasive treatments are discussed and illustrated with cases from the authors' institution. Image-guided ablation, in particular, has changed the treatment paradigm and, by virtue of its increasingly evident efficacy and low morbidity, now favors the treatment of smaller tumors in patients previously unfit for surgery. PMID- 20544229 TI - Optimizing tillage schedule for maintaining activity of the arbuscular mycorrhizal fungal population in a rainfed upland rice (Oryza sativa L.) agro ecosystem. AB - Rainfed uplands in India are predominantly mono-cropped with rice (Oryza sativa L.) in the wet season (June/July to September/October) and grown under aerobic soil conditions. The remaining fallow period (winter followed by summer) of about 8-9 months leads to natural crash in the population of native arbuscular mycorrhizal fungi (AMF) in the soil. Attempts have been made to minimize this population crash by reducing soil disturbance-induced deleterious effects on native AMF activity of improperly scheduled off-season tillage, an agronomic recommendation for weed and disease (soil-borne) management, practiced by the upland farmers. On-farm (farmers' field) evaluation of effects of all suitable off-season tillage schedule combinations on rice during wet seasons of 2004, 2005, and 2006 revealed that a maximum of two off-season tillage schedules with a minimum gap of 13 weeks between them minimized the population crash of native AMF with a concomitant increase in phosphorus (P) uptake and grain yield of upland rice (variety "Vandana"). PMID- 20544230 TI - Effects of co-inoculation with arbuscular mycorrhizal fungi and rhizobia on soybean growth as related to root architecture and availability of N and P. AB - Soybean plants can form tripartite symbiotic associations with rhizobia and arbuscular mycorrhizal (AM) fungi, but little is known about effects of co inoculation with rhizobia and AM fungi on plant growth, or their relationships to root architecture as well as nitrogen (N) and phosphorus (P) availability. In the present study, two soybean genotypes contrasting in root architecture were grown in a field experiment to evaluate relationships among soybean root architecture, AMF colonization, and nodulation under natural conditions. Additionally, a soil pot experiment in greenhouse was conducted to investigate the effects of co inoculation with rhizobia and AM fungi on soybean growth, and uptake of N and P. Our results indicated that there was a complementary relationship between root architecture and AMF colonization in the field. The deep root soybean genotype had greater AMF colonization at low P, but better nodulation with high P supply than the shallow root genotype. A synergistic relationship dependent on N and P status exists between rhizobia and AM fungi on soybean growth. Co-inoculation with rhizobia and AM fungi significantly increased soybean growth under low P and/or low N conditions as indicated by increased shoot dry weight, along with plant N and P content. There were no significant effects of inoculation under adequate N and P conditions. Furthermore, the effects of co-inoculation were related to root architecture. The deep root genotype, HN112, benefited more from co-inoculation than the shallow root genotype, HN89. Our results elucidate new insights into the relationship between rhizobia, AM fungi, and plant growth under limitation of multiple nutrients, and thereby provides a theoretical basis for application of co-inoculation in field-grown soybean. PMID- 20544231 TI - Needle puncture injury of the rat intervertebral disc affects torsional and compressive biomechanics differently. AB - Needle puncture is a common method of inducing intervertebral disc (IVD) degeneration in small animal models and may have some similarities to IVD injury conditions such as herniation. Yet, the influence of puncture injuries on IVD biomechanics is not well understood. This study quantified the acute effects of anular injury on the biomechanics of rat caudal IVDs in compression and torsion following puncture with 30, 25 and 21 G needles. In compression, puncture injury reduced elastic stiffness by 20% for all needle sizes, but differences between control and punctured discs did not remain after compressive overload. In contrast, torsional parameters associated with anular fiber tension were affected proportionally with needle size. We conclude that IVD injuries that penetrate through the thickness of the annulus affect IVD biomechanics through different mechanisms for compression and torsion. Anular injuries affect torsional properties in a manner directly related to the amount of fiber disruption and compressive properties in a manner that affects pressurization. PMID- 20544232 TI - Lack of modulatory effect of short-term repeated electroconvulsive therapy on platelet vesicular monoamine transporter 2 (VMAT2) in depressed patients. AB - We investigated the effect of electroconvulsive therapy (ECT) on platelet vesicular monoamine-transmitter-transporter 2 (pVMAT2) using high-affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2 in 11 women and 7 men, aged 53.7 +/- 15.8. The Hamilton Depression Rating Scale (HAM-D) and the binding characteristic of pVMAT2 were assessed before and after six ECTs, administered over 21 days. A significant reduction (4.5 +/- 0.46; 20.8%) was obtained in HAM-D scores (p < 0.01) following the ECTs. The pVMAT2 density (B (max)) and affinity values (K (d)) remained unaltered. Six ECTs are not sufficient for modulation in pVMAT2 expression. Long-term studies are needed to clarify the relationship between full remission and possible alterations in platelet/brain VMAT2 characteristics. PMID- 20544233 TI - LRRK2 G2019S mutation: frequency and haplotype data in South African Parkinson's disease patients. AB - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most significant genetic cause of Parkinson's disease (PD). The exact function of LRRK2 is currently unknown but the presence of multiple protein interaction domains including WD40 and ankyrin indicates that it may act a scaffold for assembly of a multi-protein signaling complex. The G2019S mutation in LRRK2 represents the most clinically relevant PD-causing mutation and has been found in both familial and sporadic forms of the disorder. This mutation is situated in the highly conserved kinase MAPKKK domain, and has been found in up to 40% of PD patients from North African Arabic, 30% of Ashkenazi Jewish and approximately 10% of Portuguese and Spanish populations. Although extensively investigated in numerous European and North American populations, studies on the frequency of G2019S in African countries have been rare. The present study is the first on the South African population. High-resolution melt analysis was used to identify the G2019S mutation and it was found in 2% (4/205) of the patients studied. G2019S was not found in any of the Black PD patients screened. In all four G2019S positive probands the mutation was shown to be present on the common haplotype referred to as haplotype 1. This reveals that the four South African G2019S positive probands (three Caucasian and one of mixed ancestry) share a common ancestor with the other haplotype 1-associated families reported worldwide. PMID- 20544234 TI - Molecular epidemiology of porcine epidemic diarrhea virus in China. AB - Since early 2006, porcine epidemic diarrhea virus (PEDV) has been reemerging in immunized swine herds. Open reading frame 3 (ORF3) is the only accessory gene in the PEDV genome. The entire ORF3 genes of 12 PEDV field strains and one vaccine strain were sequenced. The ORF3 genes of Chinese PEDV field strains (excluding CH/GSJIII/07) contain a single 672- or 675-nucleotide (nt) ORF, which encodes a 223- or 224-aa-long peptide. However, the CV777 vaccine strain and CH/GSJIII/07 contain a 276-nt ORF because of a 49-nt deletion at nt 245-293. The Chinese PEDV field strains and PEDV reference strains are divided into three groups based on the phylogenetic relationship of their ORF3 genes. Chinese PEDV field strains (excluding CH/GSJIII/07) have a close phylogenetic relationship to Korean strains and are genetically different from the PEDV vaccine strains. However, CH/GSJIII/07 has a close phylogenetic relationship to two vaccine strains, suggesting that it might have evolved from a live vaccine strain. Chinese PEDV field strains (excluding CH/GSJIII/07) can be differentiated from PEDV vaccine strains by a nested RT-PCR method. PMID- 20544235 TI - Detection of replicating negative-sense RNAs in CaCo-2 cells infected with human astrovirus. AB - Human astrovirus (HAstV) is the second most important cause of viral diarrhea and acute gastroenteritis in infants under five. However, determination of the infectivity of clinical isolates is difficult, and the replication cycle of HAstV is not yet fully understood. In this study, it was attempted to detect negative sense (-)RNAs generated during the replication of RNA viruses. We used clinical isolates of HAstV to infect CaCo-2 cells. Reverse transcription using only a sense primer followed by PCR using both sense and antisense primers showed that ( )RNAs were first detected in CaCo-2 cells between 9 and 12 h postinfection (p.i.). However, these (-)RNAs were not detected when cells were treated with the protein synthesis inhibitor cycloheximide during HAstV infection. Next, RT with only an antisense primer followed by PCR was performed to detect (+)RNA of HAstVs after production of (-)RNAs during replication. RT-PCR results using the antisense primer revealed that the amount of (+)RNA began to increase starting 9 h p.i., indicating an accumulation of the newly synthesized (+)RNA genome. Cycloheximide was observed to abrogate the increase of newly made (+)RNA during HAstV infection. In conclusion, the use of sense or antisense primers during the RT reaction together with cycloheximide enabled us to quantitatively detect ( )RNAs, and this proved to be an useful tool in understanding the replication cycle of HAstV. PMID- 20544236 TI - The dynamics of the actin cytoskeleton during sporogenesis in Psilotum nudum L. AB - The actin cytoskeleton (microfilaments, MFs) accompanies the tubulin cytoskeleton (microtubules) during the meiotic division of the cell, but knowledge about the scope of their physiological competence and cooperation is insufficient. To cast more light on this issue, we analysed the F-actin distribution during the meiotic division of the Psilotum nudum sporocytes. Unfixed sporangia of P. nudum were stained with rhodamine-phalloidin and 4',6-diamidino-2-phenylindole dihydrochloride, and we monitored the changes in the actin cytoskeleton and nuclear chromatin throughout sporogenesis. We observed that the actin cytoskeleton in meiotically dividing cells is not only part of the kariokinetic spindle and phragmoplast but it also forms a well-developed network in the cytoplasm present in all phases of meiosis. Moreover, in telophase I F-actin filaments formed short-lived phragmoplast, which was adjacent to the plasma membrane, exactly at the site of future cell wall formation. Additionally, the meiocytes were pre-treated with cytochalasin-B at a concentration that causes damage to the MFs. This facilitated observation of the effect of selective MFs damage on the course of meiosis and sporogenesis of P. nudum. Changes were observed that occurred in the cytochalasin-treated cells: the daughter nuclei were located abnormally close to each other, there was no formation of the equatorial plate of organelles and, consequently, meiosis did not occur normally. It seems possible that, if the actin cytoskeleton only is damaged, regular cytokinesis will not occur and, hence, no viable spores will be produced. PMID- 20544237 TI - Glutamate kinase from Thermotoga maritima: characterization of a thermophilic enzyme for proline biosynthesis. AB - Glutamate kinase (GK), an enzyme involved in osmoprotection in plants and microorganisms, catalyses the first and controlling step of proline biosynthesis. The proB gene encoding GK was cloned from the hyperthermophilic bacterium Thermotoga maritima and overexpressed in Escherichia coli, and the resulting protein was purified to homogeneity in three simple steps. T. maritima GK behaved as a tetramer, showing maximal activity at 83 degrees C, and was inhibited by ADP and proline. Although T. maritima GK exhibited high amino acid similarity to the mesophilic E. coli GK, it was less dependent of Mg ions and was not aggregated in the presence of proline. Moreover, it displayed a greater thermostability and higher catalytic efficiency than its mesophilic counterpart at elevated temperatures. PMID- 20544238 TI - Insight into the lithium/hydrogen bonding in (CH2)2X...LiY/HY (X: C=CH2, O, S; Y=F, Cl, Br) complexes. AB - The nature of the lithium/hydrogen bonding between (CH(2))(2)X(X: C=CH(2), O, S) and LiY/HY(Y=F, Cl, Br) have been theoretically investigated at MP2/6-311++G (d, p) level, using Bader's "atoms in molecules (AIM)" theory and Weinhold's "natural bond orbital (NBO)" methodology. The molecule formation density differences (MFDD) of the titled complexes are analyzed. Two kinds of geometries of the lithium/hydrogen bonded complexes are compared. As a whole, the nature of lithium bond and hydrogen bond are different. For the same electron donor and the same acceptor, lithium bond is stronger than hydrogen bond. For the same electron acceptor and different kind of donors, the interaction energies follows the n type> pi-type > pseudo-pi-type order. For the same (CH(2))(2)X, the interaction energy increases in the sequence of Y=F, Cl and Br for lithium bond systems while it decreases for hydrogen bond systems. Electron transfer plays an important role in the formation of lithium bond systems while it is less important in the hydrogen bond systems. PMID- 20544239 TI - Molecular dynamics simulations of Nafion and sulfonated polyether sulfone membranes. I. Effect of hydration on aqueous phase structure. AB - We measured the water uptakes and proton conductivities of a Nafion membrane and three sulfonated polyether sulfone membranes (SPESs) with different values of ion exchange capacity (IEC = 0.75, 1.0 and 1.4 meq/g) in relation to relative humidity in order to apply the findings to polymer electrolyte membrane fuel cells. The number of water molecules per sulfonic acid group lambda at each humidity level was independent of the relative humidity for all membranes, but the proton conductivities of the SPESs were inferior to that of Nafion for the same lambda value. Classical molecular dynamics simulations for the same membranes were carried out using a consistent force field at lambda = 3, 6, 9, 12 and 15. The structural properties of water molecules and hydronium ions at a molecular level were estimated from radial distribution functions and cluster size distributions of water. We found that the radial distribution function of S(sulfonic acid)-S(sulfonic acid) of Nafion at lambda = 3 indicated a significant correlation between the S-S pair, due to water channels, while the S-S pair of the SPESs showed a poor correlation. The cluster size distribution of water was also calculated in order to estimate the connectivity of the water channel. It is clear that some water is present in the SPESs as small, isolated clusters, especially when the water content is low. PMID- 20544240 TI - Molecular dynamics investigation of psalmopeotoxin I. Probing the relationship between 3D structure, anti-malarial activity and thermal stability. AB - PcFK1 is a member of the cysteine knot inhibitor family that displays anti malarial properties. The naturally occurring molecule is ~ 40 amino acids in length and forms a highly constrained 3D structure due to the presence of 3 disulfide and multiple intra-molecular H-bonds. Recent experimental studies on PcFK1 wild-type and mutants, where the cystiene residues of each disulfide bond were mutated into serine residues, suggest that alterations to these structural constraints can give rise to sizeable differences in SAR. To better understand the relationship between the dynamic inhibitor 3D structure, biophysical and biological properties we have performed solution based molecular dynamics calculations over 150 ns using the CHARMM forcefield. We have analyzed the theoretical trajectory in a systematic way using principal components analysis, which allows us to identify the correlated nature of the protein loop, turn and sheet movements. We have identified the key molecular motions that give rise to the differing SAR which has helped to more precisely direct our ongoing SAR studies in this important therapeutic area. PMID- 20544241 TI - New pre-clotting method for fibrin glue in a non-sealed graft used in an LVAD: the KYO method. AB - Pre-clotting has been applied to a vascular prosthesis with high permeability (non-sealed graft). In this study, conventional pre-clotting methods were compared with our novel method, which keeps high-yield optimization of hemostasis, the KYO method. Fibrinogen solution (A) and thrombin solution (B) of fibrin glue (Beriplast P Combi-Set((r))) were applied to the graft (Cooly low porosity woven graft) by five methods; Group 1: control, without fibrin glue; Group 2: spray method, spraying solutions A and B simultaneously; Group 3: rub method, rubbing solution A first, and then rubbing solution B on the graft; Group 4: rub-and-spray method, rubbing solution A on the graft, then spraying solutions A and B; Group 5: the KYO method, rubbing solution A into the graft with the finger, then rubbing solution B on the graft. Burst pressure, the point of saline solution leakage, was measured 10 times for each group. The grafts were microscopically examined using HE staining and electron microscopy. The average burst pressure was 12.6 +/- 1.5 mmHg in Group 1, 27.1 +/- 3.3 mmHg in Group 2, 22.4 +/- 7.1 mmHg in Group 3, 41.0 +/- 9.0 mmHg in Group 4, and 300 mmHg in Group 5. Saline solution did not leak through the graft at a pressure of 300 mmHg in Group 5. There were statistically significant differences among the groups. The relationship between fibrin glue and the graft was unclear in all groups by HE staining. Electron microscopic photographs showed a smooth surface and fibrin glue permeating the graft fibers in Group 5. The KYO method was better than the others in terms of resistance to pressure. It was a very simple method, and could thus come into widespread use. PMID- 20544242 TI - Anti-Ro antibody and clinical manifestations: lessons from systemic lupus erythematosus in the elderly. PMID- 20544243 TI - Acrylamine-induced autoimmune phenomena. AB - The objective of this study is to document a series of cases of occupationally derived autoimmune disease. Individuals with occupational exposure to acrylamides were evaluated clinically and biochemically/immunologically for evidence of autoimmune disease. Symptoms and signs and immuno-reactivity were monitored during exposure-free and re-exposure as part of the individuals' clinical evaluation. Six individuals with occupational acrylamide exposure had clinical and laboratory alterations characteristic of drug-induced autoimmune disease, specifically lupus, anti-phospholipid syndrome, Sjogren's syndrome, scleroderma, and polymyositis. The similarity of the full spectrum of disease in the reported patients to that found with procainamide strongly suggests the effects of occupational exposure. This uncontrolled study suggests the need for a full epidemiologic analysis of all individuals working with such occupational exposure, including full clinical and immunological examination. PMID- 20544244 TI - When should we use parenteral methotrexate? AB - Oral methotrexate is the benchmark against which other disease-modifying anti rheumatic drugs are measured. The use of parenteral methotrexate for those failing to tolerate or respond to oral therapy is accepted, but indications for its use and its place in the therapeutic ladder have not been fully investigated. We assessed the use of parenteral methotrexate (MTX) in our rheumatoid arthritis (RA) population and compared the characteristics of these patients to a matched group of those on oral therapy. We compared response rates to each approach using DAS 28 scores, ESR and visual analogue scales. Inferences on costs of parenteral therapy were made and predictors of response defined. We found that 10% of our total RA patient population were on parenteral methotrexate, having failed to tolerate or respond to oral therapy. Seventy-five percent of these met the criteria for the use of anti-tumour necrosis factor (TNF) agents. Overall response rates were equivalent to those obtained by responders to oral MTX. Patients on parenteral therapy were younger and were more likely to have extreme values of body mass index (BMI) than those on oral therapy. The approach was economically viable, although many patients unnecessarily attended hospital to receive their injections. We advocate consideration of parenteral MTX in all RA patients unresponsive to oral therapy prior to treatment with anti-TNF therapy. Response to parenteral therapy can be predicted by low BMI (below 22 kg/m(2)), possibly as a result of malabsorption, or by high BMI (over 30) as a result of gastrointestinal intolerance. A mechanism to deliver this option through self administration in the community should be encouraged. PMID- 20544245 TI - A long-term prospective randomized controlled study of non-specific interstitial pneumonia (NSIP) treatment in scleroderma. AB - The association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP). OBJECTIVES: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment. METHODS: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment. RESULTS: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups. CONCLUSIONS: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy. PMID- 20544246 TI - The role of zoledronic acid in the management of osteoporosis. AB - Bisphosphonates are the current standard of care for treatment of osteoporosis. However, oral bisphosphonates are associated with complicated dosing regimens because of poor absorption and have the potential for upper gastrointestinal (GI) tract irritation, resulting in poor adherence and persistence. Zoledronic acid (ZOL) 5 mg, a once-yearly intravenous bisphosphonate, is approved for treatment and prevention of postmenopausal osteoporosis, increasing bone mass in men with osteoporosis, and treatment and prevention of glucocorticoid-induced osteoporosis. Because it is administered as an infusion, ZOL ensures adherence and persistence over the entire 12-month dosing interval and bypasses the GI absorption/irritation problems associated with oral bisphosphonates. The objective of this study was to review the safety and efficacy of 5 mg ZOL and its potential for improving patient compliance. Published reports dating back to 2001 were reviewed, with emphasis on osteoporosis treatment. In the HORIZON-Pivotal Fracture Trial, annual infusions of 5 mg ZOL produced significant reductions in risk of morphometric vertebral fractures (70%) and hip fractures (41%) vs placebo over 3 years in postmenopausal women with osteoporosis. In the HORIZON-Recurrent Fracture Trial, an annual infusion of 5 mg ZOL after repair of a recent low trauma hip fracture was associated with significant reductions in risk for new clinical fractures (35%) vs placebo. In men with osteoporosis, an annual treatment of ZOL over 2 years increased lumbar spine bone mineral density (BMD) by 6% compared with baseline. In patients starting or continuing treatment with chronic glucocorticoids, ZOL resulted in significantly greater increases in lumbar spine BMD over 1 year than an oral bisphosphonate. In postmenopausal women with osteopenia, a single infusion of ZOL over a 2-year period produced significantly greater gains in lumbar spine and hip BMD than placebo. ZOL is generally safe and well tolerated. Five milligrams of ZOL has the potential to improve compliance with osteoporosis therapy and, consequently, to reduce fracture risk in clinical practice. PMID- 20544247 TI - Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study. AB - To evaluate the efficacy and safety of natalizumab in patients with active relapsing-remitting multiple sclerosis (MS). We included 285 MS patients receiving natalizumab. Clinical, neuroradiological and safety data were registered every 6 months. Neutralizing antibodies (NABs) were tested after 6 months of treatment. After 1 year, the annualized relapse rate decreased to 0.26, with a significant reduction compared to the previous year (2.13). At 24 months the proportion of "relapse free" patients was 78% while that of "MRI free" patients was 69%. Considering clinical and MRI cumulative activity, "disease free" patients were 63% at 24 months. A total of 18 patients showed NABs positivity. We reported 34 cases of treatment interruptions. In conclusion, our data confirm the remarkable efficacy of natalizumab in a group of patients with higher disease activity than that of pivotal studies. PMID- 20544248 TI - Transient supranuclear paresis of the abduction in viral encephalitis of the brainstem. AB - The supranuclear paresis of the abducens system, also known as posterior internuclear ophthalmoplegia of abduction, is a very rare disorder clinically characterized by unilateral or bilateral abduction paresis sometimes associated with nystagmus of the contralateral adducting eye, slowing of abduction saccades, and intact horizontal vestibulo-ocular reflex. Here, we report a 35-year-old woman who presented transient left side abduction deficit in conjunction, as the only symptom of self-limited viral encephalitis of the brainstem. Brain MRI including DWI and ADC maps showed an area of abnormal signal intensity in the mid right ponto-mesencephalic junction. PCR analysis of cerebrospinal fluid showed an enterovirus infection. Spontaneous clinical recovery rapidly occurred 2 days after onset. The brainstem lesion was undetectable at 5-week brain MRI follow-up. PMID- 20544249 TI - Bacterial community dynamics in the marine sponge Rhopaloeides odorabile under in situ and ex situ cultivation. AB - Cultivation of sponges is being explored to supply biomaterial for the pharmaceutical and cosmetics industries. This study assesses the impact of various cultivation methods on the microbial community within the sponge Rhopaloeides odorabile during: (1) in situ cultivation under natural environmental conditions, (2) ex situ cultivation in small flow-through aquaria and (3) ex situ cultivation in large mesocosm systems. Principal components analysis of denaturing gradient gel electrophoresis profiles indicated a stable microbial community in sponges cultured in situ (grown in the wild) and in sponges cultured ex situ in small flow-through aquaria over 12 weeks. In contrast, a shift in the microbial community was detected in sponges cultivated ex situ in large mesocosm aquaria for 12 months. This shift included (1) a loss of some stable microbial inhabitants, including members of the Poribacteria, Chloroflexi and Acidobacteria and (2) the addition of new microbes not detected in the wild sponges. Many of these acquired bacteria had highest similarity to known sponge-associated microbes, indicating that the sponge may be capable of actively selecting its microbial community. Alternatively, long-term ex situ cultivation may cause a shift in the dominant microbes that facilitates the growth of the more rare species. The microbial community composition varied between sponges cultivated in mesocosm aquaria with different nutrient concentrations and seawater chemistry, suggesting that these variables play a role in structuring the sponge-associated microbes. The high growth and symbiont stability in R. odorabile cultured in situ confirm that this is the preferred method of aquaculture for this species at this time. PMID- 20544250 TI - Non-muscle invasive bladder cancer with concomitant vaginal urothelial carcinoma: a case report and review of the literature. AB - A 74-year-old female was referred to our hospital for non-muscle invasive bladder tumors initially treated at another hospital. Preoperatively, computed tomography and magnetic resonance imaging demonstrated non-muscle invasive bladder tumors and a vaginal tumor. A second transurethral resection of the bladder tumors, transvaginal tumor resection, and systemic chemotherapy were performed. The histopathological appearances of both tumors were very similar and the diagnoses were urothelial carcinoma (UC). The pathogenesis of the vaginal UC was considered to be the primary UC or metastasis from the bladder UC. Vaginal UC is extremely rare and this is only the 15th report in the literature. PMID- 20544251 TI - Effectiveness of skin icing in reducing pain associated with goserelin acetate injection. AB - BACKGROUND: Goserelin acetate, which is injected through a 16-gauge needle, makes some patients feel substantial, although tolerable, pain. We tried to clarify whether injection pain was reduced by icing the skin at the injection site. METHODS: Pain associated with the injection of goserelin acetate was prospectively evaluated in 48 patients who had received an 10.8-mg goserelin injection at least once previously. In this study, the first injection was administered by usual methods, and 3 months later a second injection was administered after icing the skin at the injection site. Pain intensity was evaluated by visual analogue scale (VAS) pain score. RESULTS: VAS pain scores for the usual injection method were 32.4 +/- 21.7 mm [mean +/- 2 standard deviation (SD)] and was significantly lower (16.4 +/- 17.9) for the icing method (p = 0.001, paired t test). Thirty-three (68.8%), eight (16.7%), and seven (14.6%) of the 48 patients reported a decrease, no change, and increase, respectively, in VAS pain score by the icing method. CONCLUSIONS: Icing at the injection site of goserelin acetate is a safe and effective method to reduce injection pain. This method can be easily performed in daily practice if a patient complains of pain at the injection site. PMID- 20544252 TI - A case of metastatic testicular cancer complicated by pulmonary hemorrhage due to choriocarcinoma syndrome. AB - A 40-year-old man was referred to our hospital for treatment of metastatic testicular cancer. Computerized tomography revealed multiple lung, liver, and retroperitoneal lymph node metastases. In addition, magnetic resonance imaging revealed multiple brain metastases. Induction chemotherapy with bleomycin, etoposide, and cisplatin was started the day after a high orchiectomy. The pathological diagnosis of the surgical specimen was yolk sac carcinoma. The serum human chorionic gonadotropin (hCG) was markedly increased to 630,000 mIU/ml, which suggested the presence of a choriocarcinoma element at metastatic sites. The patient subsequently suffered respiratory failure due to pulmonary hemorrhage. Intensive supportive care prevented a fatal outcome. Physicians who treat advanced testicular tumors should be aware of the potential complication of acute pulmonary hemorrhage, called choriocarcinoma syndrome, in cases with a high hCG level, which indicates a rapidly progressive and high-volume choriocarcinoma. PMID- 20544254 TI - Identification of a suppressor gene for the arginine-auxotrophic argJ mutation in Corynebacterium glutamicum. AB - We recently proposed a metabolic engineering strategy for L-ornithine production based on the hypothesis that an increased intracellular supply of N acetylglutamate may further enhance L-ornithine production in a well-defined recombinant strain of Corynebacterium glutamicum. In this work, an argJ-deficient arginine auxotrophic mutant of C. glutamicum is suppressed by a different locus of C. glutamicum ATCC13032. Overexpression of the NCgl1469 open reading frame (ORF), exhibiting N-acetylglutamate synthase (NAGS) activity, was able to complement the C. glutamicum arginine-auxotrophic argJ strain and showed increased NAGS activity from 0.03 to 0.17 units mg(-1) protein. Additionally, overexpression of the NCgl1469 ORF resulted in a 39% increase in excreted L ornithine. These results indicate that the intracellular supply of N acetylglutamate is a rate-limiting step during L-ornithine production in C. glutamicum. PMID- 20544253 TI - Neuronal ciliary signaling in homeostasis and disease. AB - Primary cilia are a class of cilia that are typically solitary, immotile appendages present on nearly every mammalian cell type. Primary cilia are believed to perform specialized sensory and signaling functions that are important for normal development and cellular homeostasis. Indeed, primary cilia dysfunction is now linked to numerous human diseases and genetic disorders. Collectively, primary cilia disorders are termed as ciliopathies and present with a wide range of clinical features, including cystic kidney disease, retinal degeneration, obesity, polydactyly, anosmia, intellectual disability, and brain malformations. Although significant progress has been made in elucidating the functions of primary cilia on some cell types, the precise functions of most primary cilia remain unknown. This is particularly true for primary cilia on neurons throughout the mammalian brain. This review will introduce primary cilia and ciliary signaling pathways with a focus on neuronal cilia and their putative functions and roles in human diseases. PMID- 20544255 TI - Didymosphaeria igniaria: a new microorganism useful for the enantioselective reduction of aryl-aliphatic ketones. AB - Didymosphaeria igniaria is a promising biocatalyst in asymmetric reductions of prochiral aromatic-aliphatic ketones such as acetonaphthones, acetophenones, and acetylpyridines. The organism converted the substrates mainly to (S)-alcohols. Excellent results in terms of conversion and enantioselectivity (100% yield, >99% ee) were obtained with acetonaphthones. In case of acetyl pyridines, the optical purity of the product depended on the position of the carbonyl group on the pyridine ring and followed the order 2-acetyl ? 4-acetyl > 3-acetyl-pyridine. Transformation of o-methoxy-acetophenone gave optically pure (S)-(-)-1-(2 methoxyphenyl)-ethanol in 95% yield. The transformation of para-methyl ketone gave (R)-alcohol (81% ee), whereas para-bromo ketone gave (S)-alcohol (98% ee). Monitoring of the biotransformation of these substrates over time led to the conclusion that for both substrates, non-selective carbonyl group reduction occurred in the first step, followed by selective oxidation of the (R)-isomer of p-bromo-phenylethanol and selective oxidation of the (S)-isomer of p-methyl phenylethanol. D. igniaria exhibited poor enantioselectivity in the reduction of bicyclic aryl-aliphatic ketones such as 1- and 2-tetralones. Only (S)-5-methoxy-1 tetralol was obtained in optically pure (>99% ee) form. PMID- 20544256 TI - Bacterial community diversity in paper mills processing recycled paper. AB - Paper mills processing recycled paper suffer from biofouling causing problems both in the mill and final product. The total bacterial community composition and identification of specific taxa in the process water and biofilms at the stock preparation and paper machine areas in a mill with recycled paper pulp was described by using a DNA-based approach. Process water in a similar mill was also analyzed to investigate if general trends can be found between mills and over time. Bacterial community profiles, analyzed by terminal-restriction fragment length polymorphism (T-RFLP), in process water showed that the dominant peaks in the profiles were similar between the two mills, although the overall composition was unique for each mill. When comparing process water and biofilm at different locations within one of the mills, we observed a separation according to location and sample type, with the biofilm from the paper machine being most different. 16S rRNA gene clone libraries were generated and 404 clones were screened by RFLP analysis. Grouping of RFLP patterns confirmed that the biofilm from the paper machine was most different. A total of 99 clones representing all RFLP patterns were analyzed, resulting in sequences recovered from nine bacterial phyla, including two candidate phyla. Bacteroidetes represented 45% and Actinobacteria 23% of all the clones. Sequences with similarity to organisms implicated in biofouling, like Chryseobacterium spp. and Brevundimonas spp., were recovered from all samples even though the mill had no process problems during sampling, suggesting that they are part of the natural paper mill community. Moreover, many sequences showed little homology to as yet uncultivated bacteria implying that paper mills are interesting for isolation of new organisms, as well as for bioprospecting. PMID- 20544257 TI - Large-scale production of magnetic nanoparticles using bacterial fermentation. AB - Production of both nano-sized particles of crystalline pure phase magnetite and magnetite substituted with Co, Ni, Cr, Mn, Zn or the rare earths for some of the Fe has been demonstrated using microbial processes. This microbial production of magnetic nanoparticles can be achieved in large quantities and at low cost. In these experiments, over 1 kg (wet weight) of Zn-substituted magnetite (nominal composition of Zn(0.6)Fe(2.4)O4) was recovered from 30 l fermentations. Transmission electron microscopy (TEM) was used to confirm that the extracellular magnetites exhibited good mono-dispersity. TEM results also showed a highly reproducible particle size and corroborated average crystallite size (ACS) of 13.1 +/- 0.8 nm determined through X-ray diffraction (N = 7) at a 99% confidence level. Based on scale-up experiments performed using a 35-l reactor, the increase in ACS reproducibility may be attributed to a combination of factors including an increase of electron donor input, availability of divalent substitution metal ions and fewer ferrous ions in the case of substituted magnetite, and increased reactor volume overcoming differences in each batch. Commercial nanometer sized magnetite (25-50 nm) may cost $500/kg. However, microbial processes are potentially capable of producing 5-90 nm pure or substituted magnetites at a fraction of the cost of traditional chemical synthesis. While there are numerous approaches for the synthesis of nanoparticles, bacterial fermentation of magnetite or metal-substituted magnetite may represent an advantageous manufacturing technology with respect to yield, reproducibility and scalable synthesis with low costs at low energy input. PMID- 20544258 TI - Alkalinity and dissolved oxygen as controlling parameters for ammonia removal through partial nitritation and ANAMMOX in a single-stage bioreactor. AB - The oxidation of ammonia to dinitrogen through partial nitritation and anaerobic ammonium oxidation (ANAMMOX) in a single-stage bioreactor is based on suppressing the nitratation process. The single-stage process operated on a laboratory-scale fixed film bioreactor achieved ammonia removal of 0.7 kg NH4-N/(m(3) day) at 4 h hydraulic retention time (HRT) by controlling the nitratation process through a 'three-way control mechanism' comprising control of electron donor (nitrite), electron acceptor (oxygen) and carbon source (bicarbonate). The control of alkalinity and dissolved oxygen (DO) concentrations in feed to maintain an alkalinity to ammonia ratio of less than 8 and DO loading of less than 0.06 mg O/(mg N day), respectively, was necessary for inhibiting nitratation and enhancing partial nitritation and ANAMMOX. Therefore, feed alkalinity along with DO concentrations are critical controlling parameters in a single-stage biological process for nitrogen removal. PMID- 20544259 TI - Accommodation limits induced optical defocus in defocus experiments. AB - A common method to induce optical defocus is by means of positive lenses. However, accommodation, pupil size, and depth of focus are important factors determining the amount of defocus achieved. We therefore studied the effect of accommodation on visual acuity with a natural pupil (miosis) and in cycloplegic mydriasis. Additionally, we looked at the amount of accommodation and pupil size fluctuation during the recording of a mfVEP. We found that the amount of defocus induced with lenses of positive power is limited in non-mydriatic experiments by accommodation and actual pupil size and may show marked variation during mfVEP recording. We therefore recommend using a mydriatic drug and, if required, an artificial pupil for defocus experiments. PMID- 20544260 TI - A reappraisal of the Ca2+ dependence of fast inactivation of Ca2+ release in frog skeletal muscle. AB - Two procedures to inhibit Ca(2+) release designed to differentiate between local and common pool mechanisms for the Ca(2+) dependent, fast inactivation of Ca(2+) release in skeletal muscle of the frog were compared. Inhibition by voltage dependent inactivation of Ca(2+) release, without modification of the single channel current of the Ryanodine Receptor (RyR) and the [Ca(2+)] close to the open pore, produced a reduction in the rate of inactivation linearly related to the reduction in the peak of Ca(2+) release flux. Linear fits in the individual fibers were performed, giving average values (+/-SEM, N = 8) of the best fit parameters of 5.75 x 10(-3) +/- 7.35 x 10(-4 )microM(-1) for the slope and 0.07 +/- 0.015 ms(-1) for the ordinate intercept. Inhibition of Ca(2+) release by reducing the Ca content of the sarcoplasmic reticulum (SR) involves reduction of the Ca(2+) current through the single RyR. The reduction in rate of inactivation also followed linearly the reduction in Ca(2+) peak release flux. The average values (+/-SEM) of the best fit parameters of linear fits were 14 x 10(-3) +/- 3.76 x 10(-3 )microM(-1) and 0.019 +/- 0.006 ms(-1) (N = 7) for slope and ordinate intercept respectively. The differences between both parameters were statistically significant (by t test, at P = 0.05). The extent of inactivation, measured by the peak/final Ca(2+) release flux ratio, was differentially affected by the two procedures. Inhibition by voltage dependent inactivation, despite slowing down the fast inactivation, increased the peak/final Ca(2+) release flux ratio. In contrast, depletion of the SR reticulum reduced it. If the fast inactivation is driven by the high [Ca(2+)] attained locally, close to the open pore of the RyR, the inhibition of Ca(2+) release due to voltage dependent inactivation should not modify the rate of inactivation while inhibition by SR Ca(2+) depletion should reduce it. A process driven by [Ca(2+)] in a common pool should depend on the overall Ca(2+) release independently of how it was modified. In this case both inhibitory procedures should reduce the inactivation rate similarly. Our findings are generally consistent with a common pool process. The differences between the two protocols could be understood if the organization of RyR in junctional and parajunctional release units is considered. PMID- 20544261 TI - Specialist leaf beetle larvae use volatiles from willow leaves infested by conspecifics for reaggregation in a tree. AB - Young, gregariously living larvae of the willow leaf beetles Plagiodera versicolora are known to exhibit characteristic aggregation-dispersion reaggregation behavior and local fidelity to a host tree. In this study, we investigated whether plant volatiles induced by feeding P. versicolora larvae were involved in the reaggregation behavior. Under laboratory conditions, we conducted dual-choice bioassays and found that the first and second instars discriminated between volatiles from leaves infested by larvae and volatiles from uninfested leaves. The discriminative behavior was dependent on both the time leaves were infested and the age of discriminating larvae. First and second instars preferred odor from 1-d-infested leaves to odor from uninfested leaves, whereas third instars (solitary stage) did not discriminate between these volatile blends. Odor from 2-d-infested leaves was preferred to odor from 1-d infested leaves by first instars, whereas odor from leaves infested for 3 d was not attractive to these very young larvae. Neither was odor of leaves infested for 1 d and then left uninfested for 1 or 2 d attractive to young larvae. The data suggest that the first and second instars use volatiles from a leaf newly infested by conspecific larvae as one of the reaggregation cues. We detected several herbivore-induced compounds in the headspace of the attractive leaves. Among those, a mixture of synthetic (E)-beta-ocimene, (Z)-beta-ocimene, allo ocimene, and linalool was found to attract the larvae. PMID- 20544262 TI - Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients. AB - This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients. PMID- 20544263 TI - IL-10/TGF-beta-treated dendritic cells, pulsed with insulin, specifically reduce the response to insulin of CD4+ effector/memory T cells from type 1 diabetic individuals. AB - INTRODUCTION: Diabetogenic autoreactive T cells with effector/memory characteristics are described in type 1 diabetes patients (T1D). Alternatively activated dendritic cells (aaDCs) have been regarded as promising tools for clinical application in autoimmune diseases (ADs), although their ability to induce antigen-specific tolerance in T cells derived from ADs has yet to be determined. METHODS: Monocyte-derived dendritic cells (DCs) were produced utilizing GM-CSF and IL-4, and aaDCs by adding IL-10 and TGF-beta (10/TGF-DC) during differentiation. Both cell groups were insulin-loaded, maturated with lipopolysaccharide, and cocultured with autologous effector/memory T cells derived from T1D individuals, in order to evaluate the induction of insulin specific tolerance. RESULTS AND DISCUSSION: In five of eight T1D patients analyzed in vitro, 10/TGF-DC were able to induce insulin-specific tolerance in effector/memory CD4+ T cells (50.4% +/- 13.2 less proliferation), without affecting the proliferative response to an unrelated antigen (candidin). Tolerance induction was dependent on the current activation state of CD4+ T cells in each patient. 10/TGF-DC-stimulated T cells acquired an IL-2(low)IFN gamma(low)IL-10(high) cytokine profile, and their hyporesponsiveness could be reverted upon exposure to IL-2. This study shows a perspective about the in vitro ability of monocyte-derived 10/TGF-DC to induce antigen-specific tolerance in effector/memory T cells generated during the course of an autoimmune disease. PMID- 20544264 TI - Dual oscillator model of the respiratory neuronal network generating quantal slowing of respiratory rhythm. AB - We developed a dual oscillator model to facilitate the understanding of dynamic interactions between the parafacial respiratory group (pFRG) and the preBotzinger complex (preBotC) neurons in the respiratory rhythm generation. Both neuronal groups were modeled as groups of 81 interconnected pacemaker neurons; the bursting cell model described by Butera and others [model 1 in Butera et al. (J Neurophysiol 81:382-397, 1999a)] were used to model the pacemaker neurons. We assumed (1) both pFRG and preBotC networks are rhythm generators, (2) preBotC receives excitatory inputs from pFRG, and pFRG receives inhibitory inputs from preBotC, and (3) persistent Na(+) current conductance and synaptic current conductances are randomly distributed within each population. Our model could reproduce 1:1 coupling of bursting rhythms between pFRG and preBotC with the characteristic biphasic firing pattern of pFRG neurons, i.e., firings during pre inspiratory and post-inspiratory phases. Compatible with experimental results, the model predicted the changes in firing pattern of pFRG neurons from biphasic expiratory to monophasic inspiratory, synchronous with preBotC neurons. Quantal slowing, a phenomena of prolonged respiratory period that jumps non deterministically to integer multiples of the control period, was observed when the excitability of preBotC network decreased while strengths of synaptic connections between the two groups remained unchanged, suggesting that, in contrast to the earlier suggestions (Mellen et al., Neuron 37:821-826, 2003; Wittmeier et al., Proc Natl Acad Sci USA 105(46):18000-18005, 2008), quantal slowing could occur without suppressed or stochastic excitatory synaptic transmission. With a reduced excitability of preBotC network, the breakdown of synchronous bursting of preBotC neurons was predicted by simulation. We suggest that quantal slowing could result from a breakdown of synchronized bursting within the preBotC. PMID- 20544265 TI - Increased serum levels of epidermal growth factor in children with autism. AB - The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the cellular proliferation and the differentiation of the central and peripheral nervous system. In this study we hypothesized that EGF may play a role in the pathophysiology of autism and examined serum EGF levels in children with autism. We measured serum levels of EGF in the 27 autistic children and 28 age- matched normal controls. The serum levels of EGF in the subjects with autism were significantly higher than those of normal control subjects. However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. This is the first report demonstrating the increased serum levels of EGF in children with autism. This study suggests that increased levels of EGF might have an importance in the pathophysiology of autism. PMID- 20544266 TI - Cancer risk in Norwegian world class athletes. AB - BACKGROUND: Physical activity appears to be inversely related to cancer risk, although the evidence is convincing for colon cancer only. As physical activity levels are difficult to measure in the general population, we aimed to investigate how physical activity influences cancer risk using a cohort of Norwegian world class athletes. METHODS: The cohort includes 3,428 athletes. Individual questionnaires gave information about physical activity and lifestyle variables until attained age. To elucidate the level of cancer risk, groups of athletes were compared to the general population (external comparisons) and to each other (internal comparisons). RESULTS: A slightly reduced risk of total cancer was observed in the cohort of athletes, but stronger effects were observed for subgroups. The risk reduction was most pronounced for lung cancer and for leukemia/lymphoma. In women, a threefold increased risk of thyroid cancer was observed. CONCLUSION: This cohort of athletes seems to have a reduced risk of cancer. The beneficial association, however, is weak and may be attributed to healthy lifestyle as well as to physical activity. Prolonged strenuous exercise may also increase the risk of thyroid cancer in women. PMID- 20544267 TI - Supercilious cell cycles in the human embryo. PMID- 20544268 TI - Assessment of genetic relatedness of crossbred chicken populations using microsatellite markers. AB - To measure genetic relatedness between populations, for breeding purposes, we analyzed 170 birds from six crossbred populations of three pure lines of White Leghorn chickens, using 14 microsatellite markers. All the microsatellites were polymorphic, with 2-6 alleles. The mean number of alleles per locus was 3.21. The effective number of alleles varied from 1.14 to 3.94. The observed heterozygosity varied from 0.133 to 1.00, with a mean of 0.748. The F (IS) values were mostly negative, with an average of -0.345. The mean F (ST) value was 0.056. The Nm values ranged from 1.91 to 42.17. The highest genetic identity was observed between IWI x IWK and IWK x IWI. The relation between any two groups of crosses was more than 85%. The results suggest that the crossbred populations were very closely related. PMID- 20544269 TI - Evolution of the heterochromatic regions on maize B long arm based on the sequence structure of CL-repeat variants. AB - Evolution of heterochromatic regions in the B long arm was studied in two directions: construction of a phylogenetic tree from mutational variants of CL repeat and analysis of the XbaI fragments carrying CL-repeat and the repeat structural variants. Using tertiary trisomes and hypoploids of a set of B-10L translocations, the fragments associated with CL-repeat and the variants in each of the three distal heterochromatic (DH) regions were identified. Twenty fragments comprising the CL-repeat were observed in the B-chromosome, and each was assigned to an individual DH region. Four deletions, one insertion, and a large number of mutational variants from each of the three DH regions were isolated and sequenced. The sequences of 27 mutational variants were used to establish a phylogenetic tree which divided the 27 variants into three groups, each of which was associated with a distinct DH region and elucidated an evolution order of the three DH regions. According to the tree, the DH2 was the earliest DH region, which gave rise to the DH3 to be followed by the DH1. The distributions of the fragments including CL-repeat and structural variants in the three DH regions were consistent with such evolution order. PMID- 20544270 TI - A recess evaluation with the players: taking steps toward participatory action research. AB - This playground study conceptualizes recess as a time and space that belongs to students; their inclusion in this evaluation is a notable difference from other recess/playground research. The goal was to help elementary school students make the changes they felt were needed on their playground. After conducting structured observations and student and recess aide focus groups, a report was presented to all stakeholders, and recess changes were made. We seek to show how the process of being inclusive during the evaluation was not only valuable for determining problem definition and potential interventions, but was also necessary to determine the best methods for solutions, move toward second-order change, and to create a space to facilitate children's participation and empowerment. PMID- 20544271 TI - Lack of association between ATM C.1066-6T > G mutation and breast cancer risk: a meta-analysis of 8,831 cases and 4,957 controls. AB - Epidemiological studies have evaluated the association between ATM C.1066-6T > G (IVS10-6T > G) mutation and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of 11 studies including 8,831 cases and 4,957 controls were identified. The carrier frequency of the ATM C.1066-6T > G mutation was 0.5% (45/8,831) in patients with breast cancer and 0.7% (38/4,957) in healthy controls. When all the 11 studies were pooled into the meta-analysis, there was no evidence for significant association between C.1066 6T > G mutation and breast cancer risk (OR 0.87, 95% CI 0.55-1.37). In the subgroup analyses by source of controls and family history with BRCA1/2 status, no significant association were found in any subgroup of population. When sensitivity analyses were performed, all the results were not materially altered. In summary, the meta-analysis strongly suggests that ATM C.1066-6T > G mutation is not associated with increased breast cancer risk. PMID- 20544272 TI - Predicting breast cancer risk using mammographic density measurements from both mammogram sides and views. AB - Mammographic density is a strong risk factor for breast cancer. Which and how many x-rays are used for research, and how mammographic density is measured varies across studies. In this article, we compared three different measurements (absolute dense area, percent dense area and percent dense volume) from each of four mammograms [left, right, medio-lateral oblique (MLO) and cranio-caudal (CC) views] using three different methods of measurement [computer-assisted thresholding, visual assessment and standard mammogram form (SMF)] to investigate whether additional measurements and/or different methods of measurement provide more information in the prediction of breast cancer risk. Mammographic density was measured in all four mammograms from 318 cases and 899 age-matched controls combined from the Cambridge and Norwich Breast Screening Programmes. Measurements were averaged across various combinations of mammogram type and/or view. Conditional logistic regression was used to estimate odds ratios associated with increasing quintiles of each mammographic measure. Overall, there appeared to be no difference in the fit of the models using two or four mammograms compared to the models using just the contralateral MLO or CC mammogram (all P > 0.07) for all methods of measurement. Common practice of measuring just the contralateral MLO or CC mammogram for analysis in case-control studies investigating the association between mammographic density and breast cancer risk appears to be sufficient. PMID- 20544273 TI - Identification of immunodominant HLA-B7-restricted CD8+ cytotoxic T cell epitopes derived from mammaglobin-A expressed on human breast cancers. AB - Mammaglobin-A (MGBA), a 10-kD protein, is over expressed in 80% of primary and metastatic human breast cancers. Breast cancer patients demonstrate high frequencies of CD8(+) cytotoxic T lymphocytes (CTL) specific to MGBA. Defining CD8(+) CTL responses to HLA class I-restricted MGBA-derived epitopes assumes significance in the context of our ongoing efforts to clinically translate vaccine strategies targeting MGBA for prevention and/or treatment of human breast cancers. In this study, we define the CD8(+) CTL response to MGBA-derived candidate epitopes presented in the context of HLA-B7, which has a frequency of 17.7% in Caucasian and 15.5% in African American populations. We identified seven MGBA-derived candidate epitopes with high predicted binding scores for HLA-B7 using a computer algorithm. Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-B7 indicated that MGBA B7.3 (VSKTEYKEL), B7.6 (KLLMVLMLA), B7.7 (NPQVSKTEY), and B7.1 (YAGSGCPLL) have the highest HLA-B7 binding affinities. Further, two CD8(+) CTL cell lines generated in vitro against T2.B7 cells individually loaded with MGBA-derived candidate epitopes showed significant cytotoxic activity against MGBA B7.1, B7.3, B7.6, and B7.7. In addition, the same CD8(+) CTL lines lysed the HLA-B7(+)/MGBA(+) human breast cancer cell line DU-4475 but had no significant cytotoxicity against HLA-B7(-) or MGBA(-) breast cancer cell lines. Cold-target inhibition studies strongly suggest that MGBA B7.3 is an immunodominant epitope. In summary, our results define HLA B7-restriced, MGBA-derived, CD8(+) CTL epitopes with all of the necessary features for developing novel vaccine strategies against HLA-B7 expressing breast cancer patients. PMID- 20544274 TI - Investigation of the possible sources of heavy metal contamination in lagoon and canal water in the tannery industrial area in Dhaka, Bangladesh. AB - This study evaluated the heavy metal pollution level of tannery effluent-affected lagoon and canal water in the southwestern Dhaka, Bangladesh. The measured physicochemical parameters (electrical conductivity, chemical oxygen demand, pH, SO2-4, PO3-4, Cl-, and NO-3) and metals (As, Ca, Cd, Co, Cr, Cu, Fe, K, Mn, Ni, Pb, and Zn) were subjected to principal component (PCA) and hierarchical cluster analyses, and examining correlation matrix as well in order to explain the behavior and sources of the parameters/metals. The mean concentrations of the heavy metals in the lagoon and canal water were very high and, in most cases, exceeded the standard limits recommended by the Bangladesh Government. The following elemental associations were obtained from PCA and CA: Ca-Cd-Cr-Fe-K-Mn Pb-Zn, Co-Cu-Ni, and As, which could be linked to anthropogenic sources (i.e., processes of the tannery and paint industries with some contributions from the municipal waste system). Potassium, Ca, Cr, Mn, Fe, Zn, As, and Cd occurred as important anthropogenic markers in the lagoons and lower part of the canal. Copper, Co, and Ni were importantly distributed in the lower part of the canal, which also received metal inputs from the municipal waste and other industrial sources, including paint industry. GIS-based factor score maps, generated to show the spatial controls of the major processes affecting surface water hydrochemistry, suggest that the activities of paint and tannery industries and municipal sewage are pervasive processes in the area, whereas the contribution from pesticides (used for tanning and disinfecting hides) has localized effects. This study has provided the evidence that effluents discharged from the tannery and auxiliary industries and urban sewage system are the main sources of heavy metal pollution in the lagoon and canal water systems in the Hazaribagh area of southwestern Dhaka. The high mean concentrations (in mg/l) of Cr (5.27), Pb (0.81), As (0.59), and Cd (0.13) observed in the water samples may have serious public health and potential environmental hazard implications. PMID- 20544275 TI - Comparison of bioassessment results and costs between preserved and unpreserved macroinvertebrate samples from streams. AB - The choice to use or not use a preservative before sorting macroinvertebrate samples (i.e., dead specimens vs. living specimens) is based on studies not solely focused on the effects of preservation. Using identical sample processing protocols, we compared preserved and unpreserved samples for the following parameters: (1) the number of taxa and individuals for each major macroinvertebrate group, (2) ecological quality classes calculated with a multimetric index developed for the assessment of small Dutch lowland streams, and (3) costs of sample processing. We collected macroinvertebrate samples from three lowland streams in the Netherlands. At each site, we collected six replicate samples, of which three samples were preserved and three were not. Significantly different numbers of Ephemeroptera individuals and Hydracarina taxa and individuals were collected from preserved samples compared to unpreserved samples. In assessments based on these individual metrics, standardization of sample processing will be required. In streams with Ephemeroptera, the preservation of samples is necessary to optimize the number of Ephemeroptera individuals collected. In streams that contain Hydracarina, the preservation of samples will result in an underestimation of the number of Hydracarina taxa and individuals present. In only one instance there was a difference in ecological quality between preserved and unpreserved samples, indicating that assessing small Dutch lowland streams does not require standardization of sample preservation as part of the sample processing protocol. We detected no significant differences in sample processing costs between preserved and unpreserved samples. PMID- 20544276 TI - Hydrochemical characteristic of coastal aquifer from Tuticorin, Tamil Nadu, India. AB - This article deals with a systematic hydrochemical study carried out in coastal aquifers, Tuticorin, Tamil Nadu, to assess groundwater quality. A total of 29 groundwater samples were collected and analyzed. Results showed that total dissolved solids (TDS), sodium (Na+), magnesium (Mg2+), chloride (Cl-), and sulfate (SO42-) significantly damaged groundwater systems. The degree of salinization due to seawater mixing in a well or a given area could be indicated by an increase in nearly all major cations and anions. Toxic elements (i.e., Pb and As) were higher than the maximum permissible limits of drinking water. Cross plot of HCO3-/Cl- (molar ratios) versus TDS indicated that about 62% of the analyzed samples were saline. Factor analysis showed that groundwaters, affected by seawater intrusion/industrial activity, were separated from the clusters. An attempt was made to identify the hydrochemical processes that accompany current intrusion of seawater using ionic changes. It was estimated that the mixing rate of seawater intrusion was about 5.81% during April 2007. An index, called 'Seawater Mixing Index' (SMI), was also adopted and its value was SMI>1.18 with EC>3,000 MUS/cm about 62% of the sampled waters, were saline. Further, a few trace elements (i.e., Sr, B, and Li) were used as indicators for responding to the change in fresh to saline groundwater environments in coastal aquifers. PMID- 20544277 TI - The Bear Brook Watershed in Maine--the second decade. Preface. PMID- 20544278 TI - Assessing monthly average solar radiation models: a comparative case study in Turkey. AB - Solar radiation data are required by solar engineers, architects, agriculturists, and hydrologists for many applications such as solar heating, cooking, drying, and interior illumination of buildings. In order to achieve this, numerous empirical models have been developed all over the world to predict solar radiation. The main objective of this study is to examine and compare 147 solar radiation models available in the literature for the prediction of monthly solar radiation at Ankara (Turkey) based on selected statistical measures such as percentage error, mean percentage error, root mean square error, mean bias error, and correlation coefficient. Our results showed that Ball et al. (Agron J 96:391 397, 2004) model and Chen et al. (Energy Convers Manag 47:2859-2866, 2006) model performed best in the estimation of solar radiation on a horizontal surface for Ankara. PMID- 20544280 TI - A generalization of Turnbull's estimator for nonparametric estimation of the conditional survival function with interval-censored data. AB - Simple nonparametric estimates of the conditional distribution of a response variable given a covariate are often useful for data exploration purposes or to help with the specification or validation of a parametric or semi-parametric regression model. In this paper we propose such an estimator in the case where the response variable is interval-censored and the covariate is continuous. Our approach consists in adding weights that depend on the covariate value in the self-consistency equation proposed by Turnbull (J R Stat Soc Ser B 38:290-295, 1976), which results in an estimator that is no more difficult to implement than Turnbull's estimator itself. We show the convergence of our algorithm and that our estimator reduces to the generalized Kaplan-Meier estimator (Beran, Nonparametric regression with randomly censored survival data, 1981) when the data are either complete or right-censored. We demonstrate by simulation that the estimator, bootstrap variance estimation and bandwidth selection (by rule of thumb or cross-validation) all perform well in finite samples. We illustrate the method by applying it to a dataset from a study on the incidence of HIV in a group of female sex workers from Kinshasa. PMID- 20544279 TI - Beneficial effects of minocycline on cuprizone induced cortical demyelination. AB - In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination. PMID- 20544281 TI - Can the combination of calcium and parathormone levels above K/DOQI guidelines be used as a marker of adynamic bone disease in African Americans? AB - BACKGROUND: Patients of African American descent are at risk for the development of adynamic bone disease at parathyroid hormone levels 50% above the K/DOQI guidelines. Since a low bone formation rate is associated with hypercalcemia, attempts to reach one K/DOQI guideline may result in serum calcium levels above another K/DOQI guideline. Calcium levels above K/DOQI guidelines therefore may signal a need to stop parathyroid suppression. STUDY DESIGN: SETTING AND PARTICIPANTS: Bone biopsies were performed at the East Alabama Medical Center, in Opelika AL, USA on eight patients (four Caucasians, four African Americans) whose parathormone levels and serum calcium levels both exceeded K/DOQI guideline recommendations. RESULTS: All patients had mild to severe hyperparathyroid bone disease. No variable studied was predictive of the finding. LIMITATIONS: Small sample size and the unavailability of the original Nichols Diagnostic Institute radioimmunoassay for parathormone. CONCLUSION: We did not find hypercalcemia predictive of adynamic bone in patients of African American descent at levels of parathormone where low bone formation rates have been documented to occur. Since no parameter predicted bone histology, perhaps bone biopsies will be necessary to distinguish hyperparathyroidism from adynamic bone disease in African Americans with ESRD, hypercalcemia, and moderately elevated levels of PTH. Further studies are needed to determine appropriate therapy. PMID- 20544282 TI - Xanthogranulomatous pyelonephritis: critical analysis of 30 patients. AB - INTRODUCTION AND OBJECTIVE: Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammatory condition of the kidneys. Nevertheless, disparities between the pre operative and pathological diagnoses are frequently encountered. We reviewed all patients with XGP over a 17-year period to identify and characterize the pre operative and pathological characteristics of the disease in our patients. METHODS: A comprehensive review of all nephrectomy patients with a pre-operative diagnosis of pyelonephritis at National Taiwan University Hospital from 1991 to 2008 with the pathological diagnosis of XGP was conducted to demonstrate the clinical and radiological characteristics of XGP. RESULTS: XGP was diagnosed in 30 (18.6%) of the 160 nephrectomies performed for pyelonephritis. Of the 30 patients with XGP, 25 were women (83.3%) and 20 (66.7%) were overweight (body mass index >23). Their mean age was 55.17 years. The average serum creatinine level was 1.68 mg/dL. The image findings included renal calculi (56.7%), staghorn stones (26.7%), and spread of the disease to the retroperitoneum and psoas muscle (33.3%). Escherichia coli (36.7%) was the most prevalent pathogen. The mortality of the two-stage surgical treatment was zero, and morbidity developed in only 1 patient (4.8%). CONCLUSION: The key to accurate pre-operative diagnosis is to keep risk factors in mind such as age, sex, and renal calculi. Clinicians should maintain a high suspicion of XGP for early recognition and be aware of the care of chronic kidney disease. Finally, the association between XGP and central obesity warrants further research. PMID- 20544283 TI - Prostate-specific antigen test result interpretation when combined with risk factors for recommendation of biopsy: a survey of urologist's practice patterns. AB - INTRODUCTION: Recent data have suggested historical cutoff levels for prostate cancer (PC) screening using a prostate-specific antigen (PSA) level <= 4 ng/ml may no longer be appropriate with cancer detected at lower levels, particularly in younger men. Our aim was to conduct a contemporary survey of urologist's practice patterns toward PC detection, specifically focusing on factors determining the decision to recommend ultrasound-guided biopsy (TRUS-BX). METHODS: Three hundred and sixty active urologists from the Canadian Urological Association were requested to complete an online questionnaire focusing on scenarios of varying age, family history, ethnicity and PSA. Urologists indicated when to TRUS-BX. RESULTS: Of 360 urologists, 125 (35%) completed the questionnaire. Sixty-seven percent indicated men should be screened for PC aged 50-60 with 27% preferring 40-50 years. Seventy-seven percent would continue screening >75. Considering a 65-year-old man with no risk factors and a normal digital rectal exam 56% would offer TRUS-BX at PSA 4.5; 35% at 3.5 and 10% at 2.5 ng/ml. Considering a similar 45-year-old man, 94% would at PSA 4.5; 77% at 3.5 and 33% at 2.5 ng/ml. On multivariate analysis, offering TRUS-BX appears driven significantly (P < 0.0001) more by younger age and higher PSA (OR 4.3-20.6 and 4.4-34.9, respectively) rather than family history or ethnicity (OR 3.3 and 1.8, respectively). CONCLUSIONS: Age and PSA appear the driving factors in obtaining TRUS-BX. Also, a significant proportion of urologists would still not offer TRUS BX at the traditional PSA cutoff of 4 ng/ml for men with no risk factors. Further studies are required to ascertain whether this relates to a lack of dissemination of studies into practice. PMID- 20544284 TI - A parallel excitation based fluorescence molecular tomography system for whole body simultaneous imaging of small animals. AB - Challenges remain in imaging complete dynamic physiological processes in vivo through the whole small animal body using fluorescence molecular tomography (FMT). In this article, a novel non-contact full-angle FMT system that enables whole-body simultaneous imaging of small animals is presented. The whole-body simultaneous imaging ability is achieved by employing a line-shaped parallel excitation source, which can provide extended spatial sampling dataset to reconstruct multiple fluorescent targets distributed in whole animal body during one full-angle FMT imaging process. The key performances of this system were evaluated by a series of experiments. Quantitation linearity for over two orders of magnitude of fluorescence markers concentration was demonstrated, and an accessible simultaneous imaging domain of 4.0 x 1.5 cm2 could be achieved utilizing the parallel excitation pattern. Moreover, the in vivo imaging feasibility and performance were validated by localizing two fluorescent targets implanted at different positions of a nude mouse. The results suggest that compared with conventional single point excitation FMT system, the proposed system can achieve a whole-body simultaneous imaging domain and impart the ability to image complete dynamic physiological processes in vivo. PMID- 20544285 TI - A novel approach to monitor nonstationary dynamics in physiological signals: application to blood pressure, pulse oximeter, and respiratory data. AB - We propose a parametric time-varying (TV) algorithm which utilizes sinusoids as the basis functions which are then projected onto sets of Legendre and Walsh functions for the purpose of monitoring nonstationary dynamics. The proposed algorithm is a general-purpose algorithm that has the potential to be widely applicable to various physiological signals, but is especially well-suited for tracking blood pressure (BP), pulse oximeter, and respiratory signals, as they all exhibit periodic oscillations with TV dynamics. The proposed algorithm's efficacy was verified using both simulation examples and application to experimental data from all of the above-mentioned sources. Our results show that the method can: (1) accurately monitor abrupt frequency changes even when the data are contaminated with significant noise, (2) accurately monitor the BP and pulse oximeter signals, and (3) provide accurate estimation of respiratory rates derived directly from pulse oximeter recordings. PMID- 20544286 TI - Teriflunomide encourages cytostatic and apoptotic effects in premalignant and malignant cutaneous keratinocytes. AB - Teriflunomide (TFN) reportedly inhibits de novo pyrimidine synthesis and exhibits anti-inflammatory, disease-modifying activities in vivo. These qualities would suggest that TFN could be useful in skin cancer chemoprevention or therapy. We investigated some mechanistic aspects of this tenet by characterizing the effects of TFN on premalignant and malignant human cutaneous keratinocytes. TFN promoted a dose- and/or time-dependent cytostasis and in these cells, which was followed by apoptosis. These features occurred in the presence of a physiological concentration of uridine in the culture medium. The short-term S phase arrest triggered by TFN was reversible in the malignant keratinocytes, and the indirect apoptosis induction was apparently preceded by mitochondrial disruption and reactive oxygen species production in both the premalignant and malignant keratinocytes. Respiration deficient malignant keratinocytes were resistant to the acute cytostatic and latent apoptotic effects of TFN implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiring cells. These novel mechanistic findings support a role for TFN in skin cancer chemoprevention and therapy. PMID- 20544287 TI - Insulin increases H2O2-induced pancreatic beta cell death. AB - Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (beta) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic beta cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic beta cells. Cell death was induced by treatment with H(2)O(2), and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H(2)O(2) increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic beta cells and increased the effect of H(2)O(2). These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H(2)O(2) and, perhaps, other inducers of apoptosis. PMID- 20544288 TI - Expanded newborn screening: social and ethical issues. AB - Newborn screening and genetic testing have expanded rapidly in the last decade with the advent of multiplex (e.g., tandem mass spectrometry) and/or DNA technologies. However, screening panels include a large number of disorders, which may not meet all of the traditional screening criteria, established in late 1960s, and used for years to justify screening programs. After a period of expansion driven by technological advances, many reports have reconsidered the justification of expanded programs. Many factors have contributed to test-panel discrepancies between countries. The test-panel review methodology, the way health benefits are weighed against harms, and the socioeconomic-political environment all play a role. Expansion of screening also requires reconsideration of the infrastructure (ideally, in the context of national plans for rare diseases) to support testing, counselling, education, treatment, and follow-up. Consequently, economic aspects cannot be ignored and can be a limitation for expansion. New ethical questions have emerged: risks of discrimination or stigmatization, respect of the autonomy of persons to make decisions, parental anxiety resulting from a false positive test (especially when reporting to parents screening results for untreatable conditions identified as by-products of screening), etc. For disorders where there is not yet confirmation of benefit, it may be prudent to recommend pilot screening and to have a mechanism that can be used to adapt or even to stop a program. PMID- 20544289 TI - Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis. AB - Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk. PMID- 20544291 TI - Quality of life for head and neck cancer patients treated by combined modality therapy: the therapeutic benefit of technological advances in radiotherapy. AB - PURPOSE: To evaluate quality of life (QoL) in patients with head and neck squamous cell carcinoma (HNSCC) treated by combined modality therapy, with a focus on the therapeutic benefits of QoL that result from technological advances in radiotherapy (RT). METHODS: A cross-sectional survey of QoL using the EORTC QLQ-C30 and QLQ-H&N35 questionnaires was performed for 307 HNSCC survivors. One hundred and thirty-five patients were treated by two-dimensional RT (2DRT), 90 by three-dimensional conformal RT (3DCRT), and 82 by intensity-modulated RT (IMRT). The effect size between groups was calculated using Cohen's D coefficient. RESULTS: Those who had a higher annual family income or were treated by more advanced RT techniques had better QoL outcomes. Compared with 2DRT, the impact of 3DCRT was small (Cohen's D: 0.02-0.40) on all QoL scales. For IMRT, the impact was small on most scales and moderate (Cohen's D: 0.55-0.60) on opening mouth, dry mouth, and sticky saliva. Compared with 3DCRT, the impact of IMRT was small (Cohen's D: 0.03-0.29) on all scales. CONCLUSION: Advances in RT provided a positive effect on QoL outcome, especially on swallowing-related QoL scales, for patients with HNSCC treated by combined modality therapy. PMID- 20544290 TI - The ectopic ACTH syndrome. AB - Ectopic Cushing's syndrome usually relates to the ectopic ACTH syndrome (EAS) and represents ~20% of ACTH-dependent and ~10% of all types of Cushing's syndrome (CS). Nearly any neuroendocrine or non-endocrine tumours may be associated with EAS, but the more prevalent tumours are bronchial carcinoids, small cell lung carcinomas, pancreatic carcinoids, thymic carcinoids, medullary carcinomas of the thyroid, and phaeochromocytomas. Occult tumours are highly represented in all the series (12-38%) and constitute the more challenging cases of EAS, requiring long term follow-up. The lack of any completely reliable diagnostic test procedure and imaging to clearly reveal the source of EAS suggests that we should adopt a step by-step multidisciplinary approach for their diagnosis and therapeutic management. Clinical features are often similar in ACTH-dependent CS, but the rapid onset and progress may suggest an ectopic source. A combination of biochemical tests and imaging studies seems the most appropriate approach for the prompt identification of EAS, even if there are several pitfalls to be avoided along the way. The most appropriate management for cure of EAS, when its source is identified, is surgical excision after controlling the hypercortisolaemia by inhibitors of cortisol secretion and other newer modalities alone or in combination; bilateral adrenalectomy remains an alternative option. Tumour histology, the presence of metastases and the effective control of hypercortisolaemia affect mortality and morbidity. If a source repeatedly fails to be found, the prognosis is often favourable but the identification of a malignant tumour should still be sought during life-long follow-up to avoid the calamity of misdiagnosis. PMID- 20544292 TI - Clinical significance of human kallikrein7 gene expression in colorectal cancer. AB - BACKGROUND: The human kallikrein-related peptidases (KLK) are considered important prognostic biomarkers in cancer. The aim of the current study is to demonstrate gene expression of KLK7 in colorectal cancer (CRC) and to correlate the relative KLK7 expression level with clinicopathological factors of CRC. METHODS: KLK7 messenger RNA (mRNA) expression was examined in nine CRC cancer cell lines by real-time polymerase chain reaction. The expression levels of KLK7 mRNA in cancerous tissues (n = 136) and paired normal tissues (n = 136) of CRC patients were also examined. RESULTS: Six of the nine cell lines expressed the KLK7 gene. KLK7 mRNA expression levels in cancer tissues were significantly higher than those in normal tissues. Multivariate analysis revealed that the KLK7 mRNA expression level in cancer was an independent prognostic factor, especially in liver metastasis. CONCLUSIONS: We provide evidence suggesting that KLK7 mRNA expression is correlated with prognosis in CRC patients, especially in liver metastasis. PMID- 20544293 TI - 25-hydroxyvitamin D status does not affect intraoperative parathyroid hormone dynamics in patients with primary hyperparathyroidism. AB - BACKGROUND: Deficiency of 25-hydroxyvitamin D (25OHD) is a stimulus for the secretion of parathyroid hormone (PTH). During surgery for primary hyperparathyroidism, 25OHD deficiency may artificially elevate PTH, decreasing the sensitivity of intraoperative PTH (ioPTH) measurements. MATERIALS AND METHODS: Of 351 patients with known 25OHD status who underwent curative surgical treatment of primary hyperparathyroidism, 198 (56%) patients were 25OHD deficient (<25 ng/mL). A curative decrease in ioPTH was defined as a greater than 50% PTH decrease 5, 10, or 15 min after resection. RESULTS: There was no statistical difference between 25OHD deficient and sufficient patients in PTH, phosphorous, and alkaline phosphatase preoperatively. There was a positive correlation between PTH and calcium, alkaline phosphatase, and gland weight, while there was an inverse correlation between preoperative PTH and 25OHD. The average ioPTH decrease was not significantly different after 5, 10, or 15 min, and 25OHD status did not affect when ioPTH indicated surgical cure. CONCLUSIONS: Lower 25OHD levels are correlated with higher PTH and alkaline phosphatase levels in patients with primary hyperparathyroidism. 25OHD status did not affect the average percent ioPTH decrease or the rate of cure. 25OHD deficiency does not affect ioPTH dynamics. PMID- 20544294 TI - On the significance of defective block detectors in clinical (18)F-FDG PET/CT imaging. AB - INTRODUCTION: Clinical positron emission tomography (PET) systems based on block detector designs suffer occasional block detector failures, which can result in patient scan cancelations. In this study, we examine the effect of defective block detectors on measurements of maximum standard uptake value (SUV(max)) and clinical image quality in 3D 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) PET/computed tomography (CT) imaging. METHODS: A Data Spectrum anthropomorphic torso phantom (4.7 kBq/ml FDG concentration, defined as SUV of 1.0) was imaged in a normally functioning Siemens Biograph 16 HiRez PET/CT scanner using a whole-body imaging protocol. Spherical lesions with SUVs ranging from 10.0 to 13.5 were placed in the phantom. Defective block detectors were simulated by zeroing the appropriate lines of response in the sinograms. Eleven one-block and seventeen two-block defect configurations were simulated in the phantom sinograms. The images were reconstructed, and the measured SUV(max) was compared with the SUV(max) for the images without detector defects. Twelve clinical PET scans were evaluated before and after simulated detector defects cases ranging from a single block up to 12 blocks (bucket). The reconstructed images were independently scored for image quality and clinical diagnosis by two nuclear physicians blinded to the presence and severity of defects in the images. RESULTS: The mean change in phantom SUV(max) was -2% (range, -6% to +3%) in the presence of a single defective block detector and -3% (range, -11% to +7%) in the presence of two defective block detectors, respectively. For the clinical patient studies, there was no significant decline in image quality score from one to two defective block detectors. In the case of 3-4 defective block detectors, image quality became marginal, and image degradation was significant with a defective bucket (12 blocks). CONCLUSION: For one or two defective block detectors in a 3D PET camera, while waiting for the repair service, routine patient scans can proceed with the proviso that the reading physician is made aware of the detector failure. PMID- 20544295 TI - Targeted ultrasound contrast imaging of matrix metalloproteinase-2 in ischemia reperfusion rat model: ex vivo and in vivo studies. AB - PURPOSE: We hypothesized that post-myocardial ischemia-reperfusion (I/R) remodeling associated matrix metalloproteinase-2 (MMP(2)) activation could be detected by using novel MMP(2) targeted ultrasound imaging. PROCEDURES: We study the combination of MMP(2)-targeted microbubbles (TMB(2)) and control microbubbles with myocardium in 1 week post-I/R rats. RESULTS: In in vitro studies, TMB(2) significantly bound within the risk area (RA) of 1-week post-I/R myocardial sections while rare binding was observed in the control area (CA). In in vivo studies, increased focal retention of TMB(2) was observed within the RA, with the higher myocardial video intensity (RA 42.85 +/- 20.12 dB versus CA 25.85 +/- 13.40 dB, p < 0.01). However, there was no difference of control microbubble retention in both CA and RA. CONCLUSIONS: A targeted ultrasound contrast imaging approach that employs novel TMB(2) has the potential to provide a less-invasive, higher-resolution technique for in vivo localization of MMP(2) activation and tracking of MMP-mediated post-I/R remodeling. PMID- 20544296 TI - Exposure reduction of seed treatments through dehusking behaviour of the wood mouse (Apodemus sylvaticus). AB - BACKGROUND, AIM AND SCOPE: Seed treatments are widely used on cereals and other annual crops throughout Europe. Most of the formulated pesticide is found on the outside of the seed, the husk. Risk assessments of seed treatments are especially needed for granivorous mice living in the agricultural landscape e.g. for registration using the guidance for risk assessment for birds and mammals (EFSA 2009). The dehusking of seeds before consumption is a known behaviour of these mammals, but so far, no quantitative data on the reduction of exposure of seed treatments by dehusking were published. Therefore, we aimed at providing a first quantitative estimate of this behaviour-related exposure reduction for the wood mouse (Apodemus sylvaticus) with different seed types. MATERIALS AND METHODS: We evaluated the efficiency of dehusking behaviour of 20 wood mice captured in the wild for four different seeds (wheat, barley, maize and sunflower). One experimental setup used a fungicide seed treatment where the remaining seed husks of consumed seeds were analysed with a HPLC-MS/MS technique. In the second setup, we measured generic pigment present in a blank seed treatment formulation and determined the leftover pigment in the husks with a photometric technique. RESULTS: The exposure reduction was similar for the fungicide and the pigment design where the same seed types were studied. We could demonstrate exposure reductions ranging from around 60% for cereals to almost 100% for sunflower seeds as a result of the dehusking behaviour. DISCUSSION: Since exposure reduction was similar in both approaches, working with pigments would be a generic way to estimate the impact of dehusking behaviour on seed treatment exposure. This behaviour can result in a substantial exposure reduction and should, therefore, be considered in a seed-type specific way in the risk assessment of pesticide seed treatments. CONCLUSIONS: It is proposed to include a seed-specific dehusking factor in the calculations of estimated theoretical exposure of seed treatments for granivorous mice. The approach of accounting for a dehusking-related exposure reduction by field relevant wild mammal species seems a more promising way to advance the risk assessment instead of using generic species and neglecting behavioural traits. The pigment approach could be used to gather data for exposure reduction for other species and seed types. Its advantage is that it is harmless to the test species and comparatively cheap since no chemical analysis is involved. RECOMMENDATIONS AND PERSPECTIVES: Seed treatments are used for most of the cereal crops grown in Europe today. Their advantages usually include a lower application rate and the reduction of drift compared to a conventional spraying regime. However, there is a potential risk especially for granivorous mice, and its assessment is challenging in case of a high residue concentration on the dressed seeds. The concept of a dehusking factor in the risk assessment scheme for seed treatments for granivorous mice is a valid approach to account for the behavioural exposure reduction, and generic data could be easily generated also for other wild mammal species and other seed types, possibly analysing the pigment in commercial seed treatment formulations. PMID- 20544297 TI - Microbial dynamics in a sequencing batch reactor treating alkaline peroxide mechanical pulp and paper process wastewater. AB - BACKGROUND, AIM, AND SCOPE: For many years, highly concentrated wastewater generated from the pulp and paper industry has become the focus of much concern worldwide. The objectives of this study were to determine the treatment efficiency of the alkaline peroxide mechanical pulp (APMP) process wastewater using a sequencing batch reactor (SBR) and analyze the microbial dynamics of the wastewater treatment system using the random amplified polymorphic DNA (RAPD) method. MATERIALS AND METHODS: An SBR was applied to the treatment of APMP pulp and paper process wastewater. The wastewater characteristics and many physicochemical operator indicators in the wastewater treatment process were analyzed and determined according to standard methods. Microbial 16 S rDNA in active sludge was extracted, amplified, and analyzed using the RAPD method for the microbial dynamics of the wastewater treatment system. RESULTS AND DISCUSSION: Ten kinds of natural organic compounds of plants such as monoterpene were detected in the APMP pulp and paper process wastewater. With an influent chemical oxygen demand (COD) that varied in the range of 685.7 to 907.5 mg/L, the corresponding effluent COD was 176.5 to 266.1 mg/L and the removal efficiency was 70.3% to 79.8%. An optimal strain (S308: CAGGGGTGGA) was selected to study the population dynamics and diversity of the bacterial community. The RAPD-polymerase chain reaction (PCR) fingerprints showed very high polymorphism of the genetic bands (78-100%). Four groups of species were clustered using the unweighted pair group method with arithmetic (UPGMA) analysis, and the genetic distance was close between the species within each group. The Shannon-Weaver index was high and varied over time with the COD removal. CONCLUSIONS: The RAPD-PCR technique can be used to study microbial dynamics, which was shown to vary over time with the removal efficiency of SBR treating APMP pulp and paper process wastewater. PMID- 20544298 TI - Liver segmentation for contrast-enhanced MR images using partitioned probabilistic model. AB - PURPOSE: Liver volume segmentation is important in computer assisted diagnosis and therapy planning of liver tumors. Manual segmentation is time-consuming, tedious and error prone, so automated methods are needed. Automatic segmentation of MR images is more challenging than for CT images, so a robust system was developed. METHODS: An intensity-based segmentation method that uses probabilistic model to increase the precision of the segmentation was developed. The model was build based on 60 manually contoured liver CT exams and partitioned into 8 parts according to the (Couinaud) segmental anatomy of the liver. The partitioning allows using different intensity statistics in different parts of the organ, which makes it insensitive to local intensity differences from MR artifacts or pathology. The method employs a modality independent model with registration that exploits some LAVA image characteristics. This dependence can be eliminated to adapt the segmentation method for a wide range of MR images. RESULTS: The method was evaluated using eight representative, manually segmented MR LAVA exams. The results show that the method can accurately segment the liver volume despite various MR artifacts and pathology. The evaluation shows that the proposed method provides more precise segmentation (6% average absolute relative volume error) compared with global intensity statistics for the whole organ (20% average absolute relative volume error). The compute time of the method was 30 s in average, which is acceptable for wide range of clinical applications. CONCLUSION: An automatic method that can segment the liver in contrast-enhanced MR LAVA images was developed and tested. The results demonstrate that the method is feasible, efficient and robust to artifacts and pathology. PMID- 20544299 TI - Toward a clinical lumbar CAD: herniation diagnosis. AB - PURPOSE: A CAD system for lumbar disc degeneration and herniation based on clinical MR images can aid diagnostic decision-making provided the method is robust, efficient, and accurate. MATERIAL AND METHODS: A Bayesian-based classifier with a Gibbs distribution was designed and implemented for diagnosing lumbar disc herniation. Each disc is segmented with a gradient vector flow active contour model (GVF-snake) to extract shape features that feed a classifier. The GVF-snake is automatically initialized with an inner boundary of the disc initiated by a point inside the disc. This point is automatically generated by our previous work on lumbar disc labeling. The classifier operates on clinical T2 SPIR weighted sagittal MRI of the lumbar area. The classifier is applied slice-by slice to tag herniated discs if they are classified as herniated in any of the 2D slices. This technique detects all visible herniated discs regardless of their location (lateral or central). The gold standard for the ground truth was obtained from collaborating radiologists by analyzing the clinical diagnosis report for each case. RESULTS: An average 92.5% herniation diagnosis accuracy was observed in a cross-validation experiment with 65 clinical cases. The random leave-out experiment runs ten rounds; in each round, 35 cases were used for testing and the remaining 30 cases were used for training. CONCLUSION: An automatic robust disk herniation diagnostic method for clinical lumbar MRI was developed and tested. The method is intended for clinical practice to support reliable decision-making. PMID- 20544300 TI - The availability and nature of physician information on the internet. AB - BACKGROUND: Although patients are commonly using the Internet to find healthcare information, the amount of personal and professional physician information and patient-generated ratings freely accessible online is unknown. OBJECTIVE: To characterize the nature of online professional and personal information available to the average patient searching for physician information through a standardized web search. DESIGN, SETTING, AND PARTICIPANTS: We studied 250 randomly selected internal medicine physicians registered with the Massachusetts Board of Registration in Medicine in 2008. For each physician, standardized searches via the Google search engine were performed using a sequential search strategy. The top 20 search results were analyzed, and websites that referred to the study subject were recorded and categorized. Physician rating sites were further investigated to determine the number of patient-entered reviews. MAIN MEASURES: Number and content of websites attributable to specific physicians. KEY RESULTS: Websites containing personal or professional information were identified for 93.6% of physicians. Among those with any web sites identified, 92.8% had professional information and 32.4% had personal information available online. Female physicians were more likely to have professional information available on the Internet than male physicians (97.5% vs. 91.7%, p=0.03), but had similar rates of available personal information (32.5% vs. 32.5%, p=ns). Among personal sites, the most common categories included social networking sites such as Facebook (10.8% of physicians), hobbies (10.0%), charitable or political donations (9.6%), and family information (8.8%). Physician rating sites were identified for 86.4% of providers, but only three physicians had more than five reviews on any given rating site. CONCLUSIONS: Personal and professional physician information is widely available on the Internet, and often not under direct control of the individual physician. The availability of such information has implications for physician-patient relationships and suggests that physicians should monitor their online information. PMID- 20544301 TI - The roles of melatonin and vitamin E plus selenium in prevention of oxidative stress induced by naloxone-precipitated withdrawal in heroin-addicted rats. AB - The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, alpha-tocopherol, retinol, beta-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between alpha tocopherol, retinol, beta-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems. PMID- 20544303 TI - Thiazolidinediones as a novel class of algicides against red tide harmful algal species. AB - This paper reports the synthesis of 28 thiazolidinedione derivatives along with their algicidal activity against microalgae causing harmful algal blooming. Among the 28 compounds tested, most showed effective algicidal activity against Heterosigma akashiwo, Chattonella marina, and Cochlodinium polykrikoides, while non-harmful algae were relatively tolerant to these thiazolidinedione derivatives. Compounds 6, 13, and 22 were the most potent against C. polykrikoides with IC50 values <0.5 uM. Among the thiazolidinedione derivatives tested, compounds 7, 13, 27, and 28 were extremely competent and selective to C. polykrikoides with IC50 values ranging from 0.1 to 2 uM, while C. marina and H. akashiwo showed an IC50 value ranging from 30 to 130 uM. These results show that some thiazolidinedione derivatives can act as potent algicides against harmful algal blooms. PMID- 20544302 TI - Marginal copper deficiency increases liver neutrophil accumulation after ischemia/reperfusion in rats. AB - Copper deficiency can cause a host of major cardiovascular complications including an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the neutrophilic response to hepatic ischemia/reperfusion injury, a condition that induces an inflammatory response. Male weanling Sprague-Dawley rats were fed purified diets which were either copper-adequate (6.3 mg/kg) or copper-marginal (1.62 mg/kg) for 4 weeks prior to undergoing 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Liver injury was assessed by serum levels of alanine aminotransferase and by liver histology. Liver neutrophil accumulation was determined by tissue myeloperoxidase content. There was no significant difference in liver injury between copper-adequate and copper-marginal rats. However, liver neutrophil accumulation was significantly increased in copper-marginal rats. These findings were confirmed histologically. Liver expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), was increased in copper-marginal rats compared to copper-adequate rats. The results suggest that neutrophil accumulation is increased through enhanced ICAM-1 expression in liver of copper marginal rats after ischemia/reperfusion, but that this does not result in increased liver injury. PMID- 20544304 TI - Esterification activity of novel fungal and yeast lipases. AB - The main objective of this work was the isolation and screening of microorganisms with potential for producing lipases for the synthesis of fatty esters as well as evaluating the specificity of the enzymes produced, using different alcohols (methanol, ethanol, n-propanol, and butanol) and fatty acids (oleic and lauric acids) as substrates. Promising biocatalysts for organic synthesis were obtained in this work. The isolated strains 69F and 161Y showed ability to efficiently catalyze the reaction for production of n-propyl oleate. Other strains can also be considered of potential interest, as 74F, 111Y, and 186Y. The future development of production using different substrates could result in cheap crude lipase of high importance to industrial applicability. PMID- 20544306 TI - William R. Markesbery, M.D.: mentor and friend. PMID- 20544305 TI - Inhibitory effects of fatty acids on the activity of mushroom tyrosinase. AB - The effects of fatty acids, octanoic acid, (2E, 4E)-hexa-2,4-dienoic acid, hexanoic acid, (2E)-but-2-enoic acid, and butyric acid on the activities of mushroom tyrosinase have been investigated. The results showed that the fatty acids can potently inhibit both monophenolase activity and diphenolase activity of tyrosinase, and that the unsaturated fatty acids exhibited stronger inhibitory effect against tyrosinase than the corresponding saturated fatty acids, and the inhibitory effects were enhanced with the extendability of the fatty acid chain. For the monophenolase activity, the fatty acids could not only lengthen the lag period, but also decrease the steady-state activities. For the diphenolase activity, fatty acids displayed reversible inhibition. Kinetic analyses showed that octanoic acid and hexanoic acid were mixed-type inhibitors and (2E,4E)-hexa 2,4-dienoic acid and (2E)-but-2-enoic acid were noncompetitive inhibitors. The inhibition constants have been determined and compared. PMID- 20544307 TI - Memories of Dr. William R. Markesbery. PMID- 20544308 TI - Molluscum-like lesions in cryptococcal meningitis. PMID- 20544309 TI - The use of single versus dual antiplatelet therapy beyond 1 year following drug eluting stent implantation. PMID- 20544310 TI - Cardiac resynchronization therapy in mild heart failure: a review of the REVERSE and MADIT-CRT trials. AB - Cardiac resynchronization therapy has become part of the treatment strategy for advanced, symptomatic heart failure, but newly published trials show that more patients than previously realized may benefit from this therapy, including those with mild heart failure symptoms. The REVERSE and MADIT-CRT trials showed that cardiac resynchronization therapy reduces risk of hospitalization for heart failure and leads to beneficial reverse remodeling of the left ventricle in mild heart failure, especially in patients with prolonged QRS complexes. Ongoing studies aim to expand the indications for this therapy even further, including in patients with normal ejection fractions and a need for frequent ventricular pacing. The current body of evidence favors cardiac resynchronization therapy in patients with a depressed ejection fraction and prolonged QRS, even with minimal or no heart failure symptoms. PMID- 20544311 TI - Left atrial appendage closure. AB - Stroke prevention is the primary goal in atrial fibrillation (AF) given its clinical and socioeconomic impact. With AF, the prevalence of thromboembolic stroke continues to rise and there is an urgent need to develop better strategies of stroke prevention. Warfarin, although effective when used appropriately, is burdened by underutilization, narrow therapeutic windows, and life-threatening bleeding complications. Novel pharmacologic agents have been plagued by off target toxicity and only modest improvement in bleeding complications over warfarin. Because most thromboemboli arise from the left atrial appendage (LAA), surgical exclusion of the LAA is often used in AF patients undergoing cardiac surgery. Percutaneous device LAA closure has now been developed as an adjunct and as an alternative to pharmacotherapy in patients with AF. Promising randomized data are available with the WATCHMAN device, while several other devices are in various stages of clinical and preclinical development. PMID- 20544312 TI - Diabetes, anemia and CKD: Why TREAT? AB - The triad of diabetes mellitus, anemia, and chronic kidney disease (CKD) define a group of patients at high risk for death and cardiovascular complications. The approval of epoetin alfa in 1989 transformed the treatment of anemia in patients with CKD. However, evidence has emerged from randomized controlled trials that correcting anemia with erythropoiesis-stimulating agents in CKD patients is associated with increased risk. Most recently, the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) study of anemic type 2 diabetic patients with CKD reported that treatment with darbepoetin conferred no benefit in mortality or in attenuating cardiovascular or renal events. Instead, there was a twofold higher rate of stroke and thromboembolic complications and a higher rate of cancer deaths in patients randomized to treatment with darbepoetin. Furthermore, there was an inconsistent and modest improvement in health-related quality of life. TREAT raises questions about whether anemia in type 2 diabetic patients should be treated and under what circumstances. PMID- 20544313 TI - Scrupulosity: a unique subtype of obsessive-compulsive disorder. AB - The earliest descriptions of obsessive-compulsive disorder (OCD) were religious, as was the understanding of their origins. With the emancipation, religion in OCD was relegated to its status today: a less common symptom of OCD in most Western societies known as scrupulosity. The frequency of scrupulosity in OCD varies in the literature from 0% to 93% of cases, and this variability seems predicated on the importance of religious belief and observance in the community examined. Despite the similarities between religious ritual and compulsions, the evidence to date that religion increases the risk of the development of OCD is scarce. Scrupulosity is presented as a classic version of OCD, with obsessions and compulsions, distress, and diminished functioning similar to those of other forms of OCD. The differentiation between normal religiosity and scrupulosity is presented, and the unique aspects of cognitive-behavioral therapy in treating scrupulosity, especially in religious populations, are reviewed. PMID- 20544314 TI - Promise and pitfalls of animal models of schizophrenia. AB - Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek to develop and use animal models for translational research in schizophrenia and the responses that have emerged to those challenges, as well as the likely pathways that will lead to future progress. PMID- 20544315 TI - Do ion levels in hip resurfacing differ from metal-on-metal THA at midterm? AB - BACKGROUND: Metal-on-metal Birmingham hip resurfacing (MOM-BHR) is an alternative to metal-on-metal total hip arthroplasty (MOM-THA), especially for young and/or active patients. However, wear resulting in increased serum ion levels is a concern. QUESTIONS/PURPOSES: We asked whether (1) serum chromium (Cr), cobalt (Co), and molybdenum (Mo) concentrations would differ between patients with either MOM-BHR or MOM-THA at 5 years, (2) confounding factors such as gender would influence ion levels; and (3) ion levels would differ at 2 and 5 years for each implant type. PATIENTS AND METHODS: Ions were measured in two groups with either MOM-BHR (n = 20) or MOM-THA (n = 35) and a mean 5-year followup, and two groups with either MOM-BHR (n = 15) or MOM-THA (n = 25) and a mean 2-year followup. Forty-eight healthy blood donors were recruited for reference values. RESULTS: At 5 years, there were no differences in ion levels between patients with MOM-BHR or MOM-THA. Gender was a confounding factor, and in the MOM-BHR group at 5 years, Cr concentrations were greater in females compared with those of males. Mean ion levels were similar in patients with 2 and 5 years of followup for each implant type. Ion levels in patients were sevenfold to 10-fold higher than in controls. CONCLUSIONS: As the metal ion concentrations in the serum at 5 years were in the range reported in the literature, we do not believe concerns regarding excessive metal ion levels after MOM-BHR are justified. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence. PMID- 20544316 TI - 50 Years ago in CORR: Complications in replacement arthroplasty of the hip; experience with 68 additional cases Howard Mendelsohn, MD and Bernard N. Becker, MD CORR 1955;6:48-53. PMID- 20544317 TI - Can this prosthesis be saved?: implant salvage attempts in infected primary TKA. AB - BACKGROUND: Open debridement with polyethylene liner exchange (ODPE) remains a relatively low morbidity option in acute infection of total knee arthroplasty (TKA), but concerns regarding control of infection exist. We sought to identify factors that would predict control of infection after ODPE. METHODS: We identified 44 patients (44 knees) with culture-positive periprosthetic infection who underwent ODPE. Failure was defined as any reoperation performed for control of infection or the need for lifetime antibiotic suppression. Patients had been followed prospectively for a minimum of 1 year (mean, 5 years; range, 1-9 years). RESULTS: Twenty-five of the 44 patients (57%) failed ODPE. Of these 25 patients, two had one additional procedure, 21 had more than one additional procedure, and two required lifetime antibiotic suppression. Failure rates tended to differ based on primary organism: 71% of Staphylococcus aureus periprosthetic infection failed versus 29% of Staphylococcus epidermidis, although with the limited numbers theses differences were not significant. Age, gender, or measures of comorbidity did not influence the risk of failure. There was no difference in failure rate (58% versus 50%) when the ODPE was performed greater than 4 weeks after index TKA. After a failed ODPE, 19 of the 25 failures went on to an attempted two-stage revision procedure. In only 11 of these 19 cases was the two stage revision ultimately successful. CONCLUSIONS: Eradication of infection with ODPE in acute TKA infections is unpredictable; certain factors trend toward increased success but no firm algorithm can be offered. The success of two-stage revision for infection may be diminished after a failed ODPE. LEVEL OF EVIDENCE: Level III, retrospective comparative study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20544318 TI - The radiographic approach to child abuse. AB - BACKGROUND: Osseous injuries are a major facet of child abuse and in most patients radiographic imaging plays a major role in diagnosis. While some injuries are typically produced as a result of excessive and inappropriate force other injuries are nonspecific in terms of their causation, but become suspicious when the history provided by the caretakers is inconsistent with the type of injury produced. QUESTIONS/PURPOSES: I detail the radiographic imaging of the more characteristic of the highly specific injuries, discuss the major issues that relate to some moderate- or low-specificity injuries, and describe several diseases that mimic abuse. METHODS: A review of the current and recent literature focused on the radiographic imaging of child abuse was performed by searching the National Library of Medicine database at pubmed.gov. Keywords used included: radiology, fracture, child abuse, and/or nonaccidental trauma. RESULTS: Injuries that are highly specific for the diagnosis of abuse include metaphyseal corner fractures, posteromedial rib fractures, and sternal, scapular, and spinous process fractures. Lesions of moderate specificity include, among other injuries, multiple fractures of various ages and epiphyseal separations. Long-bone fractures and clavicular fractures, while common, are of low specificity. In addition to the appropriate accurate diagnosis of these injuries, several diseases and syndromes may mimic abuse due to the similarity in the radiographic picture. CONCLUSIONS: Stratification of fractures sustained in child abuse according to specificity and an understanding of the several diseases that mimic abuse are helpful in the accurate diagnosis of child abuse. LEVEL OF EVIDENCE: Level V, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20544319 TI - What are the risk factors for infection in hemiarthroplasties and total hip arthroplasties? AB - BACKGROUND: Late infection is the second most frequent early complication after total hip arthroplasty (THA) and the most frequent after hemiarthroplasty. Known risk factors for infection after THA include posttraumatic osteoarthritis, previous surgery, chronic liver disease, corticoid therapy, and excessive surgical time. However, risk factors for hemiarthroplasty are not clearly established. QUESTIONS/PURPOSES: We therefore determined the preoperative and intraoperative risk factors for late infection (more than 3 months after surgery) in patients with hemiarthroplasties and THAs. METHODS: We retrospectively compared 47 patients with a hip arthroplasty (23 hemiarthroplasties, 24 total hip arthroplasties) and late infection with 200 randomly-selected patients with primary arthroplasty (100 hemiarthroplasties, 100 total hip arthroplasties) during the same time period of time without any infection during followup. Potential risk factors were identified from medical records. Minimum followup was 12 months (mean, 27 months; range, 12-112 months) for the study group and 18 months (mean, 84 months; range, 18-144 months) for the control group. RESULTS: The following factors were more frequent in late infected hemiarthroplasties: female gender; previous surgery; obesity (body mass index greater than 30 kg/m(2)); glucocorticoid and immunosuppressant treatments; prolonged surgical time; inadequate antibiotic prophylaxis; prolonged wound drainage; hematoma; dislocation; and cutaneous, urinary, and/or abdominal infections. The following were more frequent in infected total hip arthroplasties: posttraumatic osteoarthritis; previous surgery; glucocorticoids; chronic liver disease; alcohol and intravenous drug abuse; prolonged surgical time; prolonged wound drainage; dislocation; subsequent surgery; and cutaneous, urinary, respiratory and abdominal infections. Diabetes did not appear to be a risk factor. CONCLUSIONS: Our data suggest there are specific risk factors for infection in hemiarthroplasties. The major risk factors for late infection in hip arthroplasty must be recognized so they can be minimized or controlled if not possible to employ prophylactic measures. PMID- 20544320 TI - Revision of broken knee megaprostheses: new solution to old problems. AB - BACKGROUND: Low-cost indigenous megaprostheses used in the developing world are prone to mechanical failure but the frequency and causes are not well established. QUESTIONS/PURPOSES: We retrospectively analyzed the causes of failure, particularly design, and suggest changes to reduce the breakage. We also report our experience with revision surgery. METHODS: We identified 28 breakages in 266 megaprosthetic knee arthroplasties performed between January 2000 and December 2006. Twenty-six breakages were revised to another prosthesis. The complications were studied and the function was evaluated. Prostheses were studied for failure by the computer-aided design program SolidWorks((r)) and Hyperworks((r)) for finite element analysis (FEA). Design improvements were performed based on these results. RESULTS: In 21 cases, the failure occurred at the stem-collar junction, the point of maximum stress predicted by FEA. Stainless steel implants were prone to failure. There was one early and one late infection. Three patients died of metastatic disease. The most difficult surgical step involved the removal of the well-cemented broken stem from the intramedullary canal. Musculoskeletal Tumor Society scores varied from 27 to 29 after revision. FEA revealed stress could be reduced by filleting the stem-collar junction and by two-piece stems. CONCLUSIONS: Revisions of broken total knee megaprostheses, though technically difficult, have allowed patients reasonable function. We recommend design analysis for custom prostheses to point to areas of weakness. Breakages can be reduced by using titanium stems and filleting the junction or by having two-piece inserted stems. Incorporating these changes has reduced the failures in our experience. PMID- 20544321 TI - Factors predicting local recurrence, metastasis, and survival in pediatric soft tissue sarcoma in extremities. AB - BACKGROUND: Pediatric soft tissue sarcomas are rare and differ from those in adults regarding the spectrum of diagnoses and treatment. Sarcomas in extremities may have different prognoses from those located elsewhere. QUESTIONS/PURPOSES: We sought risk factors predicting local recurrence, metastasis, and overall survival and asked whether radiation and chemotherapy influenced local recurrence, metastasis, and overall survival. METHODS: We retrospectively reviewed all 98 patients aged 18 years or younger diagnosed with soft tissue sarcomas in extremities from 1990 to 2008. Age, tumor size, depth, location, bone or neurovascular involvement, histologic subtypes, unplanned excision, surgical margins, metastasis at diagnosis, and adjuvant treatments were reviewed for each patient. We determined the effect of each prognostic variable on local recurrence, metastasis, and overall survival. RESULTS: Ninety-four patients underwent surgical excision and seven patients had local recurrence at a median time of 18.6 months. Radiation therapy reduced the rate of local recurrence. Fourteen patients had metastasis at diagnosis and seven patients later developed metastasis. The median time to metastasis was 20.9 months. Six patients died and the median time to death was 28.0 months. Metastasis at diagnosis was a predictive factor for death. CONCLUSIONS: When limited to extremities, radiation therapy reduced the rate of local recurrence in pediatric soft tissue sarcomas. Metastases at diagnosis predict death. PMID- 20544322 TI - Clinical benefit of SPECT/CT for follow-up of surgical treatment of osteochondritis dissecans. AB - We present the case of a 17-year-old ice-hockey player, who complained about persistent left medial knee pain having undergone a refixation of a grade III osteochondritis dissecans with biodegradable pins, a reconstruction of the anterior cruciate ligament (ACL) and a medial meniscal repair 1 year previously. Sequential MRIs performed 8 and 12 months after surgery were inconclusive, and failed to show the insufficient integration of the osteochondral fragment. Combined single photon emission and conventional computerized tomography (SPECT/CT) clearly revealed the cause of the patient's persistent knee problems the osteochondral fragment had not integrated. SPECT/CT may hold great clinical value for symptomatic patients who have previously undergone treatment for osteochondral lesions, and it should be considered as alternative diagnostic imaging modality. PMID- 20544323 TI - Role of 11C-choline PET/CT in the restaging of prostate cancer patients showing a single lesion on bone scintigraphy. AB - AIM: To assess the utility of (11)C-choline PET/CT in the restaging of prostate cancer (PC) patients who showed a single finding on bone scintigraphy (BS) that was classified as equivocal or suspected for metastatic lesion. MATERIALS AND METHODS: A total of 25 PC patients with biochemical failure (mean PSA value 11.1 ng/mL; median value 6.3 ng/mL; range 0.2-37.7 ng/mL) after primary treatment were included in this retrospective study. All of them showed a single lesion on BS reported as suspected for metastatic lesion or as equivocal finding. Patients underwent (11)C-choline PET/CT within 1-4 months from BS. Validation was established by follow-up for at least 6 months. RESULTS: On the basis of biopsy confirmation and/or 6-month follow-up, 22 of 25 patients were classified as positive for the presence of metastatic bone lesions: 13 with a single lesion and 9 with multiple lesions. (11)C-choline PET/CT was positive in 19/25 patients and, on a lesion basis, it showed 50 positive findings. BS results were confirmed in 8/25 (32%) patients. (11)C-choline PET/CT detected multiple sites of relapse in 11/25 (44%) patients: in 2/11, a single bone lesion associated with other extraosseous sites of relapse; in 6/11, multiple bone lesions; in 3/11, multiple bone lesions and other extraosseous localizations. Finally, 6/25 patients were negative on (11)C-choline PET/CT. In 3/6 patients, an osteoblastic lesion was seen on CT attenuation correction images (PET false negative; BS true positive), while in 3/6 patients only findings suggestive of the presence of degenerative disease were found (PET true negative; BS false positive). On a patient basis, (11)C-choline PET/CT showed a diagnostic sensitivity of 86% (19/22) and a specificity of 100% (19/19). CONCLUSIONS: In our study, (11)C-choline PET/CT detected unknown lesions in 11/25 patients. Patients with a single equivocal finding on BS could have important additional information from (11)C-choline PET/CT study, especially in the detection of additional metastases, to choose an appropriate treatment. PMID- 20544324 TI - Evaluation of Tourette's syndrome by (99m)Tc-TRODAT-1 SPECT/CT imaging. AB - OBJECTIVE: Clinical evidence indicates that the Tourette's syndrome (TS) is associated with hyperactivity of the dopaminergic system; however, imaging studies of dopamine transporter (DAT) in TS patients remain controversial. In this study, we aimed to study DAT binding capacities in a relatively larger sample of drug-naive patients with TS in comparison with controlled subjects by (99m)Tc-TRODAT-1 SPECT/CT imaging. We also aimed to look for any possible correlations between DAT and age, disease duration or tic severity of TS, which have not been thoroughly investigated in previous studies. We tried to provide more evidence for the understanding of the physiopathological mechanism of TS from the molecular imaging perspective. METHODS: Eighteen drug-naive patients with TS and 8 age- and gender-matched healthy subjects were recruited. Severity of TS was measured with Yale Global Tic Severity Scale. Brain SPECT/CT was performed 2.5 h after injection of (99m)Tc-TRODAT-1. Regions of interest were drawn on the striatum including its sub-regions of caudate and putamen. The cerebellum was used as the reference region. DAT uptake ratio was calculated by subtracting the mean counts per pixel in the cerebellum from the mean counts per pixel in the striatum, caudate or putamen and by dividing the result by the mean counts per pixel in the cerebellum. Comparisons of DAT uptake ratios between TS patients and controls, and comparisons in bilateral striatum and sub-regions in TS patients were carried out. Correlation analysis between DAT uptake ratios and clinical data were also conducted. RESULTS: TS patients showed significantly higher uptake of (99m)Tc-TRODAT-1 in bilateral striatum in comparison with the controls. There was no group-specific preferential lateralization in striatal uptake. DAT uptake ratios were not correlated with age and tic severity scores, but significant negative correlation with disease duration was found. CONCLUSIONS: High level of DAT was demonstrated in drug-naive TS patients compared with normal controls, and it was negatively correlated with TS duration. Therefore, with the extension of the disease duration, certain degree of adaptation might occur in TS patients to compensate for the DAT increase, which suggested that hyper-functional DAT might be involved in the early pathophysiological changes of TS. PMID- 20544325 TI - Prevalence of positive FDG-PET findings in patients with high CEA levels. AB - OBJECTIVE: The purpose of this study was to evaluate the prevalence of positive findings of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D glucose (FDG) in patients with high serum CEA levels. METHODS: A total of 303 patients who had undergone an FDG-PET scan in our institution with high serum CEA levels were analyzed. The prevalence of positive PET findings was evaluated with regard to a previous history of malignancy, absolute value of CEA levels, and the time course of CEA levels (an increasing or decreasing pattern, a change divided by time (DeltaCEA) and doubling time of CEA). RESULTS: Of 303 patients, 232 were confirmed to have malignancy, and the patient-based sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET were 87, 86, 95, 66, and 86%, respectively. There was no statistically significant difference in positive rates according to the history of previous malignancy. The prevalence of PET-positive cases was higher with an increase in absolute CEA levels, and more than 90% of the patients were positive when CEA levels were more than 20 ng/ml. The DeltaCEA was significantly higher and the doubling time was significantly shorter in patients with positive results than those with negative results. CONCLUSIONS: A high value of serum CEA levels was correlated with a higher prevalence of positive PET findings. FDG-PET scans would be justified in patients with high serum CEA levels, regardless of whether there was or was not a previous history of malignancy. PMID- 20544326 TI - Managing beta-blockers in acute heart failure: when to start and when to stop? AB - The role of beta-blockers in heart failure has been long debated. Data from chronic heart failure studies clearly indicate that beta-blockers save lives. However, data concerning use of beta-blockers in patients with acute heart failure are limited, and only recently have emerged to help guide therapy. In this review, we provide an overview of when to stop and when to start beta blockers in patients with acute heart failure. PMID- 20544327 TI - Management of malignant pleural effusions. AB - Malignant pleural effusions are a common clinical problem in patients with primary thoracic malignancy and metastatic malignancy to the thorax. Symptoms can be debilitating and can impair tolerance of anticancer therapy. This article presents a comprehensive review of pharmaceutical and nonpharmaceutical approaches to the management of malignant pleural effusion, and a novel algorithm for management based on patients' performance status. PMID- 20544329 TI - [Dermatology practice panorama. Acne treatment of Europeans especially negligent]. PMID- 20544328 TI - Delivery of siRNA therapeutics: barriers and carriers. AB - RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising therapeutic strategy. Clinical evaluations of siRNA therapeutics in locoregional treatment settings began in 2004. Systemic siRNA therapy is hampered by the barriers for siRNA to reach their intended targets in the cytoplasm and to exert their gene silencing activity. The three goals of this review were to provide an overview of (a) the barriers to siRNA delivery, from the perspectives of physicochemical properties of siRNA, pharmacokinetics and biodistribution, and intracellular trafficking; (b) the non-viral siRNA carriers including cell-penetrating peptides, polymers, dendrimers, siRNA bioconjugates, and lipid-based siRNA carriers; and (c) the current status of the clinical trials of siRNA therapeutics. PMID- 20544331 TI - [Current operative techniques for urethral stricture]. PMID- 20544332 TI - [Endoscopic management of urethral stricture]. AB - Great progress has been seen in the treatment of urethral strictures since the first endoscopic urethrotomy was performed in 1893 by Felix Martin Oberlander in Dresden, Germany. With the introduction of endoscopic laser therapy and the variety of urethral reconstruction methods other ways to treat this important urologic entity became available. Despite this progress, urethrotomy still represents the preferred treatment concept for primary, short and bulbar urethral strictures. In this study we performed a 2-year retrospective analysis of 20 patients undergoing primary endoscopic urethrotomy by single bulbar or penile narrowing. A high incidence of recurrence was seen in 70% of the patients. Nevertheless, direct vision urethrotomy represented a safe and effective transitory method to treat these patients. Moreover, 80% of the patients preferred, in cases of recurrence, a repeated urethrotomy as the treatment of choice. Although the long-term results evidence high relapse rates after the first and second procedures, there have been no sufficient data in the literature which support the use of other methods. Furthermore, primary endoscopic management of urethral strictures remains a simple, safe, and cost-effective procedure that should be indicated before more invasive approaches are taken to provide relief to these patients from this limiting problem. PMID- 20544333 TI - [Meatal stenosis. Mundane problem or surgical challenge?]. AB - There is no common pathology in strictures of the external urinary meatus in men and women. These strictures have to be considered in their complexity and history with influential factors like additional diseases and previous surgical interventions. It is necessary to distinguish a simple situation from extensive findings. Successful therapy depends on the exact evaluation and classification of the stricture. PMID- 20544334 TI - [Interventional and surgical treatment of urethral strictures. End-to-end anastomosis]. AB - Excision with primary anastomosis is an excellent reconstructive option for short bulbar and membranous urethral strictures. With adequate patient selection including history, physical examination, and radiographic staging success rates between 90 and 95% in appropriately selected patients can be achieved. Success with this reliable method is based on adequate excision of the complete urethral stricture and sufficient mobilization of the urethra with tension-free anastomosis. Complications affecting ejaculation or penile sensitivity are rare and might be avoided by appropriate surgical techniques. Resection of the stricture and urethral end-to-end anastomosis represents the "gold-standard" in the treatment of bulbar and membraneous strictures up to a length of 3 cm. PMID- 20544335 TI - [Perineal urethrostomy in complex anterior urethral stricture]. AB - Staged urethroplasty is a well-known procedure for urethral reconstruction that had already been described by Russell in 1914 and was later popularized by Johanson, Turner-Warwick, Blandy, and Schreiter. It lends itself to the treatment of complex anterior urethral stricture in combination with lichen sclerosus, failed correction of hypospadias, fistula, via falsa, abscess, carcinoma, or previously unsuccessful urethroplasty. Perineal urethrostomy can be performed as a temporary or definitive measure. Some patients even decline further urethral reconstruction because they perceive subjective satisfaction after perineal urethrostomy that was originally intended to be temporary. PMID- 20544339 TI - HERG1 channelopathies. AB - Human ether a go-go-related gene type 1 (hERG1) K+ channels conduct the rapid delayed rectifier K+ current and mediate action potential repolarization in the heart. Mutations in KCNH2 (the gene that encodes hERG1) causes LQT2, one of the most common forms of long QT syndrome, a disorder of cardiac repolarization that predisposes affected subjects to ventricular arrhythmia and increases the risk of sudden cardiac death. Hundreds of LQT2-associated mutations have been described, and most cause a loss of function by disrupting subunit folding, assembly, or trafficking of the channel to the cell surface. Loss-of-function mutations in hERG1 channels have also recently been implicated in epilepsy. A single gain-of function mutation has been described that causes short QT syndrome and cardiac arrhythmia. In addition, up-regulation of hERG1 channel expression has been demonstrated in specific tumors and has been associated with skeletal muscle atrophy in mice. PMID- 20544341 TI - Role of DNA methyltransferase 1 in hormone-resistant prostate cancer. AB - Given the poor outcome of patients with hormone-resistant (HR) prostate cancer, new strategies are needed to improve the current therapeutic regimens and/or develop novel treatments. We therefore aimed to provide a better understanding of the molecular mechanisms involved in the aggressive tumor behavior of HR and develop more rational anti-tumor therapies. Three HR prostate cancer cell lines (androgen receptor (AR)-positive LNCaP-HR and 22RV1-HR and AR-negative PC-3) were used. Changes in tumor behavior, treatment response, and related signaling in HR were investigated in vitro and in vivo. The results revealed that constitutional activation of STAT3 and overexpressions of DNMT1 were important in the transition of HR prostate cancer. Furthermore, DNMT1 expression was required for the maintenance of STAT3 activation. When DNMT1 activity in HR was blocked, aggressive tumor behavior and treatment resistance could be overcome, which was seen in both in vitro and in vivo experiments. The underlying changes associated with inhibited DNMT1 included less epithelial-mesenchymal changes, less invasion ability, slower tumor growth, and impaired DNA repair ability, which are independent of AR and p53 status. In conclusion, altered DNMT1 expression associated with activated STAT3 may be crucial in the transition of HR. Targeting DNMT1 could be a promising strategy for the treatment of HR prostate, as evidenced by inhibited tumor growth and enhanced radiosensitivity. These findings provide evidence for therapeutically targeting DNMT1 in HR prostate cancer. PMID- 20544340 TI - The regulation of class IA PI 3-kinases by inter-subunit interactions. AB - Phosphoinositide 3-kinases (PI 3-kinases) are activated by growth factor and hormone receptors, and regulate cell growth, survival, motility, and responses to changes in nutritional conditions (Engelman et al. 2006). PI 3-kinases have been classified according to their subunit composition and their substrate specificity for phosphoinositides (Vanhaesebroeck et al. 2001). The class IA PI 3-kinase is a heterodimer consisting of one regulatory subunit (p85alpha, p85beta, p55alpha, p50alpha, or p55gamma) and one 110-kDa catalytic subunit (p110alpha, beta or delta). The Class IB PI 3-kinase is also a dimer, composed of one regulatory subunit (p101 or p87) and one catalytic subunit (p110gamma) (Wymann et al. 2003). Class I enzymes will utilize PI, PI[4]P, or PI[4,5]P2 as substrates in vitro, but are thought to primarily produce PI[3,4,5]P3 in cells.The crystal structure of the Class IB PI 3-kinase catalytic subunit p110gamma was solved in 1999 (Walker et al. 1999), and crystal or NMR structures of the Class IA p110alpha catalytic subunit and all of the individual domains of the Class IA p85alpha regulatory subunit have been solved (Booker et al. 1992; Gunther et al. 1996; Hoedemaeker et al. 1999; Huang et al. 2007; Koyama et al. 1993; Miled et al. 2007; Musacchio et al. 1996; Nolte et al. 1996; Siegal et al. 1998). However, a structure of an intact PI 3-kinase enzyme has remained elusive. In spite of this, studies over the past 10 years have lead to important insights into how the enzyme is regulated under physiological conditions. This chapter will specifically discuss the regulation of Class IA PI 3-kinase enzymatic activity, focusing on regulatory interactions between the p85 and p110 subunits and the modulation of these interactions by physiological activators and oncogenic mutations. The complex web of signaling downstream from Class IA PI 3-kinases will be discussed in other chapters in this volume. PMID- 20544342 TI - Do repetitive Valsalva maneuvers change maximum prolapse on dynamic MRI? AB - INTRODUCTION AND HYPOTHESIS: This study seeks to quantify differences in anterior vaginal wall prolapse during sequential Valsalva attempts on dynamic magnetic resonance imaging (MRI). METHODS: Subjects were taken from an on-going case control study evaluating anterior vaginal wall prolapse. Women with a prolapse whose leading edge extended >or=1 cm beyond the hymenal ring were included (n = 40). All subjects performed three maximal Valsalva efforts while mid-sagittal dynamic MRI scans were obtained. Bladder descent between the first, second, and third maximal Valsalva efforts were compared. RESULTS: Forty percent of women had a greater than 2-cm increase in prolapse size from their first to third Valsalva attempt. Ninety-five percent of women extended their prolapse further with a third Valsalva. CONCLUSIONS: As is true during clinical examination, several attempts may be required to have maximal anterior compartment prolapse present during dynamic MRI of the pelvic floor. PMID- 20544343 TI - Extracellular fluctuations of dopamine and glutamate in the nucleus accumbens core and shell associated with lever-pressing during cocaine self-administration, extinction, and yoked cocaine administration. AB - RATIONALE: Dopamine and glutamate in the nucleus accumbens (NAS) are differentially implicated in cocaine-directed behavior. OBJECTIVES: We sought to compare extracellular fluctuations of dopamine and glutamate in core and shell of NAS associated with operant responding during cocaine self-administration, extinction, and yoked cocaine administration. METHODS: Rats were trained to lever press for cocaine or saline under FR1 before undergoing microdialysis testing during cocaine self-administration, extinction, or yoked cocaine administration. Microdialysis samples were collected every 20 min and were analyzed for dopamine and glutamate with high-performance liquid chromatography. RESULTS: Rats actively lever-pressed during cocaine self-administration and extinction. However, lever pressing was minimal during yoked cocaine administration in both cocaine-trained and saline-trained rats. Dopamine was elevated throughout cocaine self administration and yoked cocaine administration. The extent of cocaine-evoked dopamine was greater in shell than in core, greater in cocaine-trained than in saline-trained rats, and greater during self-administration than during yoked administration. Dopamine was also elevated in core (first 60 min) and in shell (first 40 min) during extinction. Basal concentration of glutamate, but not dopamine, was lower in cocaine-trained than in saline-trained rats. In cocaine trained rats, glutamate was elevated during cocaine self-administration and extinction but was depressed below baseline during yoked cocaine administration. The extent and direction of glutamate fluctuation was similar between core and shell. In saline-trained rats, glutamate was not affected by yoked cocaine. CONCLUSION: Distinct patterns of dopamine and glutamate fluctuations in core and shell appear to underlie characteristic patterns of lever-pressing associated with cocaine self-administration, extinction, and yoked cocaine administration. PMID- 20544344 TI - Differential regulation of calcium-activated potassium channels by dynamic intracellular calcium signals. AB - Calcium (Ca(2+))-activated K(+) (K(Ca)) channels regulate membrane excitability and are activated by an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)), leading to membrane hyperpolarization. Most patch clamp experiments that measure K(Ca) currents use steady-state [Ca(2+)] buffered within the patch pipette. However, when cells are stimulated physiologically, [Ca(2+)](i) changes dynamically, for example during [Ca(2+)](i) oscillations. Therefore, the aim of the present study was to examine the effect of dynamic changes in [Ca(2+)](i) on small (SK3), intermediate (hIK1), and large conductance (BK) channels. HEK293 cells stably expressing each K(Ca) subtype in isolation were used to simultaneously measure agonist-evoked [Ca(2+)](i) signals, using indo-1 fluorescence, and current/voltage, using perforated patch clamp. Agonist-evoked [Ca(2+)](i) oscillations induced a corresponding K(Ca) current that faithfully followed the [Ca(2+)](i) in 13-50% of cells, suggesting a good synchronization. However, [Ca(2+)](i) and K(Ca) current was much less synchronized in 50-76% of cells that exhibited Ca(2+)-independent current events (55% of SK3-, 50% of hIK1 , and 53% of BK-expressing cells) and current-independent [Ca(2+)](i) events (18% SK3- and 33% of BK-expressing cells). Moreover, in BK-expressing cells, where [Ca(2+)](i) and K(Ca) current was least synchronized, 36% of total [Ca(2+)](i) spikes occurred without activating a corresponding K(Ca) current spike, suggesting that BK(Ca) channels were either inhibited or had become desensitized. This desynchronization between dynamic [Ca(2+)](i) and K(Ca) current suggests that this relationship is more complex than could be predicted from steady-state [Ca(2+)](i) and K(Ca) current. These phenomena may be important for encoding stimulus-response coupling in various cell types. PMID- 20544346 TI - Prognostic impact of underlying liver fibrosis and cirrhosis after curative resection of hepatocellular carcinoma. AB - BACKGROUND: In the case of hepatocellular carcinoma (HCC), underlying liver pathology may not only determine the feasibility of surgery but may also affect the postsurgical outcome. We report our experience after curative liver resection for HCC in patients with normal liver, liver fibrosis, and liver cirrhosis. METHODS: A total of 72 patients after liver resection with curative intention were analyzed. Histopathologic findings of tumor-unaffected liver tissue were used for retrospective classification: group A (normal liver); group B (liver fibrosis); group C (liver cirrhosis). The groups were compared for differences in short-term surgical results, total survival, and recurrence-free survival. RESULTS: The rate of major complications was 34.7% and did not significantly differ among groups. The overall perioperative mortality rate was 9.7%, with one patient dying in group A and three patients dying in each of the other two groups. Including perioperative mortality, the median overall survival for the whole group was 37.3 months (95% confidence interval 29.3-45.2 months). The respective 1-, 2-, and 5-year survival rates for group A (n = 21) were 86%, 71%, and 50% and for group C (n = 24) 62%, 50%, and 17%. The overall survival of group B (n = 27) was intermediate (log-rank, P = 0.032). The respective recurrence-free survival rates were 76%, 42%, and 20% for group A and 39%, 13%, and 4% for group C, with group B being intermediate (log-rank, P = 0.016). CONCLUSIONS: Our data demonstrate that liver resection in the presence of compensated liver cirrhosis is feasible but associated with a significantly impaired prognosis for overall and recurrence-free survival. The management of cirrhotic patients with compensated liver function and HCC therefore also requires the opportunity for transplantation. PMID- 20544345 TI - The complete inventory of receptors encoded by the rat natural killer cell gene complex. AB - The natural killer cell gene complex (NKC) encodes receptors belonging to the C type lectin superfamily expressed primarily by NK cells and other leukocytes. In the rat, the chromosomal region that starts with the Nkrp1a locus and ends with the Ly49i8 locus is predicted to contain 67 group V C-type lectin superfamily genes, making it one of the largest congregation of paralogous genes in vertebrates. Based on physical proximity and phylogenetic relationships between these genes, the rat NKC can be divided into four major parts. We have previously reported the cDNA cloning of the majority of the genes belonging to the centromeric Nkrp1/Clr cluster and the two telomeric groups, the Klre1-Klri2 and the Ly49 clusters. Here, we close the gap between the Nkrp1/Clr and the Klre1 Klri2 clusters by presenting the cDNA cloning and transcription patterns of eight genes spanning from Cd69 to Dectin1, including the novel Clec2m gene. The definition, organization, and evolution of the rat NKC are discussed. PMID- 20544347 TI - Predictive factors for improving survival after gastrectomy in gastric cancer patients with peritoneal carcinomatosis. PMID- 20544348 TI - Increase in maximal oxygen uptake following 2-week walk training with blood flow occlusion in athletes. AB - Walk training with blood flow occlusion (OCC-walk) leads to muscle hypertrophy; however, cardiorespiratory endurance in response to OCC-walk is unknown. Ischemia enhances the adaptation to endurance training such as increased maximal oxygen uptake (VO2(max)) and muscle glycogen content. Thus, we investigated the effects of an OCC-walk on cardiorespiratory endurance, anaerobic power, and muscle strength in elite athletes. College basketball players participated in walk training with (n = 7) and without (n = 5) blood flow occlusion. Five sets of a 3 min walk (4-6 km/h at 5% grade) and a 1-min rest between the walks were performed twice a day, 6 days a week for 2 weeks. Two-way ANOVA with repeated measures (groups x time) was utilized (P < 0.05). Interactions were found in VO2(max) (P = 0.011) and maximal minute ventilation (VE(max); P = 0.019). VO2(max) (11.6%) and VE(max) (10.6%) were increased following the OCC-walk. For the cardiovascular adaptations of the OCC-walk, hemodynamic parameters such as stroke volume (SV) and heart rate (HR) at rest and during OCC-walk were compared between the first and the last OCC-walk sessions. Although no change in hemodynamics was found at rest, during the last OCC-walk session SV was increased in all five sets (21.4%) and HR was decreased in the third (12.3%) and fifth (15.0%) sets. With anaerobic power an interaction was found in anaerobic capacity (P = 0.038) but not in peak power. Anaerobic capacity (2.5%) was increased following the OCC-walk. No interaction was found in muscle strength. In conclusion, the 2-week OCC-walk significantly increases VO2(max) and VE(max) in athletes. The OCC-walk training might be used in the rehabilitation for athletes who intend to maintain or improve endurance. PMID- 20544349 TI - Acute renal failure following antithymocyte globulin therapy for aplastic anaemia report of two cases and review of literature. PMID- 20544350 TI - Antiapoptotic effect of interleukin-2 (IL-2) in B-CLL cells with low and high affinity IL-2 receptors. AB - Although B chronic lymphocytic leukemia (B-CLL) cells express the alpha chain of the interleukin-2 (IL-2) receptor CD25, little is known about the effect of IL-2 on apoptosis in B-CLL cells. We have shown previously that stimulation of B-CLL cells with a CpG-oligonucleotide induces IL-2 high affinity receptors. In our current work, we analyzed the effect of IL-2 on apoptosis in resting B-CLL cells and in our model of activated B-CLL cells (CD25 high cells). IL-2 had modest antiapoptotic activity in resting B-CLL cells. In contrast, IL-2 was much more potent to prevent apoptosis in activated cells. Prevention of cell death was also associated with the maintenance of the mitochondrial membrane potential. While only limited regulation of apoptosis controlling proteins was observed in resting B-CLL cells, IL-2 had strong effects on MCL-1, Bcl-xl, and survivin expression and inhibited Bax cleavage in CD25 high cells. Interestingly, expression of Bcl-2 was reduced. Addition of IL-2 to activated B-CLL cells caused rapid phosphorylation of Akt, while IL-2 failed to significantly phosphorylate Akt in resting B-CLL cells. Pharmacological inhibition of Akt by LY294002 restored sensitivity of activated B-CLL cells to fludarabine. IL-2 might be an important survival factor in activated B-CLL cells and might contribute to disease progression by upregulation of several critical antiapoptotic proteins. PMID- 20544351 TI - Allogeneic transplant outcomes are not affected by body mass index (BMI) in patients with haematological malignancies. AB - Bone marrow transplantation is frequently used as a consolidation therapy in patients with haematological malignancies to improve the outcome of these patients. Obese individuals have larger absolute lean body and fat masses than non-obese individuals of the same age, gender and height, which might lead to altered pharmacokinetics of chemotherapeutic agents. Data on the impact of body mass on transplant outcome is conflicting. This study included 331 patients (M, 230; F, 101) with 336 allogeneic transplant episodes from two large teaching hospitals in the West Midlands region in United Kingdom. A total of 105 patients had acute myeloid leukaemia, 83 had non-Hodgkin's lymphoma, three had myeloma, 21 had Hodgkin's lymphoma, 34 had acute lymphoblastic leukaemia, 19 had chronic myeloid leukaemia, 22 had chronic lymphocytic leukaemia, 24 had myelodysplasia, seven had T cell non-Hodgkin's lymphoma, six had aplastic leukaemia and seven had myelofibrosis. At transplantation, 40% (N = 133) of the patients had normal and 60% (N = 198) had high body mass index (BMI) with 14% of the patients being obese (BMI >30). After a median follow-up of 24 months (range, 2-79), the mean overall survival (OS) in patients undergoing allograft with normal BMI was 31 months as compared to 39 with high BMI (p:0.06). The mean progression free survival (PFS) in patients undergoing allograft with normal BMI was 33 months as compared to 38 with high BMI (p = 0.13). Of the patients in the high and obese BMI group, 16% developed acute GvHD with 8% grade III-IV and 28% in the normal BMI group with 14% grade III-IV acute GvHD (p = 0.11). Of the patients in the high BMI group, 17% developed chronic GvHD and 30% of the patients in the normal BMI group (p = 0.09). However, higher infection rates and more days of inpatient stay in the first year post-transplant were observed in the high BMI and obese patients, but there was no difference in ITU admissions. This study shows that high BMI and obesity does not adversely impact on either OS or PFS in patients undergoing allogeneic transplantation for haematological malignancies, but it does have a significant impact on infection rates and hospitalisation of high BMI and obese patients. We recommend that patients with high BMI should not be excluded from allogeneic transplantation; however, good supportive care and careful patient selection on the basis of comorbidity index should be undertaken in order to avoid the risks from the increased rates of infection. PMID- 20544354 TI - Allergic rhinitis and chronic suppurative otitis media. AB - Allergic inflammation in upper airways can act as a predisposing factor for infectious ear diseases. There are some evidences about the role of allergic rhinitis in chronic otitis media with effusion, but its role in establishing chronic suppurative otitis media (CSOM) has not been clearly shown. 68 adult patients with established CSOM, who were candidates for ear surgery, and 184 age- and sex-matched controls were evaluated for the presence of allergic rhinitis. Standard questionnaire was filled out for all participants. All patients and controls underwent skin prick test for 28 common regional aeroallergens, and serum total IgE was measured by means of ELISA method. Allergic rhinitis were defined as a positive responses to the questionnaire, positive skin prick test to at least one allergen, and/or high level of serum total IgE. Allergic rhinitis was diagnosed in 20 (29.41%) and 41 (22.28%) of patients and controls, respectively (P = 0.241) (OR = 1.28, CI = 0.69-2.36). Outdoor allergens, especially grass pollen, were the most prevalent allergens among both groups, but indoor allergens like mites and molds have a low prevalence. The study did not show a significant difference in the prevalence of AR in the CSOM patients compared to the controls. The intermittent nature of allergy and other less known intervening factors in the etiopathogenesis of CSOM make such a conclusion difficult. PMID- 20544353 TI - [Ocular involvement in spondyloarthropathies: HLA B27 associated uveitis]. AB - The most frequent extraarticular manifestation in spondyloarthropathies (SpA) is eye involvement, which is found in 30%-50% of patients. HLA B27 positive patients in particular--mostly those in the subgroup with ankylosing spondylitis--are affected. Prevalence of uveitis increases with duration of disease. Typical eye involvement is sudden-onset unilateral anterior uveitis (iridocyclitis). Most cases respond well to topical corticosteroids. Frequently relapsing or chronic cases may require oral corticosteroids in addition to classical immunosuppressive drugs and, to an increasing extent, also TNF-alpha inhibitors. In the case of the latter, monoclonal antibodies are preferred over receptor antagonists. Acute anterior uveitis may occur as a minimal variation or initial symptom of SpA. These patients should also be seen by a rheumatologist since undiagnosed SpA may be present in a significant percentage and should be included in therapeutic considerations. PMID- 20544352 TI - Modern dental imaging: a review of the current technology and clinical applications in dental practice. AB - A review of modern imaging techniques commonly used in dental practice and their clinical applications is presented. The current dental examinations consist of intraoral imaging with digital indirect and direct receptors, while extraoral imaging is divided into traditional tomographic/panoramic imaging and the more recently introduced cone beam computed tomography. Applications, limitations and current trends of these dental "in-office" radiographic techniques are discussed. PMID- 20544355 TI - Sensation of nasal patency compared to rhinomanometric results after septoplasty. AB - The primary aim of the present study was to investigate the relationship between the subjective sensation of nasal airflow resistance, the rhinoscopic findings and the objective measures of nasal obstruction in patients followed up after septoplasty. A further goal was to determine which of the above modalities is most suitable for assessment of the severity of nasal obstruction and which best indicates the need for surgery. 86 patients who had previously undergone septoplastic surgery were recruited. Objective and subjective measures of nasal obstruction were recorded by using active anterior rhinomanometry, rhinoscopy and a visual analogue scale. The Spearman rank order correlation model revealed a significant correlation between the VAS score and the airway resistance of the more obstructed nasal cavity (r = 0.24); furthermore, between the VAS score and rhinoscopic findings (r = 0.35). By applying the generalized linear model, we also found significant relation between the VAS score and the rhinomanometric data, and between the rhinoscopic findings and the airway resistance of the more obstructed nasal cavity (p = 0.02). The correlation between the subjective sensation of nasal airflow resistance, the rhinoscopic findings, and the rhinomanometric data proved to be significant, but weak even in the group of patients that underwent septoplasty. Every postoperative complaint should therefore be evaluated carefully. Rhinomanometry is an appropriate diagnostic tool with which to determine the measure of obstruction caused by nasal pathological factors. It is suitable for making objective the patients' complaints. Rhinoscopy, beyond the assessment of the degree of obstruction, is capable of analysis of its cause. The decision as to the need for surgery should be based on rhinoscopy, or nasal endoscopy, and can be supported by pathologically elevated resistance of the more obstructed nasal cavity. PMID- 20544356 TI - Different mechanical loading protocols influence serum cartilage oligomeric matrix protein levels in young healthy humans. AB - The purpose of the study was to investigate whether a relationship between the loading mode of physical activity and serum cartilage oligomeric matrix protein (COMP) concentration exists and whether the lymphatic system contributes to COMP release into the serum. Serum COMP levels were determined in healthy male subjects before, after and at 18 further time points within 7 h at four separate experimental days with four different loading interventions. The loading intervention included high impact running exercise, slow but deep knee bends, and lymphatic drainage of 30 min duration, respectively, and a resting protocol. The serum COMP levels were measured using a commercially available quantitative enzyme-linked immunosorbent assay. An increase (p < 0.001) in serum COMP concentration was detected immediately after 30 min running exercise. Slow but deep knee bends did not cause any significant changes in serum COMP levels. Lymphatic drainage also had no effect on the serum COMP concentration. After 30 min of complete rest the serum COMP level was significantly (p = 0.008) reduced. The elevation of COMP serum concentration seems to depend on the loading mode of the physical activity and to reflect the extrusion of COMP fragments from the impact loaded articular cartilage or synovial fluid. PMID- 20544357 TI - A mathematical model of neuromuscular adaptation to resistance training and its application in a computer simulation of accommodating loads. AB - A large corpus of data obtained by means of empirical study of neuromuscular adaptation is currently of limited use to athletes and their coaches. One of the reasons lies in the unclear direct practical utility of many individual trials. This paper introduces a mathematical model of adaptation to resistance training, which derives its elements from physiological fundamentals on the one side, and empirical findings on the other. The key element of the proposed model is what is here termed the athlete's capability profile. This is a generalization of length and velocity dependent force production characteristics of individual muscles, to an exercise with arbitrary biomechanics. The capability profile, a two dimensional function over the capability plane, plays the central role in the proposed model of the training-adaptation feedback loop. Together with a dynamic model of resistance the capability profile is used in the model's predictive stage when exercise performance is simulated using a numerical approximation of differential equations of motion. Simulation results are used to infer the adaptational stimulus, which manifests itself through a fed back modification of the capability profile. It is shown how empirical evidence of exercise specificity can be formulated mathematically and integrated in this framework. A detailed description of the proposed model is followed by examples of its application-new insights into the effects of accommodating loading for powerlifting are demonstrated. This is followed by a discussion of the limitations of the proposed model and an overview of avenues for future work. PMID- 20544358 TI - Tobacco harm to the developing child. PMID- 20544361 TI - Difficult postpartum management of a patient complicated by severe PIH and prolonged PRES. PMID- 20544359 TI - Interdisciplinary approach to design, performance, and quality management in a multicenter newborn hearing screening project. Discussion of the results of newborn hearing screening in Hamburg (part II). AB - Previously presented results of the newborn hearing screening in Hamburg and the perspectives are subsequently discussed. Minimum standards referring a participation of 95% of the neonates and a fail rate of less than 4% hearing impaired children at the primary screening are fulfilled in Hamburg. Systematic screening of newborn hearing by an interdisciplinary approach provides early identification and intervention for children with permanent unilateral and bilateral hearing loss. But a newborn hearing screening on a voluntary basis alone cannot be maintained in the long run. Further, an anonymous data collection is not sufficient in regard to an uninterrupted tracking of conspicuous and unscreened neonates. A lost-to-follow-up rate of 31.3% at primary screening in Hamburg is much too high and emphasizes the need for a public health approach to a population-based newborn hearing screening with an elaborate and name-based tracking system. The legislation and implementation of a nationwide newborn hearing screening program in Germany and the association of German newborn hearing screening centers are highlighting long efforts of hearing professionals. But the implementation of a newborn hearing screening only makes sense if there exists an efficient tracking system. Sad to say, we are still a long way from the implementation of such a tracking system. PMID- 20544362 TI - Long-term facial nerve function evaluation following surgery for large acoustic neuromas via retrosigmoid transmeatal approach. AB - PURPOSE: By evaluating the postoperative facial nerve function of large acoustic neuromas, the purpose of this study was to analyze the factors that influence the facial nerve function outcome and to explore the surgical strategy for large acoustic neuromas. METHODS: A retrospective study of surgical outcome was performed on 89 patients with large acoustic neuromas. All operations were performed via the retrosigmoid transmeatal approach using the intraoperative electrophysiological monitoring. RESULTS: Gross total resection was performed in 38 (42.7%) of the 89 patients, near total resection in 35 (39.3%), and subtotal resection in 16 (18.0%). The facial nerve was anatomically intact at the end of surgery in 83 (93.3%) patients. At 1 year after surgery, 48 (53.9%) patients had good facial nerve function (House-Brackmann (HB) Grades I-II), 23 (25.8%) patients had regular facial nerve function (HB Grades III-IV), and 18 (20.2%) patients had poor facial nerve function (HB Grades V-VI). CONCLUSIONS: For large acoustic neuromas, the goal of complete tumor resection and preservation of acceptable facial nerve function can be attained via the retrosigmoid transmeatal approach, using the intraoperative facial nerve monitoring. The surgical strategy of near total resection is indicated for the large acoustic neuromas with severe adherence or inclusion in order to preserve facial nerve function. PMID- 20544363 TI - An alternative projection for fluoroscopic-guided needle insertion in the foramen ovale: technical note. AB - PURPOSE: Puncture of the ganglion Gasseri through the foramen ovale and subsequent thermocoagulation, balloon compression, or glycerin injection is a well-established technique to treat trigeminal neuralgia. However, direct puncture of the foramen is sometimes difficult. Here, the authors present a simple technique of improved biplane fluoroscopic control for insertion of the needle into the foramen ovale. METHODS: The authors evaluated an alternative oblique X-ray trajectory for the correct placement of a needle into the foramen ovale on cadaveric skull models. After determination of the ideal X-ray trajectory, 13 subsequent patients suffering from trigeminal neuralgia were subjected to intraforaminal needle placement with application of the alternative X-ray trajectory. RESULTS: An oblique projection with the X-ray tube (mean rotation 20.9 degrees and angulations 28 degrees ) aligned coaxially to the inserted needle is proposed. On cadaver skull models, this oblique trajectory appeared to be ideal for visualization of the correct needle position. In the 13 patients, an immediate needle insertion into the foramen ovale was achieved under this direct oblique fluoroscopic control. No complications were observed. CONCLUSIONS: Experimentally and clinically, the new projection demonstrated three distinct advantages over the standard submental projection: Firstly, the foramen ovale can be better visualized independent of the patient's position. Secondly, needle correction or insertion can be performed much easier because of the direct fluoroscopic control. Thirdly, the correct needle position in the foramen ovale is more reliably determined than with the submental projection due to projection geometry. Further studies are needed to give evidence that the needle insertion into the foramen ovale is easier achieved with the coaxial projection than with the standard technique. PMID- 20544365 TI - Colon cancer and diverticula: a single-institution experience. PMID- 20544364 TI - The copper centers of tyramine beta-monooxygenase and its catalytic-site methionine variants: an X-ray absorption study. AB - Tyramine beta-monooxygenase (TBM) is a member of a family of copper monooxygenases containing two noncoupled copper centers, and includes peptidylglycine monooxygenase and dopamine beta-monooxygenase. In its Cu(II) form, TBM is coordinated by two to three His residues and one to two non-His O/N ligands consistent with a [Cu(M)(His)(2)(OH(2))(2)-Cu(H)(His)(3)(OH(2))] formulation. Reduction to the Cu(I) state causes a change in the X-ray absorption spectroscopy (XAS) spectrum, consistent with a change to a [Cu(M)(His)(2)S(Met) Cu(H)(His)(3)] environment. Lowering the pH to 4.0 results in a large increase in the intensity of the Cu(I)-S extended X-ray absorption fine structure (EXAFS) component, suggesting a tighter Cu-S bond or the coordination of an additional sulfur donor. The XAS spectra of three variants, where the Cu(M) Met471 residue had been mutated to His, Cys, and Asp, were examined. Significant differences from the wild-type enzyme are evident in the spectra of the reduced mutants. Although the side chains of His, Cys, and Asp are expected to substitute for Met at the Cu(M) site, the data showed identical spectra for all three reduced variants, with no evidence for coordination of residue 471. Rather, the K-edge data suggested a modest decrease in coordination number, whereas the EXAFS indicated an average of two His residues at each Cu(I) center. These data highlight the unique role of the Met residue at the Cu(M) center, and pose interesting questions as to why replacement by the cuprophilic thiolate ligand leads to detectable activity whereas replacement by imidazole generates inactive TBM. PMID- 20544366 TI - Abdominal wall closure: resident education and human error. AB - PURPOSE: Secure abdominal wall closure for laparotomy incisions is paramount in prevention of hernia formation. Despite the importance, abdominal closure is often delegated to the resident surgeon. The purpose of this study was to assess residents' formal training, knowledge, and technique in abdominal wall closure. METHODS: All surgical residents in our training program participated in a skills laboratory and completed a questionnaire. The skills portion involved closure of a 10-cm incision on a simulated abdominal wall. Participants were timed, videotaped, and graded using a standardized grading system. Lengths of the suture bites were measured. Regression analysis was used to compare results based on number of closures. A P-value of <0.05 was considered significant. RESULTS: Ten surgical residents participated. The average time for closure was 4:23 min (range 3:08-5:65 min). The average distance between the bite and the incision was 0.9 cm and between bites was 0.8 cm. All knots were satisfactory and intact following closure. Participants' experience varied with a range from 0 to 230 previous abdominal closures. All residents chose to perform closure in a continuous fashion using a slowly absorbing suture. All but one resident stated that sutures should be placed 1 cm from the incision with 1 cm advances. Only one resident knew the correct suture-to-wound length ratio for closure, and only four residents were familiar with the literature about abdominal wall closure. With increasing closure experience, there was significant improvement in time and motion of suturing (P = 0.02), respect of tissue (P = 0.0002), instrument handling (P = 0.004), orientation of needle (P = 0.0076), and flow of closure (P = 0.046). Residents who had performed more closures took significantly larger suture bites (P = 0.03) with larger distances between bites (P = 0.03). CONCLUSIONS: Surgical technique improves with increased experience with abdominal closures; however, residents at all levels have the physical ability to adequately perform this task. Education regarding closure appears to be lacking, and further study warranted. PMID- 20544367 TI - Contralateral occurrence after laparoscopic total extraperitoneal hernia repair for unilateral inguinal hernia. AB - PURPOSE: Although laparoscopic total extraperitoneal repair (TEP) has been reported to have a low recurrence rate and relatively little postoperative pain, there have been few studies reported regarding contralateral occurrence after TEP. Although a high incidence of occult contralateral hernias has been reported in the literature, it is unknown whether occult hernias have any significance in clinical settings. The aim of this study was to evaluate the incidence of contralateral occurrence after TEP for unilateral inguinal hernia. METHODS: We retrospectively reviewed the medical charts of 157 TEPs between April 2003 and May 2009. No patients had undergone contralateral exploration during TEP for unilateral inguinal hernias. RESULTS: Five (3.2%) of 157 unilateral TEPs developed a hernia on the contralateral side. In three patients, the initial hernia was on the right side, and in two it was on the left side. In four patients the initial hernia was indirect, and in one it was direct. The mean duration to contralateral occurrence was 12.2 months. Three patients had contralateral occurrence within 6 months after the primary TEP, while in two over a year passed before contralateral occurrence. All five patients had undergone TEP for contralateral occurrence. The mean operation time was 87.2 min, and there was little intraoperative blood loss. There were no complications during and after the second TEP. CONCLUSIONS: The incidence of contralateral occurrence after TEP was found to be low. TEP is a valuable procedure with a low contralateral occurrence rate, and repeated TEP for contralateral occurrence can be performed easily. PMID- 20544368 TI - Necrotising fasciitis of the lower limb due to perforated inguinal hernia. AB - Acute inguinal hernia complications (incarceration, strangulation) are relatively frequent conditions, especially in the elderly. Urgent surgery is the appropriate treatment if manual reduction is not achieved or strangulation or perforation is suspected. We present a 77-year-old patient with necrotising fasciitis of the lower limb as a consequence of extraperitoneal perforation of a sliding inguinal hernia. This devastating condition was diagnosed 20 h after the manual reduction of the hernia. Suspicion arose at the physical examination (crepitation, signs of cellulitis) and clinical deterioration of the patient, and was confirmed by computed tomography (CT) scanning. Urgent surgery was performed, including sigmoidectomy, debridement of the necrotic tissues of the medial and anterior thigh compartment, and fasciectomy, combined with optimal intensive care support. No signs of peritoneal or pelvic involvement were found. However, the comorbidities, advanced age and the progression of the disease led to fatal outcome. Early recognition of the complications of strangulated hernias is of vital importance for successful treatment in these cases, even if no signs of acute abdomen are present. PMID- 20544369 TI - Laparoscopic repair of potentially contaminated abdominal ventral hernias using a xenograft: a case series. AB - BACKGROUND: The aim of this study was to describe the preliminary experience of definitive single stage laparoscopic reconstruction of the abdominal wall utilizing a tissue matrix in a potentially contaminated surgical field. METHOD: Retrospective review of potentially contaminated ventral hernias repaired with a minimally invasive technique utilizing biological mesh. Reconstruction required the laparoscopic restoration of the midline with or without a minimally invasive component separation technique and reinforcement with a xenograft (StratticeTM Reconstructive Tissue Matrix, LifeCell, Branchburg, NJ). RESULTS: We describe the first three cases of a xenograft placed laparoscopically in a potentially contaminated ventral hernia. There were no mesh-related complications or early recurrences during short-term 6 month follow-up. CONCLUSION: StratticeTM Reconstructive Tissue Matrix appears to be a promising new biological matrix for laparoscopic ventral hernia repair, especially in potentially contaminated fields. Further studies and long-term follow-up are still required. PMID- 20544370 TI - Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population. AB - Cytokines are crucial in activation of the cell-mediated immunity required for eliminating pathogens and controlling intracellular growth of Mycobacterium tuberculosis (TB). Genetic variants in the IL12-IFNG axis are hypothesized to be involved in the development and progression of TB. Genetic polymorphisms of rs2243115 and rs568408 in IL12A, rs3212227 in IL12B and rs2430561 in IFNG(+874) were detected in 522 pulmonary TB cases and 527 controls recruited from Yangzhong and Wujin County of China. It was found that genetic variants TG/GG of rs2243115(IL12A) were associated with a decreased risk of TB, with odds ratio (95% confidence interval) of 0.70 (0.49-0.99), whereas variant genotypes AT/TT of rs2430561(IFNG) conferred 82% less risk for treatment failure, with a hazard ratio of 0.18 (95% confidence interval 0.04-0.73). Cumulative effects analysis revealed that the risk of TB increased significantly with the number of unfavorable genotypes in IL12 genes. Furthermore, MDR analysis showed potential higher-order gene-gene and gene-environment interactions and indicated different outcomes based on distinct genotype profiles. Results from this study demonstrate that genetic polymorphisms of the IL12-IFNG pathway may individually or jointly contribute to the susceptibility to and prognosis of pulmonary TB. PMID- 20544372 TI - Challenges for data storage in medical imaging research. AB - Researchers in medical imaging have multiple challenges for storing, indexing, maintaining viability, and sharing their data. Addressing all these concerns requires a constellation of tools, but not all of them need to be local to the site. In particular, the data storage challenges faced by researchers can begin to require professional information technology skills. With limited human resources and funds, the medical imaging researcher may be better served with an outsourcing strategy for some management aspects. This paper outlines an approach to manage the main objectives faced by medical imaging scientists whose work includes processing and data mining on non-standard file formats, and relating those files to the their DICOM standard descendents. The capacity of the approach scales as the researcher's need grows by leveraging the on-demand provisioning ability of cloud computing. PMID- 20544373 TI - TCP/IP optimization over wide area networks: implications for teleradiology. AB - Radiology examinations are large. The advent of fast volume imaging is making that statement truer every year. PACS are based on the assumption of fast local networking and just-in-time image pull to the desktop. On the other hand, teleradiology has been developed on a push model to accommodate the challenges of moderate bandwidth, high-latency wide area networks (WANs). Our group faced the challenging task of creating a PACS environment that felt local, while pulling images across a 3,000-mile roundtrip WAN link. Initial tests showed WAN performance lagging local area network (LAN) performance by a factor of 30 times. A 16-month journey of explorations pulled the WAN value down to only 1.5 times slower than the LAN. PMID- 20544374 TI - Population-based incidence and survival of central nervous system (CNS) malignancies in Girona (Spain) 1994-2005. AB - The purpose of this study was to describe the incidence and survival of primary Central Nervous System (CNS) malignancies using data from the population-based cancer registry for Girona province (north-east Spain).We included all cases of primary CNS malignancies registered between 1994 and 2005. Pathological diagnoses were reviewed and grouped according to the 2007 WHO Classification. Meningeal, soft tissue tumours, spinal cord tumours and primary CNS lymphoma were not included. Cases notified only by death certificate were excluded from the survival analysis. Kaplan and Meier survival curves were calculated from date of diagnosis to death or end of study (31 December 2005), as was relative survival. A total of 493 new CNS cancer patients were registered during the study period: 49.3% astrocytic, 3.4% oligodendroglial and oligoastrocytic tumours, 2.6% ependimal tumours, 3.7% embryonal tumours, 0.2% choroid plexus and 41% without histological confirmation. The mean age (in years) for embryonal tumours was 18.17 years, these being the younger patients in the sample, and 66.34 years for those without histological confirmation, the older patients. Overall, the age standardised incidence rate was 5.88 cases/100,000 people/year (men = 6.81; women = 4.99) with an increasing trend by age until the 70-74 age group. Five-year observed survival rates were: 14.6% for astrocytic tumours, 35.7% for oligodendroglial and oligoastrocytic tumours, 41.0% for ependymal tumours, 32.4% for embryonal tumours and 7.5% for those without histological confirmation (log rank test: P < 0.001). Five-year observed survival rates for astrocytic tumours were analyzed separately by tumour grading, with 37% for diffuse astrocytoma, 7.1% for anaplastic astrocytoma and 4.7% for glioblastoma (log rank test: P < 0.001).Our results show that astrocytic tumours are most frequently diagnosed and glioblastoma patients have the worst survival figures for the area covered by our population cancer registry.The high observed incidence of histologically unverified tumours is most probably due to easy access to state of the art CNS imaging in our area. PMID- 20544375 TI - 13C-direct detected NMR experiments for the sequential J-based resonance assignment of RNA oligonucleotides. AB - We present here a set of (13)C-direct detected NMR experiments to facilitate the resonance assignment of RNA oligonucleotides. Three experiments have been developed: (1) the (H)CC-TOCSY-experiment utilizing a virtual decoupling scheme to assign the intraresidual ribose (13)C-spins, (2) the (H)CPC-experiment that correlates each phosphorus with the C4' nuclei of adjacent nucleotides via J(C,P) couplings and (3) the (H)CPC-CCH-TOCSY-experiment that correlates the phosphorus nuclei with the respective C1',H1' ribose signals. The experiments were applied to two RNA hairpin structures. The current set of (13)C-direct detected experiments allows direct and unambiguous assignment of the majority of the hetero nuclei and the identification of the individual ribose moieties following their sequential assignment. Thus, (13)C-direct detected NMR methods constitute useful complements to the conventional (1)H-detected approach for the resonance assignment of oligonucleotides that is often hindered by the limited chemical shift dispersion. The developed methods can also be applied to large deuterated RNAs. PMID- 20544376 TI - Mammary gland studies as important contributors to the cause of epithelial mesenchymal plasticity in malignancy. PMID- 20544377 TI - An analysis of reentrant loops. AB - Reentrant loops are an important structural motif in alpha-helical transmembrane proteins. A reentrant loop is a structural motif that goes only halfway through the membrane and then turns back to the side from which it originates. The question of what causes the reentrant loops to form such a unique topology is still unanswered. In this study, we try to answer this question by analyzing the hydrophobicity distribution on the amino acid sequences of the reentrant loops. Our results show that reentrant loops have very low hydrophobicity around the deepest point buried in the membrane and relative high hydrophobicity close to the membrane surfaces. We speculate that this hydrophobicity distribution is a major force that stabilizes the unique reentrant loop structure. Our results also show that this hydrophobicity distribution results in special patterns on protein sequences, which can be captured using profile hidden Markov models (HMMs). The resulting profile HMMs can detect reentrant loops on protein sequences with high sensitivity and perfect specificity. PMID- 20544378 TI - Designing a highly efficient chemical chaperone system using chitosan-coated alginate. AB - In the present work we prepared chitosan-coated alginate beads, to use as a chemical chaperone based on the electrostatic interaction between the carboxylate groups of alginate and the ammonium groups of chitosan. This procedure was an attempt for designing a highly efficient chemical chaperone to improve protein stability and refolding. Based on enzyme recovered activity, turbidity, far-UV CD and fluorescence data, alkaline phosphatase can be stabilized and refolded to a higher degree in the presence of alginate capsules compared with unassisted form and was further improved by including chitosan. Finally the maximum yield was obtained when the refolding process was achieved under a well worked out temperature program: incubation of the captured-enzyme for 20 min at 4 degrees C followed by overnight incubation at 22 degrees C, which showed that aggregation is a major limitation to refolding. PMID- 20544379 TI - Cloning, overexpression, purification and preliminary characterization of human septin 8. AB - Mammalian septins comprise a family of 14 genes that encode GTP-binding proteins involved in important cellular processes such as cytokinesis and exocytosis. Expression of three different constructs encoding human septin 8 were analyzed and the results show that SEPT8GC, a clone expressing the conserved domain plus C terminal domain of human septin 8 yields the highest amount of recombinant protein. This protein was purified by affinity chromatography followed by a gel filtration chromatography. CD spectrum of SEPT8GC is characteristic of folded proteins and it presents a transition profile with a T (m) of 54 degrees C. Fluorescence emission spectra, analytic gel filtration and DLS reflect the sample oligomeric heterogeneity with the predominance of dimers in solution. Homology models indicate clearly that the preferred dimer interface is the one comprising the GTP binding site. PMID- 20544380 TI - The effects of husband's alcohol consumption on married women in three low-income areas of Greater Mumbai. AB - Gender-based violence rooted in norms, socialization practices, structural factors, and policies that underlie men's abusive practices against married women in India is exacerbated by alcohol. The intersection of domestic violence, childhood exposure to alcohol and frustration, which contribute to drinking and its consequences including forced sex is explored through analysis of data obtained from 486 married men living with their wives in a low-income area of Greater Mumbai. SEM shows pathways linking work-related stress, greater exposure to alcohol as a child, being a heavy drinker, and having more sexual partners (a proxy for HIV risk). In-depth ethnographic interviews with 44 married women in the study communities reveal the consequences of alcohol on women's lives showing how married women associate alcohol use and violence with different patterns of drinking. The study suggests ways alcohol use leads from physical and verbal abuse to emotional and sexual violence in marriage. Implications for gendered multi-level interventions addressing violence and HIV risk are explored. PMID- 20544381 TI - Alcohol use and sex risk behaviors among HIV-infected female sex workers (FSWs) and HIV-infected male clients of FSWs in India. AB - Unprotected heterosexual transactional sex plays a central role in the spread of HIV in India. Given alcohol's association with risky sex in other populations and alcohol's role in HIV disease progression, we investigated patterns of alcohol use in HIV-infected female sex workers (FSWs) and HIV-infected male clients of FSWs in Mumbai. Analyses identified factors associated with heavy alcohol use and evaluated the relationship between alcohol use and risky sex. We surveyed 211 female and 205 male individuals; 80/211 FSWs (38%) and 127/205 male clients (62%) drank alcohol in the last 30 days. Among females, 32 and 11% drank heavily and were alcohol-dependent, respectively; among males the respective proportions were 44 and 29%. Men's heavy alcohol use was significantly associated with inconsistent condom use over the last year (AOR 2.40, 95% CI 1.21-4.77, P = 0.01); a comparable association was not seen in women. These findings suggest a need to address alcohol use both to avoid the medical complications of its heavy use in this population and to mitigate inconsistent condom use, the latter issue possibly requiring gender specific approaches. Such efforts to reduce drinking will be an important dimension to secondary HIV prevention in India. PMID- 20544382 TI - Two sides of the same story: alcohol use and HIV risk taking in South India. AB - This qualitative study examines the role of alcohol in sexual risk among male migrant workers and female sex workers in two South Indian states. Most men reported using alcohol for increased energy and courage prior to their sexual experiences and to reduce feelings of loneliness and isolation. Sex workers, on the other hand, often stated that they avoided alcohol prior to sex in order to stay alert and reduce the risk of violence. Both groups reported that drinking often increased male aggression and reduced condom use. Research is needed to examine the prevalence of these patterns as well as factors associated with sexual risk and violence, in order to develop targeted interventions for these groups. Future risk reduction programs may benefit from addressing safer ways of meeting the needs expressed by the participants. This may include strategies to defuse volatile situations, safe ways of improving the sexual experience, and interventions aimed at alleviating loneliness and isolation for migrants. PMID- 20544383 TI - Facts, attitudes, and health reasoning about HIV and AIDS: explaining the education effect on condom use among adults in sub-Saharan Africa. AB - In contrast to earlier in the HIV/AIDS pandemic, net of other demographic factors, formal education acts as a preventative factor in sub-Saharan Africa. Despite this trend, there has been almost no research on the causal mechanisms behind the widely reported education effect. Consistent with the education effect, structural equation modeling of the influence of education attainment on condom use with Demographic Health Survey data from nine sub-Saharan Africa nations collected between 2003 and 2005 finds that net of control variables, there is a robust, positive influence of education on condom use among sexually risky adults. Information-transfer and attitude change, the two most commonly assumed educational influences on the use of condoms, are tested, and although education attainment increases acquisition of basic facts and the inculcation of positive attitudes about HIV/AIDS, these factors have only weak influence on condom use. Given this, a new hypothesis about education's enhancement of health reasoning is developed from neuro-developmental and decision-making research. Modeling finds that education robustly influences health reasoning ability and this factor mediates a significant proportion of the education effect on condom use. The results raise concern about the enormous effort by NGOs in the region to use mainly fact- and attitude-based educational programs to reduce future HIV infections. Future research on the causal mechanisms behind the association between education and HIV/AIDS prevention should focus how on schooling enhances the cognitive skills needed for health reasoning. PMID- 20544384 TI - Predicting pregnancy in HIV-1-discordant couples. AB - This study examines the incidence and predictors of pregnancy in HIV-1-discordant couples from Nairobi, Kenya. Women from 454 discordant couples were followed for up to 2 years. One-year cumulative incidence of pregnancy was 9.7%. Pregnancy rates did not differ significantly between HIV-1-infected and uninfected women (HR = 1.46). The majority of pregnancies occurred among women < 30 years old reporting a desire for future children (1-year incidence 22.2%). Pregnancy rates may be high among discordant couples, indicating desire for children may override concerns of HIV-1 transmission and increase unprotected sex, and highlighting the need to make conception safer. PMID- 20544385 TI - Interactive links between theory of mind, peer victimization, and reactive and proactive aggression. AB - This study investigated the relation between theory of mind and reactive and proactive aggression, respectively, as well as the moderating role of peer victimization in this context. The 574 participants were drawn from a longitudinal study of twins. Theory of mind was assessed before school entry, when participants were 5 years old. Reactive and proactive aggression as well as peer victimization were assessed a year later in kindergarten. Results from multilevel regression analyses revealed that low theory of mind was related to a high level of reactive aggression, but only in children who experienced average to high levels of peer victimization. In contrast, a high theory of mind was related to a high level of proactive aggression. Again, this relation was especially pronounced in children who experienced high levels of peer victimization. These findings challenge the social skills deficit view of aggression and provide support for a multidimensional perspective of aggressive behavior. PMID- 20544387 TI - Factors in the development of clinical informatics competence in early career health sciences professionals in Australia: a qualitative study. AB - This paper reports on a qualitative study investigating how Australian health professionals may be developing and deploying essential clinical informatics capabilities in the first 5 years of their professional practice. It explores the experiences of four professionals in applying what they have learned formally and informally during their university education and during workplace learning and training. This study is based on a broad review of the literature on clinical informatics education and training; its findings support international analyses and suggest that new strategic efforts among stakeholders in the healthcare system are required to make progress in building workforce capacity in this field, in Australia and elsewhere. PMID- 20544388 TI - Radiofrequency ablation of Barrett's esophagus: let's not get ahead of ourselves. PMID- 20544389 TI - Fluidic measurement of electric field sensitivity of Ti-GaAs Schottky junction gated field effect biosensors. AB - We report the electric field and pH sensitivity of fluid gated metal semiconductor hybrid (MSH) Schottky structures consisting of a Titanium layer on n-type GaAs. Compared to standard field-effect sensors, the MSH Schottky structures are 21 times more sensitive to electric field of -46.6 V/cm and show about six times larger resistance change as pH of the solution is decreased from 8.17 to 5.54. The potential change at the fluidic gate and passivation layer interface by bias voltages and pH are mirrored by the metal shunt, resulting in larger depletion widths under the Schottky junction and resistance change as compared to sensors with no Schottky junction. 2D numerical simulation results are in good agreement with the measured data and suggest thinner mesa with lower doping density can further increase device sensitivity. PMID- 20544390 TI - Structural and immunochemical characteristics of the neuronal organization of field 4 of the sensorimotor cortex in cats. AB - Inhibitory interneurons in the cortex are regarded as an important intracortical module-forming factor. We report here our studies of the expression of three calcium-binding proteins in interneurons in the sensorimotor cortex of the cat. Calbindin-expressing non-pyramidal neurons were found to be distributed non uniformly in layer III, forming large groups. Three-dimensional modeling showed that these groups formed continuous columns of width 400-1500 microm, which extended 6000-8000 microm mediolaterally both along the walls of the cruciate sulcus and on the free surfaces of the posterior and anterior sigmoid gyri. These data led to the hypothesis that these groups of inhibitory interneurons may create the conditions for selecting groups of efferent neurons within their areas and to recruit them into a single physiological act. PMID- 20544391 TI - Reversible and irreversible stages in the development of amnesia after disruption of the reactivation of associative memory in snails. AB - Our previous studies on common snails have demonstrated that inhibition of NMDA glutamate receptors during reactivation of a skill consisting of refusal of a defined foodstuff leads to impairment of long-term memory. We report here our studies of the dynamics of the development of amnesia. Snails were trained to refuse a defined foodstuff and were injected 24 h later with the NMDA glutamate receptor antagonist MK-801, and were then presented with the conditioned food stimulus (a reminder). Testing on days 1 and 3 after exposure to MK-801 and the reminder showed gradual decreases in the number of refusals of the conditioned food stimulus. Repeat training of the animals to refuse the same foodstuff performed during these periods led to restoration of the skill seen after the initial training. The number of refusals by snails of the conditioned food stimulus 10 days after MK-801 and the reminder decreased to a minimal level. Repeat training at this time did not lead to the formation of a conditioned reflex to food. Thus, we have provided the first demonstration that impairment of the reactivation of long-term memory induces two stages in the development of amnesia. The first, reversible, stage, which lasted less than 10 days, was characterized by the potential for long-term memory to be restored by repeat training of the snails. The second, irreversible, stage developed 10 days after induction of amnesia and was characterized by disruption of the ability of long term memory to be restored. These results may have practical value in terms of understanding the mechanisms of acute memory loss due to trauma and neurological diseases. PMID- 20544392 TI - Crossbills (Loxia curvirostra) are able to form the "larger than" concept. AB - An original method for studying cognitive abilities in largely wild passerine birds was developed. Studies of five crossbills (Loxia curvirostra) showed that this approach could be used to assess their ability to form concepts. All five crossbills learned selection rules for the "larger number" feature over the range "1-10." The birds successfully transferred this to stimuli significantly different from those used in training, which were not comparable in terms of all quantitative properties, but only some (only area or number). Only one bird was able to transfer the learned choice rule to multiples in a new range ("10-20"). Thus, the ability of representative small forest passerine birds to form the "larger than" concept was demonstrated. PMID- 20544393 TI - Corticospinal influences on the distal muscles of the hand in conditions of inertial loading. AB - Electromyographic activity and synchronous discharges in the muscles of the wrist induced by transcranial magnetic stimulation of the motor cortex as the thumb and index finger were used to hold a handle bearing a weight were studied during performance of a number of motor tasks. When the subject increased grip force, for example, in response to increases in the weight of the attached load or by voluntarily squeezing the handle, the evoked response increased proportionally to muscle activity. If the subject moved the hand holding the handle up and down with an amplitude of 10 cm and a frequency of 0.5-1 Hz, grip force changed in accordance with the predicted inertial loading. The muscle response in the adductor pollicis muscle increased to a greater extent than the activity in the muscle. The response to sudden inertial loading consisted of a reflex increase in grip force, the muscle response increasing to a lesser extent than activity in the muscle. This suggests that larger increases in evoked muscle responses on up and down movement of the hand with a load are associated with anticipatory changes in grip force. These results are assessed from the point of view of the involvement of the motor cortex in generating anticipatory changes in muscle activity in the distal muscles. PMID- 20544394 TI - Interhemisphere asymmetry of auditory evoked potentials in humans and mismatch negativity during sound source localization. AB - Results of studies in humans of long-latency auditory evoked potentials and mismatch negativity in conditions of dichotic stimulation during presentation of deviant stimuli producing instantaneous changes in stimulus azimuth from the null to +22.5 degrees or movement at rates of 11.25-112.5 degrees/sec from the midline of the head across the left and right hemispheres towards each ear are presented. These studies showed that the total amplitude of the components of the N1-P2 complex of auditory evoked potentials in the frontal lead of the right hemisphere was greater than that in the left hemisphere. Mismatch negativity parameters showed significant relationships with the spatial position of the sound source, namely, its displacement into the right hemisphere from the position of the sound image of the standard signal. Questions of the involvement of the right hemisphere in discriminating the spatial characteristics of sound sources are discussed. PMID- 20544395 TI - Cytotoxic effect of artocarpin on T47D cells. AB - In our screening projects for anticancer agents from natural resources, artocarpin [6-(3-methyl-1-butenyl)-5,2',4'-trihydroxy-3-isoprenyl-7 methoxyflavone] isolated from wood of jack fruit (Artocarpus heterophyllus) showed potent cytotoxic activity on human T47D breast cancer cells. The mode of action of artocarpin was evaluated by its effect on cell viability, nuclear morphology, cell cycle progression, expression of protein markers for apoptosis, and mitochondrial membrane potential (Delta psi m). These results showed that artocarpin caused a reduction of cell viability in a concentration-dependent manner and an alteration of cell and nuclear morphology. Moreover, the percentage of the sub-G1 phase formation was elevated dose-dependently. Artocarpin induced activation of caspase 8 and 10 as indicated by stronger signal intensity of cleaved-caspase 8 and weaker signal intensity of caspase 10 markers detected after artocarpin treatment. In addition, we also noticed the activation of caspase 3 by artocarpin. There were negligible changes in mitochondrial membrane potential (Delta psi m) due to artocarpin treatment. All together, these data indicated that artocarpin induced apoptosis in T47D cells possibly via an extrinsic pathway. PMID- 20544396 TI - PinX1 inhibits telomerase activity in gastric cancer cells through Mad1/c-Myc pathway. AB - INTRODUCTION: The aim of this study was to investigate the role of Mad1/c-Myc in telomerase regulation in gastric cancer cells in order to gain insight into telomerase activity and to evaluate PinX1 as a putative inhibitor of gastric cancer. METHODS: PinX1 and PinX1siRNA eukaryotic expression vectors were constructed by recombinant technology and transfected into gastric carcinoma cells using Lipofectamine 2000. Telomerase activity was measured by the telomeric repeat amplification protocol. Apoptosis of gastric cancer cells was analyzed by flow cytometry and transmission electron microscopy. Reverse transcription polymerase chain reaction and Western blotting were used to assess the expression levels of PinX1 and Mad1/c-Myc. RESULTS: We found that PinX1-negative gastric cancer cells showed significantly higher telomerase activity than did the PinX1 postive cells. PinX1-transfection reduced telomerase activity in PinX1-negative gastric cancer cells and exhibited an upregulation of Mad1 and downregulation of c-Myc expression. Pinx1 RNAi treatment led to downregulation of Mad1 and upregulation of c-Myc. CONCLUSION: Suppression of telomerase activity mediated by PinX1 is involved in the Mad1/c-Myc pathway. PMID- 20544397 TI - Impact of resection for primary colorectal cancer on outcomes in patients with synchronous colorectal liver metastases. AB - PURPOSE: This study was designed to evaluate the impact of resection for primary colorectal cancer on oncologic outcomes in patients with synchronous colorectal liver metastases. METHODS: A retrospective analysis was performed on 91 consecutive patients with synchronous colorectal liver metastases who underwent resection of the primary colorectal cancer between December 1999 and December 2007. Of the 91 patients, 54 (59.3%) also underwent complete (R0) resection for liver metastases, and 84 (92.3%) received postoperative chemotherapy. The oncologic outcomes and prognostic factors were analyzed. RESULTS: Operative mortality was 1.1%, and morbidity was 37.4%. The 3- and 5-year overall survival rates were 44.5% and 26.8%, respectively. A multivariate analysis revealed that residual disease after surgery (non-R0 resection; p = 0.003), lymph node metastasis of the primary tumor (p = 0.015), and no postoperative chemotherapy (p = 0.001) were independent prognostic factors for poor survival. Independent predictors of an inability to achieve a complete resection were the presence of three or more liver metastases and the presence of extrahepatic disease at exploration. Significant differences in survival existed among the three risk stratification groups (no-, low-, and high-risk groups; p < 0.001). CONCLUSIONS: The inability to safely render the liver and colon microscopically free of disease should cause a surgeon to reconsider synchronous colectomy and hepatectomy. A multidisciplinary approach that combines both complete resection of synchronous colorectal liver metastases and postoperative chemotherapy may achieve improved survival in patients with synchronous colorectal liver metastases. PMID- 20544399 TI - Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. AB - BACKGROUND: Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation. METHODS: Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made. RESULTS: We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (beta = 0.37, p = 0.02) and after surgery (beta = 0.59, p < 0.0001) and negatively with weight loss after surgery (beta = -0.37, p = 0.003). When expressed as a percentage of change, the decrease of RBP4 was related to the reduction in the levels of triglycerides and with the increase in HDL-cholesterol (beta = 0.73, p = 0.02 and beta = 0.62, p = 0.04, respectively). Others parameters analyzed, including inflammatory markers, were not related to RBP4. CONCLUSIONS: This study shows that, in obese women and after a substantial weight loss due to bariatric surgery, RBP4 was related to weight status and lipid parameters rather than to insulin sensitivity or inflammatory markers. PMID- 20544400 TI - A first reported case of dedifferentiated liposarcoma of the esophagus with molecular diagnosis. PMID- 20544401 TI - Gastrointestinal cancer educational case series: the history and management of complex cases in gi oncology. A 72 year-old man with metastatic gastric cancer. AB - INTRODUCTION: Gastric cancer is the third most common cancer worldwide and the second leading cause of cancer deaths. Appropriate staging and treatment options relate to the stage of disease and performance status of the patient. CASE REPORT: Here we present the case of a 72 year old male, with an initial presentation of apparently locally advanced gastric cancer. On discovery of metastatic disease, the utility of palliative gastrectomy, and first and second line chemotherapy are discussed. DISCUSSION: This case demonstrates the potential value of sequential lines of chemotherapy in good performance status patients with advanced gastric cancer. Further research will be necessary in order to assess the utility of newer targeted agents in this setting. PMID- 20544402 TI - Minding the aging brain: technology-enabled cognitive training for healthy elders. AB - Cognitive training refers to theory-driven behavioral intervention, ideally supported by a strong conceptual framework and specified neurocognitive mechanisms. Within this field, neurotechnology promises many advantages, and a growing literature establishes technology-enabled cognitive training as a promising modality to promote positive cognition in consumer, research, clinical, and public health settings. Methodologic challenges remain, and specific cognitive training recommendations for healthy elders must be tentative in the context of an emerging evidence base. PMID- 20544404 TI - Increased drug efflux along with midkine gene high expression in childhood B lineage acute lymphoblastic leukemia cells. AB - Multidrug resistance (MDR) induced by drug efflux has been identified as the major clinical obstacle in the treatment of childhood acute lymphoblastic leukemia (ALL). To explore the possible effects of midkine (MK) gene on the chemotherapeutic drugs efflux, we examined the MK gene expression in 139 B lineage ALL patients and 15 children with nonmalignant hematological diseases. Meanwhile, we detected the degree of drug accumulation in 30 progressing B lineage ALL patients and the 15 control individuals (as control). The results showed that the significant statistic difference in MK gene expression was found among the normal group, the complete remission (CR), and progressing B-lineage ALL patients (p < 0.01). In the Rhodamine 123 (Rh123) efflux test, mean fluorescence intensity (MFI) in the leukemia cells was obviously lower than that in normal pre-B cells (p < 0.01). Furthermore, there was an evident negative correlation between the MFI and MK mRNA expression (r = -0.869, p < 0.001) but no correlation with the MDR1 mRNA expression (p > 0.05). We concluded that there was powerful drug efflux ability in lymphoblastic leukemia cells with high MK gene expression. MK gene may take part in multidrug resistance. PMID- 20544403 TI - Multiple myeloma in Korea: past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party. PMID- 20544405 TI - Deconstruction of nurse-delivered patient self-management interventions for symptom management: factors related to delivery enactment and response. AB - This research examines the processes by which patient self-management interventions are related to symptom responses among cancer patients. A total of 333 patients from two randomized clinical trials were combined. Each patient received a six-contact 8-week patient self-management intervention delivered by a nurse to address symptoms. Nurses' decisions to deliver the strategies, patient enactment of strategies, and their success were investigated using patient- and symptom-level characteristics. Generalized estimating equation modeling accounted for clustering of symptoms and strategies delivered for each symptom within patient. Patient self-management intervention strategies were classified into four classes. Strategies were delivered by nurses for symptoms with higher interference and longer duration. Patient and symptom factors were related to enactment strategies. Symptom responses were related to number of strategies tried by patients. Delivery and enactment of strategies were related to both patient and symptom characteristics. PMID- 20544407 TI - [Sixteenth meeting of the local branch of the SPE (Tropical Diseases Society) in Reunion, 9th March 2010]. PMID- 20544406 TI - Co-administration of GP96 and Her2/neu DNA vaccine in a Her2 breast cancer model. AB - Heat-shock proteins have biochemical and immunological roles in chaperoning/signaling and activation of innate and adaptive immune responses, respectively. Their effect on the immune response is due to a phenomenon known as cross-priming of antigen, in which exogenous antigens are presented via MHC class I by antigen presenting cells. GP96 exerts adjuvant activity with some viral and bacterial antigens when applied in the form of a DNA vaccine. In this study, animals with Her2-expressing tumors were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines. Analyses of the immune response, 2 weeks after the last immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased IFN-gamma/IL-4 level. Nevertheless, the graph of tumor size demonstrated a bi-phasic pattern in which partial control of tumor progression initially occurred, but finally its effectiveness was inversely affected by tumor size. PMID- 20544408 TI - Where have all the conscripts gone? PMID- 20544409 TI - Interdisciplinary evidence-based recommendations for the follow-up of testicular cancer patients: a joint effort. AB - Detailed recommendations for the treatment of testicular cancer exist and due to the stringent application of the standard therapies, most patients can nowadays be cured. Moreover in the treatment of early stage disease, active surveillance is now a cornerstone of treatment. Hence there is a clear need for recommendations regarding the long term follow-up of these young patients. These have to be safe, feasible and the intensity of procedures have to reflect the known risk of recurrence. Different proposals have been published but they differ widely especially in terms of frequency and modality of imaging. In the last few years, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging in follow-up and the risks of excessive radiation due to imaging, in particular with CT scans. In this article, an interdisciplinary, multinational working group has reviewed the evidence and based on this has formulated practical recommendations for the follow-up of patients with testicular cancer. PMID- 20544410 TI - Work-life conflicts and health among Swiss physicians--in comparison with other university graduates and with the general Swiss working population. AB - QUESTION UNDER STUDY: The present study aimed to compare the prevalence of work life conflicts and the health status of physicians, with a representative sample of university graduates as well as with a representative sample of the general Swiss working population. Furthermore, it aimed to analyse whether work-life conflicts correlate with the health of physicians, as it does in the general working population. METHODS: The present cross-sectional study analysed data from 2007 originating from the SwissMedCareer Study (a prospective cohort study of physicians who graduated in 2001; n = 543) and the Swiss Household Panel (a representative Swiss survey on living and working conditions; university graduates of the same age range: n = 172, general working population of the same age range: n = 670). Data were analysed with Chi2 tests, correlations and logistic regressions. RESULTS: Physicians reported strong time-based as well as strain-based work-life conflicts more frequently than university graduates and the general working population. Significantly more physicians reported "moderate" to "very poor" health than the other two samples. Surprisingly, on the other side of the scale ("very good" health), physicians outnumbered the other samples too. Strong associations between work-life conflict and self-rated health as well as various health complaints were found for physicians. CONCLUSION: The high prevalence of work-life conflicts may explain the comparably high prevalence of poor self-rated health in the physicians' sample. PMID- 20544411 TI - Tobacco use among the elderly: The first Brazilian National Survey (BNAS). AB - OBJECTIVE: This study describes the prevalence and pattern of tobacco use among the elderly in Brazil and establishes its association with socio-demographic characteristics, other substance use and depression. METHOD: The analyses were performed in 400 individuals aged 60 years and over who participated in the first Brazilian national alcohol survey (BNAS) in 2000. RESULTS: Nearly 60% of the sample had ever smoked, of them one in three were still smoking at the time of the interview. Most (94.3%) of the tobacco users were smoking everyday and 34.3% consuming more than 20 cigarettes a day. Only 1% of the former smokers had received support to quit. Over half of the current users (65%) would use free treatment to quit if it existed in Brazil, and just under half of them (47.4%) would consider quitting if cigarettes' price were higher. Currently, tobacco users were more likely to be men and alcohol abusers. Prevalence of depression was high regardless participant smoking status (33.0% among non-smokers, 34.7% among current smokers and 39.3% among former smokers). There was no significant association between smoking and depression. CONCLUSION: This study found a disturbingly high proportion of tobacco users among the elderly in Brazil. According to the Global Burden of Disease project, tobacco has the highest mortality risk of all substance use categories, especially for the elderly. This study shows there is an urgent need to develop smoking cessation interventions targeted specifically to the elderly. PMID- 20544412 TI - The effects of childlessness on the care and psychological well-being of older adults with disabilities. AB - OBJECTIVES: Adult children are a primary focus of family and caregiver research. In contrast, relatively little is known about childless elders with a disability, including their care needs and the state of their overall well-being compared to elderly parents. We addressed this gap by examining the relationship between childlessness and the care and well-being of adults aged 75 and older with a disability. METHODS: Parents and childless persons aged 75 and older were compared using data from the 1998 to 2004 waves of the Health and Retirement Study (HRS). We used logistic regression to examine the relationship between childlessness and care provision (personal care and assistive devise use) and ordinal regression to examine the relationships of parental status, personal care, and use of assistive devices with well-being. The analysis was based on 2048 observations from 1456 community-dwelling respondents who had difficulty walking across a room or getting into or out of bed. RESULTS: Compared to parents, childless elders with a disability generally do not receive less care or have worse psychological well-being. However, being unmarried reduces the likelihood of having personal care and is associated with depressive affect. Use of assistive devices is associated with less depressive affect. CONCLUSION: Childless older adults are similar to parents on measures of psychological well being and care provision. This finding has important implications, as it is projected that 30% of baby boomers who will need assistance will lack care from spouses or adult children. Further exploration of compensatory resources is suggested. PMID- 20544413 TI - EDUCA study: Psychometric properties of the Spanish version of the Zarit Caregiver Burden Scale. AB - OBJECTIVES: The Zarit Caregiver Burden Scale, translated and validated into Spanish, is sensitive to the application of a Psychoeducational Intervention Program (PIP) for the prevention and reduction of burden in caregivers of Alzheimer's disease (AD) patients (EDUCA study). The data obtained in EDUCA was used to reanalyse its psychometric properties and the cut-off points of the Zarit scale. METHODS: The scale was administered to 115 caregivers of patients with AD who were randomised to receive a PIP or standard care for four months. Internal reliability and a factorial analysis of principal components were assessed, and the impact of PIP on each of the subscales was evaluated. A cut-off point was defined for the Zarit scale to identify the caregivers most sensitive to receiving a PIP. RESULTS: A good internal reliability (Cronbach alpha coefficient of 0.92) was obtained, with three principal components (burden, competency and dependence) explaining 54.75% of the variance. The application of PIP showed statistically significant differences versus standard care for the dependence subscale (p = 0.0082) (p = 0.062 for the burden scale). The Zarit scale cut-off points which combine better sensitivity and specificity were 56/57 and 59/60, for the 5/6 and 6/7 cut-off points of the General Health Questionnaire (GHQ-28) scale, respectively. CONCLUSIONS: This study confirms the good psychometric properties of the Zarit scale found in previous studies. The dependence component appeared to be most influenced by the application of a PIP in the clinical trial. Caregivers with a Zarit scale score of 60 or more benefit most from the PIP. PMID- 20544414 TI - Implicit learning of affective responses in dementia patients: a face-emotion association paradigm. AB - The aim of the present study was to develop and evaluate an ecologically valid approach to assess implicit learning of affective responses in dementia patients. We designed a Face-Emotion-Association paradigm (FEA) that allows to quantify the influence of stimuli with positive and negative valence on affective responses. Two pictures of neutral male faces are rated on the dimensions of valence and arousal before and after aversive versus pleasant fictitious biographical information is paired with each of the pictures. At the second measurement time point, memory for pictures and biographical content is tested. The FEA was tested in 21 patients with dementia and 13 healthy controls. Despite severely impaired explicit memory, patients changed valence and arousal ratings according to the biographical content and did not differ in their ratings from the control group. The results demonstrate that our FEA paradigm is a valid instrument to investigate learning of affective responses in dementia patients. PMID- 20544415 TI - What happened to multiple sexual partnerships in Swaziland? Analysis of five linked national surveys between 2002 and 2008. AB - Multiple sexual partnerships are a driver of the HIV epidemic in southern Africa. Five linked cluster surveys in 2002, 2005, 2006, 2007 and 2008 allowed us to measure changes in rates of multiple partnerships in these clusters in Swaziland. We selected a stratified random sample of census enumeration areas in 2002 and survey teams subsequently revisited this same sample (a random sub-sample in 2005 and 2006). For this study, analysis includes only people aged 18-29 years interviewed in communities included in all five surveys (1862 men and 2701 women). Among men, there was a significant fall in the proportion having multiple partners in the last 12 months (MP12), among those that had any, between 2002 (61%) and 2007 (46%), followed by a slight rise in 2008 (49%). For multiple partnerships in the last six months (MP6 - measured in 2005 and 2006), there was a decrease between 2005 (43%) and 2006 (25%). There was a significant decrease in multiple partnerships in the last month (MP1) between 2005 (35%) and 2006 (16%), followed by an increase in 2007 (24%) and 2008 (25%). Among women, there was a significant decrease in MP12 between 2002 (22%) and 2007 (9%), then a significant increase in 2008 (15%). There was little difference in women's MP6 between 2005 (7%) and 2006 (6%). There was also little change in women's MP1 between 2005 (5%) and 2006 (3%), with an increase from 2007 (3%) to 2008 (6%); the 2006-2008 difference was significant. A 2006 campaign to reduce multiple partnerships may have changed behaviour among men or it may have made them less likely to admit to multiple partners. The recent increase in MP12 and MP1, especially among women, may reflect behaviour or it could reflect increased willingness to report. PMID- 20544416 TI - Suicidal ideation among HIV+ former blood and/or plasma donors in rural China. AB - Suicidal ideation is life-threatening and is prevalent among people living with HIV (PLWH). A dearth of such studies was conducted in China. This study investigated the prevalence of suicidal ideation and associated factors among PLWH who were former blood and/or plasma donors (FBPD) in a rural county in central China. Prospective respondents were randomly selected from a local registry; 176 PLWH who were FBPD joined the study. With informed consent, these PLWH and their spouse were interviewed separately and anonymously. Respectively, 34 and 8% of the sampled (index) PLWH self-reported having suicidal ideation and making a suicidal attempt in the last year. The multivariate analyses results showed that the index PLWH's Physical Function subscale score of the Medical Outcomes Study HIV Health Survey scale (Odds ratio (OR)=6.67, 95% CI=1.69-26.27, 75 percentiles), the Depression subscale score of the Depression, Anxiety, and Stress Scales (DASS; OR=9.26, 95% CI=1.32-64.77), and the spouse's Depression subscale score of the DASS (OR=7.64, 95% CI=1.37-42.77) were independently associated with the index PLWH's suicidal ideation. HIV related variables (e.g., duration of diagnosis, treatment and side effects) and perceived discrimination of the index PLWH, and HIV status of the PLWH's spouse, were not significant factors. Depression is a risk factor for suicides. Moreover, depression may be contagious and the depression status of the spouse also matters. Treatments for depression and prevention intervention for suicides targeting PLWH in rural China are not readily available. Such services are greatly warranted and need to be provided to both the PLWH and his/her spouse. PMID- 20544417 TI - Vagal influence during worry and cognitive challenge. AB - The primary foci of the study were exploration of the linkage between cognitive and autonomic inflexibility of worry and generalized anxiety disorder (GAD) and examination of the effects of an analog cognitive restructuring task on this relationship. Cardiac responses of GAD and non-GAD participants were measured to examine the sympathetic and parasympathetic effects of worry and cognitive challenge. Diagnostic groups of undergraduate students were determined via administration of a structured interview, yielding a GAD group (n=16) and a control group (n=19) of individuals without GAD, depression, or panic disorder diagnoses. Cardiac autonomic responses were acquired via electrocardiogram during rest, worry, and cognitive challenge conditions by an experimenter blind to diagnosis. Metrics were compared between the two groups and across the three conditions. Individuals diagnosed with GAD did not differ significantly from controls on autonomic indices. Worry was associated with significantly decreased parasympathetic influence and increased sympathetic activity. Cognitive challenge did not result in significant increased cardiac responsivity. The results indicate that worry behavior is associated with decreased vagal activity, suggest a linkage between autonomic and cognitive inflexibility, and provide further suggestions for improving protocols to assess the autonomic effects of cognitive therapy techniques. PMID- 20544418 TI - Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review. AB - The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system. PMID- 20544419 TI - Screening and identification of differentially expressed genes from chickens infected with Newcastle disease virus by suppression subtractive hybridization. AB - Newcastle disease is an important viral infectious disease caused by Newcastle disease virus (NDV), which leads to severe economic losses in the poultry industry worldwide. The molecular mechanisms involved in the pathogenesis of NDV and the host-directed antiviral responses remain poorly understood. In this study, we screened and identified the differentially expressed transcripts from chicken spleen 36 h post NDV infection using suppression subtractive hybridization (SSH). From the SSH library, we obtained 140 significant differentially expressed sequence tags (ESTs), which could be divided into three categories: high homology genes (58), high homology ESTs (62) and novel ESTs (20). The 58 high homology genes could be grouped into nine clusters based on the best known function of their protein products, which involved signalling transduction (HSPC166, PDE7B, GRIA4, GARNL1), transcriptional regulation (ANP32A, LOC423724, SATB1, QKI, ETV6), cellular molecular dynamics (MYLK, MYO7A, DCTN6), cytoskeleton (LAMA4, LAMC1, COL4A1), stress response (DNAJC15, CIRBP), immune response (TIA1, TOX, CMIP), metabolism (RPS15A, RPL32, GLUT8, CYPR21, DPYD, LOC417295), oxidation-reduction (TXN, MSRB3, GCLC), and others. In addition, we found that the 20 novel ESTs provide a clue for the discovery of some new genes associated with infection. In summary, our findings demonstrate previously unrecognized changes in gene transcription that are associated with NDV infection in vivo, and many differentially expressed genes identified in the study clearly merit further investigation. Our data provide new insights into better understanding the molecular mechanism of host-NDV interaction. PMID- 20544420 TI - Investigations on the diagnosis and retroviral aetiology of renal neoplasia in budgerigars (Melopsittacus undulatus). AB - The high susceptibility of budgerigars (Melopsittacus undulatus) to neoplasia, and specifically renal neoplasia, has often been reported. Further investigations led to a suspicion of a retrovirus as the causative agent for renal neoplasia in budgerigars, but definitive proof has yet to be found. In the present study, 32 budgerigars suspected of having renal neoplasia (based on the clinical presentation) were examined. The objectives were to investigate the use of different diagnostic methods for the ante-mortem diagnosis of this condition and to find more supporting evidence of a retroviral aetiology. The predominant clinical signs observed in budgerigars with renal neoplasia were lameness and absence of deep pain sensation of one leg. Alterations in haematology, plasma chemistry, and urine analyses could not pinpoint the cases of renal neoplasia. Contrast radiography of the intestinal tract proved to be diagnostically more useful compared with plain radiographic studies. Histology confirmed the renal neoplasia as adenocarcinoma. Investigations for virus identification included product-enhanced reverse transcriptase assay and enzyme-linked immunosorbent assay for the detection of avian leucosis virus group-specific antigen. Cell cultures and electron microscopy were performed on a limited number of patients. These investigations could find no presence of an exogenous, replicating retrovirus, neither could viral particles be detected by electron microscopy. Based on the current findings, it can be concluded that there is no evidence of retroviral involvement in the occurrence of renal neoplasia in budgerigars. PMID- 20544421 TI - Reovirus tenosynovitis in a flock of layer breeders. AB - The present paper describes a reovirus infection with clinical course in a flock of layer breeders. Lameness and tenosynovitis of flexor tendons were observed in approximately 15% of the cockerels and 3% of the hens from 17 weeks of age onwards. Affected birds did not die; on the contrary, most of them recovered clinically within a period of 8 weeks. Two other breeds of layer parents that were housed in close contact with the affected flock did not develop clinical signs, although serology indicated that infection with reovirus had taken place. These field observations constitute the first report of clinical reovirus tenosynovitis in layer parents and indicate different susceptibilities of layer parent breeds in developing clinical signs following reovirus infection. PMID- 20544422 TI - Cryptosporidium baileyi infection associated with an outbreak of ocular and respiratory disease in otus owls (Otus scops) in a rehabilitation centre. AB - Cryptosporidiosis has been reported in more than 30 avian species worldwide. Although some cases of cryptosporidiosis have been described in captive birds of prey in the order Falconiformes, to date there have been no reports of the disease in wild raptors. Here we describe for first time an ocular and respiratory disease associated with Cryptosporidium baileyi in wild scops owl (Otus scops, order: Strigiformes). Sixteen otus owl fledglings born in the wild during the summer of 2008 were admitted to the Torreferrussa Wildlife Rehabilitation Centre (Catalonia, northern Spain) in July and August of the same year. In the middle of September, blepharoedema, conjunctival hyperaemia and mucopurulent ocular discharge were diagnosed unilaterally in 75% (12/16) of the birds and bilaterally in 25% (4/16). Moreover, five birds (31%) developed diffuse epithelial corneal oedema, one owl (6%) displayed mild anterior exudative uveitis and another developed rhinitis (6%). Two birds were euthanized because of the severity of disease. The histopathology demonstrated cryptosporidia-like structures in the conjunctival cells and in the nasal respiratory epithelium of one owl. Cryptosporidium spp. oocysts (6.5 to 7.0 x 5.0 to 5.5 microm) were identified by immunofluorescent antibody test (IFAT) in histological sections from eyelids, trachea and respiratory sinuses and in swab samples from the glottis, choanal slit and conjunctival sac. Polymerase chain reaction and DNA sequence analysis confirmed the presence of C. baileyi. Birds were treated orally with azithromycin (40 mg/kg) once a day for 15 days, and by the end of the treatment all owls tested negative for the parasites, by IFAT, and did not display further signs of disease. PMID- 20544423 TI - Observations on the incidence and aetiology of valvular endocarditis in broiler breeders and detection of a newly described taxon of Pasteurellaceae, Avibacterium endocarditidis. AB - A total of 122 dead broiler breeders randomly selected from a flock showing normal production parameters and covering the age from 44 to 61 weeks were subjected to a comprehensive routine post-mortem examination including examination for lesions of endocarditis. Forty-two hens (34%) showed valvular endocarditis caused by Avibacterium endocarditidis (43%), Enterococcus faecalis (31%), Staphylococcus aureus (5%) and Streptococcus pluranimalium (5%), while growth was not obtained from 17% with the methods used for isolation. Gross lesions associated with the different bacterial pathogens did not allow separation according to pathogens involved. Port of entry and pathogenesis associated with the high prevalence of valvular endocarditis remained speculative. The present findings demonstrated the newly described species of Pasteurellaceae, Avibacterium endocarditidis associated with endocarditis in chickens and confirm previous observations on the prevalence of endocarditis in chickens, partly explaining the slightly increased mortality normally observed in broiler breeders during the last weeks of production. PMID- 20544424 TI - Role of Marek's disease herpesvirus in the induction of tumours in Japanese quail (Coturnix coturnix japonica) by methylcholanthrene. AB - The QT35 cell line, established from 20-methylcholanthrene (MCA)-induced tumours in Japanese quail, is positive for Marek's disease virus (MDV), and therefore we examined whether MDV is important for the development of MCA-induced tumours. Japanese quail were inoculated with the JM16 strain of MDV at 1 or 3 days of age or left uninoculated. At 3 weeks of age, quail were injected in the breast muscle with 4 mg MCA in corn oil or corn oil alone. Quail were observed for tumours three times/week and at post mortem at 11 to 12 weeks of age. MDV DNA was detected by polymerase chain reaction (PCR) in spleens of 14/20 birds inoculated with JM16+corn oil and of 53/71 birds inoculated with JM16+MCA. Interestingly, 1/74 quail was positive in the MCA group alone for MDV DNA. Tumours were collected for histopathology, cell line development, and PCR and reverse transcriptase-PCR for the presence of MDV. Tumours developed in 38/83 MCA-treated and 32/85 JM16+MCA-treated quail. Fibrosarcomas without metastasis were the only tumours observed in the MCA-treated quail, while quail treated with JM16 and MCA developed undifferentiated tumours, fibrosarcomas, lymphosarcomas or combinations with or without metastasis. One out of 20 quail receiving JM16 alone developed a lymphosarcoma. Cell line development was not influenced by JM16. Tumours from MCA treated quail were negative for MDV, while 19/29 were positive in the JM16+MCA group. MDV transcripts were present in 13/18 tumours examined in the JM16+MCA group. In conclusion, MDV did not affect tumour development but did influence tumour aggression and histological type. PMID- 20544425 TI - Genetic and antigenic characterization of sigma C protein from avian reovirus. AB - Avian reovirus (ARV) causes viral arthritis, tenosynovitis, liver infection and immunosuppression in birds. Live-attenuated and inactivated vaccines for ARV are available, but do not efficiently protect against recent variants. Sigma C, which mediates virus attachment to target cells, is the most variable protein in ARV. Antibodies to this protein neutralize viral infection. The purpose of the present study was to characterize sigma C in isolates of ARV from infected birds, as compared with the vaccine strain. Amino acids 27 to 293 of sigma C from 28 Israeli isolates were compared, classified and analysed using bioinformatics tools. Large variations were found among the isolates, and the vaccine strain was shown to differ from most of the studied strains, which could explain the failure of commonly used vaccinations in protecting birds against ARV infection. Based on sigma C protein sequences from all over the world, ARV can be divided into four groups. Isolates from all groups were found in the field simultaneously, possibly explaining the insufficient protection achieved by the vaccine strain, which is represented in one of the groups. The results point out the need and the difficulty in producing a wide-ranging vaccine. Several conserved regions among all reported ARV sigma C proteins were identified. These peptides were further studied for structural and functional properties, and for antigenic characterization. The results of this study shed light on peptide selection for a broad and efficient vaccine. PMID- 20544426 TI - Characterization of antimicrobial resistance of recent Salmonella enterica serovar Gallinarum isolates from chickens in South Korea. AB - Salmonella enterica serovar Gallinarum isolates (n=105) from chickens in South Korea between 2002 and 2007 were tested for antimicrobial susceptibility by determining minimum inhibitory concentrations of 16 antimicrobials, and their predominant resistance profiles were genetically characterized. Most isolates (99/105; 94.3%) were resistant to nalidixic acid and resistant/intermediately resistant to fluoroquinolones, and 63.8% (67/105) of the isolates were resistant to three or more antimicrobials. Forty-two quinolone-resistant isolates, of which the quinolone resistance-determining regions of the gyrA genes were sequenced, contained a substitution of a Ser to a Phe or Tyr at position 83 (71.4%), or a substitution of an Asp to an Asn, Gly, or Tyr at position 87 (28.6%). Fifty-seven sulphamethoxazole-resistant isolates were tested for the presence of class 1 integrons by polymerase chain reaction, and their resistance gene cassettes were analysed by sequencing. Three different class 1 integrons containing the resistance-gene insert aadA (52.6%; n=30), aadB (12.3%; n=7), or aadB-aadA (12.3%; n=7) were identified. Most isolates harbouring the integron containing aadB-aadA displayed resistance to all three aminoglycosides tested and also showed increased resistance to fluoroquinolones. These findings suggest that fluoroquinolone resistance may be epidemiologically linked to multiple aminoglycoside resistance. PMID- 20544427 TI - Development and application of an RT-PCR test for detecting avian nephritis virus. AB - The development of a reverse transcriptase-polymerase chain reaction (RT-PCR) test for detecting avian nephritis virus (ANV) is described. Primers, which amplified a fragment of 182 base pairs (bp), were located in the conserved 3' untranslated region (UTR) of the genome. The limit of detection of the test was estimated to be approximately 18 viral copies using a 10-fold dilution series of in vitro transcribed RNA. Positive signals were produced with representative ANV samples, some of which were not detected by previously described RT-PCR tests for detecting ANV, but other avian astroviruses including chicken astrovirus isolates and duck hepatitis virus types 2 and 3 tested negative. When applied to gut content samples from UK, German and US broiler flocks with enteritis/growth problems, ANVs were detected by RT-PCR in 82/82 (100%) samples. ANVs were also detected in 80/96 (83%) pooled gut content samples from longitudinal surveys of four broiler flocks displaying below-average performance. Whereas all samples collected on day 0 from the surveys were negative for ANV, all samples collected at days 4/5, 7, 10, 14, 21 and 28 tested positive. Sequence determinations performed with amplicons produced with 14 field samples confirmed the ANV specificity of the test, while comparative and phylogenetic analyses based on 109 nucleotide 3'-UTR sequences demonstrated that the majority of ANVs investigated were more closely related to the serotype 2 ANV (accession number AB 046864) than to the serotype 1 ANV (accession number NC 003790). PMID- 20544428 TI - Evaluation of the protection induced by avian influenza vaccines containing a 1994 Mexican H5N2 LPAI seed strain against a 2008 Egyptian H5N1 HPAI virus belonging to clade 2.2.1 by means of serological and in vivo tests. AB - Since 2006 Egypt has been facing an extensive epidemic of H5N1 highly pathogenic avian influenza (HPAI) with a huge number of outbreaks both in rural and intensively reared poultry areas. The use of efficacious vaccines in this country has been, and still remains, essential for the control and possible eradication of HPAI. The present study was performed to establish whether the administration of inactivated vaccines containing an H5 virus belonging to a different lineage to the Eurasian H5N1 HPAI viruses guarantees protection from clinical signs, provides significant immune response and is able to achieve a reduction of viral shedding in the face of a challenge with a contemporary H5N1 virus isolated in Egypt. Despite the genetic and antigenic differences between the vaccine strain (H5N2/Mexico) and the challenge strain (H5N1/Egypt), confirmed by molecular and serological (haemagglutination inhibition) tests, it was established that the immune response induced by these conventional vaccines is sufficient to prevent infection in the majority of birds challenged with a contemporary H5N1 Egyptian strain. The data reported in this study also indicate that there may be a low degree of correlation between haemagglutination inhibition titres, clinical protection and reduction of shedding. PMID- 20544429 TI - Beak necrosis in Hungarian partridges (Perdix perdix) associated with beak-bits and avian poxvirus infection. AB - Proliferative growth, consistent with poxvirus infection, encapsulated plastic beak-bits and covered the dorsal portion of the upper beak and nares of adult male and female captive-raised Hungarian partridges. Three representative birds were submitted to the Wisconsin Veterinary Diagnostic Laboratory for necropsy. Lesions in the necropsied birds extended through the nares, where the plastic bit ends are designed to rest. The lesions also variably extended caudally into the oropharynx and cranially within the beak epithelium, and included palate deformity and beak necrosis. Poxvirus was diagnosed in all of the birds examined based on histopathology, electron microscopy, and polymerase chain reaction amplification and sequencing. This report is the first to describe avian pox lesions associated with the application of beak-bits and the resulting beak and oral pathology. PMID- 20544430 TI - Rapid heat-treatment attenuation of infectious bronchitis virus. AB - In the present study we describe the rapid development of an attenuated live vaccine for GA08, a new serotype of infectious bronchitis virus, using a heat treatment method. Incubation of the GA08 strain of IBV at 56 degrees C and passage in embryonated eggs was used as a method to fast track the attenuation process. The virus was incubated in a 56 degrees C water bath and aliquots were removed every 5 min for up to 1 h, and then each aliquot was inoculated into 10 day-old embryonated eggs. Virus with the longest incubation time that produced lesions in the embryos was harvested, again incubated at 56 degrees C as described and passaged in embryonated eggs. Attenuation of the virus, designated GA08/GA08HSp16/08, was verified in 1-day-old specific pathogen free chicks. A 10x dose of the vaccine was found to be safe for 2-week-old broiler chicks of commercial origin. The efficacy of the heat-treated attenuated virus was determined by vaccinating broiler chicks of commercial origin at 1 and 14 days of age intraocularly/intranasally. Vaccinated birds that were challenged with 10(4.5) median embryo infectious doses of pathogenic GA08 virus/bird at 28 days of age were protected from the disease, and challenge virus was only detected in the trachea of one of 21 birds by real-time reverse transcriptase-polymerase chain reaction at 5 days post challenge. The attenuation process took 10 weeks to complete, which is a substantially shorter time than required to attenuate infectious bronchitis virus by serial passage in embryonated eggs without heat treatment (38 weeks or more). PMID- 20544431 TI - Analysis of sequence and haemagglutinin activity of the HN glycoprotein of Newcastle disease virus. AB - Reverse transcription-polymerase chain reaction (RT-PCR) was used to generate sequence data for recent Taiwanese strains of Newcastle disease virus (NDV) isolated from 1999 to 2003, covering the full length of the haemagglutinin neuraminidase (HN) gene and protein. Nucleotide sequence analysis of the HN gene of these recent isolates revealed that the whole HN gene carries an open reading frame encoding 571 amino acids and possesses a shorter C-terminal extension. Six amino acid substitutions in epitopes on the HN glycoprotein of the recent Taiwanese NDV isolates were also found. All the recent Taiwanese NDV isolates have the amino acid sequence (112)RRQKRF(117) for the F protein. A phylogenetic tree analysis based on the nucleotide sequences of the F gene revealed that all recent Taiwanese isolates were related to genotype VII viruses. Since the recent Taiwanese NDV isolates exhibited a low level of haemagglutination (HA) activity, we generated two sets of mutants to elucidate whether mutations in the heptad repeat region of the HN protein could affect the HA activity. To demonstrate the presence of the viruses used in the HA test, a real-time RT-PCR was established to determine the copy number of NDV isolates. From sequence analysis, site directed mutagenesis, and haemadsorption assays, it was found that the HN glycoprotein of recent Taiwanese NDV isolates carrying a substitution at the amino acid residue 81 (I to M) in the heptad repeat region in the stalk domain showed a dramatic decrease in the activity of HA. We infer from these results that a specific amino acid sequence within the heptad repeat region of the stalk is important for the HA activity of the HN glycoprotein. PMID- 20544433 TI - Phage control of dual species biofilms of Pseudomonas fluorescens and Staphylococcus lentus. AB - Despite the recent enthusiasm for using bacteriophages as bacterial control agents, there are only limited studies concerning phage interaction with their respective hosts residing in mixed biofilm consortia and especially in biofilms where the host species is a minor constituent. In the present work, a study was made of mono and dual species biofilms formed by Pseudomonas fluorescens (Gram negative) and/or Staphylococcus lentus (Gram-positive) and their fate after infection with phages. The dual species biofilms consisted predominantly of S. lentus. The exposure of these biofilms to a cocktail containing both P. fluorescens and S. lentus phages effectively killed and removed the hosts from the substratum. Additionally, this cocktail approach also controlled the hosts released from the biofilms to the planktonic phase. The ability of phages to control a host population present in minority in the mixed species biofilm was also assessed. For this objective, the biofilms were challenged only with phage phiIBB-PF7A, specific for P. fluorescens and the results obtained were to some extent unpredicted. First, phiIBB-PF7A readily reached the target host and caused a significant population decrease. Secondly, and surprisingly, this phage was also capable of causing partial damage to the biofilms leading to the release of the non-susceptible host (S. lentus) from the dual species biofilms to the planktonic phase. The efficiency of phage treatment of biofilms was to some extent dependent on the number of cells present and also conditioned by the infection strategy (dynamic or static) utilized in the infection of the biofilms. Nevertheless, in most circumstances phages were well capable of controlling their target hosts. PMID- 20544434 TI - 'Flying barnacles': implications for the spread of non-indigenous species. AB - The presence of adult barnacles of Fistulobalanus pallidus (Darwin) and Fistulobalanus albicostatus (Pilsbry) attached to field-readable plastic leg rings on the Lesser Black-backed Gull Larus fuscus in Northern Europe is reported. L. fuscus is a long-distance palaearctic migrant, breeding in temperate areas spreading widely over inland and marine habitats outside the breeding season. The species is known to perform long-distance migration to Africa and the Middle East. Combining present knowledge on the birds' migratory pattern and the home range of the barnacle species, it is concluded that the cypris larvae of F. pallidus must have settled in African waters, whereas the area where F. albicostatus settled on the bird leg rings is less certain. The barnacles were of adult size and must thus have been attached for a period of no less than 2 months. More than 30 individual barnacles could occur together on a single field readable plastic leg ring. The barnacles could therefore, if ported alive to a new area, reproduce successfully and thus either introduce the species or genetically affect other native populations. This may pose a new and wholly unexpected transportation pathway for barnacles as invasive species. PMID- 20544435 TI - Efficacy of various chemical disinfectants on biofilms formed in spacecraft potable water system components. AB - As the provision of potable water is critical for successful habitation of the International Space Station (ISS), life support systems were installed in December 2008 to recycle both humidity from the atmosphere and urine to conserve available water in the Station. In-flight pre-consumption testing from the dispensing needle at the Potable Water Dispenser (PWD) indicated that bacterial concentrations exceeded the current ISS specifications of 50 colony-forming units (CFU) ml(-1). Subsequent investigations revealed that a corrugated stainless steel flex hose upstream of the dispensing needle in the PWD was filled with nonsterile water and left at room temperature for more than 1 month before launch. To simulate biofilm formation that was suspected in the flight system, sterile flex hoses were seeded with a consortium of bacterial isolates previously recovered from other ISS water systems, including Ralstonia pickettii, Burkholderia multivorans, Caulobacter vibrioides, and Cupriavidus pauculus. After incubation for 5 days, the hoses were challenged with various chemical disinfectants including hydrogen peroxide (H2O2), colloidal silver, and buffered pH solutions to determine the ability of the disinfectants to decrease and maintain bacterial concentrations below ISS specifications. The disinfection efficacy over time was measured by collecting daily heterotrophic plate counts after exposure to the disinfectants. A single flush with either 6% H2O2 solution or a mixture of 3% H2O2 and 400 ppb colloidal silver effectively reduced the bacterial concentrations to <1 CFU ml(-1) for a period of up to 3 months. PMID- 20544436 TI - Searching for the right word: performance on four word-retrieval tasks across childhood. AB - Word retrieval was assessed in 207 normally developing Hebrew-speaking children aged 8-17 through four tasks: picture naming, phonemic fluency, semantic fluency, and homophone meaning generation (HMGT). Scores on all tests correlated positively and significantly with participant age. Yet, age effects and the correlation between age and test scores were weakest for the naming test and strongest for the HMGT. We discuss the nature of the word search involved in each task and suggest that the more executive demands required by a test the steeper the slope of performance increase on this test. PMID- 20544437 TI - Schizophrenia impairs phonological speech production: a preliminary report. AB - INTRODUCTION: Schizophrenia causes clinically conspicuous impairment of syntax and semantics as part of the disorganisation syndrome; however, little is known regarding its effect on the phonological stage of speech, where word meanings are resolved into speech imagery. METHODS: We used a "tongue-twister" task to probe phonological speech production and its clinical associations in six schizophrenia patients and 16 controls. RESULTS: Errors induced by phonological similarity were more common in the patients (p=.003), were positively associated with psychomotor poverty symptoms (p=.02) and negatively associated with reality distortion symptoms (p=.03). CONCLUSIONS: Our findings suggest that phonological speech production is markedly disrupted by schizophrenia. Further, this phonological abnormality is distinct from disorganisation syndrome. PMID- 20544439 TI - Research activities on supercritical fluid science in food biotechnology. AB - This article serves as an overview, introducing the currently popular area of supercritical fluids and their uses in food biotechnology. Within each application, and wherever possible, the basic principles of the technique, as well as a description of the history, instrumentation, methodology, uses, problems encountered, and advantages over the traditional, non-supercritical methods are given. Most current commercial application of the supercritical extraction involve biologically-produced materials; the technique may be particularly relevant to the extraction of biological compounds in cases where there is a requirement for low-temperature processing, high mass-transfer rates, and negligible carrying over of the solvent into the final product. Special applications to food processing include the decaffeination of green coffee beans, the production of hops extracts, the recovery of aromas and flavors from herbs and spices, the extraction and fractionation of edible oils, and the removal of contaminants, among others. New advances, in which the extraction is combined with reaction or crystallization steps, may further increase the attractiveness of supercritical fluids in the bioprocess industries. To develop and establish a novel and effective alternative to heating treatment, the lethal action of high hydrostatic pressure CO(2) on microorganisms, with none or only a minimal heating process, has recently received a great deal of attention. PMID- 20544440 TI - Designing new meals for an ageing population. AB - Today's ageing population is an ever-increasing, highly diverse group of people wanting to live a healthy and enjoyable life. Seniors increasingly see the importance of eating healthy and delicious food in a pleasant environment in achieving happiness and well-being. Up until now, the food industry has been rather slow in transforming the wealth of available knowledge regarding the nutritional needs and sensory perception of the ageing into new food products. Based on our own and the published research of others, we discuss here how the design of new meals for an ageing population can be tackled by a consumer-led approach to food product development. After a brief overview of the underlying concepts and practices, a detailed description is given of how this approach could be used in the design of Home Meal Replacements for senior households. This description includes also a comprehensive review of the major determinants of food preference and meal choice behavior in a later age. Finally, relevant implications are derived from the work presented and future trends in the technological development of foods for the ageing highlighted. PMID- 20544441 TI - Review of rapid tests available for measuring the quality changes in frying oils and comparison with standard methods. AB - Repeated use of oils and fats for frying of food brings about many changes in their physical and chemical properties. Due to increasing health concerns, the assessment of the quality of reused oils has received much attention, since such assessment is useful in determining the discarding point of the oils. The official analytical methods used in laboratories for this purpose need skill, time, and a large consumption of solvents. To make the oil testing simpler, several rapid test kits have been developed based on either physical parameters (such as viscosity or dielectric changes) or chemical parameters (such as free fatty acids, oxidized fatty acids, or carbonyl compounds). These test kits usually comprise a portable instrument or colorimetric reaction sticks, capable of providing a direct or indirect measurement of a single parameter. The review presented in this paper evaluates the use of such rapid test kits and highlights the need to develop multi-parameter test kits in order to establish the quality of reused oil and the point at which it should be discarded. The review also encompasses pertinent details on the standard analytical methods, and deterioration of frying oils that occur during and after their use and the associated health consequences. PMID- 20544442 TI - Factors influencing the chemical stability of carotenoids in foods. AB - In recent years, a number of studies have produced evidence to suggest that consuming carotenoids may provide a variety of health benefits including a reduced incidence of a number of cancers, reduced risk of cardiovascular disease, and improved eye health. Evolving evidence on the health benefits of several carotenoids has sparked interest in incorporating more carotenoids into functional food products. Unfortunately, the same structural attributes of carotenoids that are thought to impart health benefits also make these compounds highly susceptible to oxidation. Given the susceptibility of carotenoids to degradation, particularly once they have been extracted from biological tissues, it is important to understand the major mechanisms of oxidation in order to design delivery systems that protect these compounds when they are used as functional food ingredients. This article reviews current understanding of the oxidation mechanisms by which carotenoids are degraded, including pathways induced by heat, light, oxygen, acid, transition metal, or interactions with radical species. In addition, several carotenoid delivery systems are evaluated for their potential to decrease carotenoid degradation in functional food products. PMID- 20544443 TI - EU legislation on food and potable water safety which could be potentially applied on board ferries and cruise ships: a comparison with US legislation. AB - The high number of people moving around by ferries and cruise ships in conjunction with great amounts of food and potable water transported (occasionally overloaded) and consumed by passengers constitute a possible risk for communicable diseases. Another issue of equally great importance is the food handlers who come from diverse origin and have a different mentality, habits, and background. In this paper an attempt is made to present comparatively EU and US legislation that could be potentially applicable to passenger ships food premises and potable water supplies. Moreover, food and water related hazards, not currently covered by EU legislation, were assessed together with US legislation and other guidelines for cruise ships. PMID- 20544444 TI - The use of near-infrared spectrometry in the olive oil industry. AB - The enormous possibilities offered by near-infrared (NIR) spectroscopy for the (on/in/at-line) quality control process of olive fruits, pastes, and oils are summarized throughout this paper. Special attention has been paid to the combination of NIR and chemometric treatments for the on-line analysis of olive fruits and also for the quality parameters evaluation on olive oils and pastes which can enhance the production of a high quality olive oil and the selection of olive fruit with superior properties. The implementation of NIR sensors in olive mills with successful results has also been reviewed and the commercial olive fruit and oil analyzers highlighted. PMID- 20544445 TI - Sexuality and health in Vietnam--new directions. Introduction. PMID- 20544446 TI - 'Fasting and prayer don't concern the doctors ... they don't even know what it is': communication, decision-making and perceived social relations of Pakistani Muslim patients with long-term illnesses. AB - OBJECTIVES: Pakistani Muslims have the poorest overall health profile in Britain, for reasons which at present remain poorly understood. We sought to explore the impact of religious identity and beliefs on self-management of long-term conditions, on patient-professional communication and decision-making and health inequalities within Pakistani Muslim communities. DESIGN: Ethnographic study involving in-depth interviews and participant observation. RESULTS: Religious identity plays a central role in many individuals' attempts to make sense of their personal illness narrative. Practitioners and patients are typically unwilling to engage in discussion about religious influences on patient decision making, reflecting patients' lack of confidence in the appropriateness of raising such issues, and professionals' lack of awareness of their importance. Patients consequently receive little or no support from professionals about decisions involving such influences on self-care. The policy vacuum and lack of patient professional engagement in this area allows the use of stereotypes of Pakistani Muslims by practitioners to remain unchallenged in most healthcare settings. Social dynamics within these settings reflect those in wider UK society, in which many Pakistani respondents believe they are unwelcome. These factors affect the psychosocial well-being of Pakistani Muslims and on their ability to manage long term conditions. CONCLUSION: Shared understanding about the context in which patients manage long-term conditions is a precursor to effective lay-professional partnerships. Religious identity influences the health beliefs and practices of many British Pakistani Muslim patients. Failure to acknowledge and discuss this influence on long-term illness management leads to a vacuum in professional knowledge, inadequate support for patients' decision-making and poor responses to their requests for assistance. Findings indicate a need for practitioners to initiate more open discussion and raise questions about the pathways leading to higher rates of complications and the relationship between social status and health inequalities in this population. PMID- 20544447 TI - Age-related preservation of top-down control over distraction in visual search. AB - Visual search studies have demonstrated that older adults can have preserved or even increased top-down control over distraction. However, the results are mixed as to the extent of this age-related preservation. The present experiment assesses group differences in younger and older adults during visual search, with a task featuring two conditions offering varying degrees of top-down control over distraction. After controlling for generalized slowing, the analyses revealed that the age groups were equally capable of utilizing top-down control to minimize distraction. Furthermore, for both age groups, the distraction effect was manifested in a sustained manner across the reaction time distribution. PMID- 20544448 TI - Age differences and format effects in working memory. AB - Format effects refer to lower recall of printed words from working memory when compared to spoken words or pictures. These effects have been attributed to an attenuation of attention to printed words. The present experiment compares younger and older adults' recall of three or six items presented as pictures, spoken words, printed words, and alternating case WoRdS. The latter stimuli have been shown to increase attention to printed words and, thus, reduce format effects. The question of interest was whether these stimuli would also reduce format effects for older adults whose working memory capacity has fewer attentional resources to allocate. Results showed that older adults performed as well as younger adults with three items but less well with six and that format effects were reduced for both age groups, but more for young, when alternating case words were used. Other findings regarding executive control of working memory are discussed. The obtained differences support models of reduced capacity in older adult working memory. PMID- 20544449 TI - Age-related differences in the attention network test (ANT). AB - This study investigates the effect of aging on alerting, orienting, and conflict resolution by assessing younger (mean age = 25.8) and older (mean age = 67.9) adults' performance in the Attention Network Test that combines, in a single experimental paradigm, a flanker task with alerting and orienting cues. The analyses of response times indicated equivalent orienting and conflict resolution effects in younger and older adults. By contrast, alerting was found to be significantly reduced in the elderly. This result is only marginally in accordance with recent studies addressing the issues of age-related differences in alerting, which provide mixed results. The possible role of methodological differences across studies in accounting for the controversial results concerning the aging affect on alerting is discussed. PMID- 20544450 TI - Dividing time: concurrent timing of auditory and visual events by young and elderly adults. AB - This article examines age differences in individual's ability to produce the durations of learned auditory and visual target events either in isolation (focused attention) or concurrently (divided attention). Young adults produced learned target durations equally well in focused and divided attention conditions. Older adults, in contrast, showed an age-related increase in timing variability in divided attention conditions that tended to be more pronounced for visual targets than for auditory targets. Age-related impairments were associated with a decrease in working memory span; moreover, the relationship between working memory and timing performance was largest for visual targets in divided attention conditions. PMID- 20544451 TI - The effects of age and exogenous support on visual search performance. AB - The authors investigated whether precueing a location attenuated age-related declines in selective attention and intraindividual variability on a visual search task. The cue improved response time on the single-feature search condition for both young and older adults. On the conjoined-feature search condition, only the older adults used the cue to facilitate performance, particularly when it reduced the number of searched items. The cue also mitigated intraindividual variability observed on both conditions. Not only did the cue facilitate the scaling of attention and improve search strategy, but also it decreased the waxing and waning observed in the older group's performance. PMID- 20544452 TI - Tomatoes and apples or red and green lines: are age-related interference effects based on competition among concepts or percepts? AB - Using a negative priming paradigm, the authors tested whether age-related interference effects are due to age differences in perceptual distractibility or in resolving conceptual competition. In samples of 40 younger adults (aged 22-34) and 40 older adults (aged 58-76), the authors found a greater reduction in processing speed for older than for younger adults in trials in which targets were superimposed with distracting objects as compared to single-target trials. When trials were paralleled for perceptual features, that is, when single-target trials were supplemented with nonsense distractors, the age effect became nonsignificant. The results suggest that age-related interference effects are primarily due to age differences in perceptual distractibility. PMID- 20544453 TI - Decline of bone marrow-derived hematopoietic progenitor cell quality during aging in the rat. AB - Several studies have shown that aging is associated with quantitative and qualitative alterations of the stem and progenitor cell compartment. The current results indicate that there is a significant age-associated decline in the proliferative capacity of rat myeloid progenitor cells. In contrast, no difference was found in the frequency of myeloid progenitor cells in the bone marrow of young versus old rats. Furthermore, a significant shift towards higher proliferative capacity of myeloid progenitors was observed after lifelong voluntary exercise. These data emphasize that aging is accompanied by a loss of proliferative capacity and that voluntary exercise could retard this process. PMID- 20544454 TI - Detection of adulteration of anti-hypertension dietary supplements and traditional Chinese medicines with synthetic drugs using LC/MS. AB - A sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS) method was developed for the analysis of 18 drugs used for the treatment of anti-hypertension, including diuretics, calcium antagonists, and angiogenesis-converting enzyme inhibitors (ACEI) as adulterants in dietary supplements and traditional Chinese medicines. Separation was accomplished on a Xtimate C18 reversed-phase column using a mixture of methanol, acetonitrile and 20 mM ammonium formate buffer (pH 3.2) as mobile phase. The method demonstrated linearity from 0.03 to 21.52 mg kg(-1). Limits of detection ranged from 6.5 to 86.0 microg kg(-1). The recoveries of spiked samples ranged from 71% to 109%. The procedure was successfully applied in routine inspection analysis. PMID- 20544455 TI - Determination of malachite green and crystal violet in processed fish products. AB - This paper presents analysis of malachite green (MG) and crystal violet (CV) residues in processed fish products. Samples were homogenized and extracted with ammonium acetate buffer and acetonitrile. The extracted residues were partitioned into dichloromethane, in situ oxidized to chromic forms with 2,3-dichloro-5,6 dicyano-1,4-benzoquinone, and cleaned up on neutral alumina and propylsulfonic acid cation-exchange solid-phase extraction (SPE) cartridges. MG and CV were determined at 618 and 588 nm using HPLC with a visible detector (LC-VIS) and confirmed by LC-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The recoveries were as follows: MG (74.8-83.8%), LMG (80.0-88.4%), CV (68.6 73.9%), and LCV (85.5-90.0%). The method modified in this study has been evaluated by application in-house to a survey of 253 processed fish products. As a result of monitoring, MG and CV were positive in one shrimp and one eel sample, respectively. Our results showed that regular monitoring of these antibiotic residues is recommended for protection of public health. PMID- 20544456 TI - Analytical strategy for the determination of non-steroidal anti-inflammatory drugs in plasma and improved analytical strategy for the determination of authorized and non-authorized non-steroidal anti-inflammatory drugs in milk by LC MS/MS. AB - A sensitive and selective method for the determination of six non-steroidal anti inflammatory drugs (NSAIDs) in bovine plasma was developed. An improved method for the determination of authorized and non-authorized residues of 10 non steroidal anti-inflammatory drugs in milk was developed. Analytes were separated and acquired by high performance liquid chromatography coupled with an electrospray ionisation tandem mass spectrometer (ESI-MS/MS). Target compounds were acidified in plasma, and plasma and milk samples were extracted with acetonitrile and both extracts were purified on an improved solid phase extraction procedure utilising Evolute ABN cartridges. The accuracy of the methods for milk and plasma was between 73 and 109%. The precision of the method for authorized and non-authorized NSAIDs in milk and plasma expressed as % RSD, for the within lab reproducibility was less than 16%. The % RSD for authorized NSAIDs at their associated MRL(s) in milk was less than 10% for meloxicam, flunixin and tolfenamic acid and was less than 25% for hydroxy flunixin. The methods were validated according to Commission Decision 2002/657/EC. PMID- 20544457 TI - Assessment of the dietary habits and polycyclic aromatic hydrocarbon exposure in primary school children. AB - Thirty Italian children, 7-9 year aged, living in Naples were investigated on their dietary habits and on polycyclic aromatic hydrocarbon (PAH) exposure by a food diary-questionnaire and one week duplicate diet sample analyses. Daily total food consumption mean value was 632 +/- 215 g day(-1), median value 613 g day( 1). The daily energy intake and the diet composition meanly agreed with the official guidelines for the Italian children. Sixteen PAHs were simultaneously detected and, according to the European Food Safety Authority (EFSA) approach, benzo[a]pyrene; benzo[a]pyrene + chrysene (PAH2); PAH2 + benz[a]anthracene + benzo[b]fluoranthene (PAH4); PAH4 + benzo[k]fluoranthene + benzo[ghi]perylene + dibenz[a, h]anthracene + indeno[1,2,3-cd]pyrene (PAH8) were considered in evaluating the children's dietary exposure to PAHs. The benzo[a]pyrene (BaP) median concentrations in foods varied from 0.06 to 0.33 microg kg(-1). Only three samples of cooked foods (one fish and two meat samples) exceeded legal limits fixed by the European Union for BaP. Daily median intakes of benzo[a]pyrene, PAH2, PAH4, and PAH8 were 153; 318; 990; 1776 ng day(-1); their median exposure values were 5; 10; 28; 54 ng kg(-1) bw day(-1). The Margins of Exposure (MOEs) in median consumers agreed with the EFSA safety values except for PAH8. PMID- 20544458 TI - Relationships between elderly care recipients and their migrant live-in home care workers in Israel. AB - In Israel more than 54,000 immigrant live-in home care workers are providing personal care to frail elders. These home care workers emigrate from various countries and different cultures, speak other languages, and have other religions. The purposes of this study were: (a) to examine the patterns of the interpersonal relationships that develop between disabled elderly persons who were being cared for by migrant live-in home care workers, and (b) to explore the factors that best explain the patterns of these relationships. A convenience sample that included 100 frail elderly people was selected and respondents were face-to-face interviewed at their homes, using a structured questionnaire. The findings showed that the relationships that developed between migrant live-in home care workers and elderly care recipients were close and that language was not a significant barrier in establishing close relationships between them. Further, the findings showed that perceived similarity in personal qualities played the most significant role in determining the extent to which the relationships between them will be close. A similar cultural background such as ethnicity, and nonverbal and good understanding, rather than speaking a common language, were significant factors in facilitating close relationships. PMID- 20544459 TI - Intention to leave the job among live-in foreign home care workers in Israel. AB - In Israel, almost all around-the-clock home care services are provided by foreign workers. Despite the fact that these workers are considered temporary, the Israeli government has acknowledged the need for consistency in care and now allows workers to stay in the country for as long as their care recipient is alive. Nonetheless, there have been increasing concerns about the tendency of foreign home care workers to view Israel as a temporary station on their way to more attractive destinations, such as Canada or England. Using the job rewards and concerns model, this article evaluates determinants of foreign home care workers' intentions to leave their job. This study was a cross-sectional analysis of 178 Filipino home care workers in Israel. Only 15 workers (8.4%) reported that they would be likely or very likely to leave their job within the next 3 months. The final model suggested that negative experiences within the home/work environment as well as within Israeli society at large contribute to depression and posttraumatic stress symptoms. However, caring for an older adult with dementia was the only predictor of intention to leave the job. The majority of workers do not report an intention to leave their job. Nonetheless, greater supervision of this caregiving arrangement in an attempt to protect the rights of foreign home care workers within the home/work environment is an important step, which has to be followed up by attitudinal changes within society at large. Specific training in dementia care is also warranted. PMID- 20544460 TI - Health information use in home care: brainstorming barriers, facilitators, and recommendations. AB - There is growing recognition of the importance of sharing health information in home care; however, limited research exists to identify appropriate strategies, especially with home care providers. We engaged home care stakeholders from three locations in Ontario to determine facilitators, barriers, and recommendations for using health information in home care. The results suggest that health professionals recognize the potential of these systems to enhance communication through several emergent themes; however, there was a lack of agreement on the current facilitators, barriers, and recommendations for future interventions. More research is needed to achieve consensus before strategies for improvement can be initiated. PMID- 20544461 TI - Road traffic safety in African countries - status, trend, contributing factors, countermeasures and challenges. AB - Road traffic crashes and injuries constitute a major health, economic and developmental challenge for many African countries. With only 4% of the world's motor vehicles, African roads witness more than 10% of the world total collision fatalities. With further motorisation, the number of road traffic crashes, injuries and fatalities are expected to grow. This study updates on the status, trends, causes, countermeasures and issues in traffic safety in African countries by reviewing studies published in the past 12 years. The study found that traffic fatalities continued its upward trend in recent years. Similar to those in motorised countries, the study identified that human behaviour and incapacitation account for more than 85% of the contributing factors reported by police in Africa. Unlike in developed countries, the victims of traffic casualties are primarily vulnerable road users. Pedestrians alone account for more than 40% of the total fatalities on African roads. Limited countermeasures were reported in the literature. The outcomes of these programmes are mixed and the research methods have inconsistent validity. Investigation in the feasibility of transferring proven programmes from motorised countries is suggested as an efficient measure for traffic safety improvement. PMID- 20544462 TI - A review of factors that moderate autobiographical memory performance in patients with major depressive disorder. AB - Studies of autobiographical recall in patients with major depressive disorder (MDD) reveal overgeneralization, where autobiographical memory (AM) comprises primarily factual or repeated information as opposed to details specific in time and in place and definitive of episodic re-experiencing. In addition to reviewing AM impairment in MDD, we explore the contribution of key method, demographic, and clinical variables to this dysfunction. Several candidate variables emerge, including testing method, emotion, mood state, illness burden, medication status, electroconvulsive therapy (ECT), comorbidity, trauma, age, ruminative state, and executive and memory function. These variables appear to interact in a complex manner to influence AM performance in MDD. PMID- 20544463 TI - Faith-based mental health treatment of minors: a call for legislative reform. PMID- 20544464 TI - Reforming health care: the paradoxes of cost. PMID- 20544465 TI - Protecting hospital ratings with copyright law. PMID- 20544468 TI - Airborne diazinon concentrations during and after outdoor spray application. AB - Airborne concentrations of the organophosphate pesticide diazinon were assessed using personal sampling on an applicator and area sampling at several locations within ornamental plant beds sprayed with the chemical. As part of field work testing a prototype pesticide monitor, diazinon was applied to azalea bushes, from a backpack sprayer, on two separate occasions. Personal and area sampling was used to measure concentrations during the application and over multiple time scales after the initial sampling. The area measurements indicated that diazinon concentrations during and immediately after application were similar to the consensus occupational exposure limit (OEL) of 10 mug/m(3) for airborne diazinon. Concentrations measured from personal samples worn by the applicator were 57-82% of the occupational limit during the application period. Therefore, an applicator and anyone else near ornamental plants being sprayed with diazinon should use personal protective equipment, including appropriate respiratory protection. Concentrations declined substantially with time during the subsequent 24-hr period. In 2006, the U.S. Environmental Protection Agency (EPA) set the restricted-entry interval (REI) after diazinon is applied to ornamental plants to 2 days, assuming only dermal exposures are relevant after spraying. However, the results of this study suggest that the health risks posed by estimated potential doses caused by inhalation exposures after spraying are of the same order of magnitude as the risks posed by potential dermal doses using the risk assessment methodology employed by EPA. Thus, EPA should not dismiss inhalation exposures when developing REIs for diazinon in the future. PMID- 20544469 TI - Religiosity and sexual risk behavior among Croatian college students, 1998-2008. AB - A substantial increase in religious identification has been observed in most European post-communist countries. As religiosity has been associated with sexually transmitted infection (STI) and HIV vulnerability among young people, this article examined the impact of religious upbringing and personal religiosity (religiousness) on sexual risks among University of Zagreb first-year undergraduate students, using data collected in 1998, 2003, and 2008. Female participants who reported strict religious upbringing were less knowledgeable about human sexuality than other women. Religiousness was negatively correlated with basic knowledge of human sexuality, but again only among women. Contrary to expectations, no significant associations were found between religious upbringing or religiousness and condom use. Both measures of religiosity, however, were related to decreased odds of sexual debut among young women. In the case of male participants, the impact of religiosity was marginal. Religious upbringing was associated (negatively) with sexual literacy and sexual debut-but only at the beginning of the observed period. Overall, religiosity does not seem to substantially reduce STI- and HIV-related risk-taking, particularly among men. Since the observed increase in the proportion of sexually active students during the 1998 through 2008 period was not matched by an increase in condom use, reducing STI and HIV vulnerability among Croatian youth remains an essential task. PMID- 20544471 TI - Editor's Introduction. PMID- 20544470 TI - Managing sexual difficulties: a qualitative investigation of coping strategies. AB - Biomedical interventions offer effective treatment for only a small proportion of individuals experiencing sexual difficulties. Where treatment fails, individuals have to find ways to cope and adjust. Currently, little is known about how individuals do this. This article presents data from 32 semi-structured interviews with individuals representing a range of sexual function experience. Three broad coping approaches are identified. The first, changing circumstances to fit goals, included strategies such as seeking biomedical treatment and ending a relationship. The second approach, changing goals to fit circumstances, included strategies such as changing one's definition of "good-enough" sex. The final approach, living with a gap between goal and circumstances, included strategies such as normalizing and avoiding the problem. Several factors appeared to be key in determining successful adjustment: the severity of the problem, causal attributions made about the problem, and the partnership context. The findings are explained in terms of Brandstadter's distinction between accommodative and assimilative coping strategies, and suggest that a flexible definition of good-enough sex, as well as a flexible stance toward the importance of sex, may enhance the process of adjustment. PMID- 20544472 TI - Special introduction. PMID- 20544473 TI - Father passed. PMID- 20544474 TI - Death of a child. PMID- 20544475 TI - Promoting advance care planning through the National Healthcare Decisions Day initiative. AB - National Healthcare Decisions Day is a nationwide campaign aimed at increasing advance care planning among adults throughout the country. This broad-scale initiative simultaneously seeks to encourage Americans to express their wishes regarding future healthcare decision making, rally a national media campaign to promote the importance of planning in advance for care, and mobilize national, state, and community organizations to develop a wide range of educational activities. The movement culminates in an annual day of multiple events throughout the country designed to inundate the public about advance care planning. The national event originated from the successful statewide Virginia Advance Directives Day's inaugural event, conducted on April 18, 2006. Social workers are encouraged to participate in this growing initiative through a variety of activities and roles. A description of a successful event conducted in a suburban Southeastern community is provided to illustrate the activities and roles performed by social work. PMID- 20544476 TI - Life-sustaining treatment decisions: a social work response to meet needs of health care surrogates. AB - Surrogates must possess essential patient information prior to legitimately exercising legal and moral obligations to act on patients' medical care preferences. This descriptive, in vivo study examined factors influencing surrogate and proxy decisions (N = 132) following life-sustaining treatment decisions. Patient communication and self-efficacy variables accounted for approximately 38% of the variance in surrogates' perceptions of benefits/barriers associated with decision making. Guided by patients' advanced communication, respondents (97.8%) expressed high self-reliance and significant appreciation of benefits associated with their decisions. Clarifying surrogates' and providers' understanding of patient care preferences during ICU/CCU admission may facilitate better adherence to patient wishes. PMID- 20544477 TI - Levels, types, and predictors of family caregiver strain during hospice home care for an older adult. AB - Academic researchers and professionals from a hospice organization collaborated to assess physical, emotional, social, economic, and spiritual strain stemming from providing care to a terminally ill older relative among 162 family caregivers to older adults newly admitted to hospice home care. The study investigated predictors of the different types of strain, as well as cumulative strain. Hierarchical multiple regressions revealed that caregivers' age and race, hospice patients' major illnesses (particularly cancer), caregivers' appraisals of their situation, and resources were significant risk or protective factors for caregiver strain, although the predictors varied by type of strain and amount of strain. Discussion focuses on the importance of identifying family caregivers at risk of higher strain during hospice home care and implications for family caregiver interventions. PMID- 20544478 TI - Terminally ill elders' anticipation of support in dying and in death. AB - This study explored terminally ill elders' anticipation of future support, which may be particularly important due to their vulnerable state and resulting support needs. Qualitative data was gathered from face-to-face interviews with 100 elders receiving hospice care; 85 of whom discussed anticipating future support. Content analysis revealed that anticipating support was based on current experiences of received support and that the definition of future extended beyond death for some who anticipated surviving loved ones receiving grief support. Not all anticipation of support evoked positive feelings. Some respondents anticipated receiving unhelpful support or felt guilty about anticipating support from overburdened caregivers. Implications are discussed regarding the role of social workers in working with caregivers to insure that the terminally ill elders they care for can anticipate future support in their dying process and after death. PMID- 20544479 TI - Interdisciplinary education in end-of-life care: creating new opportunities for social work, nursing, and clinical pastoral education students. AB - This article describes an interdisciplinary, interuniversity program that prepares social work, nursing, and chaplaincy students for competent practice when working with individuals and families facing end-of-life circumstances. Built upon a teaching format that provides knowledge-to-skill-building opportunities, the program immerses students in a range of related content. To maximize integration, the program relies on interdisciplinary team teaching (building knowledge) followed by practice sessions (building skill), in which volunteer actors play the roles of care recipients. With year 3 completed, program administrators have important indicators of the program's effectiveness in offering content specific to end-of-life care using a combination of discipline-specific and interdisciplinary learning strategies. This process has provided valuable lessons related to the nature of interdisciplinary education in end-of-life care. PMID- 20544482 TI - Short-term resistance training with blood flow restriction enhances microvascular filtration capacity of human calf muscles. AB - Resistance training increases muscle strength and endurance but may require high intensity and long duration to enhance capillarity. Vascular occlusion during low load resistance training augments the strength and endurance gains compared with low-load resistance training alone, but in this study we investigated whether it also promotes microvascular filtration capacity, an index of capillarity. Nine healthy males performed short-term low-intensity resistance training of the calf muscles (four sets of 50 heel raises, three times a week for 4 weeks) under restricted (thigh cuff inflated to 150 mmHg on the non-dominant leg) or unrestricted (dominant leg without thigh cuff) blood flow conditions. Before and after resistance training, calf filtration capacity and resting blood flow were assessed by strain gauge plethysmography, and calf muscle strength and fatigue were assessed respectively by maximal voluntary contraction and force decline during electrically evoked ischaemic contractions in both legs. Calf filtration capacity increased by 26% in the restricted leg but did not increase significantly in the unrestricted leg. Calf muscle strength was 18% greater in the restricted leg but unchanged in the unrestricted leg. Calf muscle fatigue and resting blood flow did not change in either leg. Resistance training promoted microvascular filtration capacity, an effect that was somewhat enhanced by blood flow restriction, and could be due to increased capillarization. PMID- 20544483 TI - Protective effects of therapeutic cold and heat against the oxidative damage induced by a muscle strain injury in rats. AB - The mechanisms of action of physical agents commonly used to treat skeletal muscle lesions are not well understood. In this study, we examined whether the modulation of oxidative stress is involved in the beneficial effects of cold and heat on gastrocnemius muscle strain injury. Adult male Wistar rats were submitted to a strain injury and treated with therapeutic agents in an isolated or combined form. Strain damage caused an increase in muscle and blood oxidative damage. We suggest that this oxidative damage might be related to the impairment of the muscle cell structure, since we observed a significant positive correlation between increased plasma creatine kinase activity and both oxidized dichlorofluoresceine and lipid peroxidation levels in muscle and blood. The intensity of the inflammatory response appears also to be an important factor in the genesis of oxidative damage immediately following a muscle strain injury. Therapeutic cold seems to be more effective in preventing the damage induced by a strain injury, possibly due to its capacity to control the impairment of muscle cell structure and to modulate the intensity of the inflammatory response that follows a muscle strain injury. PMID- 20544484 TI - Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery. AB - High-intensity exercise training contributes to the production and accumulation of blood lactate, which is cleared by active recovery. However, there is no commonly agreed intensity or mode for clearing accumulated blood lactate. We studied clearance of accumulated blood lactate during recovery at various exercise intensities at or below the lactate threshold after high-intensity interval runs that prompted lactate accumulation. Ten males repeated 5-min running bouts at 90% of maximal oxygen uptake (VO(2max)), which increased blood lactate concentration from 1.0 +/- 0.1 to 3.9 +/- 0.3 mmol l(-1). This was followed by recovery exercises ranging from 0 to 100% of lactate threshold. Repeated blood lactate measurements showed faster clearance of lactate during active versus passive recovery, and that the decrease in lactate was more rapid during higher (60-100% of lactate threshold) than lower (0-40% of lactate threshold) (P < 0.05) intensities. The more detailed curve and rate analyses showed that active recovery at 80-100% of lactate threshold had shorter time constants for 67% lactate clearance and higher peak clearance rates than 40% of lactate threshold or passive recovery (P < 0.05). Finally, examination of self regulated intensities showed enhanced lactate clearance during higher versus lower intensities, further validating the intensity dependence of clearance of accumulated blood lactate. Therefore, active recovery after strenuous exercise clears accumulated blood lactate faster than passive recovery in an intensity dependent manner. Maximum clearance occurred at active recovery close to the lactate threshold. PMID- 20544485 TI - Adjusting athletes' body mass index to better reflect adiposity in epidemiological research. AB - The aim of the present study was to identify when body mass index (BMI) is unlikely to be a valid measure of adiposity in athletic populations and to propose a simple adjustment that will allow the BMI of athletes to reflect the adiposity normally associated with non-athletic populations. Using data from three previously published studies containing 236 athletes from seven sports and 293 age-matched controls, the association between adiposity (sum of 4 skinfold thicknesses, in millimetres) and BMI was explored using correlation, linear regression, and analysis of covariance (ANCOVA). As anticipated, there were strong positive correlations (r = 0.83 for both men and women) and slope parameters between adiposity and BMI in age-matched controls from Study 1 (all P < 0.001). The standard of sport participation reduced these associations. Of the correlations and linear-regression slope parameters between adiposity and BMI in the sports from Studies 2 and 3, although still positive in most groups, less than half of the correlations and slope parameters were statistically significant. When data from the three studies were combined, the ANCOVA identified that the BMI slope parameter of controls (5.81 mm (kg m(-2))(-1)) was greater than the BMI slope parameter for sports (2.62 mm (kg m(-2))(-1)) and middle-distance runners (0.94 mm (kg m(-2))(-1)) (P < 0.001). Based on these contrasting associations, we calculated how the BMI of athletes can be adjusted to reflect the same adiposity associated with age-matched controls. This simple adjustment allows the BMI of athletes and non-athletes to be used with greater confidence when investigating the effect of BMI as a risk factor in epidemiological research. PMID- 20544486 TI - Energy turnover during 24 hours and 6 days of adventure racing. AB - Energy turnover was assessed in two conditions of mixed ultra-endurance exercise. In Study 1, energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2, energy expenditure was assessed in six males during an 800-km Adventure race (mean race time 152.5 h). Individual correlations between heart rate and oxygen uptake (VO(2)) were established during pre-tests when kayaking, cycling, and running. During exercise, energy expenditure was estimated from continuous heart rate recordings. Heart rate and VO(2) were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse. Mean energy expenditure was 18,050 +/- 2,390 kcal (750 +/- 100 kcal h(-1)) and 80,000 +/- 18,000 kcal (500 +/- 100 kcal h(-1)) in Study 1 and Study 2 respectively, which is higher than previously reported. Energy intake in Study 1 was 8,450 +/- 1,160 kcal, resulting in an energy deficit of 9,590 +/- 770 kcal. Body mass decreased in Study 1 (-2.3 +/- 0.8 kg) but was unchanged in Study 2. Fat mass decreased in Study 2 (-2.3 +/- 1.5 kg). In Study 1, muscle glycogen content decreased by only 60%. Adventure racing requires a high energy expenditure, with large inter-individual variation. A large energy deficit is caused by inadequate energy intake, possibly due to suppressed appetite and gastrointestinal problems. The oxygen pulse, comparing start to 12 h of exercise and beyond, increased by 10% and 5% in Study 1 and Study 2 respectively. Hence, estimations of energy expenditure from heart rate recordings should be corrected according to this drift. PMID- 20544487 TI - Performance analysis research: meeting the challenge. PMID- 20544488 TI - Emotional contagion in soccer penalty shootouts: celebration of individual success is associated with ultimate team success. AB - We examined the association between celebratory responses after successful soccer penalty kicks and the outcome of a penalty shootout. Individually displayed post shot behaviours in penalty shootouts held in World Cups and European Championships (N = 151) were rated on the presence of universally distinct and recognizable behaviours associated with positive emotions. Using chi-square analyses we investigated which behaviours were associated with winning the shootout, when the relative standing between the teams was equal. Players who engaged in certain celebratory post-shot behaviours were more likely to be in the team that ultimately won the penalty shootout. In particular, celebrations including both arms were associated with winning the shootout. It was more likely that the next kick taken by an opponent was missed after a player displayed these behaviours after a goal than when he did not. The findings are interpreted in terms of emotional contagion - that is, the transference of emotions from individuals onto teammates and opponents. It is suggested that the individual expression of post-performance emotions serves a direct purpose in enhancing future team performance and that emotional contagion is an important process in the context of elite sport performance. PMID- 20544489 TI - Effects of aerobic training on serum omentin-1 and cardiometabolic risk factors in overweight and obese men. AB - Omentin-1 is a newly discovered protein expressed and secreted from visceral adipose tissue that increases insulin sensitivity.We examined the effects of 12 weeks of aerobic training on serum omentin-1 concentrations together with cardiovascular risk factors in overweight and obese men. Eighteen overweight and obese participants (age 43.1 +/- 4.7 years, BMI >= 25 kg . m -2 ) were assigned to exercise training (n = 9) and control (n = 9) groups. A matched control group of normal weight participants (n = 8; age 42.2 +/- 3.8 years, BMI < 25 kg . m -2 ) were also recruited for baseline comparison. The obese exercise group participated in 12 weeks of progressive aerobic training 5 days a week. Measures of serum omentin-1, insulin resistance, lipid profiles, blood pressure, and body composition were obtained before and after the 12 weeks. At baseline, normal weight participants had significantly higher serum omentin-1 concentrations than overweight and obese participants, and there were inverse correlations between omentin-1 and each of waist circumference, fasting glucose, insulin resistance, total cholesterol,triglyceride, and systolic blood pressure (P < 0 .05). After the aerobic training, waist circumference, percent body fat, fasting glucose, insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and systolic blood pressure were all significantly decreased (P < 0.05). In contrast, serum omentin-1 concentration was significantly increased after the aerobic programme (P < 0.05), and correlated with changes in insulin resistance (r = - 0.67, P= 0.04), glucose (r = - 0.65, P = 0.05), waist circumference (r = -70, P = 0.03), and aerobic fitness r = -.68, P = 0.04). Aerobic training resulted in an improvement in cardiometabolic risk factors in obese participants, and this improvement was accompanied by increased omentin-1 concentrations. PMID- 20544490 TI - Differences in self-regulatory skills among talented athletes: the significance of competitive level and type of sport. AB - Research has shown that talented athletes outscore their mainstream peers on the basis of self-regulation. Although valuable, this does not tell us more about the distinction between good athletes and the best, which is a prerequisite in talent development. Therefore, we examined the self-regulatory skills of 222 male and female talented athletes aged 12-16 years as a function of competitive sport level (junior international or junior national athletes) and type of sport (individual or team sports). Multivariate analyses of covariance in combination with a discriminant function analysis revealed that "reflection" distinguishes between athletes at the highest levels of excellence. Furthermore, athletes playing individual sports had higher scores on "planning" and "effort" than team sport athletes, highlighting the importance of differences between types of sport. In conclusion, we emphasize the importance of reflection as a self regulatory skill. Reflection facilitates the development of sport-specific characteristics, which may vary by type of sport. This means that an advanced sense of reflection may help talented athletes to acquire desirable characteristics during their "talent" years to ultimately reach adult elite levels of competition. PMID- 20544491 TI - Sequential effects after practice with the dominant and non-dominant hand on the acquisition of a sliding task in schoolchildren. AB - This study was designed to investigate sequential effects after practice with the dominant and non-dominant hand on the acquisition of a new motor task. A total of 64 middle school children were asked to practise a cent-slide task, which required them to slide coins from one side of a cardboard into a circular target on the opposite side. Four groups practised this task within different practice schedules: (1) participants practised only with their dominant hand (right-only group); (2) participants used only their non-dominant hand (left-only group); (3) participants started to practise the skill with their dominant hand and then switched to their non-dominant hand (right-to-left group); or (4) participants started to practise the skill with their non-dominant hand and then switched to their dominant hand (left-to-right group). The acquisition of the task was facilitated after initial practice with the non-dominant hand. This was reflected in a better retention of the task and a stronger performance under a modified testing situation of the left-to-right group when compared to all other groups. Also, the left-only group showed larger interlimb transfer effects to the untrained hand than the right-only group. It is concluded that the sequence in which the dominant and non-dominant hands are used to practise influences the acquisition of new motor tasks. PMID- 20544492 TI - Kissing right? On the consistency of the head-turning bias in kissing. AB - The present study investigated the consistency of the head-turning bias in kissing. In particular we addressed what happens if a person who prefers to kiss with the head turned to the right kisses a person who prefers to kiss with the head turned to the left. To this end, participants (N=57) were required to kiss a life-sized doll's head rotated in different orientations that were either compatible or incompatible with the participants' head-turning preference. Additionally, participants handedness, footedness, and eye preference was assessed. Results showed that a higher percentage of participants preferred to kiss with their head turned to the right than to the left. In addition, the right turners were more consistent in their kissing behaviour than left-turners. That is, with the doll's head rotated in an incompatible direction, right-turners were less likely to switch their head to their non-preferred side. Since no clear relationships between head-turning bias and the other lateral preferences (i.e., handedness, footedness, and eye preference) were discerned, the more consistent head-turning bias among right-turners could not be explained as deriving from a joint pattern of lateral preferences that is stronger among individuals with rightward as compared to individuals with leftward lateral preferences. PMID- 20544493 TI - Lateral biases in lighting of abstract artwork. AB - Previous studies examining perceptual biases in art have revealed that paintings tend to be lit from above and to the left. Abstract images provide a way of testing for the left-light bias while controlling for cues such as posing biases, ground line, shadows, and reflections. A total of 42 participants completed a task that required moving a "virtual flashlight" across the surface of abstract images presented on a computer screen: 20 images (presented both right-side-up and upside down) were used in the study. The participant's only instruction was to "light the painting in a way that is most aesthetically pleasing to you". As predicted, participants on average focused the "virtual flashlight" in the top left quadrant. This study reveals that lateral lighting biases in artwork are not dependent on perception of local light source or interactions with discrete, concrete visual representations in the artwork. PMID- 20544494 TI - Infant-holding side biases: comparison of laterality patterns in childcare professionals and mothers or students. AB - Among the various interactions between an adult and an infant, postural behaviours and their lateral biases expressed by adults for holding an infant represent a growing field of investigation. To better understand the building up of mother/child relationships, the current study reports data concerning infant holding biases collected in a new population, namely childcare professionals, where experience with and emotional relationships with infants could be classified as intermediate between basic and advanced. Two sub-populations of childcare professionals were studied: women who work in maternity hospitals and women who work in day-care centres. Their infant-holding side preferences were correlated with emotional perceptive biases to ascertain whether hemispheric specialisation influences holding side biases as well as in basic holding relationships. Results showed that childcare professionals behaved like mothers, which means like participants with advanced holding relationships. The discussion emphasises the complexity of infant-holding behaviours and the importance of considering the nature of holding relationships in the study of side-of-hold biases. PMID- 20544495 TI - Sex differences in face processing are mediated by handedness and sexual orientation. AB - Previous research has demonstrated sex differences in face processing at both neural and behavioural levels. The present study examined the role of handedness and sexual orientation as mediators of this effect. We compared the performance of LH (left-handed) and RH (right-handed) heterosexual and homosexual male and female participants on a face recognition memory task. Our main findings were that homosexual males have better face recognition memory than both heterosexual males and homosexual women. We also demonstrate better face processing in women than in men. Finally, LH heterosexual participants had better face recognition than LH homosexual participants and also tended to be better than RH heterosexual participants. These findings are consistent with differences in the organisation and laterality of face-processing mechanisms as a function of sex, handedness, and sexual orientation. PMID- 20544496 TI - Short-term memory for emotional faces in dysphoria. AB - The study aimed to determine if the memory bias for negative faces previously demonstrated in depression and dysphoria generalises from long- to short-term memory. A total of 29 dysphoric (DP) and 22 non-dysphoric (ND) participants were presented with a series of faces and asked to identify the emotion portrayed (happiness, sadness, anger, or neutral affect). Following a delay, four faces were presented (the original plus three distractors) and participants were asked to identify the target face. Half of the trials assessed memory for facial emotion, and the remaining trials examined memory for facial identity. At encoding, no group differences were apparent. At memory testing, relative to ND participants, DP participants exhibited impaired memory for all types of facial emotion and for facial identity when the faces featured happiness, anger, or neutral affect, but not sadness. DP participants exhibited impaired identity memory for happy faces relative to angry, sad, and neutral, whereas ND participants exhibited enhanced facial identity memory when faces were angry. In general, memory for faces was not related to performance at encoding. However, in DP participants only, memory for sad faces was related to sadness recognition at encoding. The results suggest that the negative memory bias for faces in dysphoria does not generalise from long- to short-term memory. PMID- 20544497 TI - Volatile oil constituents and antibacterial activity of different parts of Falcaria vulgaris Bernh. growing wild in two localities from Iran. AB - The chemical composition of essential oils obtained by hydrodistillation from the flower, leaf and stem of Falcaria vulgaris Bernh., which is endemic to Iran, were analysed by GC and GC/MS (samples were from two different localities: A from Ardabil and B from Khalkhal). alpha-Pinene was the major constituent in all the three oils (flower, leaf and stem) from sample A (43.8%, 33.0% and 50.9%, respectively). The oil of F. vulgaris flower was characterised by a higher amount of beta-caryophyllene (25.2%) and 1,8-cineole (12.8%) among the eight components comprising 96.2% of the total oil detected. alpha-Terpinyl acetate (23.2%) and limonene (14.4%) predominated in the leaf oil. In the oils of sample B, alpha pinene (16.1% in the flower oil, 31.5% in the leaf oil and 34.5% in the stem oil) was the major compound. Limonene (14.2%) and germacrene D (32.1%) were also the main constituents found in the leaf oil from sample B. alpha-Terpinyl acetate (21.9% in the leaf oil) and limonene (29.8% in stem oil) were the other major compounds obtained from this sample. Antibacterial activity was determined by the measurement of growth inhibitory zones. PMID- 20544498 TI - Antioxidant activity and chemical composition of Sideritis libanotica Labill. ssp. linearis (Bentham) Borm. (Lamiaceae). AB - Sideritis libanotica ssp. linearis was screened for the isolation of new natural antioxidant compounds. The antioxidant activity of flavones obtained from the methanol extract of the plant was evaluated in vitro using total antioxidant, reduction power and free radical scavenging activity. Results were compared with the positive controls of antioxidant standards (alpha-tocopherol and butylated hydroxytoluene). The results indicate that the flavones possess a higher antioxidant activity when compared to the other components in the plant. The lowest antioxidant activity was observed in fatty acids (FAs) and hydrocarbons. The FAs were methylated with MeOH and KOH and analysed by GC-MS. The structures of the isolated compounds were established based on spectroscopic evidence (NMR, GC-MS, HPLC, IR and UV). In this work, the isolated pure flavone (3'-O methylhypolaetin 7-O-[6"'-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]-6"-O-acetyl beta-D-glucopyranoside) was found to possess the highest antioxidant activity. PMID- 20544499 TI - Caffeic acid and quercitrin purified from Houttuynia cordata inhibit DNA topoisomerase I activity. AB - A methanol extract of Houttuynia cordata showed an inhibitory effect on mammalian DNA topoisomerase I. Two topoisomerase I inhibitory compounds were purified and identified as caffeic acid and quercitrin. Caffeic acid and quercitrin inhibited the activity of topoisomerase I with IC(50) values of about 0.15 and 0.05 mM, respectively. A concentration of 45 uM caffeic acid caused 50% growth inhibition in human leukaemia U937 cells, but not on those of normal fibroblast NIH3T3 cells. However, quercitrin mysteriously stimulated proliferation of U937 and NIH3T3 cells. Caffeic acid-induced cell death was characterised with the cleavage of poly (ADP-ribose) polymerase and procaspase-3, indicating that this inhibitor triggered apoptosis. The apoptotic induction by caffeic acid was also confirmed using flow cytometry analysis. Because DNA topoisomerase I is an important target for tumour chemotherapy, the present study suggests that caffeic acid, but not quercitrin, may function by suppressing oncogenic disease through the inhibition of cellular topoisomerase I activity. PMID- 20544500 TI - Antiproliferative and cytotoxic activity of extracts from Cistus incanus L. and Cistus monspeliensis L. on human prostate cell lines. AB - Benign prostatic hypertrophy (BPH) is a common condition in elderly men that impairs quality of life and leads to a number of medical complications. The use of phytotherapeutic compounds in patients with relatively moderate BPH symptoms has been growing steadily. In the present study, acute toxicity of lyophilised aqueous extracts of Cistus incanus L. and Cistus monspeliensis L., collected in Sicily, was evaluated on the shrimp (Artemia salina L.) lethality assay, an alternative test to determine the toxicity of natural products. The cytotoxic and growth inhibitory effects were studied on normal human prostate cells (PZ-HPV-7 and PNT1A) and on a lung fibroblast cell line (V79-4). Cell proliferation was evaluated by MTT and SRB assays. Cytotoxicity was measured using the Trypan blue exclusion assay. Cistus extract treatment on prostate cell lines resulted in an almost identical growth inhibitory response and in a significant decrease in an cell viability. These findings indicate the biologically relevant effect of polyphenolic compounds present in Cistus extracts, and suggest that these substances may prove beneficial in BPH treatment. PMID- 20544501 TI - Size matters: a study on naming and size knowledge in dementia of the Alzheimer type. AB - Category-specificity was longitudinally studied over a period of 12 months in seven Alzheimer disease patients, with two semantic tasks differing with respect to verbal processing demands: picture naming and a size ordering task. Items from each task were matched on all cognitive and psycholinguistic variables known to differ across domains (living-nonliving). Naming performance of patients was poorer than that of normal controls. Regarding category-specific effects, while naming performance of patients was parallel to that of normal controls, patients' performance with the size ordering task revealed a different scaling of living things while that of nonliving things mirrored performance of normal controls. This suggests that caution is needed when the picture naming task is exclusively used to document category-specific effects. PMID- 20544502 TI - Effectiveness of a low intensity outpatient cognitive rehabilitation programme for patients in the chronic phase after acquired brain injury. AB - The aim of this prospective cohort study was to examine the effectiveness of a low intensity outpatient cognitive rehabilitation programme for patients with acquired brain injury in the chronic phase. Twenty-seven patients with acquired brain injury (i.e., stroke, traumatic brain injury, subarachnoid haemorrhage; 52% male) with a mean age of 49.5 (SD 9.2) years and 25 relatives with a mean age of 48.8 (SD 8.8) years were recruited to the study. Mean time since injury in the patient group was 1.9 years (SD 2.0). The group programme consisted of 15 weekly sessions of 2.5 hours and included cognitive strategy training, social skills training, and psycho-education. Patients also received homework. Relatives were invited to attend twice. Repeated measurements were taken: prior to treatment (baseline, T0); directly after treatment (T1, 21 weeks); and at follow-up (T2, 45 weeks). Primary outcome measures were individualised goals (GAS), cognitive failures (CFQ), and quality of life (SA-SIP). Patients did improve significantly on individual goals (p < .05) between T0 and T1 and the level of attainment remained stable between T1 and T2. Goals were mostly set in the cognitive and behavioural domains. There were no significant differences between the measurements (T0-T1-T2) on the CFQ and the SA-SIP. The programme had a positive effect on the individual goals set by the patients. However, this did not result in a higher participation level or a better quality of life. This may be due to the low intensity and short duration of the programme. PMID- 20544503 TI - Purine and pyrimidine metabolism in the fist decade of the 21st century- highlights and perspectives. PMID- 20544505 TI - In memoriam: Dr. Hermione Anne Simmonds. PMID- 20544506 TI - Novel strategies in the thiopurine treatment of inflammatory bowel disease. AB - Thiopurine drugs are widely used as immunomodulatory and corticosteroid-sparing agents in inflammatory bowel disease. Despite being old drugs, a renewed research and clinical interest in their application has emerged during the last decade. The application of pharmacogenetic insights and metabolic monitoring, together with treatment strategies in combination with anti-TNFalpha-antibodies and possibilities to modulate their metabolism, has paved the way to a "modern" use of the thiopurines. These aspects are briefly overviewed herein. PMID- 20544507 TI - How should thiopurine treatment be monitored?--methodological aspects. AB - Monitoring of thiopurine metabolites is important due to a complex metabolism with large interindividual variation, but the suitability of currently used methods has been questioned. The drawbacks include poor reproducibility, the inability to differentiate between the different analytes, as well as the use of a nontarget matrix. Further research should be directed toward measuring thiopurine metabolites in mononuclear cells, measuring the different nucleotides specifically, as well as measuring the incorporation of thioguanine into DNA. The studies should not be limited to thioguanosine nucleotides but include methylthioinosine nucleotides as well. PMID- 20544508 TI - Limited intra-individual variability in hypoxanthine-Guanine phosphoribosyl transferase, thiopurine S-methyl transferase, and xanthine oxidase activity in inflammatory bowel disease patients during 6-thioguanine therapy. AB - 6-Thioguanine (6-TG) may be indicated in case of intolerance of or resistance to conventional thiopurines in the treatment of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the intrapatient variability in the 6-TG metabolizing enzymes: hypoxanthine-guanine phosphoribosyl transferase (HGPRT), thiopurine S-methyl transferase and xanthine oxidase. We performed a pharmacokinetic study of 6-TG after oral and intravenous administration in IBD patients in remission. The enzyme activities were determined at baseline and 1 week after the initiation of 6-TG in red blood cells, peripheral blood mononuclear cells (PBMC) or plasma. From the results we conclude that HGPRT activity in erythrocytes decreases following the initiation of 6-TG therapy, which may imply that HGPRT is a rate limiting enzyme in 6-TG metabolism. Moreover, little intrapatient variability in enzyme activities was observed except for HGPRT activity in PBMC. These data may have implications in regard of future therapeutic drug monitoring. PMID- 20544509 TI - Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism. AB - Inherited mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. On the other hand, PRPS1 mutations cause PRPP synthetase superactivity associated with hyperuricemia and gout, sometimes including neurodevelopmental abnormalities. We have identified two mutations in two Lesch-Nyhan families after our last report. One of them, a new single nucleotide substitution (130G>T) resulting in a missense mutation D44Y was detected in exon 2 of HPRT1. RT-PCR amplification showed not only a cDNA fragment with normal size, but also a small amount of shorter fragment skipping exons 2 and 3. The other missense mutation F74L (222C > A) was detected in a Japanese patient but has been reported previously in European families. In four hyperuricemic patients with mild neurological abnormality, no mutations responsible for partial HPRT deficiency were identified in HPRT1. In these four patients, we also performed molecular analysis of PRPS1, but no mutations in PRPP synthetase were found. PMID- 20544510 TI - Partial HPRT deficiency phenotype and incomplete splicing mutation. AB - Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of enzyme deficiency. The complete deficiency causes Lesch-Nyhan syndrome (LNS). Partial HPRT-deficient patients can show a variable degree of neurological manifestations. Both diseases have been associated with mutations in the HPRT1 gene. Documented mutations in HPRT deficiency show a high degree of heterogeneity in type and location within the gene. In fact, more than 300 disease-associated mutations have been described. Splice mutations accounts for more that 16% of HPRT mutations and in most cases cause a complete LNS phenotype. A 16 year-old boy consulted to La Paz University Hospital because of hyperuricemia (9.4 mg/dL). At age one year he was given a diagnosis of dystonic cerebral palsy. Although he usually employs a wheelchair, under certain circumstances, he is able to stand up and walk by himself. He has never showed self injurious behavior. This patient presented a splice mutation (NM_000194.2: c.552 -2 A > G) causing exon 5 exclusion. An exon-5 specific PCR was designed, and a minor amount of normally spliced HPRT mRNA was found. Normally spliced HPRT mRNA was quantified by real time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients. No correlation was found between the percentage of the normally spliced HPRT mRNA and the phenotype. We conclude that the partial HPRT deficient phenotype of this patient can not be explained by the finding of a minor amount of normally splice HPRT mRNA. It is possible that the amount of normally splice mRNA vary among different tissues. PMID- 20544511 TI - Methylation status of HPRT1 promoter in HPRT deficiency with normal coding region. AB - Lesch-Nyhan syndrome is an X-linked recessive inborn error of metabolism due to a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity (OMIM 300322). Partial deficiency of HPRT (OMIM 300323) is characterized by the effects of excess uric acid synthesis and a continuum spectrum of neurological manifestations, without the manifestations of full-blown Lesch-Nyhan syndrome. Both diseases have been associated with mutations in the HPRT1 gene. We have described one Lesch-Nyhan patient and four partial HPRT deficient patients with a normal HPRT1 coding region. These patients showed markedly decreased HPRT mRNA expression, but no mutation in their genomic regulatory sequences from HPRT1 gene. In this study, we analyzed the promoter region methylation status of the HPRT1 gene in these five HPRT deficient patients. METHODS: DNA was bisulphite modified and a 620 bp fragment including 320 bp 5' to start codon was amplified and sequenced. The methylation status of 35 CpG island 5' to start codon and 28 CpG island 3' to start codon were investigated in male controls, female controls, patients, and the patient's mothers. Primer pairs were designed for methylated specific and unmethylated-specific amplification and PCR was performed employing DNA bisulphite treated as template. RESULTS: No alterations in the methylation pattern of the HPRT1 promoter were found in the five HPRT deficient patients. CONCLUSIONS: The promoter region methylation status of these five HPRT deficient patients was similar to that of normal subjects. Thus, some other genetic alteration must explain a reduced enzyme activity with a normal gene coding region. PMID- 20544512 TI - Delayed treatment effects of xanthine oxidase inhibition on systolic overload induced left ventricular hypertrophy and dysfunction. AB - The nonpurine selective xanthine oxidase (XO) inhibitor febuxostat attenuates development of left ventricular (LV) hypertrophy and dysfunction in mice when treatment is initiated within 1 hour of transverse aortic constriction (TAC). This study investigated whether a 7-day delay of treatment with the XO inhibitors febuxostat or allopurinol would reverse TAC-induced changes after onset of heart failure (HF). Neither treatment significantly affected TAC-induced LV hypertrophy; only febuxostat caused a modest improvement in LV function ( approximately 10% increase in LV ejection fraction). However, the purine analog allopurinol tended to increase mortality compared with vehicle or febuxostat in HF mice. PMID- 20544513 TI - Establishment and analysis of SLC22A12 (URAT1) knockout mouse. AB - In order to elucidate the mechanisms of post-exercise acute renal failure, one of the complications of hereditary renal hypouricemia, we have targeted the mouse Slc22a12 gene by the exchange of exons 1-4 with pMC1neo-polyA. The knockout mice revealed no gross anomalies. The concentration ratio of urinary urate/creatinine of the knockout mice was significantly higher than that of wildtype mice, indicating an attenuated renal reabsorption of urate. The plasma levels of urate were around 11 muM and were similar among the genotypes. Although the fractional excretion of urate of knockout mice was tend to higher than that of wildtype mice, the urate reabsorption ability remained in the kidney of knockout mice, indicating a urate reabsorptive transporter other than Urat1. PMID- 20544514 TI - Effects of three strong statins (atorvastatin, pitavastatin, and rosuvastatin) on serum uric acid levels in dyslipidemic patients. AB - We have retrospectively investigated the effects of three strong statins, atorvastatin, pitavastatin, and rosuvastatin, on serum uric acid (SUA) levels. SUA levels after a few months of statin treatment were compared with those before treatment in 150 outpatients with dyslipidemia. In the atorvastatin (n = 62) and rosuvastatin (n = 45) groups, the SUA levels were reduced by 6.5% (p < 0.0001) and 3.6% (p = 0.03) respectively, but in the pitavastatin group (n = 43), the SUA level increased by 3.7% (p = 0.38). Because uric acid is considered a risk factor for cardiovascular disorders, atorvastatin or rosuvastatin treatment may be recommended when statins are used in patients at high risk for cardiovascular disorders complicated with hyperuricemia. PMID- 20544515 TI - Metabolic syndrome characteristics in gout patients. AB - Gout is commonly associated with obesity, arterial hypertension, diabetes, and dyslipidemia. However, the prevalence of metabolic syndrome has not been widely recognized in patients with gout. We studied 41 patients (37 males) with primary gout to assess the prevalence and characteristics of the associated metabolic syndrome. Twenty-one patients with gout (51%) showed >or=3 criteria for the metabolic syndrome. Pathological conditions associated were obesity (21/41), high blood pressure (30/41), dyslipidemia (30/41), and fasting plasma glucose >or= 100 mg/dL (22/41). The most frequent triad was the presence of increased waist circumference, elevated fasting plasma glucose, and hypertension. Mean serum urate concentration did not differ significantly in gout patients with the metabolic syndrome (8.5 mg/dl) and without (8.1 mg/dl). Given the complications associated with metabolic syndrome, its diagnosis may determine the long-term treatment of patients with gout. PMID- 20544517 TI - Role of nucleoside transporters in nucleoside-derived drug sensitivity. AB - Nucleoside-derived drugs are currently used clinically as anticancer drugs. To exert their pharmacological action first they need to enter into the cell across plasma membrane transporters and be metabolized. Thus, efficacy of treatment and acquisition of resistance can rely on a variety of events. In this article, we will focus in the role of nucleoside transporters in the sensitivity to nucleoside-derived drugs used in chemotherapy. Evidence of different transporter protein expression patterns in tumors compared to normal tissues, besides inter individual variability in the levels of nucleoside transporters in tumors, suggest a major role of nucleoside transporters in the cytotoxicity of nucleoside analogs. In fact, different studies have linked nucleoside transporter function to drug sensitivity and clinical outcome in cancer patients. However, prospective clinical studies analysing nucleoside transporters and metabolic enzymes, as biomarkers of drug metabolism and action are required to better establish the role these proteins might play in cancer chemotherapy. PMID- 20544516 TI - Uric acid metabolism in patients with primary gout and the metabolic syndrome. AB - Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73 m(2) in the former and 609 mg/day/1.73 m(2) in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS. PMID- 20544518 TI - Thymidine kinase 1 deficient cells show increased survival rate after UV-induced DNA damage. AB - Balanced deoxynucleotide pools are known to be important for correct DNA repair, and deficiency for some of the central enzymes in deoxynucleotide metabolism can cause imbalanced pools, which in turn can lead to mutagenesis and cell death. Here we show that cells deficient for the thymidine salvage enzyme thymidine kinase 1 (TK1) are more resistant to UV-induced DNA damage than TK1 positive cells although they have thymidine triphosphate (dTTP) levels of only half the size of control cells. Our results suggest that higher thymidine levels in the TK cells caused by defect thymidine salvage to dTTP protects against UV irradiation. PMID- 20544519 TI - Thymidine kinase 1 is a potential marker for prognosis and monitoring the response to treatment of patients with breast, lung, and esophageal cancer and non-Hodgkin's lymphoma. AB - Thymidine kinase 1 (TK1) is converting thymidine to thymidine monophosphate, and is related to DNA replication and cell proliferation. The use of the TK1 protein levels as a proliferation marker in malignancies is here summarized. TK1 protein in serum (STK1p) and TK1 expression in tissues were determined by a chemoluminescent dot blot assay and by immunohistochemistry staining, respectively. The expression of TK1 in tumor tissues correlated to pathological stages and clinical grades of carcinomas (ca) of esophagus, lung and in premalignancy of breast ductal ca. STK1p could monitor the out-come of tumor therapy by being correlated to remission [breast ca, non-Hodgkin's lymphoma], relapse [breast ca] and to survival [non-Hodgkin's lymphoma] of patients. In a health screening study of 12,641 persons, STK1p seemed to predict the risk of development of neoplasia related diseases at early stage. PMID- 20544520 TI - Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs. AB - In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1), was identified. The PmTK1 gene was sub-cloned into Escherichia coli KY895 and it sensitized the host towards 2',2' difluoro-deoxycytidine (gemcitabine, dFdC), 3'-azido-thymidine (AZT) and 5-fluoro deoxyuridine (5F-dU). PmTK1 was over-expressed and purified with two different tags. Apparently, deoxyuridine (dU), and not thymidine (dT), is the preferred substrate. We suggest that PmTK1s could be employed as a species-specific activator of uracil-based nucleoside antibiotics. PMID- 20544521 TI - Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. AB - The central enzyme on the de novo pathway for synthesis of DNA precursors, the deoxyribonucleoside triphosphates, is ribonucleotide reductase (RNR). Deoxythymidine triphosphate (dTTP) has a key role in control of RNR activity shifting the specificity from pyrimidine to purine nucleotide reduction. Apart from the complex de novo synthesis of dTTP through UDP reduction, dTTP is provided through salvage of thymidine catalyzed by the thymidine kinases, the cytosolic and cell cycle regulated TK1 and the mitochondrial and constitutively expressed TK2. The complex enzymatic regulation of TK1 and TK2 and the possible physiological significance of this regulation will be discussed. PMID- 20544522 TI - Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion. AB - Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed. PMID- 20544523 TI - Identification and characterization of mitochondrial factors modulating thymidine kinase 2 activity. AB - Thymidine kinase 2 (TK2) is one of four deoxynucleoside kinases (dNKs) in humans and plays a crucial role in the initial phosphorylation of pyrimidine nucleosides in the salvage pathway in mitochondria. Nucleoside analogues, like AZT, are substrates of TK2 and induced mitochondrial toxicity in long-term therapy. We found that AZT and FLT inhibited dThd phosphorylation but stimulated dCyd phosphorylation catalyzed by TK2. However, mitochondrial phosphorylation of both dThd and dCyd was inhibited by AZT and FLT. Here a preliminary identification and characterization of mitochondrial factors is reported. PMID- 20544524 TI - The activity of the lipophilic nucleoside derivatives elacytarabine and CP-4126 in a panel of tumor cell lines resistant to nucleoside analogues. AB - The clinical activity of pyrimidine analogues (araC and gemcitabine) is impaired by different mechanisms of resistance and several efforts to overcome this problem have been undertaken. Elacytarabine (CP-4055, araC-5'elaidic acid ester) and CP-4126 (gemcitabine-5'elaidic acid ester) are lipophilic fatty acid derivatives of the nucleoside analogues araC and gemcitabine, respectively, that are currently investigated in clinical trials in solid tumors and hematological malignancies. Here, we present results on the activity of elacytarabine and CP 4126 in a panel of tumor cell lines that are resistant to araC and gemcitabine and we discuss the potential use of these agents in the treatment of patients with drug resistance phenotypes. We conclude that elacytarabine and CP-4126 are active in cells with deficient nucleoside membrane transport and altered mismatch repair. These results should be taking into consideration for future clinical development of elacyatrabine and CP-4126. PMID- 20544525 TI - Induction of resistance to the lipophilic cytarabine prodrug elacytarabine (CP 4055) in CEM leukemic cells. AB - The deoxynucleoside analogs cytarabine (Ara-C) and gemcitabine (dFdC) are widely used in the treatment of cancer. Due to their hydrophilic nature they need the equilibrative (hENT) and concentrative (hCNT) nucleoside transporters to enter the cell. To bypass drug resistance due to decreased uptake, lipophilic 5'elaidic acid esters were synthesized, elacytarabine (CP-4055, from ara-C) and CP-4126 (from gemcitabine), which are currently in clinical development for solid and hematological tumors. We investigated whether resistance can be induced in vitro, and treated the CEM leukemic cell line with weekly increasing elacytarabine concentrations, up to 0.28 microM (10 times IC(50)). The IC(50) of the resistant CEM/CP-4055 was 35 microM, about 1,000 times that of the wildtype CEM, and comparable to that of CEM/dCK- (deoxycytidine kinase deficient) (22 microM). CEM/CP-4055 was also cross-resistant to Ara-C, gemcitabine and CP-4126 (28 and 33 microM, respectively). A low level of mRNA dCK was observed, and similar to CEM/dCK-, CEM/CP-4055 did not accumulate Ara-CTP after exposure to Ara-C or elacytarabine, which is consistent with a deficiency in dCK. In conclusion, elacytarabine induced resistance similar to Ara-C. This resistance was caused by downregulation of dCK. PMID- 20544526 TI - Tissue specific distribution of pyrimidine deoxynucleoside salvage enzymes shed light on the mechanism of mitochondrial DNA depletion. AB - Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency. PMID- 20544527 TI - Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability. AB - Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We have recently shown that dCK is a phosphoprotein. Four in vivo phosphorylation sites were identified: Thr-3, Ser-11, Ser-15, and Ser-74. Site-directed mutagenesis demonstrated that phosphorylation of Ser-74, the major phosphorylated residue, strongly influences dCK activity in eucaryotic cells. Here, we show that phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify dCK activity, but phosphorylation of Thr-3 could promote dCK stability. PMID- 20544528 TI - Methylation specific PCR to characterize methylation of the promoter of deoxycytidine kinase. AB - Deoxycytidine kinase (dCK) is essential for phosphorylation of natural deoxynucleosides and analogs, such as gemcitabine and cytarabine, two widely used anticancer compounds. We hypothesized that DNA methylation of SP1 binding sites in the dCK promoter region might affect dCK expression. Using methylation specific PCR (MSP), methylation was detected in one of the SP1 binding sites of the dCK promoter, in most tested cancer cell lines and in patient samples from brain tumors and leukemia. This SP1 site is a 3'GC box, which upon hypomethylation negatively regulates dCK mRNA expression. In conclusion, we developed a new MSP method showing methylation of the 3' GC-box in the dCK promoter region in tumor cells and patient samples. Methylation might therefore regulate transcription of dCK, and should be studied further to understand its role in influencing gemcitabine and cytarabine activity. PMID- 20544529 TI - Effect of clofarabine on apoptosis and DNA synthesis in human epithelial colon cancer cells. AB - Clofarabine, a new-generation purine nucleoside analogue, was thought to work via three mechanisms: incorporation into DNA; induction of apoptosis; and inhibition of ribonucleotide reductase, and showed significant efficacy in pediatric relapsed/refractory acute lymphoblastic leukemia (ALL) and hematologic malignancies in adults. By way of its unique metabolic properties, clofarabine is being explored in lymphoproliferative disorders and solid tumors. In this study, the effect of clofarabine on the DNA synthesis of human colon carcinoma cells (HCT116) was investigated by LigandTracer White which provides a simple and accurate method for investigating the uptake, phosphorylation, retention and DNA incorporation of nucleosides in cells. Clofarabine enters into HCT116 cells in a clearly detectable manner. At 100 nM, the interaction is visible and at 10 microM a high signal is achieved and approaches equilibrium after 1 approximately 2 hours. The thymidine incorporation into the DNA synthesis was rapidly stopped by incubation with 10 microM clofarabine and a 3-fold increase in apoptosis induction in HCT116 cells by clofarabine was detected. PMID- 20544530 TI - Study of apoptosis induction and deoxycytidine kinase/cytidine deaminase modulation in the synergistic interaction of a novel ceramide analog and gemcitabine in pancreatic cancer cells. AB - This study investigated the interaction between the novel ceramide analog AL6 and gemcitabine in MIA PaCa-2 and PANC-1 pancreatic cancer cell lines, harboring different polymorphic variants of the gemcitabine catabolism enzyme cytidine deaminase (CDA). AL6 dose-dependently inhibited cell growth, induced apoptosis and synergistically enhanced the cytotoxic activity of gemcitabine. Moreover, it triggered apoptosis, which was significantly enhanced by the combination, and increased the ratio between gene expression of the activating enzyme deoxycytidine kinase (dCK) and CDA, potentially favoring gemcitabine activity. In conclusion, AL6 displays synergistic cytotoxic activity, enhances apoptosis, and favorably modulates enzymes involved in gemcitabine metabolism, supporting future investigation of this combination in pancreatic cancer. PMID- 20544531 TI - How to use the computing environment R to analyze ATP-induced ribonucleotide reductase R1 hexamerization data. AB - R is an object oriented free and open source statistical computing environment. The R package Combinatorially Complex Equilibrium Model Selection is being developed to meet the analysis challenges of ribonucleotide reductase (RNR). An example of its use is given here. This example involves ATP-induced R1 hexamerization dynamic light scattering data that suggests that R1 hexamers have two types of a-sites, one that binds ATP and another that does not (here, R1 is the large subunit of RNR). PMID- 20544532 TI - Ribosylurea accumulates in yeast urc4 mutants. AB - Yeast Saccharomyces (Lachancea) kluyveri urc4 mutants, unable to grow on uracil, biotransformed (14)C(2)-uracil into two labeled compounds, as detected by high performance liquid chromatography (HPLC). These two compounds could also be obtained following organic synthesis of ribosylurea. This finding demonstrates that in the URC pyrimidine degradation pathway, the opening of the uracil ring takes place when uracil is attached to the ribose moiety. Ribosylurea has not been reported in the cell metabolism before and the two observed compounds likely represent an equilibrium mixture of the pyranosyl and furanosyl forms. PMID- 20544533 TI - Synthesis, biological properties and anti-HIV-1 activity of new pyrimidine P1,P2 dinucleotides. AB - New homo- and hetero-P(1),P(2)-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2 thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5 propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P(1),P(2) dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5-45 nM, and therapeutic indexes were higher than 4666-14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5' triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug. PMID- 20544534 TI - Nucleoside phosphorylases from clostridium perfringens in the synthesis of 2',3' dideoxyinosine. AB - Four Clostridium perfringens phosphorylases were subcloned, overexpressed and analyzed for their substrate specificity. DeoD(1) and PunA could use a variety of purine substrates, including an antiviral drug 2',3'-dideoxyinosine (ddI). In one pot synthesis using Clostridium phosphorylases, 2',3'-dideoxyuridine and hypoxanthine were converted to ddI at yield of about 30%. PMID- 20544535 TI - Protection of mouse heart against hypoxic damage by AMP deaminase inhibition. AB - Clinical observation in patients with heart disease indicates that reduced activity of AMP deaminase could be protective in heart failure and ischemic heart disease. This study evaluated the effect of 3-[2-(3-carboxy-4-bromo-5,6,7,8 tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo [4,5-d][1,3]diazepin-8-ol, an AMP deaminase inhibitor (AMPDI) in the mouse heart subjected to hypoxia. ApoE/LDLR knock-out mice were subjected to reduced oxygen tension in breathing air. AMPDI was infused before hypoxia in the treated group. We observed amelioration of elcetrocardiographic changes during hypoxia in the treated group that are consistent with a protective effect. PMID- 20544536 TI - Cardiac muscle AMP-deaminase from a 10-year-old male heterozygous for the AMPD1 C34T mutation. AB - A C34T mutation in the AMPD1 gene is proposed to cause local or systemic augmentations in blood adenosine level and improvement of prognoses in heart diseases like congestive heart failure or heart ischemic disease. This study examines some physico-chemical properties of AMP-deaminase isolated from cardiac muscle of a 10-year-old boy heterozygote for this mutation. PMID- 20544537 TI - Biological efficiency of AMP deaminase inhibitor: 3-[2-(3-carboxy-4-bromo-5,6,7,8 tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo[4,5]-[1,3]diazepin-8-OL. AB - AMP deaminase could be a potential target for treatment of heart disease but experimental evaluation of this concept is difficult due to limited availability of inhibitors with proven efficiency in biological systems. This study evaluated the effect of 3-[2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl]-3,6,7,8 tetrahydroimidazo [4,5-d][1,3]diazepin-8-ol, an AMP deaminase inhibitor (AMPDI) on the pathways of nucleotide metabolism in perfused rat heart. We show that AMPDI at 0.3 mM concentration effectively inhibits AMP deaminase in this experimental model. PMID- 20544538 TI - Determination of adenosine deaminase activity in dried blood spots by a nonradiochemical assay using reversed-phase high-performance liquid chromatography. AB - Adenosine deaminase (ADA) deficiency is a rare metabolic disease causing severe combined immunodeficiency (SCID). An assay to determine ADA activity in dried blood spots was developed using reversed-phase HPLC. The assay was linear with reaction times up to at least 4 hours, and protein concentrations up to at least 2.2 mg/ml. The intra-assay CV and the inter-assay CV for the complete assay was 3.5 and 8.4%, respectively. The ADA activity in a control blood spot, stored at 4 degrees C, remained stable for at least one year. Only a slightly decreased ADA activity (35 +/- 13 nmol/mg/h, n = 4) was observed in heterozygotes for a c.704G > A mutation in the ADA gene when compared to that observed in controls (41 +/- 13 nmol/mg/h, n = 108). In addition, increased ADA activity as found in a rare form of congenital anemia can be assessed, as observed in a bloodspot from a patient diagnosed with Diamond Blackfan anemia (ADA activity 150 nmol/mg/h). PMID- 20544539 TI - Identification of purine nucleoside phosphorylase deficiency in dried blood spots by a non-radiochemical assay using reversed-phase high-performance liquid chromatography. AB - Purine nucleoside phosphorylase (PNP) deficiency results in severe T cell dysfunction and hypouricemia. An assay to measure PNP activity in dried blood spots was developed using reversed-phase HPLC. The assay was linear with reaction times between 5 and 12.5 minutes, and protein concentrations ranging from 0.4 to 1.8 mg/ml. The intra-assay CV and the inter-assay CV for the complete assay was <3.6%. The PNP activity in a control blood spot, stored at 4 degrees C, remained stable for at least one year. In a patient suffering from a PNP deficiency, the residual PNP activity was only 0.3% compared to that observed in controls (1431 +/- 238 nmol/mg/h, n = 114). The PNP activity (483 +/- 35 nmol/mg/h, n = 3) in heterozygotes for the c.614A > C mutation (p.E205A) in the PNP gene was 34% compared to controls. Thus, the analysis of the PNP activity in blood spots can readily detect patients with a PNP deficiency. PMID- 20544540 TI - PARP activity and NAD concentration in PMC from patients affected by systemic sclerosis and lupus erythematosus. AB - The enzyme poly(ADP-ribose) polymerase (PARP-1, EC 2.4.2.30) is activated by DNA strand breaks caused by several agents and utilizes NAD to form polyADPR, bound to acceptor proteins. The involvement of PARP-1 in autoimmune diseases has been suggested: antiPARP autoantibodies are described in systemic lupus erythematosus (SLE), DNA strand breaks have been evidenced in systemic sclerosis (SSc). We tested poly(ADP-ribosyl)ation activity and NAD concentration in PMC from patients affected by SLE or SSc and from controls. Lower PARP-1 activity and higher NAD concentration were observed in pathological conditions than controls, supporting the role of PARP-1 activation in modulating NAD concentration. PMID- 20544541 TI - Region-specific distribution of dihydroorotate dehydrogenase in the rat central nervous system points to pyrimidine de novo synthesis in neurons. AB - An increasing body of evidence has suggested a role of pyrimidine nucleotides not only in metabolic pathways in the developing nervous system but also in adult brain functions. There is still little known about the cellular sources of pyrimidine synthesis and the distribution of enzymes involved in the biosynthetic pathway of pyrimidines in the central nervous system (CNS) of mammals. Therefore, we investigated the activity of dihydroorotate dehydrogenase (DHODH), the fourth enzyme in the pyrimidine de novo synthesis, by catalytic enzyme histochemistry in adult rat brain. Its distribution was confirmed by Western blot analysis of dissected brain regions and by immunohistochemical analysis of paraffin-embedded formalin fixed sections employing an affinity-purified highly specific antibody. Microscopic analysis of brain sections revealed the presence of enzymatically active DHODH in many CNS regions, albeit at different intensities. High levels of both DHODH activity and immunoreactivity were observed in the neocortex, hippocampus, spinal cord and choroid plexus; lower levels were seen in the cerebellum, and only marginal expression in brainstem. The prominent staining of neuronal cell bodies in these regions suggests a neuronal location of DHODH. Neuronally derived pyrimidine de novo synthesis in the rodent CNS, independent of exogeneous sources, would provide pyrimidines for dynamic processes of membrane assembly, rearrangement and neuronal plasticity, as well as supplying uridine nucleotides as neuronal signalling molecules. PMID- 20544542 TI - Increased migration by stimulation of thymidine phosphorylase in endothelial cells of different origin. AB - Thymidine phosphorylase (TP) catalyzes the phosphorylytic cleavage of thymidine to thymine and deoxyribose-1-phosphate. The latter may be involved in the angiogenic stimulation of TP. In the present study, we investigated whether thymidine and deoxyribose (dR) could stimulate angiogenesis in vitro of two types of endothelial cells (isolated from umbilical veins (HUVEC) and endothelial colony forming cells (ECFC)), and whether the stereoisomer L-deoxyribose (L-dR) and the thymidine phosphorylase inhibitor (TPI) could reduce this. Both cell types had a low TP activity. Thymidine increased the migration of both HUVECs and ECFCs, but dR only that of the ECFCs. The invasion was not changed by any of the agents tested. In conclusion, TP may play a role in the migration of HUVECs and ECFCs, but not the invasion. PMID- 20544543 TI - Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma. AB - Uridine phosphorylase (UPase) has been shown to be induced in various human and murine tumors and could potentially serve as a specific target for the modulation of tumor-selectivity of fluoropyrimidines. However, the signaling mechanisms underlying the regulation of UPase gene expression have not been determined. In this study, we investigated the effects of IFN-gamma on the regulation of TNF alpha-induced UPase activity and have uncovered the molecular mechanisms of this potentiation, utilizing murine EMT6 breast cancer cells. Our data has shown that IFN-gamma can significantly increase UPase mRNA expression and the enzymatic activity induced by TNF-alpha in a dose-dependent manner, resulting in an enhanced sensitivity to 5-fluorouracil (5-FU) and 5'-Deoxy-5-fluorouridine (5'DFUR). We have previously shown that TNF-alpha activates NF-kappaB through increased translocation of NF-kappaB p65 from the cytoplasm into the nuclei. Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter. Notably, the activation of NF-kappaB and STAT1 in human breast tissues is consistent with UPase activity; signifying their role in the up-regulation of the UPase gene expression in human tumors. PMID- 20544545 TI - Dihydropyrimidine dehydrogenase deficiency caused by a novel genomic deletion c.505_513del of DPYD. AB - Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine degradation pathway. In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells. Analysis of the gene encoding DPD (DPYD) showed that the patient was homozygous for a novel c.505_513del (p.169_171del) mutation in exon 6 of DPYD. PMID- 20544544 TI - Relationship between plasma uridine and insulin resistance in patients with non insulin-dependent diabetes mellitus. AB - OBJECTIVE: It has been demonstrated that uridine infusion induces insulin resistance in rats. Furthermore, it was recently reported that plasma uridine is correlated with homeostasis model assessment of insulin resistance (HOMA-R) in hypertensive patients. Therefore, we investigated whether plasma uridine was correlated with HOMA-R in patients with non-insulin-dependent diabetes mellitus (NIDDM). SUBJECTS AND METHODS: The subjects were 23 male patients with NIDDM (average age 63 years) and 18 healthy males (average age 60 years). Blood samples were drawn after an overnight fast, plasma uridine was then measured using high performance liquid chromatography. RESULTS: The average plasma uridine concentration in patients with NIDDM was higher than that in healthy subjects (P < 0.05). Furthermore, plasma uridine values were positively correlated with HOMA R (r = 0.48, P < 0.05), serum insulin (r = 0.46, P < 0.05), and serum C-peptide radioimmunoreactivity (CPR) (r = 0.44, P < 0.05) values, whereas they were not significantly correlated with fasting blood glucose or hemoglobin A1c values. CONCLUSION: We found a positive relationship between plasma uridine value and HOMA-R, serum insulin, and CPR, suggesting that plasma uridine is a marker of insulin resistance in patients with NIDDM. PMID- 20544546 TI - Development of LC-MS method for detection of mutant uromodulin protein. AB - Mutations in the uromodulin gene cause the autosomal disorders familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease type 2 (MCKD2). However, methods to detect the mutant form of the uromodulin protein have not been developed. In this study, we developed a liquid chromatography-mass spectrometry (LC-MS) method for detection of the mutated uromodulin peptide (C148W). Our method can distinguish the mutant peptide, GWHWE, from wildtype peptide, GWHC*E. Using MS/MS analysis with a selected reaction monitoring (SRM) mode, peptide-specific fragment ions (m/z 714 --> 381, 471, 567, and 679 for GWHWE and m/z 688 --> 381, 445, 541, and 653 for GWHC*E) were detected. PMID- 20544547 TI - Analysis of purine in purine-rich cauliflower. AB - Purine is a general term for purine nucleotides, nucleosides, bases, and nucleic acid. The amount of purine nucleotides, nucleosides, and bases in purine-rich cauliflower was determined with the use of LC-MS and HPLC, and the ratio of these molecules were compared with in raw and in heated condition. Total purine content of raw and heated cauliflower was 42.6 and 43.2 mg/100 g, respectively. Nucleotide content was increased from 0.02 to 50.8 micromol/100 g, and nucleoside content was decreased from 12.4 to 7.7 micromol/100 g, by heating. PMID- 20544548 TI - Quantitative structure-activity relationships for cycloguanil analogs as PfDHFR inhibitors using mathematical molecular descriptors. AB - Computed molecular descriptors were used to develop quantitative structure activity relationships (QSARs) for binding affinities (K(i)) for a set of 58 cycloguanil (2,4-diamino-1,6-dihydro-1,3,5-triazine) analogues for dihydrofolate reductase (DHFR) enzyme extracted from wild and A16V+S108T mutant type (a double mutation) malaria parasite Plasmodium falciparum (Pf). High-quality models were obtained in both cases. The results of statistical analyses show that ridge regression (RR) outperformed the two other modelling methods, principal component regression (PCR) and partial least squares (PLS). For both enzymes, recognition of the inhibitors was based on four broad categories of descriptors encoding information on: (1) the electronic character of the various atoms in the molecule, (2) the size and shape of the structure, (3) the degree of branching in the molecular skeleton, and (4) two to five atom molecular fragments with aliphatic carbon at one end and aliphatic or aromatic carbon or nitrogen at the other end. The subsets of influential descriptors underlying the QSARs for the wild versus the mutant DHFR are quite non-overlapping. This indicates that the two enzymes recognize the inhibitor molecules on the basis of mutually distinct structural attributes. Such differential QSARs can be useful in the design of novel drugs active against malaria parasites which are growing in resistant to existing chemotherapeutic agents. PMID- 20544549 TI - Quantitative structure-activity relationship studies of TIBO derivatives using support vector machines. AB - A quantitative structure-activity relationship (QSAR) study is suggested for the prediction of anti-HIV activity of tetrahydroimidazo[4,5,1 jk][1,4]benzodiazepinone (TIBO) derivatives. The model was produced by using the support vector machine (SVM) technique to develop quantitative relationships between the anti-HIV activity and ten molecular descriptors of 89 TIBO derivatives. The performance and predictive capability of the SVM method were investigated and compared with other techniques such as artificial neural networks and multiple linear regression. The results obtained indicate that the SVM model with the kernel radial basis function can be successfully used to predict the anti-HIV activity of TIBO derivatives with only ten molecular descriptors that can be calculated directly from only molecular structure. The contribution of each descriptor to the structure-activity relationships was evaluated. Hydrophobicity of the molecule was thus found to take the most relevant part in the molecular description. PMID- 20544550 TI - Antibacterial activity and QSAR of chalcones against biofilm-producing bacteria isolated from marine waters. AB - Biofouling in the marine environment is a major problem. In this study, three marine organisms, namely Bacillus flexus (LD1), Pseudomonas fluorescens (MD3) and Vibrio natriegens (MD6), were isolated from biofilms formed on polymer and metal surfaces immersed in ocean water. Phylogenetic analysis of these three organisms indicated that they were good model systems for studying marine biofouling. The in vitro antifouling activity of 47 synthesized chalcone derivatives was investigated by estimating the minimum inhibitory concentration against these organisms using a twofold dilution technique. Compounds C-5, C-16, C-24, C-33, C 34 and C-37 were found to be the most active. In the majority of the cases it was found that these active compounds had hydroxyl substitutions. A quantitative structure-activity relationship (QSAR) was developed after dividing the total data into training and test sets. The statistical measures r(2), [image omitted] (>0.6) q(2) (>0.5) and the F-ratio were found to be satisfactory. Spatial, structural and electronic descriptors were found to be predominantly affecting the antibiofouling activity of these compounds. Among the spatial descriptors, Jurs descriptors showed their contribution in all the three antibacterial QSARs. PMID- 20544551 TI - Prediction of acute toxicity to mice by the Arithmetic Mean Toxicity (AMT) modelling approach. AB - A modelling approach based on the structural and physicochemical similarity of chemicals to their nearest neighbours is proposed for toxicity estimation. This approach, called Arithmetic Mean Toxicity (AMT) modelling, is illustrated by means of an AMT model for predicting acute rodent toxicity. The AMT approach uses one or a few pairs of nearest structural neighbours. Each pair contains a chemical with a higher descriptor value and with a smaller descriptor value compared with the chemical of interest. Arithmetic mean toxicity values of those pairs are considered as toxicity of chemical of interest. The toxicity of the chemical of interest was not included in the development of the AMT model. The approach was applied to calculate the toxicity of chemicals to mice following intravenous injection. A toxicity data set containing 10,241 organic neutral compounds was formed from the SYMYX Toxicity database. The toxicity (log (1/LD(50)), mmol/kg), where LD(50) is the median lethal dose, of 10,227 chemicals was calculated with a standard deviation +/-0.52. A cascade AMT model was applied to estimate error values in calculations of toxicity of chemicals having different number structural neighbours and level of similarity. It was found that 7085 chemicals (about 69% of all chemicals in the data set) were calculated with a standard deviation in the interval (+/-0.33)-(+/-0.48), which is comparable to the experimental error of determination. For the remaining 3142 chemicals (about 31% of the data set), the standard deviation was +/-0.64. In the regulatory assessment of chemicals, the AMT approach could be used as a means of filling data gaps when experimental data are missing. PMID- 20544552 TI - Quantitative structure-activity relationship modelling of the carcinogenic risk of nitroso compounds using regression analysis and the TOPS-MODE approach. AB - Worldwide, legislative and governmental efforts are focusing on establishing simple screening tools for identifying those chemicals most likely to cause adverse effects without experimentally testing all chemicals of regulatory concern. This is because even the most basic biological testing of compounds of concern, apart from requiring a huge number of test animals, would be neither resource nor time effective. Thus, alternative approaches such as the one proposed here, quantitative structure-activity relationship (QSAR) modelling, are increasingly being used for identifying the potential health hazards and subsequent regulation of new industrial chemicals. This paper follows up on our earlier work that demonstrated the use of the TOPological Substructural MOlecular DEsign (TOPS-MODE) approach to QSAR modelling for predictions of the carcinogenic potency of nitroso compounds. The data set comprises 56 nitroso compounds which have been bio-assayed in female rats and administered by the oral water route. The QSAR model was able to account for about 81% of the variance in the experimental activity and exhibited good cross-validation statistics. A reasonable interpretation of the TOPS-MODE descriptors was achieved by means of bond contributions, which in turn afforded the recognition of structural alerts (SAs) regarding carcinogenicity. A comparison of the SAs obtained from different data sets showed that experimental factors, such as the sex and the oral administration route, exert a major influence on the carcinogenicity of nitroso compounds. The present and previous QSAR models combined together provide a reliable tool for estimating the carcinogenic potency of yet untested nitroso compounds and they should allow the identification of SAs, which can be used as the basis of prediction systems for the rodent carcinogenicity of these compounds. PMID- 20544553 TI - Prediction of skin sensitization potential using D-optimal design and GA-kNN classification methods. AB - Modelling of skin sensitization data of 255 diverse compounds and 450 calculated descriptors was performed to develop global predictive classification models that are applicable to whole chemical space. With this aim, we employed two automated procedures, (a) D-optimal design to select optimal members of the training and test sets and (b) k-Nearest Neighbour classification (kNN) method along with Genetic Algorithms (GA-kNN Classification) to select significant and independent descriptors in order to build the models. This methodology helped us to derive multiple models, M1-M5, that are stable and robust. The best among them, model M1 (CCR(train) = 84.3%, CCR(test) = 87.2% and CCR(ext) = 80.4%), is based on six neighbours and nine descriptors and further suggests that: (a) it is stable and robust and performs better than the reported models in literature, and (b) the combination of D-optimal design and GA-kNN classification approach is a very promising approach. Consensus prediction based on the models M1-M5 improved the CCR of training, test and external validation datasets by 3.8%, 4.45% and 3.85%, respectively, over M1. From the analysis of the physical meaning of the selected descriptors, it is inferred that the skin sensitization potential of small organic compounds can be accurately predicted using calculated descriptors that code for the following fundamental properties: (i) lipophilicity, (ii) atomic polarizability, (iii) shape, (iii) electrostatic interactions, and (iv) chemical reactivity. PMID- 20544554 TI - Internet resources for agent-based modelling. AB - The use of agent-based models (ABMs) is steadily increasing in all the disciplines including environmental chemistry and toxicology. This growth is mainly driven by their ability to address problems that conventional modelling techniques cannot, such as the change of scale or the emergence of unanticipated phenomena resulting from interactions between their constitutive goal-directed agents. After a brief introduction on the basic principles of agent-based modelling and the presentation of selected case studies, the main software resources available on the Internet are presented. An attempt is made to estimate the complexity of these tools versus their potentialities and flexibility. PMID- 20544555 TI - Exploring the binding features of polybrominated diphenyl ethers as estrogen receptor antagonists: docking studies. AB - The polybrominated diphenyl ethers (PBDEs) accumulating in nature are known to be endocrine-disrupting compounds. Of first concern are those interacting with and altering activity of the human estrogen receptor alpha (hERalpha). In this study a docking study was carried out to explore the binding modes of PBDE compounds as hERalpha antagonists. It was found that some of the PBDE compounds with antiestrogenic activity extended into the channel of the estrogen receptor (ER), which is usually occupied by the alkylamine side chain of the ER antagonists raloxifene (RAL) and 4-hydroxytamoxifen (OHT), while most PBDE compounds without antiestrogenic activity adopted binding modes similar to that of ER agonist 17beta-estradiol (E2), located in the binding cavity and which did not protrude into the channel. The present study suggests that pose comparison based on docking is useful for discriminating whether or not PBDE compounds have antiestrogenic activity. Knowing the binding modes of compounds in hERalpha can help to screen out antiestrogenic compounds and further develop descriptive and predictive models in ecotoxicology. PMID- 20544556 TI - A quantitative structure-activity relationship study on serotonin 5-HT6) receptor ligands: indolyl and piperidinyl sulphonamides. AB - The serotonin 5-HT(6) binding affinity of indolyl- and piperidinyl-sulphonamide derivatives has been analysed with topological and molecular features with DRAGON software. Analysis of the structural features in conjunction with the biological endpoints in combinatorial protocol in multiple linear regression (CP-MLR) led to the identification of 25 descriptors for modelling the activity. The study clearly suggested the role of an average Randic-type eigenvector-based index from adjacency matrix, VRA2, number of secondary aliphatic amines, nNHR, the sum of the topological distance between N and O, T(N...O), ring tertiary carbon atoms, nCrHR, and CH2RX type fragment, C-006, in a molecular structure to optimize the 5 HT(6) binding affinities of titled compounds. The PLS analysis confirmed the dominance of information content of CP-MLR identified descriptors for modelling the activity when compared with those of leftover ones. PMID- 20544557 TI - Neural responses to faces reflect social personality traits. AB - Faces are a developmentally primary and critically important source of social information, and they are processed differently from most other visual percepts. Studies of brain electrophysiology reveal a face-sensitive component, the N170, which is typically enhanced to faces relative to other stimuli. Research in social disabilities suggests that an atypical N170 response in this population may stem from decreased developmental exposure to faces secondary to reduced social interest. Here we examined the relationship between neural responses to faces and social personality characteristics in a normative sample. Participants were pre-screened to identify individuals scoring high on extraversion or introversion. Both groups were presented with upright and inverted face stimuli. An inversion effect, a marker of expertise for faces, was observed in people with high extraversion but not in those with high introversion. These findings suggest that, within typically developing populations, social attitudes are reflected in the neural correlates of face perception. PMID- 20544558 TI - Embedded indices of effort in the repeatable battery for the assessment of neuropsychological status (RBANS) in a geriatric sample. AB - The clinical utility of embedded indices of effort in the RBANS was examined in a geriatric sample. Patients were classified as providing suspect effort (n = 45) or probable good effort (n = 258) using the TOMM and clinical consensus. Following the methodology of Silverberg and colleagues (2007), selected individual subtests and a summary Effort Index were evaluated. Setting specificity at approximately 85% yielded cut-offs of <15 on List Recognition, <8 on Digit Span, and >3 on the Effort Index. The modest sensitivity (51.1-64.4%) suggests that the indices should be used in conjunction with additional effort measures. In addition, the RBANS Picture Naming subtest was examined and showed modest sensitivity to detect suboptimal effort, but did not show notable incremental validity for detecting suboptimal effort beyond the Effort Index. PMID- 20544559 TI - The impact of left temporal lobe seizure disorder on learning disorders: a case study. AB - This case study describes the relationship between left temporal lobe epilepsy (TLE) and learning disabilities in a 26-year-old male college student. The client developed seizures following an episode of mycoplasma encephalitis at the age of 7. The client underwent a left temporal lobectomy involving resection of the left mesial temporal lobe, amygdala, hippocampus, and part of the brain stem 6 years prior to the current evaluation, in an attempt to address the frequency of the seizures. The surgery was extensive, including neocortical resection extending posterior to the vein of Labbe along the inferior temporal gyrus. The lobectomy reportedly successfully eliminated the seizures and the need for anti-seizure medications, but no neurological or neuropsychological follow-up occurred until 2009 when he was referred by his academic program for an evaluation of learning disabilities. Results of the neuropsychological evaluation indicated significant expressive language functioning deficits, with generally better-preserved receptive language. However, compared to a pre-surgical neuropsychological evaluation there was evidence for subtle to mild improvement in several aspects of cognitive functioning, likely due to seizure elimination and discontinuation of the anti-seizure medication. Nonetheless, his deficits resulted in significant functional impact on his academic abilities, thus implications for academic intervention were discussed. PMID- 20544560 TI - Sense of agency over speech and proneness to auditory hallucinations: the reality monitoring paradigm. AB - This study investigated the effects of imagining speaking aloud, sensorimotor feedback, and auditory feedback on respondents' reports of having spoken aloud and examined the relationship between responses to "spoken aloud" in the reality monitoring task and the sense of agency over speech. After speaking aloud, lip synching, or imagining speaking, participants were asked whether each word had actually been spoken. The number of endorsements of "spoken aloud" was higher for words spoken aloud than for those lip-synched and higher for words lip-synched than for those imagined as having been spoken aloud. When participants were prevented by white noise from receiving auditory feedback, the discriminability of words spoken aloud decreased, and when auditory feedback was altered, reports of having spoken aloud decreased even though participants had actually done so. It was also found that those who have had auditory hallucination-like experiences were less able than were those without such experiences to discriminate the words spoken aloud, suggesting that endorsements of having "spoken aloud" in the reality-monitoring task reflected a sense of agency over speech. These results were explained in terms of the source-monitoring framework, and we proposed a revised forward model of speech in order to investigate auditory hallucinations. PMID- 20544561 TI - Evaluative conditioning and conscious knowledge of contingencies: a correlational investigation with large samples. AB - Evaluative conditioning (EC) is a change in the valence of a stimulus that results from pairing the stimulus with an affective stimulus. Two high-powered studies (total N = 1,161) investigated the nature of the relationship between EC and contingency awareness measured as contingency memory. Stronger EC occurred among people with more accurate and more confident memory of the pairings. Awareness was a necessary condition for EC, but EC was not necessary for awareness. Supporting a propositional account of EC, we found evidence for intentional reliance on the contingency for the evaluation of stimuli. We also found evidence that contingency memory was based both on the actual contingency and on preexisting attitudes. PMID- 20544562 TI - Disruption of short-term memory by distractor speech: does content matter? AB - Four experiments replicate the finding that auditory distractors that are lexically identical to the visual target items dramatically increase the irrelevant-speech effect on serial recall. This effect was previously attributed to interference of incompatible order cues. The present results suggest that a different interpretation of this effect is required. Experiment 2 replicates the order congruence effect observed by Hughes and Jones (2005), but shows that this effect is most likely due to an attenuation of interference that is caused by strategic attention shifts to the nominally irrelevant material. Experiments 3 and 4 show that the between-stream similarity effect generalizes to a condition in which the distractor items were drawn from the same category as the targets, but were not identical to them. By showing that nonacoustic distractor features can increase interference in serial recall of lists of supposedly "meaningless" items such as digits or consonants, the results are most consistent with models that postulate an integration of short-term and long-term memory such as the embedded-processes model and the feature model and are inconsistent with classical structural accounts of memory. PMID- 20544563 TI - Temporal preparation decreases perceptual latency: evidence from a clock paradigm. AB - A clock paradigm was employed to assess whether temporal preparation decreases the time to detect the onset of a stimulus-that is, perceptual latency. In four experiments participants watched a revolving clock hand while listening to soft or loud target tones under high or low temporal preparation. At the end of each trial, participants reported the clock hand position at the onset of the target tone. The deviation of the reported clock hand position from the actual position indexed perceptual latency. As expected, perceptual latency decreased with target tone intensity. Most importantly, however, greater temporal preparation decreased perceptual latency in all four experiments, especially for soft tones, which supports rather directly the idea that temporal preparation diminishes the duration of perceptual processing. PMID- 20544564 TI - A roadside survey of alcohol and drug use among drivers in British Columbia. AB - OBJECTIVE: The purpose was to determine the prevalence of alcohol and drug use among a random sample of nighttime drivers. METHODS: Drivers were randomly selected from the traffic stream in three cities in British Columbia and asked to provide a breath sample to determine alcohol content and a sample of oral fluid to be tested for the presence of psychoactive drugs. The survey was conducted between the hours of 9:00 p.m. and 03:00 a.m. on Wednesday through Saturday nights in June 2008. RESULTS: Of the 1533 vehicles selected, 89 percent of drivers provided a breath sample and 78 percent provided a sample of oral fluid. Key findings include: 10.4 percent of drivers tested positive for drug use. 8.1 percent of drivers had been drinking. 15.5 percent of drivers tested positive for alcohol, drugs, or both. Cannabis and cocaine were the drugs most frequently detected in drivers. Alcohol use among drivers was most common on weekends and during late-night hours; drug use was more evenly distributed across all survey nights and times. Alcohol use was most common among drivers aged 19 to 24 and 25 to 34; drug use was more evenly distributed across all age groups. Though driving after drinking has decreased substantially since previous surveys, the number of drivers with elevated alcohol levels (over 80 mg/dL) was higher than in the past. CONCLUSIONS: The finding that drug use is more common than alcohol use among drivers highlights the need for a unique and separate societal response to the use of drugs by drivers commensurate with the extent of safety risks posed to road users. The observed differences between driving after drug use and driving after drinking have implications for enforcement and prevention. PMID- 20544565 TI - Risky driving behavior and road traffic crashes among young Asian Australian drivers: findings from the DRIVE study. AB - OBJECTIVE: To examine differences in risky driving behavior and likelihood of traffic crash according to the country of birth of recently licensed young drivers. The groups examined include those born in Australia, those born in Asia, and those born in other countries. DESIGN AND SETTING: The DRIVE study is a prospective cohort study of drivers aged 17-24 years holding their first-year provisional driver license in New South Wales, Australia. Information obtained from 20,822 participants who completed a baseline questionnaire was linked to police-reported traffic crashes. MAIN OUTCOME MEASURES: Self-reported risky driving behaviors and police-reported traffic crashes in young drivers. RESULTS: Young drivers who were born in Asian countries were less likely to report engaging in risky driving behaviors than their Australian-born counterparts. The proportion of participants reporting a high level of risky driving was 31.5 percent (95% confidence intervale [CI], 30.8-32.1) among Australian-born drivers compared to 25.6 percent (95% CI, 23.1-28.2) among Asian-born drivers and 30.4 percent (95% CI, 28.4-32.5) among those born in other regions. Asian-born participants had half the risk of a crash as a driver than their Australian-born counterparts (relative risk [RR] 0.55; 95% CI, 0.41-0.75) after adjusting for a number of demographic factors and driving and risk-taking behaviors. The comparative risk was even lower among those aged 17 years (RR 0.29; 95% CI, 0.29 0.75). Risk estimates for people born in other regions did not differ to those for Australian-born respondents. CONCLUSIONS: The study highlights the lower level of risky driving and significantly reduced crash risk for Australian drivers born in Asian countries relative to those born locally. Further research is needed to examine factors underlying this reduced risk and the impact of the length of residence in the host country. PMID- 20544566 TI - Symmetric relationship between self and others in aggressive driving across gender and countries. AB - OBJECTIVE: It was hypothesized that the combination of self-reported aggressive behaviors committed by the driver himself/herself ("self" scale) and perceiving himself/herself as an object of other drivers' aggressive acts ("other" scale) increases road accident involvement risk across gender and countries. The aim of this study was, therefore, to investigate this symmetric relationship between aggressive driving of self and other and its relationship on accident involvement among British, Dutch, Finnish, and Turkish drivers. METHODS: Survey studies of 3673 drivers were carried out in four countries; that is in Finland, Great Britain, The Netherlands, and Turkey. Analyses were conducted separately for men and women. RESULTS: Overall, the interaction among aggressive warnings, hostile aggression, and revenge factors indicated that aggressive warnings might have a potential to release anger and escalate aggression both "within drivers" and "between drivers." Symmetric interpersonal aggression between aggressive warnings and hostile aggression and revenge factors of self and others created a serious risk for road accident involvement in every country except among British male and Finnish female drivers. CONCLUSIONS: The other driver's aggressive behavior is significantly associated with increased accidents, except for Turkish male drivers. It seems that another driver's aggressive behavior can be important in predicting crashes-even more important than aggressive behavior on the part of the driver him- or herself. PMID- 20544567 TI - Graduated licensing laws and fatal crashes of teenage drivers: a national study. AB - OBJECTIVES: The objective of the current study was to quantify the effects of the strength of US state graduated driver licensing laws and specific licensing components on the rate of teenage driver fatal crash involvements per 100,000 teenagers during 1996-2007. The strengths of state laws were rated good, fair, marginal, or poor based on a system developed previously by the Insurance Institute for Highway Safety. METHODS: Analysis was based on quarterly counts of drivers involved in fatal crashes. Associations of overall ratings and individual licensing components with teenage crash rates were evaluated using Poisson regression, with the corresponding fatal crash rate for drivers ages 30-59 controlling for state- or time-dependent influences on crash rates unrelated to graduated licensing laws. RESULTS: Compared with licensing laws rated poor, laws rated good were associated with 30 percent lower fatal crash rates among 15- to 17-year-olds. Laws rated fair yielded fatal crash rates 11 percent lower. The longer the permit age was delayed, or the longer the licensing age was delayed, the lower the estimated fatal crash rates among 15- to 17-year-olds. Stronger nighttime restrictions were associated with larger reductions, and reductions were larger for laws limiting teenage passengers to zero or one than laws allowing two or more teenage passengers or laws without passenger restrictions. After the effects of any related delay in licensure were accounted for, an increase in the minimum learner's permit holding period showed no association with fatal crash rates. An increase in required practice driving hours did not appear to have an independent association with fatal crash rates. CONCLUSIONS: Graduated licensing laws that include strong nighttime and passenger restrictions and laws that delay the learner's permit age and licensing age are associated with lower teenage fatal crash rates. States that adopt such laws can expect to achieve substantial reductions in crash deaths. PMID- 20544568 TI - A community initiative to increase use of seat belts in Northern British Columbia: impacts on casualty crashes. AB - OBJECTIVE: The study aimed to establish an association between seat belt ticketing by police, seat belt wearing rates, and decreases in casualty rates following the implementation of a community seat belt initiative in a northern region of British Columbia. METHODS: Annual and monthly violation ticket rates and the percentage of casualties unbelted in collisions were computed for the North Central region and a comparison region, the Southern Interior. The trends in annual seat belt ticket rates, seat belt use among injured victims, and injury data from 2001 through 2007 were examined by descriptive/univariate methods and with intervention time series analysis. Use of a casualty rate measure controlled for changes in collision frequency over time. The primary outcome measure was injury claim incidents involving injuries other than to soft tissue. Injury claims involving only soft tissue were examined as a control series, because it was reasoned this subset of casualties would be less impacted by seat belt use. RESULTS: Seat belt tickets per capita increased in the North Central (NC) region over the study period, exceeding levels in all other regions. The percentage of unbelted occupants in casualty crashes fell by about 3 percent per year in the NC region after the initiative was introduced compared to about 1 percent per year in the SI region. The time series models revealed a significant reduction in non soft tissue casualties per 100 collisions per month. No significant reduction in the soft tissue only injury criterion was detected. CONCLUSIONS: A strong community initiative backed by support at the provincial level can be successful in a largely rural and sparsely populated northern region despite the challenges faced in such regions. PMID- 20544569 TI - Many diabetic patients with recurrent severe hypoglycemias hold a valid driving license. A community-based study in insulin-treated patients with diabetes. AB - OBJECTIVE: We studied retrospectively the current driving license status in insulin-treated diabetic patients, who had severe hypoglycemia (SH) within an observation period of one year and who lived in two Finnish communities. METHODS: The episodes of SH were identified from local ambulance registers, the databases of local health care units and from patient questionnaires in 680 insulin-treated diabetic patients. The data on current driving licenses were obtained from local police authorities. RESULTS: Of type 1 and type 2 insulin-treated diabetic patients 31.0 and 12.3 percent, respectively, had at least one self-reported SH, whereas 53 (7.8%) of them reported even three or more episodes of SH. Of insulin treated patients with clustering of SH 68 percent still held a driving license, and 21percent of them held even a license for commercial vehicles up to 3.5 tons. CONCLUSIONS: Recurrent episodes of SH occur in a minority of insulin-treated diabetic patients. However, two thirds of them still held a valid driving license even for commercial vehicles, which violates the medical standards for diabetes and driving. PMID- 20544570 TI - Traffic rule violations of private bus drivers and bus crashes in Sri Lanka: a case-control study. AB - OBJECTIVE: To explore the association between self-reported traffic rule violations of private sector bus drivers and bus crashes in the Kandy district, Sri Lanka. METHODS: We carried out a case-control study from August to September 2006. Cases were all the private bus drivers registered in the Kandy district and involved in crashes reported to the police between November 2005 and April 2006 (n = 63). We included two control groups: the private bus drivers working on the same routes of the cases (n = 90; matched controls) and the drivers selected randomly from the other routes of the district (n = 111; unmatched controls). We used a self-administered questionnaire to collect data on the self-reported traffic rule violations and analyzed the association between the self-reported traffic rule violations and crashes using logistic regression. RESULTS: The following variables showed significant associations with private bus crashes: illegal overtaking (matched controls, adjusted odds ratio [AOR] = 14.78, unmatched controls, AOR = 1.04), taking passengers outside the bus bays (matched controls, AOR = 3.96, unmatched controls, AOR = 2.29), and overloading (matched controls, AOR = 10.26, unmatched controls, AOR = 1.93). However, we did not observe an association between high-speed driving and bus crashes matched controls, AOR = 1.22, unmatched controls, AOR = 0.81. CONCLUSIONS: Traffic rule violations, such as illegal overtaking, overloading, and taking passengers outside the bus bays, are significant risk factors for private bus crashes in Sri Lanka. PMID- 20544571 TI - Volvo and Infiniti drivers' experiences with select crash avoidance technologies. AB - OBJECTIVES: Vehicle-based crash avoidance systems can potentially reduce crashes, but success depends on driver acceptance and understanding. This study gauged driver use, experience, and acceptance among early adopters of select technologies. METHODS: Telephone interviews were conducted in early 2009 with 380 owners of Volvo vehicles equipped with forward collision warning with autobrake, lane departure warning, side-view assist, and/or active bi-xenon headlights and 485 owners of Infiniti vehicles with lane departure warning/prevention. RESULTS: Most owners kept systems turned on most of the time, especially forward collision warning with autobrake and side-view assist. The exception was lane departure prevention; many owners were unaware they had it, and the system must be activated each time the vehicle is started. Most owners reported being safer with the technologies and would want them again on their next vehicles. Perceived false or unnecessary warnings were fairly common, particularly with side-view assist. Some systems were annoying, especially lane departure warning. Many owners reported safer driving behaviors such as greater use of turn signals (lane departure warning), increased following distance (forward collision warning), and checking side mirrors more frequently (side-view assist), but some reported driving faster at night (active headlights). CONCLUSIONS: Despite some unnecessary or annoying warnings, most Volvo and Infiniti owners use crash avoidance systems most of the time. Among early adopters, the first requirement of effective warning systems (that owners use the technology) seems largely met. Systems requiring activation by drivers for each trip are used less often. Owner experience with the latest technologies from other automobile manufacturers should be studied, as well as for vehicles on which technologies are standard (versus optional) equipment. The effectiveness of technologies in preventing and mitigating crashes and injuries, and user acceptance of interfaces, should be examined as more vehicles with advanced technologies penetrate the fleet. PMID- 20544572 TI - Parental awareness and perception for correct use of child occupant restraints in Korea. AB - OBJECTIVE: To determine the rate of correct use of child occupant restraints (CORs) and to evaluate the parental awareness and perception associated with the use of CORs. METHODS: A cross-sectional survey using self-report questionnaires was performed at 10 different hospitals. A total of 1573 parents and 2209 of their children 6 years of age or younger were studied. RESULTS: The overall percentage of parents using CORs or adult seat belt was 57.7 percent. However, only 44.4 percent of those parents, which corresponds to 25.6 percent of all parents recruited, were correctly using the restraints for their children. The overall percentage of children using CORs or adult seat belt was 53 percent. However, the percentage of children correctly using the restraints was 14.3 percent for infants (<12 months of age), 42 percent for children one years old, 43.8 percent for children 2 years old, 28.7 percent for children 3 years old, 18.9 percent for children 4 years old, 13.9 percent for children 5 years old, and 10.5 percent for children 6 years old. The logistic regression analysis revealed that the mother's level of education, number of children in each household, child's age when parents started to use the CORs, and parental awareness about the fine for violation of car seat laws were the most influential variables associated with the correct use of CORs. The rates of correct use of CORs and parental preferences about CORs, respectively, differed by ages of their children. Most parents showed a negative perception of placing children in the front passenger seat. However, many parents were prematurely using adult seat belts for children without realizing the risk of injury. CONCLUSION: More aggressive educational campaigns and increased enforcement of the car seat laws are needed to improve the awareness of parents on the efficacy of CORs. PMID- 20544573 TI - A parametric study of hard tissue injury prediction using finite elements: consideration of geometric complexity, subfailure material properties, CT thresholding, and element characteristics. AB - OBJECTIVE: The objectives of this study were to examine the axial response of the clavicle under quasistatic compressions replicating the body boundary conditions and to quantify the sensitivity of finite element-predicted fracture in the clavicle to several parameters. METHODS: Clavicles were harvested from 14 donors (age range 14-56 years). Quasistatic axial compression tests were performed using a custom rig designed to replicate in situ boundary conditions. Prior to testing, high-resolution computed tomography (CT) scans were taken of each clavicle. From those images, finite element models were constructed. Factors varied parametrically included the density used to threshold cortical bone in the CT scans, the presence of trabecular bone, the mesh density, Young's modulus, the maximum stress, and the element type (shell vs. solid, triangular vs. quadrilateral surface elements). RESULTS: The experiments revealed significant variability in the peak force (2.41 +/- 0.72 kN) and displacement to peak force (4.9 +/- 1.1 mm), with age (p < .05) and with some geometrical traits of the specimens. In the finite element models, the failure force and location were moderately dependent upon the Young's modulus. The fracture force was highly sensitive to the yield stress (80-110 MPa). CONCLUSION: Neither fracture location nor force was strongly dependent on mesh density as long as the element size was less than 5 x 5 mm(2). Both the fracture location and force were strongly dependent upon the threshold density used to define the thickness of the cortical shell. PMID- 20544574 TI - Severe-to-fatal injury risks in crashes with two front-seat occupants by seat belt use. AB - PURPOSE: This study investigates the risk of severe-to-fatal injury (Maximum Abbreviated Injury Score, MAIS 4+F) in crashes with two front-seat occupants. It determines the relative risk of injury in the same crash by belt use and seating position. METHODS: 1993-2008 NASS-CDS was analyzed for crashes with occupants in both front-outboard seats. The effect of belt use was investigated for the driver and passenger. Light vehicles were included with model year 1990+. Injury severity was subdivided into MAIS 0-2 and 4+F in NASS-CDS to compare no-to moderate injury with severe-to-fatal injury. Standard errors were calculated in SAS and the z-test was used to determine the significance of differences in risk. Relative risks were determined by seat belt use and seating position; odds ratios were determined for one or both occupants being severely injured. RESULTS: In 76.7 percent of the MAIS 4+F crashes, either the driver (32.4%) or passenger (44.3%) was severely injured, rather than both occupants (23.3%). When both were belted, one occupant was severely injured in 86.5 percent of crashes. When both were unbelted, both occupants were severely injured in 68.9 percent of the crashes. Both occupants were belted in 74.7 percent of the cases and unbelted in 18.6 percent. In 6.7 percent of crashes, either the driver (4.4%) or passenger (2.3%) was unbelted when the other was belted. The highest risk occurred with an unbelted driver and belted passenger (4.98 +/- 0.73% vs. 1.97 +/- 0.38%, z = 3.65, p < .05). When both occupants were belted, the driver and passenger injury risk was similar (0.459 +/- 0.098% vs. 0.449 +/- 0.047%, z = 0.10, ns). CONCLUSIONS: In crashes with two front occupants, typically one occupant was severely injured, not both. Overall, the odds ratio was 3.28 for one compared to two occupants being severely injured; and, risks vary by seat belt use and seating position. The highest relative risk for unbelted versus belted occupants was 9.22 when both occupants were severely injured in the same crash. PMID- 20544575 TI - Incorporation of lower neck shear forces to predict facet joint injury risk in low-speed automotive rear impacts. AB - Lower neck shear force remains a viable candidate for a low-velocity automotive rear-impact injury criterion. Data were previously reported to demonstrate high correlations between the magnitude of lower neck shear force and lower cervical spine facet joint motions. The present study determined the ability of lower neck shear force to predict soft-tissue injury risk in simulated automotive rear impacts. Rear-impact tests were conducted at two velocities and with two seatback orientations using a Hybrid III anthropomorphic test device (ATD) and stock automobile seats from 2007 model year vehicles. Higher velocities and more vertical seatback orientations were associated with higher injury risk based on computational modeling simulations performed in this study. Six cervical spine injury criteria including NIC, Nij, Nkm, LNL, and lower neck shear force and bending moment, increased with impact velocity. NIC, Nij, and shear force were most sensitive to changes in impact velocity. Four metrics, including Nkm, LNL, and lower neck shear force and bending moment, increased for tests with more vertical seatback orientations. Shear force was most sensitive to changes in seatback orientation. Peak values for shear force, NIC, and Nij occurred approximately at the time of head restraint contact for all four test conditions. Therefore, of the six investigated metrics, lower neck shear force was the only metric to demonstrate consistency with regard to injury risk and timing of peak magnitudes. These results demonstrate the ability of lower neck shear force to predict injury risk during low velocity automotive rear impacts and warrant continued investigation into the sensitivity and applicability of this metric for other rear-impact conditions. PMID- 20544576 TI - A new biofidelic sagittal plane surrogate neck for head-first impacts. AB - OBJECTIVE: To evaluate a prototype sagittal plane surrogate neck model designed to provide a biofidelic response to head-first impacts with a straightened cervical posture. METHODS: Published biomechanical studies were used in the design to define the range of motion (ROM) and stiffness in both flexion extension rotation and axial compression. The neck was tested in a series of head first impacts on a drop tower to investigate the temporal aspects of the kinetic axial force response for the head and neck. A separate series of flexion extension tests was conducted in a spinal motion simulator to assess its ROM and bending stiffness. RESULTS: In impacts with a 104 N axial preload, the surrogate head and neck displayed a bimodal response to force development in agreement with published studies of cadaveric head-first impacts. In bending without an axial preload, the neck had an ROM and bending stiffness representative of cadaveric human spines and it included a large neutral zone, but with the incremental addition of axial preload these metrics were somewhat reduced. CONCLUSIONS: The model appears suitable for studying the scenario of sagittal plane, aligned column impacts. Further design refinements are required to provide biofidelity in both sagittal bending and head-first impacts using a single level of axial preload. This would be necessary to study impact scenarios where considerable sagittal plane neck rotation occurs at impact. The model has identified some key concepts that must be considered for continued design and improvement of a dedicated dummy neck for head-first impacts. PMID- 20544577 TI - The frontal-impact response of a booster-seated child-size PMHS. AB - OBJECTIVES: This article presents the response of a child-size postmortem human subject using a booster seat in a series of three frontal impact sled tests. METHODS: A 54-year-old female cadaver was seated in a booster seat in the rear seat of a buck representing a mid-sized American sedan. Two different restraint systems (conventional belt and pretensioning, force-limiting belt) were used to run three simulated frontal impacts (one at 29 km/h, two at 48 km/h). Instrumentation included accelerometers rigidly mounted on relevant body landmarks as well as chest bands. Trajectories were assessed through high-speed video cameras. RESULTS: Specific focus was on the whole-body kinematics and resulting head trajectories under two different restraint conditions (booster seat and standard belt, booster seat and force-limiting pretensioning belt) in a rear seat environment. At 48 km/h, the pretensioning, force-limiting seat belt reduced the forward excursion of both the head (353 mm vs. 424 mm) and the h point (120 mm vs. 152 mm) compared to the standard system. Maximum torso pitch was similar for both seat belts. CONCLUSIONS: A complete description of the outcome of the tests is presented in the article. These results suggest that the introduction of a pretensioning force limiting belt in the rear seat can be beneficial for small size occupants like children using booster seats. PMID- 20544578 TI - Imaging of brain metastases of bronchial carcinomas with 7 T MRI - initial results. AB - PURPOSE: To compare the depiction of brain metastases of bronchial carcinomas on susceptibility-weighted and contrast-enhanced images with 7 T and at 1.5 T MRI. MATERIALS AND METHODS: Twelve patients with brain metastases of bronchial carcinomas underwent 7 T and 1.5 T MRI. Minimum intensity projections (MinIP) of a 1.5 T SWI sequence (voxel size = 0.9 x 0.9 x 2.0 mm(3)) were compared to 7 T SWI MinIPs (voxel size = 0.4 x 0.4 x 1.5 mm(3)). A T 1-w 3D MPRAGE at 1.5 T (voxel size = 1 x 1 x 1 mm(3) after double-dose (DD) gadoterate meglumine, Gd DOTA) was compared to a 7 T MPRAGE sequence (voxel size = 0.7 x 0.7 x x 0.7 mm(3), single dose (SD) Gd-DOTA) in all patients, and to DD Gd-DOTA in 6 patients after a 10 minute delay. The number of intracranial microhemorrhages in SWI MinIPs and the number of contrast-enhancing metastases in MPRAGE images were compared in each patient grouped into three size ranges (< or = 2 mm, > 2 mm and < 6 mm, > or = 6 mm) by two radiologists in consensus. RESULTS: In all 12 patients the 7 T SWI with spatially higher resolution allowed the identification of 87 versus 67 cerebral microhemorrhages at 1.5 T. 7 T T 1-w images after SD Gd DOTA depicted 198 brain metastases versus 238 at 1.5 T after DD Gd-DOTA. After doubling the contrast dose in six patients, 4 additional brain metastases were identified at 7 T. CONCLUSION: Our preliminary results indicate that despite the higher spatial resolution the detection of brain metastases on 7 T MPRAGE images is almost equal to 1.5 T MPRAGE images. The 7 T SWI sequence with spatially higher resolution allowed the detection of 20 % more microhemorrhages in brain metastases compared to the 1.5 T SWI sequence. PMID- 20544579 TI - [Consensus Meeting of Course Directors in Breast Imaging, 9 May 2009, in Frankfurt am Main - Topic: Masses]. AB - Fourteen directors of breast imaging courses met on behalf of the German Society of Radiology to discuss the actual standards of the diagnosis of masses. Open questions on the fields of mammography, breast ultrasound and breast MRI were elucidated by a presentation of one of the 14 panel members, followed by an electronic anonymous voting. Beside of the panel members, more than 300 participants of the consensus meeting contributed their opinions by electronic voting. Answers with definite majorities (> 75 %), answers with narrow majorities and those with missing majorities were discriminated from each other. The opinions of the plenum were compared to the majorities of the podium and showed only a few critical differences. Due to unequivocal majorities seven answers to important questions concerning the diagnosis of masses can lead to a further standardization of breast cancer diagnosis. PMID- 20544580 TI - [Uterine artery embolization (UAE) for myoma treatment--results of the 3rd radiologic gynecologic expert meeting]. PMID- 20544581 TI - [Adult medulloblastoma]. PMID- 20544582 TI - Effect of functional overreaching on executive functions. AB - The aim of this study was to investigate whether cognitive performance was a valid marker of overreaching. 10 well-trained male endurance athletes increased their training load by 100% for 2 weeks. They performed a maximal graded test, a constant speed test, a reaction time task and a computerized version of the Stroop color word-test before and after this overload period. Regarding performance results, five participants were considered as overreached and the five remaining were considered as well-trained. We found no significant differences between groups in performing the Stroop test. Noteworthy, we found a small increase in response time in the more complex condition in overreached athletes (1 188+/-261 to 1 297+/-231 ms, effect size=0.44), while it decreased moderately in the well-trained athletes (1 066+/-175 to 963+/-171 ms, effect size=-0.59). Furthermore, we found an interaction between time and group on initiation time of the reaction time task, since it increased in overreached athletes after the overload period (246+/-24 to 264+/-26 ms, p<0.05), while it remained unchanged in well-trained participants. Participants made very few anticipation errors, whatever the group or the period (error rate <2%).We concluded that an unaccustomed increase in training volume which is accompanied by a decrement in physical performance induces a deterioration of some executive functions. PMID- 20544583 TI - Alternatives to rapid weight loss in US wrestling. AB - Amateur wrestling at the high school and collegiate level in the United States often involves exercise and thermal dehydration as well as food and fluid restriction to "make weight". Available evidence suggests this is the opposite of what is optimal for high-intensity exercise performance. A high-intensity taper will substantially improve performance when conducted after a period of high volume high intensity training. Additionally, dehydration of approximately 3-4% of body weight will most definitely impair muscular endurance during high intensity exercise although it likely will not impair maximal muscular strength or power. Even more gradual weight loss practices over a few days, which result in a reduction of body weight by approximately 3.3 to 6% will result in impaired performance as assessed by wrestling specific tests. It would seem of paramount importance for wrestlers to maintain a high-carbohydrate diet of approximately 8 10 g carbohydrate/kg body weight/day to maintain training intensity and optimize performance during individual matches and tournaments. Thus, the evidence would suggest that, prior to competition, collegiate wrestlers should be: 1) tapered, 2) in the euhydrated state, and 3) have ingested a high carbohydrate diet, rather than undergo rapid weight loss prior to competition. PMID- 20544584 TI - Does electrode placement influence quality of intraoperative monitoring in vestibular schwannoma surgery? AB - OBJECT: Continuous recording of electromyographic signals (EMG) is a standard method for intraoperative monitoring of facial nerve function in cerebello pontine angle surgery. Subcutaneous needle electrodes in the facial muscles are used in different setups. The goal of this study was to compare two commonly used electrode setups concering sensitivity for pathological EMG activity. PATIENTS AND METHODS: A group of 10 patients undergoing vestibular schwannoma surgery were examined. Continuous EMG from facial muscles was recorded using needle electrodes in setups according to Kartush or Moller, with narrow or wide interelectrode distances, respectively. Quantity of pathological A-train activity and signal-to noise ratios were compared between setups. RESULTS: A-train activity was seen in all patients. On average, 37% of A-train activity was seen in the Kartush setup alone, 4% in Moller setups alone and 59% in both setups synchronously (p<0.05; ratio of median train time--Kartush:Moller 3:2). The wide interelectrode distance of the Moller setup was found to be significantly more susceptible to artefacts, especially to low frequency and power line noise. Artefacts were the main reason for the Moller setup to fail detecting A-train activity. CONCLUSIONS: For continuous intraoperative monitoring of facial nerve function, narrow interelectrode distance should be used. PMID- 20544585 TI - Delayed diagnosis of subarachnoid hemorrhage associated with Tako-tsubo cardiomyopathy. PMID- 20544586 TI - [Retrospective analysis of tuberculosis caused by Mycobacterium bovis 2004 - 2008]. AB - BACKGROUND: mycobacterium bovis is a rare cause of tuberculosis in Germany. Epidemiological data are sparse. METHODS: we have carried out a retrospective analysis of all patients diagnosed with tuberculosis caused by M. BOVIS in a pneumological referral centre between 2004 and 2008. RESULTS: M. bovis was isolated in 8 out of 203 (3,9 %) patients with a new diagnosis of tuberculosis. The median age of these patients was 69 years, and 7 out of 8 showed risk factors for reactivation of a latent tuberculosis infection. In 4 patients (50 %) an extrapulmonary manifestation was present. All isolates of M. bovis were resistant to pyrazinamide, one isolate had an additional resistance to isoniazide. In 6 out of 8 patients prolonged tuberculostatic treatment of 8 - 12 months was recommended. CONCLUSIONS: the proportion of tuberculosis caused by M. bovis was higher than that reported for Germany (3.9 vs. 1,5 %). Predominantly elderly patients with risk factors for reactivation of a latent tuberculosis infection were affected. In accordance with the literature a high rate of extrapulmonary manifestations was detected. Because of the genetic resistance of M. bovis to pyrazinamide prolonged antimycobacterial treatment is recommended. PMID- 20544587 TI - [Management of an Outbreak with Cases of Nosocomial Pneumonia Caused by a Novel Multi-Drug-Resistant Acinetobacter baumannii Clone]. AB - We describe the detection and investigation of an outbreak involving a multi-drug resistant acinetobacter (A.) baumannii clone in the neurological intensive care unit (ICU) at the University hospital Rostock (Germany). The bacteria were isolated from 7 ICU patients within 20 weeks, six of them showing signs of pneumonia. Among 24 tested antibiotics, the isolates were only susceptible to colistin. An epidemiological investigation revealed the presence of multi-drug resistant A. BAUMANNII isolates in 13 of 37 samples from medical devices, patient associated objects and room equipment from the patients' environment. When investigating the source of this strain in our hospital, we found that it first appeared three years before. Since then it has caused sporadic infections in the medical and neurological ICUs prior to the presented outbreak. The identity of all isolated strains with the novel clone was demonstrated with pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). A multimodal intervention program was introduced by the hygiene staff on the affected ICU. It included consequent enforcement of standard hygiene precautions, repeated staff education and elaborated disinfection protocols specifically addressing the patients' environment. The procedures led to cessation of A. baumannii detection in environmental samples. Thereafter, the outbreak was cleared within 20 weeks. PMID- 20544588 TI - [Epidemiology of psoriasis in Germany--analysis of secondary health insurance data]. AB - BACKGROUND: In Germany, population-based data on the epidemiology of psoriasis are still rare. This study aims to assess the prevalence of psoriasis in the total population as well as for subgroups relevant to health care. As further epidemiological parameters the severity and regional distribution of psoriasis were analysed. METHODS: A secondary analysis of data collected routinely for the members of a nationwide statutory health insurance company was conducted. Prevalences were calculated for a closed cohort of continuously insured persons in 2005. Defined criteria for the existence of psoriasis were at least one diagnoses of psoriasis (ICD-10) relating to ambulatory or hospital treatment or disability. RESULTS: 33,981 of the 1,344,071 continuously insured persons in 2005 were diagnosed with psoriasis, thus the one-year-prevalence in this cohort was 2.53%. Up to the age of 80 years the prevalence rate was increasing with increasing age and highest for the age groups from 50 to 79 years (range: 3.99 4.18%). Insured persons up to 20 years had a prevalence of 0.73%. Regional differences showed up after stratification for broad categories (1 digit) of ZIP codes: Lowest prevalence rates were seen in the south (2.17%) and highest (2.78%) in the north and western regions of Germany. CONCLUSIONS: If the prevalence rate of 2.5% assessed in this study is applied to the total resident population, 2 million people are treated because of psoriasis in Germany. Routine data from health insurance companies are a relevant and suitable data source to assess the prevalence of chronic diseases (under medical treatment) in the population. PMID- 20544589 TI - [Funnel plots for comparing pressure ulcer and fall rates in 76 nursing homes]. AB - AIM OF THE STUDY: The aim of this study was to display the values of the quality indicators "falls in the institution" and "institutionally acquired pressure ulcers" of 76 German nursing homes in bar graphs and funnel plots and to discuss the advantages and disadvantages of both methods. METHODS: In 2009 a nationwide prevalence study has been conducted in 76 nursing homes (n= 5 521). Among others two trained data collectors assessed the fall and pressure ulcer risks, the presence of pressure ulcers and whether nursing home residents fell. Risk adjusted fall and pressure ulcer prevalence rates were calculated per institution and displayed in bar graphs and funnel plots. RESULTS: The proportions of residents with pressure ulcers grade 2, 3 or 4 varied between 0 and 11%. The average pressure ulcer prevalence was 2.5%. On average, 6% of residents at risk for falling fell during the last 2 weeks. The proportions of fallen residents varied between 0% and 100%. In bar graphs differences between institutions and rankings can be displayed. However, the precision of the point estimates is not taken into account. Furthermore, criteria for determining conspicuous institutions are arbitrary. In funnel plots values are plotted against their precision. Although there were differences between the investigated nursing homes, most of them could be explained by chance. CONCLUSION: Funnel plots should be used when comparing medical or nursing performance between health care institutions. They take the precision of estimates into account that is usually the size of the institution. Despite differences, there was no nursing home with a prevalence of institutionally acquired pressure ulcers that was significantly higher than those in all the other institutions. In 2 out of 75 nursing homes the proportions of fallers were higher than expected by chance. In terms of performance improvement the reasons for this should be further investigated. However, in spite of the advantages of funnel plots they do not provide guidance as to whether the measured results can be tolerated and are acceptable. PMID- 20544590 TI - [Health promotion effectiveness: testing the German statutory health insurance agencies evaluation system in health promotion, and preliminary findings from 212 health training courses]. AB - The purpose of this study was to develop a measurement system for the evaluation of health promotion training courses offered by German statutory health insurance companies. In a field test, N=1 671 participants from 212 youth and adult courses for the promotion of either physical activity, coping with stress or nutritional improvement were included. 80% were female. Participants were questioned in a pre post-design with a three month follow-up. The questionnaires covered health behaviour and health status. Participants' compliance and psychometric quality of the measurement instruments were good. On average, the health insurance companies assigned participants to different interventions adequately according to the participant's individual health problems. The health promotion courses triggered improvements of high effect sizes for health behaviour patterns, of moderate effect sizes for physical complaints, subjective health ratings, and health related quality of life. Effects decreased after the end of the intervention but remained significantly above the initial values. BMI values continued their improvement after the end of the training courses. Thus, health promotion training courses generated stable health improvements of practically relevant effect sizes. The interventions provided good support and health improvements for all subgroups of participants, regardless of age, gender and educational background. Thus, the health promotion curricula of the health insurance companies offer a ubiquitous and easily accessible but effective intervention for health promotion in Germany, although men are clearly underrepresented among the participants. The trainings may be recommended and used by other health-care suppliers. The evaluation toolkit provides practical and valid instruments for a routine evaluation of health promotion trainings. It should be applied within random sampling designs. PMID- 20544591 TI - [On prevalence of parenthood in schizophrenia patients]. AB - A clinical sample of n=370 patients suffering from schizophrenia/schizo-affective disorder (ICD-10 diagnosis F20/25) was investigated as to the prevalence of parenthood along with socio-demographic and clinical aspects. Data analysis yielded that 26.5% of the patients were parents, with women having three times more often children than men. Among those patients who had children, 41% were living together with them in the same household. The results point out that parental roles should be much more considered when treating mentally ill patients with children. This is a vital interest for the parents affected as well as for their children. Furthermore, a working cooperation between adult psychiatry and the youth help system needs to be established. PMID- 20544593 TI - [Speaking about psychopathy]. PMID- 20544592 TI - [Regional differences in the use of 'no substitution' in the elderly after introduction of rebate contracts]. AB - AIM: As of 1 April 2007, pharmacists in Germany filling prescriptions covered by the statutory health insurance system (Gesetzliche Krankenversicherung, GKV) are required, whenever possible, to dispense a preparation for which a rebate contract is in effect. The physician can block drug substitution by crossing out 'aut idem' ('or the like') on the prescription form, for which regional variations were found. We have studied the differences between physicians belonging to different regional Associations of Statutory Health Insurance Physicians (Kassenarztliche Vereinigungen, KVs) in the use of the no-substitution option in the elderly. METHODS: We used claims data of the Gmunder ErsatzKasse (GEK) and drew a random sample stratified according to the 17 KVs and 3 age groups (65-74; 75-84; 85+ years) of at least 75 continuously insured persons in October 2008 per stratum. After that, all prescriptions in which the physician could potentially have exercised a no-substitution option were selected and all relevant original prescriptions were examined. All estimates were weighted according to KVs, age groups and sex as of the structure of the GKV. RESULTS: The sample comprised of 3 672 persons and 5 745 prescriptions. The percentage of no substitution prescriptions was 20.1% (95% confidence interval [95% CI] 18.7-21.5) and we found no differences according to age and sex. Considerable differences were seen between the KVs that vary 6.8-fold between 6.2% (95% CI: 3.2-9.2) in Saarland and 42.2% (95% CI: 34.1-50.4) in Saxony. CONCLUSION: The use of the no substitution option does not depend on age and sex of the patient but rather depends on regional factors. These considerable regional differences show that, in several regions, the use of the no-substitution regulation influences the effect of rebate contracts. PMID- 20544594 TI - [Lithium levels need to be monitored: discrepancies between guidelines and practice]. AB - BACKGROUND: Since lithium can affect the thyroid gland and the kidneys, it is important to perform regular checks on levels of lithium, creatinine and thyroid stimulating hormone (TSH). AIM: To investigate whether psychiatrists and general practitioners (GPs) perform the required checks twice a year on the levels of lithium, creatinine and tsh in accordance with the Dutch guidelines on bipolar disorder as laid down in 2001. METHOD: The study was based on data that the clinical-chemical laboratory had regarding the lithium checks performed in 2004 in GPs' practices or by the mental health authority in Apeldoorn and the surrounding area. About 250,000 people live in this region. RESULTS: Some of the psychiatrists (11%) and GPs (about 25%) did not check lithium levels as frequently as recommended in the guidelines of 2001. The GPs checked significantly less frequently that the psychiatrists. Both the GPs and the psychiatrists monitored creatinine and TSH less frequently than recommended in the guidelines, creatinine was monitored in 65.8 and 61.2% and TSH in 68.3 and 58% respectively. CONCLUSION We recommend that a warning system be installed in the laboratory which will alert the doctor when a patient has missed a check. Another suggestion is that lithium should be prescribed only by psychiatrists, and not by GPs. PMID- 20544595 TI - [Personality disorders in older adults: a Delphi-study conducted among Dutch and Belgian experts concerning specific diagnostic and therapeutic aspects]. AB - BACKGROUND: In psychiatry for older adults (> 60 years) personality disorders play an important part in diagnosis and treatment and in the advice given to health professionals and carers on how to deal with this age group. So far, however, research in this area has been inadequate. AIM: To investigate age related diagnostic and therapeutic aspects of personality disorders occurring in adults over the age of 60. METHOD: A Delphi-study was conducted among 35 Dutch and Belgian experts in the field of personality disorders in older adults. This multidisciplinary panel consisted of psychiatrists, psychologists, psychotherapists, geriatricians and psychiatric nurses. In four rounds 21 gerontological statements to be assessed on a 5-point Likert scale were presented to the panel of experts. Agreement was said to be reached when at least two thirds of the experts agreed or fully agreed with a statement.RESULTS Satisfactory agreement was reached in the case of 20 of the 21 diagnostic and/or therapeutic statements about older adults with personality disorders. CONCLUSION There seem to be various age-specific aspects in the diagnosis and treatment of personality disorders in older adults. Therefore, it is advisable to pay more attention to this highly complex group of older adults when guidelines and protocols are being drawn up and scientific research is being planned or conducted. PMID- 20544596 TI - [The neurobiology of antisocial behaviour]. AB - BACKGROUND: Neuro-imaging is being used increasingly to provide explanations for antisocial behaviour. AIM: To make a neurobiological contribution to the diagnosis of many types of antisocial behaviour. METHOD: The literature was searched using PubMed and combinations of the keywords 'psychopathy', 'antisocial', 'neurobiology' and 'neuro-anatomy' for the period 1990-2009. RESULTS: Impairments in the prefrontal cortex, amygdala, hippocampus, superior temporal gyrus, corpus callosum and anterior cingulate cortex provide a possible explanation for a large number of the symptoms associated with antisocial behaviour. The concept of psychopathy is connected mainly with impairments in a prefrontal-temporal-limbic system. CONCLUSION Combinations of deficiencies in the associated brain areas and malfunctioning of the communication between the various brain structures seem to play a more important role than deficiencies in the separate brain structures. PMID- 20544598 TI - [Apathy]. PMID- 20544597 TI - [Apathy: from symptom to syndrome]. AB - BACKGROUND: Apathy is a major behavioural problem in dementia and other neuropsychiatric diseases. AIM: To provide an overview of the development of the concept of apathy and its importance for clinical practice. METHOD: The article is based on a review of the literature. RESULTS: There is evidence that apathy should be regarded as a syndrome rather than a symptom. Apathy is a construct that has several aspects and can occur across a range of diseases.It can occur as part of depressive disorders or cognitive deterioration or it can occur independently. Recently, diagnostic criteria for the diagnosis of the apathy syndrome have been formulated on the basis of an international consensus. CONCLUSION: The diagnostic criteria that have been formulated recently will make it much easier to validate measuring instruments and research into the epidemiology, aetiology, pathophysiology and treatment of apathy. PMID- 20544599 TI - [Life threatening symptoms of withdrawal of gamma-hydroxybutyrate]. AB - Acute psychosis and extreme agitation brought about by gamma-hydroxybutyrate GHB withdrawal can be life-threatening. In order to prevent states of excitement accompanied by aggression and somatic complications it is advisable to intervene by administering strong sedatives. It is argued that GHB should be tapered off as an alternative treatment for fixation and high doses of benzodiazepines. PMID- 20544600 TI - [Olanzapine in the treatment of adolescents with anorexia nervosa]. AB - This article, which was triggered by a case study of a 15-year-old female patient, gives an overview of the literature on the use of olanzapine as an adjunctive treatment for anorexia nervosa in adolescents. On the basis of studies performed so far (two small double-blind placebo-controlled studies, two open label trials, one retrospective study, a number of case studies that included adolescents, and four series of case studies on adolescents alone), the short term results of using olanzapine were promising. However, careful monitoring is needed. PMID- 20544601 TI - 2010 He Huliau--Department of Native Hawaiian Health. PMID- 20544602 TI - Closing the gap "Disparity in Native Hawaiian cardiac care". AB - PURPOSE: Queen's Heart, the cardiac service line at the Queen's Medical Center (QMC), Honolulu, Hawaii, recognizes the importance of closing the health disparity gap that affects the Native Hawaiian population. The purpose of this study was to examine the process and outcomes of health care among Native Hawaiians with heart disease, and to evaluate the impact of a multidisciplinary, culturally sensitive effort to improve quality of care. An inpatient program was created by assembling a team of practitioners who have an affinity for Native Hawaiian culture to address the health care of the Native Hawaiian people. METHODS: All Native Hawaiian patients who were admitted to The Queen's Medical Center from January 2007 to December 2008 became participants of the program. Baseline outcomes data for cardiac core measures, length of stay, 30 day readmission rates, and adverse events were reviewed by the team before the study was initiated. Educational materials were developed to provide culturally specific disease management information to patients and family members. The patient educators and discharge counselors provided patients with the education and tools they needed to engage in self care management. Heart failure disease management ensured that all Native Hawaiian patients receive appropriate quality care, individualized heart failure education, and a definitive plan for out patient follow up. The Integrative Care Program provided a holistic perspective of healing. RESULTS: All quality indicators for Native Hawaiian patients with cardiac disease have improved. Patient satisfaction rates have remained at the 99th percentile. There has been a marked improvement in adverse events following percutaneous coronary interventions (PCI) for Native Hawaiian patients. Readmissions that occurred in less than 30 days for patients admitted with myocardial infarctions and heart failure have improved and are now essentially the same as all other patient populations. CONCLUSIONS: Culturally sensitive and patient centered care, delivered by the team of specialists from Queen's Heart, has allowed patients to incorporate cultural preferences into their care and recovery. Readmission rates have decreased, mortality rates have improved, and patient and family satisfaction is enhanced. PMID- 20544603 TI - Effects of perceived racism and acculturation on hypertension in Native Hawaiians. AB - OBJECTIVE: To examine the effects of perceived racism and acculturation on the hypertension status of Native Hawaiians. DESIGN: Cross-sectional data from 94 Native Hawaiian adults were obtained which included the following: 1) socio demographic variables and self-reported hypertension status; 2) a 5-item Hawaiian cultural identity subscale (HCSS) and a 5-item American cultural identity subscale (ACSS); and 3) perceived racism based on a 6-item modified version of the 32-item Oppression Questionnaire (OQ). RESULTS: Based on logistic regression analysis, the ACSS scores and OQ scores had significant (p<.05) and independent effects on hypertension status, after considering the effects of age, sex, and education level, and HCSS scores. Of the variables examined, OQ scores had the greatest magnitude of effect on hypertension status. CONCLUSION: More perceived racism and a greater identification with the American mainstream culture were both, independently, related to self-reported hypertension in Native Hawaiians. These findings have important clinical and public health implications. PMID- 20544604 TI - Diet, psychosocial factors related to diet and exercise, and cardiometabolic conditions in Southern Californian Native Hawaiians. AB - OBJECTIVE: Native Hawaiians are at higher risk for cardiometabolic disease, including diabetes and cardiovascular disease compared with other ethnic groups. Diet, body mass index (BMI) and psychosocial, as well as cultural issues may influence risk for cardiometabolic disease. Our team conducted a community-based participatory research study and examined diet, height/weight, psychosocial factors, and community health concerns in Native Hawaiians living in Southern California. DESIGN AND METHODS: Cross-section of 55 participants, <18-years-old. Dietary data were collected via three 24-hr dietary recalls, anthropometrics were measured, and psychosocial factors and cardiometabolic conditions were self reported. Talk story related to diet and health was completed in a sub-sample. Means and frequencies were calculated on dietary intakes, cardiometabolic disease and BMI. Independent t-test and chi square analyses, as appropriate, were performed to assess differences in dietary intakes, obesity and psychosocial factors between those with and without a pre-existing cardiometabolic condition. RESULTS: Of those with pre-existing health conditions (n=28), 72% reported being diagnosed with a cardiometabolic condition. For those with pre-existing cardiometabolic conditions, the daily vegetable consumption was 2.57 servings (+/ 1.66) and the mean fruit consumption was 1.43 servings (+/-0.1.99). The mean fiber intake was 16.24 grams (+/-6.92), the mean percentage energy from fat was 34.82% (+/-6.40) and the mean % energy from carbohydrate was 47.15 (+/-6.77). The psychosocial data showed significantly (p<0.05) lower social support, social interaction, self-monitoring and cognitive-behavioral strategies related to exercise for those with cardiometabolic disease compared with those without disease. All the talk story discussion groups expressed concern over diabetes and weight management, both as an individual and community issue. CONCLUSIONS: The dietary data indicate that Native Hawaiians residing in Southern California should aim to increase their vegetable, fiber, and reduce % energy from fat and saturated fat. Additionally, the psychosocial data suggests that implementing physical activity programs based on socio-cultural values such as ohana, community gatherings, as well as individual self-monitoring and cognitive behavioral strategies may improve cardiometabolic outcomes. In efforts to reduce cardiometabolic disease disparity, these data suggest that Native Hawaiians in Southern California are aware and concerned about cardiometabolic disease in the community, and that implementation of an effective energetic (diet plus physical activity) intervention that is socially, and culturally specific for Native Hawaiians in Southern California is critical. PMID- 20544605 TI - Culturally-specific physical activity measures for Native Hawaiian and Pacific Islanders. AB - INTRODUCTION: Physical activity is an important contributor to the health disparities experienced by Native Hawaiian and Pacific Islander (NHPI) populations. A culturally-specific measurement instrument that minimizes interpretation bias is necessary to obtain accurate assessments of this lifestyle behavior. The purpose of this study was to 1) create two versions of the Pacific Islander Physical Activity Questionnaire (PIPAQ-short and PIPAQ-long) for United States NHPI, and 2) pilot test the PIPAQ instruments and two objective physical activity monitors to evaluate cultural-appropriateness and acceptability. METHODS: Forty NHPI adults (20M, 20F) aged 21-65 years attended focus group discussions addressing cultural perspectives related to physical activity. Feedback from participants, community leaders and physical activity experts guided cultural modifications to existing questionnaires to create PIPAQ-short and PIPAQ-long with accompanying showcards. Pilot testing of both PIPAQs and two objective physical activity monitors, the Actiheart and ActiTrainer, was carried out in another sample of 32 NHPI adults (17M, 15F) aged 18-63 years. Participants were instructed to wear one monitor for >=10 hours/day for 7 consecutive days. At the follow-up visit, participants completed PIPAQ-short and PIPAQ-long, and a written and verbal exit interview to provide feedback on both subjective and objective instruments. RESULTS: The majority of participants felt PIPAQ-long provided a more accurate reflection of activity levels, compared to PIPAQ-short. The Actiheart was the preferred monitor due to higher comfort and lower participant burden. Self-reported duration of physical activities was most difficult to recall, compared to activity type, frequency and intensity. CONCLUSION: Both PIPAQ instruments and the Actiheart monitor have demonstrated cultural acceptability and appropriateness for NHPI adults. Future studies will investigate the validity and reliability of both PIPAQ instruments in larger samples of NHPI adults. PMID- 20544606 TI - Perspectives on the crisis and challenge of cardiovascular disease in the diverse Asian populations of California. AB - Recent data demonstrate alarming increases in mortality from cardiovascular disease and increase in risk factors that are pushing this disease to epidemic proportions in Asians living in the Bay Area of Northern California. Although genetics may have an important role, environmental factors including diet, stress and lack of exercise are contributing to the incidence of hypertension, diabetes and obesity in this population. Research at the San Francisco Heart and Vascular Institute in Daly City, California shows that this trend is continuing, and combined with a delay in seeking treatment in this diverse ethnic group, leads to poorer outcomes in revascularization therapies used to treat these patients. More intensive community education that includes patients and his/her family and more aggressive preventive treatment programs are needed to slow the progress of this growing health problem. PMID- 20544607 TI - Diabetes care in a predominantly Native Hawaiian and Pacific Islander outpatient population. AB - PURPOSE: Racial differences in diabetes care and outcomes, particularly among African Americans and Hispanics, have been well-recognized. The goal of this study was to evaluate the quality of diabetes care, using nationally recognized standards of care, in a multispecialty, hospital-based clinic that cares for a predominantly Native Hawaiian and Pacific Islander population. METHODS: We identified patients with a new primary or secondary diagnosis of diabetes during a visit (baseline visit) between January 2005 and June 2006 at the Queen Emma Clinics. Each patient's medical record was reviewed to obtain demographic and clinical information related to diabetes, including laboratory and test results and medications, from the baseline visit through 12 months follow-up. Performance indicators were selected from those recommended by the National Diabetes Quality Improvement Alliance and included selected 8 measures: 1) Hemoglobin A1c >=9.0%; 2) Annual lipid panel checked; 3) Systolic blood pressure <140 mmHg; 4) LDL cholesterol <130 mg/dL) 5) Annual fundoscopic examination; 6) Foot examination; 7) Aspirin use; 8) Annual evaluation for urine protein. RESULTS: We identified 364 patients, the majority Pacific Islanders (58%), with Asians (15%) and Native Hawaiians (17%) more frequent than Caucasians (10%). Compared with Caucasians, Native Hawaiians and Pacific Islanders were significantly more likely to have poor glucose control. There were no significant differences between groups for the other measures. Patients compared favorably when compared with national benchmarks. For 2 indicators, adherence was significantly higher for the total study population compared with the US average (systolic blood pressure <140 mmHg, aspirin therapy). For 2 indicators, there were no significant difference (LDL cholesterol <130 mg/dL, annual foot exam) and for 2 indicators, adherence was significantly lower for the study population (hemoglobin A1c >9%, annual fundoscopic examination). CONCLUSIONS: Native Hawaiians and Pacific Islanders with diabetes have poorer blood glucose control compared with Caucasians and Asians, but the overall care is otherwise generally similar. The diabetes care received by patients in this clinic that treats a generally underserved population compares favorably with national benchmarks. PMID- 20544608 TI - Diastolic dysfunction: search for therapeutic interventions. PMID- 20544609 TI - Diabetes mellitus and sudden cardiac death: what are the data? AB - Diabetes mellitus has long been linked to an increased risk of sudden cardiac death. However, the magnitude of this association, and the mechanism accounting for this phenomenon, have not been precisely defined. In this review, we evaluate the epidemiological data pertaining to the association between diabetes mellitus and sudden cardiac death and discuss various proposed mechanisms that may account for this relationship. Potential factors contributing to the increased risk of sudden cardiac death observed in patients with diabetes mellitus include silent myocardial ischemia, autonomic nervous system dysfunction, abnormal cardiac repolarization, hypoglycemia, a hypercoaguable state secondary to diabetes mellitus, diabetic cardiomyopathy, and impaired respiratory response to hypoxia and hypercapnea. We conclude that diabetes mellitus does appear to be associated with an increased risk of sudden cardiac death. Although this increased risk is relatively modest, given the large number of diabetic patients worldwide, the absolute number of sudden cardiac deaths attributable to diabetes mellitus remains significant. Little evidence exists to support any specific mechanism(s) accounting for this association. Further investigation into the pathophysiology of sudden cardiac death in diabetes mellitus may yield improved risk stratification tools as well as identify novel therapeutic targets. PMID- 20544610 TI - Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy. AB - This anesthetic drug may cause a rare condition named propofol infusion syndrome, characterized by unexplained lactic acidosis, lipemia, rhabdomyolysis, cardiovascular collapse and Brugada-like electrocardiographic pattern or Brugada electrocardiographic phenocopy changes following high-dose propofol infusion over prolonged periods of time. Several articles have contributed to our understanding of the cause of the syndrome, and the growing number of case reports has made it possible to identify several risk factors. Uncertainty remains as to whether a genetic susceptibility exists. The favorable recovery profile associated with propofol offers advantages over traditional anesthetics in clinical situations in which rapid recovery is important. Propofol is a safe anesthetic agent, but propofol infusion syndrome is a rare lethal complication. PMID- 20544611 TI - Influence of exercise training on left ventricular diastolic function and its relationship to exercise capacity in patients after myocardial infarction. AB - BACKGROUND: The study's aim was to examine the effect of exercise training on left ventricular diastolic function (LVDF) and whether LVDF could predict an improvement in exercise capacity (EC) in post-myocardial infarction patients. METHODS: Forty-eight males, aged 56.4 +/- 7.2 years, with preserved left ventricular systolic function (LVSF) and mild diastolic dysfunction (the ratio of transmitral early left ventricular filling velocity to early diastolic mitral annulus velocity E/E' > 8 as the average of the septal and lateral annulus velocities), were assigned to either a training group (TG, n = 32) or controls (n = 16). Before, and at the end of the study, all patients underwent a cardiopulmonary test and echocardiography with tissue Doppler imaging (TDI). RESULTS: After a 4.5-month training program, maximal oxygen consumption increased significantly in TG (26.66 +/- 3.88 vs. 28.79 +/- 5.00 mL/kg/min, p < 0.0001). TDI-derived E/E' did not change after the training program. After dividing TG according to septal E/E's > 10 and < 10 and lateral E/E'l > 8 and < 8, exercise capacity improved significantly only in patients with E/E's < 10 and E/E'l < 8. CONCLUSIONS: A 4.5-month training program in post-myocardial infarction patients with preserved LVSF and mild diastolic dysfunction led to improved exercise capacity only in TG. The diastolic function did not change significantly. The improvement in exercise capacity was significantly greater in patients with a better LVDF measured by TDI. PMID- 20544612 TI - Physical activity profile in heart failure patients from a Brazilian tertiary cardiology hospital. AB - BACKGROUND: Physical activity (PA) has proven benefits in the primary prevention of heart diseases such as heart failure (HF). Although it is well known, HF PA habits and physicians' advice have been poorly described. The aim of this study was to investigate if physicians were advising HF patients to exercise and to quantify patients' exercise profiles in a complex cardiology hospital. METHODS: All 131 HF patients (80 male, average age 53 +/- 10 years, NYHA class I-V, left ventricular ejection fraction 35 +/- 11%, 35 ischemic, 35 idiopatic, 32 hypertensive and 29 with Chagas disease) went to the hospital for a HF routine check-up. On this occasion, after seeing the physician , we asked the patients if the physician had advised them about PA. Then, we asked them to fill in the international physical activity questionnaire (IPQA) Short Form to classify their PA level. RESULTS: Our data showed a significant difference between patients who had received any kind of PA advice from physicians (36%) and those who had not (64%, p<0.0001). Using the IPAQ criteria, of the 36% of patients who had received advice, 12.4% were classified as low and 23.6% as moderate. Of the 64% of patients who did not receive advice, 26.8% were classified as low and 37.2% as moderate. Etiology (except Chagas), functional class, ejection fraction, sex and age did not influence the PA profile. CONCLUSIONS: Physicians at a tertiary cardiology hospital were not giving patients satisfactory advice as to PA. Our data supports the need to strengthen exercise encouragement by physicians and for complementary studies on this area. PMID- 20544613 TI - One center experience in pulmonary artery stenting without long vascular sheath. AB - BACKGROUND: Pulmonary artery stenting without a long vascular sheath has a special significance, particularly for children with low body weight. Using only a short sheath often permits the implantion of a stent of the correct size; moreover, it improves access to peripherally located stenoses. The aim of this paper is to present the results of a balloon expandable stent implantation into pulmonary arteries without using a long vascular sheath. METHODS: The subjects were divided into two groups. The first group (28 patients, mean age 3.2 years) comprised patients with a single-ventricle heart after bi-directional Glenn procedure (Fontan procedure). The second group (22 patients, mean age 8.3 years) consisted of patients with a two-ventricle heart. Patients were retrospectively analyzed with regard to stenosis size widening and change in trans-stenotic pressure gradient after stenting. RESULTS: In our data, no statistically significant differences between the two groups in terms of the number of complications and incorrect stent position following implantation were noted (3% and 4%). Good treatment results, with a decrease in trans-stenotic pressure gradient in the first group of 3.2 mm and in the second group of 13.4 mm of mercury, and a widening of the stenosis, were obtained in most cases in both groups (97% and 96%). The average change of the vessel's diameter was in the first group 4.2 mm and in the second 5.4 mm. CONCLUSIONS: The obtained results suggest that pulmonary artery stenting with a short vascular sheath has numerous advantages and can be successfully performed in children. In the case of single ventricle hearts after a Glenn procedure, it may indeed be the method of choice. PMID- 20544614 TI - Signs of myocardial ischemia on electrocardiogram correlate with elevated plasma cardiac troponin and right ventricular systolic dysfunction in acute pulmonary embolism. AB - BACKGROUND: Plasma cardiac troponins (cTn) are frequently elevated in acute pulmonary embolism (APE). ST-segment abnormalities on electrocardiography are also commonly observed in APE patients. However, it has not been defined which ventricle is a potential source of cTn release. We assessed the potential relationship between electrocardiographic signs of myocardial ischemia, systolic dysfunction of both ventricles at echocardiography and cTn levels in APE. METHODS: We evaluated 94 consecutive patients (42 male, 52 female, aged 63 +/- 19 years) with APE. On admission, blood samples were collected for cTnI or cTnT and standard 12-lead electrocardiogram was performed. The following signs of myocardial ischemia were analyzed: T-wave inversion [T (-)] and ST-depression or elevation (> or = 1 mV, at > or = 2 leads). The assessment of systolic function of both ventricles was performed by echocardiography. RESULTS: In 33 (35%) patients, cTn exceeded the upper reference limit of our laboratory. The history of coronary artery disease (27% vs. 31%) and previous myocardial infarction (12% vs. 10%) did not differ in patients with elevated cTn [cTn (+)] and non-elevated cTn [cTn (-)]. In cTn (+) group T (-) or ST-depression were observed more frequently than in cTn (-) [32 (97%) vs. 46 (75%), p < 0.01]. However, both groups presented similar frequency of ST-elevation [7 (21%) vs. 11 (18%), p = NS). Interestingly, cTn levels correlated with the number of leads with T (-) or ST-depression (R = 0.30, p < 0.01). Moreover, in cTn (+) group right ventricular systolic dysfunction was more frequent [15 (54%) vs. 4 (7%), p = 0.0001], while left ventricle contractility abnormalities occurred similarly in both groups [3 (11%) vs. 8 (15%), p = NS]. CONCLUSIONS: Signs of myocardial ischemia (ST-segment changes) on electrocardiography in APE correlate with an elevated cTn and with the impairment of right, but not left, ventricle systolic function at echocardiography. PMID- 20544615 TI - Ageing and ankle pulse pressure. AB - BACKGROUND: Pulse pressure (PP) is a marker of arterial stiffness. Ageing of the arterial system is accompanied by atherosclerosis of coronary arteries and atherosclerosis of popliteal artery. However, severe impairment of the brachial artery is rare. This study investigates whether there is any significant inter limb (brachial/ankle) PP difference. METHODS: Blood pressure was measured in a group of young and a group of old non-smoking men; all were free from medication and disease with a mean age of 22 +/- 1.3 and 59 +/- 2 years respectively. The blood pressure was taken while they were in a supine position on three separate occasions. Lower limb pressure was measured by placing the cuff on the calf muscle. For auscultation of Korotkoff sounds the stethoscope was placed on the posterior surface of the internal malleolus. The mean of the second and third readings were rounded off and used for analysis. RESULTS: Significant differences were found between brachial and ankle PP in both groups (p < 0.01). The ratio of brachial PP to ankle PP in the young men was greater than 1. In the old men it was less than 0.15. There was no significant difference between the brachial PP in the two groups, but on both sides the ankle PP was significantly greater in the old men (p < 0.01). CONCLUSIONS: With the ageing of the arterial system, raised PP is more prominent in the lower limb (e.g. ankle). Cuff measurement of blood pressure at this site may be a useful index of peripheral PP changes with ageing. PMID- 20544616 TI - Efficacy of ivabradine in four patients with inappropriate sinus tachycardia: a three month-long experience based on electrocardiographic, Holter monitoring, exercise tolerance and quality of life assessments. AB - BACKGROUND: Inappropriate sinus tachycardia (IST) is an uncommon disorder characterized by an exaggerated heart rate (HR). It is mostly treated with b blockers or verapamil leaving the sinus node modulation for refractory cases. Ivabradine, a pure HR lowering agent, has proven anti-anginal efficiency linked to the If current inhibition. We conducted a small prospective experience investigating its efficacy in IST. METHODS: Four women exhibiting sinus rhythm with a resting HR > or = 100 bpm and an average HR > or = 90 bpm (Holter monitoring) were followed for three months. Structural heart disease and other causes of tachycardia were discarded. Electrocardiographic, Holter monitoring, exercise tolerance and quality of life determinations were performed. Ivabradine was initiated at 5 mg (bid) and increased to 7.5 mg (bid) after one week. RESULTS: All patients (mean age 33.7 years) presented a typical history of effort intolerance, palpitations and tachycardia. Resting HR (bpm) was decreased: 106.5 +/- 3 to 88.5 +/- 2 (week 1), to 77.0 +/- 3 (week 2) and to 73.7 +/- 13 (month 3). Reductions (Holter monitoring) of the maximum, average and minimum HR (beats) were: 152.0 +/- 19 to 128.5 +/- 18; 96.0 +/- 1.4 to 73 +/- 3.2 and 63.2 +/- 6 to 48.2 +/- 3. Total exercise time was amplified (555 +/- 99 to 679 +/- 90 s) and quality of life improved. CONCLUSIONS: IST causes an elevated HR and its control is the treatment objective. If future data confirm our results, ivabradine could be used for this purpose. More information is necessary in order to define its role: initial option, second step (beta-blockers non-responders or intolerants) or combined (refractory cases). PMID- 20544617 TI - Arrhythmogenic right ventricular cardiomyopathy/dysplasia in Iraq. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a disorder that involves replacement of the right ventricular myocardium with fibro-fatty tissue. Ventricular tachycardia is a main presenting feature. There are no known reports of this disease from the Arab countries in the Middle East. This is the first report of 34 patients from Iraq. METHODS: Thirty four patients with ARVC/D diagnosed from January 2003 to May 2007 according to the International Task Force criteria were included in this study. RESULTS: All patients presented with ventricular tachycardia of left bundle branch block morphology. The following findings were seen on the 12-lead electrocardiography during sinus rhythm: T wave inversion V1-V3 or beyond in 80%, epsilon wave in 28%, and parietal block in 48%. Right ventricular enlargement by echocardiography was seen in 69%. Twenty two per cent had a family history of sudden cardiac death. All patients were treated with implanted cardioverter-defibrillators. CONCLUSIONS: ARVC/D is a disease seen in Iraq. It requires a high diagnostic suspicion with verification using the international task force criteria. PMID- 20544618 TI - Predictors of successful iatrogenic pseudoaneurysm compression dressing repair. AB - BACKGROUND: Complications to femoral artery puncture may result in formation of a pseudoaneurysm (PSA). We investigated whether PSA obliteration may be achieved by compression dressing repair (CDR) and sought to determine the predictors of successful CDR. METHODS: Sixty two patients (30 male, mean age 61.0 +/- 12.8) with femoral PSAs due to cardiac catheterization were included in the study. In all patients, duplex ultrasound followed by CDR was performed to evaluate PSA morphology and flow velocities in the PSA neck. RESULTS: Forty six (74.2%) patients did not respond to CDR. Predictors of successful CDR were forward [0.18 (0.07-0.47), p = 0.0004] and reverse [0.08 (0.02-0.33), p = 0.0006] flow velocities in the PSA neck. The forward velocity was identified as an independent predictor of CDR outcome (p = 0.02). CONCLUSIONS: Compression dressing repair may serve as an alternative method of femoral pseudoaneurysm management in patients with low forward and reverse velocities of the flow in pseudoaneurysm neck. The forward velocity is an independent predictor of compression dressing repair result. PMID- 20544619 TI - Multifactorial QT interval prolongation. AB - Acquired long QT interval has been widely reported to be a consequence of drug therapy and electrolyte disturbances. We describe two cases of multifactorial acquired QT interval prolongation and torsades de pointes. In the first case, the drugs venlafaxine, amiodarone and domperidone may have contributed to QT interval prolongation in a patient with hypokalemia and hypomagnesaemia. In the second case, QT interval prolongation occurred in a patient taking quetiapine and citalopram, and whose use of hydrocholorothiazide and history of chronic alcohol abuse likely contributed by rendering the patient hypokalemic. These cases highlight the potential risks associated with polypharmacy and demonstrate that though torsades de pointes is an uncommon arrhythmia, the combination of multiple factors known to prolong QT interval may precipitate this life-threatening arrhythmia. PMID- 20544620 TI - Myocardial infarction in a low risk patient with hereditary hemorrhagic telangiectasia. AB - We describe the case of a 57 year-old woman with NSTE ACS, a history of recurrent and prolonged epistaxis, and low prior cardiovascular risk. Additional findings revealed anemia and an aneurysm in her central nervous system. During her hospital stay, hereditary hemorrhagic telangiectasia (HHT) was diagnosed. After application of two antiplatelet drugs, the patient was scheduled for coronarography, followed by coronary artery bypass grafting. During her hospital stay, only a minor episode of epistaxis was observed. We conclude that anemization due to HTT may significantly accelerate the progress of ischemic heart disease, resulting in acute coronary syndrome. Moreover, coronarography preceded by routine application of two antiplatelet drugs seems not to increase the risk of hemorrhage in HHT patients complicated with myocardial infarction. PMID- 20544621 TI - Thromboembolic events of mitral valve endocarditis. PMID- 20544622 TI - Bidirectional tachycardia in a patient with pulmonary embolism. AB - We report a 55 year-old man with sudden cardiac arrest. Electrocardiography revealed runs of bidirectional ventricular tachycardia, and transthoracic echocardiography showed indirect findings of pulmonary embolism. PMID- 20544623 TI - Elongated pigtail complicating pericardiocentesis. PMID- 20544624 TI - High degree atrio-ventricular block: what is the mechanism? PMID- 20544625 TI - Integrated heart failure telemonitoring system for homecare. AB - The integrated telemonitoring system (ITS) for homecare has been designed to improve quality of care as measured by increased nursing productivity, improved patients' clinical and behavioral outcomes and reduction of cost. The system incorporates managerial, organizational, operational and clinical tasks optimized for delivery of quality care through telemonitoring. A secure, multi-modal computer network that integrates homecare nurses, patients and those who care into one seamless environment has been developed. The network brings together a new generation of small, hand-held, wireless terminals used by nurses and patients with a HIPPA-compliant electronic patient record system at the caregiver's site. Wireless terminals use Gobi multi-standard networking technology for connectivity to any available wireless network. The unique features of ITS include a) picture recognition technology capable of extracting numeric data from in-home physiological signal monitor displays that include blood pressure, weight, oxygen saturation, transmission of lung sounds, and capturing echocardiography and electrocardiography data from mobile units; b) in home caregiver-assisted interactive examinations of signs and symptoms that include visual impressions of ankle swelling, jugular vein distension measurement, and weight gain; c) video-conference capability, facilitating face to-face two-way communication of nursing personnel with the patients. The ITS network has been designed to improve patients' clinical and behavioral outcomes, increase nursing productivity, and reduce the cost of homecare. Patients' co operation and compliance has been achieved through use of easy-to-use videoconferencing terminals. PMID- 20544626 TI - Lead-dependent infective endocarditis: an old problem, a new name. AB - This paper presents a literature review on right heart endocarditis in patients with a permanent pacemaker (PM) or implantable cardioverter-defibrillator (ICD). We postulate putting a great deal more emphasis on separation of lead-dependent infective endocarditis from other types of infective endocarditis. We stress the need for screening patients with PM/ICD and pulmonary signs using transesophageal echocardiography. Antibiotic therapy and PM/ICD removal is the treatment of choice in such patients. PMID- 20544627 TI - Prof. Dr. Joao Tranchesi: chronology of a fruitful life, 8 February 1922 - 12 October 1978. PMID- 20544628 TI - Bidirectional ventricular tachycardia or not? That is the question. PMID- 20544629 TI - Does pheochromocytoma mimic or cause acute myocardial infarction? PMID- 20544630 TI - Prevalence and pattern of renal bone disease in end stage renal disease patients in Ile-Ife, Nigeria. AB - BACKGROUND: Information on renal bone disease (RBD) is sparse in Nigeria. The prevalence of RBD in a dialysis population worldwide ranges between 33% and 67% and it increases with progression of renal insufficiency. OBJECTIVE: To determine the prevalence and magnitude of RBD in patients with end stage renal disease (ESRD). METHODS: Thirty consecutive ESRD patients were recruited. They had thorough clinical evaluation and investigations which included serum calcium, phosphate, alkaline phosphatase, albumin and skeletal survey. The serum iPTH, osteocalcin, and 1,25 (OH2) D3 were assessed in 20 patients. RESULTS: The patients were aged 18-72 years with a mean of 38.93+/-15.7 years. There was a male:female ratio of 4:1. Uraemic symptoms were the major presenting complaints. None of the patients complained of bone pain or fracture. The mean values for serum creatinine, urea, creatinine clearance, calcium, phosphate, albumin, alkaline phosphatase, iPTH, osteocalcin and 1,25 (OH)2 Vit D3 were 1478.96 +/- 771.12 micromol/L, 22.33 +/- 7.42 mmol/L, 3.38 +/-2.22 mls/min, 1.8 +/- 0.5 mmol/L, 1.61 +/- 0.65 mmol/L, 30.2 +/- 6.1 g/L, 124.33 +/- 63.37 IU/L, 22.66 +/- 24.72, 45.14 +/- 43.8, 37.7 +/- 22.3 respectively. There were hypocalcaemia and hyper-phosphataemia in 80% and 60% of the patients respectively. Alkaline phosphatase was elevated in 44% of the patients while 11.8% had hyperparathyroidism. Level of 1,25 (OH)2 Vit D3 was low in 83.3% of the patients. There was a significant negative correlation between serum calcium and iPTH levels (r = -0.915, p=0.029). There was also significant negative correlation between alkaline phosphatase and 1,25 (OH)2 Vit D3 and serum albumin. Radiological evidence of RBD occurred in only 16.7% of the patients. CONCLUSION: Renal bone disease is common in our patients with ESRD associated most commonly with low bone turnover while occurrence of hyperparathyroid bone disease appears low. PMID- 20544631 TI - Predictors of newborn systolic blood pressure. AB - BACKGROUND: Tracking of blood pressure from childhood to adulthood is well known. It is therefore important to determine predictors of blood pressure as early as at birth. OBJECTIVE: To determine the association between maternal and neonatal factors on the blood pressure at birth of a group of Nigerian babies. METHODS: Consecutive full term neonates delivered in a tertiary centre in Nigeria were recruited for the study. Each newborn's systolic blood pressure (NSBP) was measured within the first four days of life. The mothers' weight, height, body mass index (BMI) and socioeconomic status (SES) were determined while the babies' weight and crown-heel length were measured as well. RESULTS: Four hundred and seventy-three mother/baby pairs were recruited for the study. The mean NSBP was 69.2 +/- 8.3 mmHG. The birth weight significantly correlated with NSBP,(r = 0.235, p = 0.0001). The NSBP rose an average of 3.61 mmHg per 0.5 kg increase in birth weight. The mean NSBP of babies of mothers with BMI <30 was significantly lower than in babies whose mothers had BMI>30, p=0.031. The mean NSBP of babies from low SES was significantly higher than middle or high SES groups p=0.022. CONCLUSION: The study shows that child birth weight is the most significant predictor of newborn systolic blood pressure. PMID- 20544632 TI - Audit of diabetic soft tissue infection and foot disease in Accra. AB - BACKGROUND: Soft tissue infection and foot disease are well known complications among diabetes mellitus patients. With an increasing prevalence of diabetes mellitus in Africa, management of these complications is expected to become a major problem. OBJECTIVE: To audit the surgical management of diabetic soft tissue infection and foot disease over a two-year period in Accra, Ghana. METHODS: A prospective study of all patients admitted to the General Surgical Unit of the 37 Military Hospital between May 2005 and April 2007 was conducted. Diabetic patients with soft tissue infections and foot disease were selected for study. Doppler studies using a monopolar 8 MHz Nicolet vascular probe was used in assessing the ankle to brachial pressure index (ABPI). Patients were managed based on admitting diagnosis and outcomes were noted. RESULTS: Eighty (8.3%) of 966 surgical patients had diabetes mellitus and soft tissue infection or foot disease. The peak age of presentation of diabetics with soft tissue infection or foot disease was 50-59 years. Diabetic foot disease (53.0%) was the commonest followed by cellulitis of the leg and other soft tissue infections. Overall amputation rate was 33.3% while mortality was 8.8%. CONCLUSION: Foot infections, cellulitis, abscesses and gangrene are the common surgical complications of diabetes mellitus patients in Ghana. Abscess of the hand is the commonest non foot soft tissue surgical complication and had good outcomes. Overall, females presented earlier and had better outcomes than males. PMID- 20544633 TI - Epidemic yellow fever in Borno State of Nigeria: characterisation of hospitalised patients. AB - BACKGROUND: In 1990, an outbreak of a febrile illness with high mortality was reported in border villages, later spreading to other areas of Borno State of Nigeria. OBJECTIVE: To present a report of the investigation of that outbreak, with emphasis on the characterisation of hospitalised patients. METHODS: Selected centres reporting cases of acute febrile illness during the months of August to December, 1990 were visited, to establish surveillance. Case investigation forms were used to obtain clinical and demographic data; and blood samples were obtained from patients for analyses. Only hospitalised patients with adequate clinical information from three centres were included in the analysis. RESULTS: The outbreak, which involved five of the six health zones in the state, and spread into adjoining Gongola state and the Cameroun Republic, was caused by the yellow fever virus. Fever, central nervous system (CNS) involvement, jaundice and haemorrhage were the most common clinical manifestations of 102 hospitalised patients. Eighty -three (81%) of hospitalised patients died and most within two days of admission. CNS manifestations were more common in dying patients than in survivors. CONCLUSION: The reasons for this rare outbreak of yellow fever in the dry Savannah belt of Borno State remain unclear. Improved surveillance and more effective prevention strategies are needed to avert the recurrence of such outbreaks. PMID- 20544634 TI - Retrospective analysis of intra-oral salivary gland tumours in Ibadan, Nigeria. AB - BACKGROUND: Salivary gland neoplasms constitute an important group of intraoral tumours, with their malignant histological types being the second most frequently diagnosed intraoral malignancy. The incidence as well as the anatomical distribution of this heterogeneous group of neoplasms varies from one racial group and geographical location to the other. However, studies from Africa on intraoral salivary gland neoplasms are relatively sparse in the medical literature. OBJECTIVE: To report the frequency and anatomical distribution of the various histological types of minor salivary gland neoplasms diagnosed at the University College Hospital, Ibadan and to provide data for comparison with other epidemiological findings in different geographic locations. METHODS: A retrospective study of intraoral salivary gland neoplasms diagnosed at the University Teaching Hospital, Ibadan between January I991- December 2007. Included in the study were charts of patients with minor salivary glands in the mouth. Information obtained about each patient included age, sex, tumour location and histological classification based on the 1991 WHO recommendations. RESULTS: Of a total of 309 neoplasms of salivary gland origin, 92 were from the intra-oral minor salivary glands constituting 4.5% of head and neck neoplasm. There was no significant gender predilection. Fifty-seven (62%) cases were malignant, while 35 (38%) were benign. The most frequently diagnosed tumour was adenoid cystic carcinoma 35(38%), followed by pleomorphic adenoma 30(32.6%). About 73% of the salivary gland neoplasms affected the palate, followed by the buccal mucosa (16.3%). Patients with malignant neoplasms were about 10 years older than those with benign tumours (p=0.012). CONCLUSION: A large proportion of intraoral salivary gland neoplasms are malignant, the most frequently affected site being the palate. PMID- 20544635 TI - An analysis of listening skills of healthcare students in Nigeria. AB - BACKGROUND: Listening is a primary communication skill essential for human learning and reported to be positively correlated with school achievement. It enables the healthcare professional to explore fully the ideas and concerns of the patient during a healthcare encounter. It is especially needed by healthcare students and professionals in light of the study showing that the typical physician will interrupt a patient after about 18-23 seconds. OBJECTIVE: The objective of this study was to measure the listening skills of the undergraduate health sciences students in a Nigerian setting and to attempt to explain different levels of individual listening skills. METHODS: Selected undergraduate students in medicine, dentistry, nursing and physiotherapy who volunteered to complete a self-administered questionnaire were studied. The questionnaire contained seventeen items, ranked on a 5-point Likert scale on the various habits people adopt when listening to others and the students' three most recent academic test scores. RESULTS: The mean (SD) score for the seventeen items was 2.72 (1.14) out of 5. Seven items had mean scores greater than 3.00, eight items had mean scores between 2.00 and 3.00, and two items had mean less than 2.00. The students had a minimum score of 27 and a maximum score of 67 compared with a possible 17 and 85. The mean (SD) score for the listening scale by the students was 46.87 (7.33). Eighty percent of the respondents had good listening skills. There were no statistically significant associations between the listening skills scores of the students and several possible explanatory variables - age, gender, course being studied and test scores. CONCLUSION: The findings indicate that neither males nor females are the better listeners. It showed impressively high levels of listening skills among the respondents. There was the absence of explanatory variables which were significant in explaining differences between individual listening skill scores. PMID- 20544636 TI - Acute sigmoid volvulus in a West African population. AB - BACKGROUND: Acute sigmoid volvulus is one of the commonest causes of benign large bowel obstruction. Its incidence varies considerably from one geographic area to another. OBJECTIVE: To review the management of acute sigmoid volvulus in a relatively high prevalence area. METHODS: All adult patients with acute sigmoid volvulus seen at the Royal Victoria Teaching Hospital (RVTH) Banjul, between September 2000 and January 2005 were studied. Information obtained for analysis from the records included age, sex, clinical features, test results, and outcomes. RESULTS: A total of 48 patients, 45 (93.8%) males and three (6.3%) females, with a male: female ratio of 14.3:1, age range of 19 to 78 years and mean age of 45.8 +17.6 years, underwent treatment for acute sigmoid volvulus. Twenty-one (43.8%) of the patients were aged 40 to 59 years. Two (4.2%) had rectal tube detortion followed by elective sigmoidectomy and primary anastomosis on the same admission, while 24 (50%) had emergency laparotomy at which bowel decompression, one-stage resection and primary anastomosis without on-table lavage was done. The rest of the patients, 22 (45.8%) had gangrenous sigmoid colons at laparotomy and consequently had Hartmann's procedure done. Fourteen patients (29.1%) developed wound infection and five (10.4%) had prolonged ileus that was managed conservatively. There was no anastomotic leak. The mean hospital stay was 11.1 days. There were five deaths giving a mortality rate of 10.4%. CONCLUSION: Acute sigmoid volvulus in the Gambia is almost exclusively a male disease. Sigmoid colectomy and primary anastomosis can be carried out safely in those with viable colon without on-table colonic lavage. PMID- 20544637 TI - Laparoscopic cholecystectomy at the Korle Bu Teaching Hospital, Accra, Ghana: an initial report. AB - BACKGROUND: Laparoscopic cholecystectomy (LC) the preferred treatment for gallstones was not available in Ghana until 2005. OBJECTIVE: To report experience from Ghana of laparoscopic cholecystectomy in the treatment of galestones. METHODS: In a prospective study of patients with gallstones, information was obtained on demography, duration of various stages of the operation, analgesia and complication of patients with gallstones. All patients had general anaesthesia using endotracheal intubation, muscle relaxant and intermittent positive pressure ventilation. A standard four-trocar technique and maximum pneumoperitoneum pressure of 14 mmHg were maintained during surgery. RESULTS: There were 50 women and two men aged 17-72 years (mean 44.2 years). All had symptomatic gallstones treated by interval LC. The main indications were biliary colic 23(44%) and previous cholecystitis 15(29%). There were scars from previous abdominal surgery in 22 (42%), mainly pfannenstiel. The Verres needle was used to obtain pneumoperitoneum in 40 (77%). Only one patient (1.9%) had the operation converted to open cholecystectomy. Most patients, 47/51 (92%), were discharged in 24 hours. The mean durations of various stages were: anaesthesia (110 minutes), pneumo-peritoneum (67.5 minutes) and reverse trendelenburg (47.8 minutes). The mean operating time reduced from 81 to 68 minutes in the last 20 patients. Complications were sore throat 11(21.6%), infection of the umbilical wound 3(5.9%), right shoulder tip pain (3; 5.9%) and bile leak 1(2%). There was no peri operative mortality. CONCLUSION: Elective laparoscopic cholecystectomy can be performed with good results in patients with symptomatic gallstones in Accra. PMID- 20544638 TI - Involutional lower eyelid entropion: combined Wheeler's and Wedge resection of tarsal plate. AB - BACKGROUND: Involutional entropion, a common eyelid condition, has different methods of surgical correction and attendant variable recurrence rates, depending to a large degree on the method used. OBJECTIVE: To describe and evaluate a modified technique of entropion repair where the Wheeler's method is combined with wedge resection of the tarsal plate. METHODS: This was a chart review study of 49 patients who had the modified technique carried out to correct their involutional entropion. The technique essentially involves dissecting and separating the lower lid pre-tarsal orbicularis muscle from the tarsal plate, resecting a down-base triangular wedge of the tarsus followed by shortening the orbicularis and anchoring it to the tarsal plate superiorly. RESULTS: Over the three and a half-year review period, 54 eyelids of 49 patients underwent the procedure to correct their lower eyelid entropion. Of these, 28(57%) were females and 21(43%) males with a mean age of 73.5 years. The mean follow up period was 30.3 months. One (1.9%) recurrence was recorded in all the cases during the follow-up period. Complications were minimal. CONCLUSION: The combined Wheeler and wedge resection of the tarsal plate produces very good post-operative results and can be used in primary involutional entropion or as the procedure of choice if an initial different surgical technique used fails. PMID- 20544639 TI - Pregnancy associated with recurrent acromegaly: a case report. AB - BACKGROUND: Acromegaly is an uncommon endocrine disorder. Pregnancy is an unusual event in acromegalic females because fertility is often reduced. With the advent of advanced surgical and medical management, more acromegalic women will achieve pregnancy. Reports of pregnancy in acromegaly and recurrent acromegaly postpartum are rare. OBJECTIVE: To present a rare occurrence of pregnancy in acromegaly after macroadenectomy and recurrent acromegaly postpartum. METHODS: Clinical and biochemical evaluation of a 39-year-old female Nigerian with features of acromegaly before and after macroadenectomy and postpartum was done. Investigations carried out included oral glucose tolerance test with serial growth hormone assays and insulin-like growth factor 1 as well as computed tomography scan and magnetic resonance imaging of the pituitary. RESULTS: There was a history of menorrhagia, swelling of the feet and increasing coarsening of the facial appearance. She had biochemical evidence of acromegaly and subsequently had a transsphenoidal macroadenectomy. There was postoperative clinical and biochemical remission. Magnetic resonance imaging done six months postsurgery showed no evidence of tumour regrowth. Clinical and biochemical evidence of acromegaly recurred after pregnancy. Magnetic resonance imaging confirmed tumour regrowth. CONCLUSION: Pregnancy in treated acromegaly, though a rare occurrence, is achievable but is capable of provoking recurrence of acromegaly. PMID- 20544640 TI - Cerebellar toxoplasmosis in HIV/AIDS: a case report. AB - BACKGROUND: Toxoplasma encephalitis is a common presentation of Toxoplasma gondii infection of the central nervous system in the late stage of human immunodeficiency viral (HIV) infection. The definitive diagnosis requires demonstration of toxoplasma in brain tissue. However, neuroradiologic demonstration (using Computed Tomography or Magnetic Resonance Imaging) of ring enhanced multiple or single focal intracranial lesions in the presence of immunosuppression and prompt response to presumptive therapy are diagnostic in the absence of histological facilities. The rarity of toxoplasma lesions in the cerebellum prompts a high index of clinical suspicion and early institution of presumptive therapy in poor resource sub-Saharan countries like Nigeria. OBJECTIVE: To illustrate the presentation of recurrent cerebellar toxoplasmosis in a patient with HIV/AIDS. METHODS: A 34-year-old previously diagnosed HIV/AIDS male patient with right-sided cerebellar signs on neurological evaluation and a ring-enhancing lesion in the right cerebellar hemisphere on CT brain scan. An initial response to antitoxoplasmic drugs was short-lived due to poor compliance resulting in recurrence of lesion. RESULTS: On initial evaluation a diagnosis of cerebellar space occupying lesion in a patient with HIV/AIDS was made. He responded to treatment with clindamycin, pyremethamine and pyridoxine. Following default in treatment for three months he represented with florid cerebellar features, but again responded rapidly to treatment. CONCLUSION: Cerebellar toxoplasmosis is an infrequent complication of HIV/AIDS. Early diagnosis with neuro-imaging techniques and prompt institution of appropriate therapy results in remarkable improvement. PMID- 20544641 TI - Surgical presentation of primary extranodal gastrointestinal non-Hodgkin's lymphoma. PMID- 20544642 TI - Suspected incidence of aspirin resistance. PMID- 20544643 TI - Migration and wear of the Duraloc "1200 series" cup associated with Enduron UHWMPE using the EBRA method and the Imagika software. AB - We report a retrospective study on 122 THA using Duraloc "1200 series" cups. All patients received a 28-mm head (107 Al2O3, 15 CoCr). The mean age of the patients at surgery was 56.3 years and the mean follow-up was 137 months.Mean migration at two years using the EBRA method was 0.18 mm cranially and 0.16 mm medially. Mean polyethylene wear was 0.03 mm/year using the Imagika software and 0.06 mm/year using EBRA. Only one patient presented with abnormal polyethylene wear of 1.7 mm at 90 months with Imagika and 2.4 mm with EBRA. The Duraloc cup seems to be a reliable implant in respect of bone fixation and resistance to wear. PMID- 20544644 TI - Total hip arthroplasty in inflammatory arthritis in patients under 35 years. A 7 to 19 year follow-up. AB - Total hip arthroplasty in patients with inflammatory arthritis is compromised by the young age of patients at presentation, intake of non-steroidal anti inflammatory drugs, steroid use and autoimmune diseases which negatively affect bone quality. This study evaluates the survival of total hip arthroplasties (THA) in 32 patients with inflammatory hip disease who were under the age of 35 at the index operation and on which 57 primary total hip arthroplasties were performed between 1989 and 2001. Polished straight tapered cemented stems were used in all 57 hips. There were 10 cemented and 47 uncemented cups. The average follow-up was 12.2 years (range 7-19). Forty-seven hips had more than 10 years follow-up. There were 3 revisions of cemented metal-backed cups for aseptic loosening at 11, 13 and 16 years post-operatively. No uncemented cups and no stems needed revision. Heterotopic ossifications occured in 3 hips with Brooker type-I ossification in 1 hip and Brooker type-II in 2 hips. Cemented polished tapered straight stems demonstrate excellent survival in young patients suffering from inflammatory arthritis. PMID- 20544645 TI - Epiphyseal reperfusion after subcapital realignement of an unstable SCFE. AB - We present a case of epiphyseal reperfusion in a 12-year-old boy following subcapital realignment of a unstable slipped capital femoral epiphysis. The case demonstrates that even if delayed, anatomical surgical realignment of the femoral head can be successful in preserving or reestablishing blood flow to the femoral epiphysis. PMID- 20544646 TI - Total hip arthroplasty using a short-stemmed femoral component in the presence of a proximal femoral fixation device - a case report. AB - A patient previously treated by cannulated screws fixation of a femoral neck fracture and plate and screw fixation of an ipsilateral shaft fracture presented for a total hip arthroplasty due to femoral head avascular necrosis. The cortical bone at the previous fracture site was weak and damage on the proximal femur was considered likely during removal of the plate. We were also concerned that a periprosthetic fracture might occur during or after the insertion of a conventional femoral stem. We used a short-stemmed femoral component for total hip arthroplasty in this patient, to avoid the risk of potential complications. PMID- 20544647 TI - Acetabular reconstruction using fresh frozen bone allograft. AB - The success of total hip arthroplasty has led to a move toward operating on a wider and younger population. All implants have a finite useful life, and bone loss is associated with all major causes of failure. The use bone allograft, either morselized or structural has the aim of reconstituting the bone stock. We retrospectively reviewed the clinical and radiological results of 72 acetabular reconstructions both primary and revision, done at our institute between May 1999 and October 2004 with a minimum follow-up of one year. The Harris Hip Score (HHS) was calculated and follow-up radiographs were evaluated for graft incorporation; evidence of loosening and migration. Preoperatively 28 acetabular defects were type III (AAOS), 18 were type II, 16 were type I and 10 were type IV. 60 reconstructions were done using cementless acetabular prostheses, and the remaining twelve had cemented implants. Patients were followed up for an average of 30.69 months (range 12 - 64 months). The mean preoperative HHS was 36.13 points which improved to a mean of 81.6 points (range 61 to 91) at final follow up. None of the patients required reoperation. Dislocation was the commonest complication (8 hips). Short and medium term results were encouraging with the use of this technique. PMID- 20544648 TI - Unilateral vs. bilateral total hip arthroplasty - the influence of medial femoral head offset and effects on strength and aerobic endurance capacity. AB - The purpose of the present study was to determine whether unilaterally operated total hip arthroplasty (THA) patients were superior to bilaterally operated THA patients with respect to aerobic endurance capacity, muscle strength and gait patterns 3-5 years after surgery, and to what extent medial femoral head offset (FO) influenced hip abductor strength. 10 unilaterally operated THA patients with normal FO (UNO), 10 bilaterally operated THA patients with normal FO (BNO) and 10 bilaterally operated THA patients with abnormal offset (BDO) participated in the study. Improved muscle strength in the healthy leg of the UNO did not result in differences compared to the BNO and the BDO in work efficiency, gait patterns or maximal oxygen consumption (VO2max ) A reduced FO in the BDO did not result in lower hip abduction strength compared to the BNO. However, a correlation between reduced FO and low abduction strength was found in the BDO (r=0.866, p=0.001). Future focus should be on the quality of rehabilitation. PMID- 20544649 TI - The orthogeriatric unit for acute patients: a new model of care that improves efficiency in the management of patients with hip fracture. AB - We performed a prospective, quasi-experimental, randomised, interventional study comparing two models of care for patients admitted with osteoporotic hip fractures between February and August 2007 in a tertiary university hospital. The usual model of care was treatment of patients admitted to the orthopaedics ward, with consultation by the geriatrician (CG model). The study model involved admission to an acute orthogeriatric unit (OGU model), with joint care provided by geriatricians and orthopaedic surgeons which included immediate geriatric assessment, coordinated daily clinical care, weekly combined ward rounds, and joint planning of the surgical schedule, initial mobilisation, discharge date and destination. No differences were found between CG patients (123) and OGU patients (101) in terms of previous characteristics, number of patients surgically treated, functional level obtained, or discharge destination. OGU patients had earlier geriatric assessment (median 1 day, P25-P75: 1-2) than CG patients (median 4 days, P25-P75: 3-8), earlier surgery (median 5 days from admission to OGU, P25-P75: 3-6, versus 6 days in the CG group, P25-P75: 5-9), and had a shorter acute hospital stay (33% reduction, median 12 days in OGU, P25-P75: 9-14, versus 18 days, P25-P75: 13-23 in the CG group) and total (acute and subacute) hospital stay (30% reduction, median 14 days in OGU, P25-P75: 10-31, versus 20 days, P25-P75: 14-30 in the CG group). All these comparisons were statistically significant (p<0.01). The organization of an OGU in a tertiary hospital allowed hip fracture patients to receive earlier geriatric assessment and surgical treatment. Acute hospital stay was reduced by 33%, and total hospital stay was reduced by 30% with no differences at discharge in clinical and functional outcomes. PMID- 20544651 TI - Bilateral simultaneous femoral neck fractures secondary to a post-infarct generalized tonic-clonic seizure. A case report. AB - Bilateral femoral neck fractures are generally associated with high-energy trauma or defects in bone metabolism. We present a patient who had not been subjected to high-energy trauma and in whom there was no bone metabolism disorder. PMID- 20544650 TI - A comparison of subsidence of Exeter standard and long stems. AB - The survivorship of the polished, double taper Exeter stem is related to subsidence within the cement mantle. Long Exeter stems have altered geometry which may influence subsidence characteristics. Using digitised x-rays and appropriate computer software we measured the subsidence of 35 standard and 40 long stem Exeter implants. Measurements were taken from initial postoperative radiographs and repeated at intervals up to 5 years. Long stem implants were used in cemented revisions without the use of impaction bone grafting. Subsidence rates of the standard length stems in our study were comparable to that in published literature. Long stems did not replicate this subsidence pattern and had subsided less at 6, 12 and 24 months. However, the 205mm long stem, which has a fully tapered design, did follow the subsidence characteristics of the standard stem. Subsidence of long stem Exeter implants does not mirror that of the standard length stem. Loss of the fully tapered geometry of the longer stem implants may account for this finding. We suggest that whenever possible, the 205mm long stem should be used if the biomechanical principles of the standard Exeter stem are to be utilised. PMID- 20544652 TI - Is Kalamchi and MacEwen Group I avascular necrosis of the femoral head harmless in developmental dysplasia of the hip? AB - The aim of this clinical study was to evaluate the influence of Kalamchi and MacEwen group I avascular necrosis of the femoral head (AVN) on the radiographic and clinical outcomes in developmental dysplasia of the hip (DDH). Preoperative and follow-up (at 2-3, 4-6, 7-9 and 10-15 years of age) Sharp's acetabular angles (AA) and the final Wiberg's center-edge angles (CEA) and proximal femoral center trochanter distances (CTD) of 13 hips with group I AVN (AVN group) were compared with measurements of 22 hips without AVN (control group). All hips were initially treated by the same soft tissue surgical procedure (posteromedial limited surgery) under the age of 18 months and were completely followed up to at least 10 years of age. Radiographic diagnosis of group I AVN was made between 6 and 12 months postoperatively. The period for complete radiographic recovery of group I ischemic changes was between 2 to 4.5 years. Preoperative mean AA values of both groups were similar. However, the mean AA was found to be worse in the AVN group than in the control group during follow-up. Control group hips had a better mean CEA and higher number of hips having normal CTD than the AVN group, at latest follow-up. In conclusion, when compared with uncomplicated hips, group I ischemic changes retard acetabular development and have quantitative unfavorable effects on lateral femoral head coverage and proximal femoral anatomy in DDH. In addition, the healing process in group I AVN patients is extended. PMID- 20544653 TI - Severe heterotopic ossification after total hip arthroplasty in Schnitzler syndrome. AB - Schnitzler syndrome is a rare disorder characterized by monoclonal IgM gammopathy, urticaria, recurrent fever, evidence of inflammation, bone pain, and arthralgia. We present the case of a patient affected by Schnitzler syndrome who developed Della Valle type C heterotopic ossification after total hip arthroplasty. A relationship between the underlying syndrome and the considerable heterotopic ossification observed is compatible with the patient's clinical history and incidental findings. We suggest prophylaxis against heterotopic ossification when performing hip arthroplasty on patients with Schnitzler syndrome. PMID- 20544654 TI - Osteochondral allograft in a femoral head chondroblastoma: a case report. AB - Osteoarthritis of the hip joint secondary to femoral head collapse may develop after curettage of lesions in the femoral head. We report the case of a patient with chondroblastoma of the femoral head who was treated with wide curettage of the lesion and implantation of an osteochondral allograft to prevent femoral head collapse. PMID- 20544655 TI - Impact of preoperative variables on the functional and radiological outcome of an uncemented femoral stem: a prospective two-year follow-up. AB - The demand for improved clinical outcomes in total hip arthroplasty (THA) has led to improvements in fixation, bone ingrowth and designs providing an increased range of motion.The purpose of this prospective clinical study was to evaluate the outcome of a new cementless stem (Hipstar). The variables of body mass index (BMI), gender, preoperative function and age were explored as predictors for recovery after surgery. Clinical and radiological evaluation of 100 patients were undertaken preoperatively and at 6, 12 and 24 months postoperatively using the Harris Hip Score (HHS), WOMAC-Score and the SF-36-Score. The mean preoperative HHS was 53.6 + or - 14.5 points and it increased significantly to 82.8 + or - 15.4 at the postoperative evaluation at 24 months (WI-test p<0.001). Diminished preoperative function led to a lower postoperative score, but BMI, age and gender were not predictors of clinical and radiological outcome. Due to stress-shielding the straight Hipstar stem revealed radiolucent lines of between 41.5% and 68.5% in the proximal Gruen zones, which indicates a higher primary and secondary stability by enhanced osseous integration compared to other straight stems. Our clinical results are encouraging, but long-term follow-up will be necessary to confirm the successful introduction of the new Hipstar stem. PMID- 20544656 TI - Total hip arthroplasty for fractures of the proximal femur in older patients. AB - Displaced fractures of the proximal femur are common in older patients. The optimal treatment is still under debate. We retrospectively reviewed the results of 53 consecutive total hip arthroplasties (THA) performed in 12 men and 41 women for treatment of an acute fracture of the proximal femur. Men had an average age of 75.1 years (range, 61 to 90) and women 78.2 years (range, 61 to 91). At time of fracture, 42 patients (79.3 %) had radiological signs of hip osteoarthritis. At time of surgery, 8 patients (15.1%) needed trochanteric reconstruction in addition to the implanted THA.Clinical and radiological follow-up was available for 39 patients (73.6 %). The average follow-up time was 55.5 months. The mean Harris Hip Score was 86.3 points (range, 68-97.7). The 4 month mortality rate was 1.9 % (1 patient). Four patients (7.5%) had had early postoperative complications, including dislocation in 3 patients (5.6%) and one (1.9%) minor reoperation (wound haematoma). One patient (1.9%) had revision surgery because of aseptic stem loosening 67 months after primary implantation. In elderly patients, THA is a safe long-term solution for treatment of displaced fractures of the proximal femur, allowing early weight bearing and assisting with rehabilitation. PMID- 20544657 TI - Acid etching does not improve CoCrMo implant osseointegration in a canine implant model. AB - Induction of bone ingrowth by topographical changes to implant surfaces is an attractive concept. Topographical modifications achieved by acid etching are potentially applicable to complex 3D surfaces. Using clinically relevant implant models, we explored the effect of wet etching porous bead-coated CoCrMo. The study was designed as two paired animal experiments with 10 dogs. Each dog received four implants; one in each medial femoral condyle (loaded 0.75-mm-gap model) and one in each proximal tibia (press-fit). The implants were observed for 6 weeks and were evaluated by biomechanical pushout tests and histomorphometry. We found that wet etching porous bead-coated CoCrMo implants failed to improve implant performance. Moreover, a tendency towards increased fibrous tissue formation, decreased new bone formation, and decreased mechanical fixation was observed. Surface topography on implants is able to stimulate bone-forming cells, but the clinical performance of an implant surface perhaps relies more on 3D geometrical structure and biocompatibility. Caution should be exercised regarding the results of wet etching of porous bead-coated CoCrMo and there is a need for more preclinical trials. PMID- 20544658 TI - Infections after primary and revision total hip replacement caused by enterobacteria producing extended spectrum beta-lactamases (ESBL): a case series. AB - Implant infection remains a feared complication after total hip replacement. A higher rate of infection is observed after revision surgery. An additional threat for such patients arises from the fact that bacteria resistant to a multitude of antibiotics are encountered with increasing frequency in the hospital setting. Among them enterobacteria producing extended spectrum beta-lactamases (ESBL) are the second most frequent group of multiresistant isolates. ESBLs are enzymes which hydrolyse third and fourth generation cephalosporins resulting in a distinctive resistance against these antibiotics. Even though ESBLs were first described in the early 1980's and now represent pathogens of importance in intensive care units, they have been only rarely encountered in orthopaedic and trauma surgery. We report on three cases of ESBL-associated infections in hip arthroplasty, resulting in 1) resolution of infection after removal of the hip implant, 2) death after developing a nosocomial pulmonary infection due to ESBL producing bacteria, and 3) resolution of infection after two-stage revision. The infections, caused by multi-resistant ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates, demonstrate the difficulties in managing implant associated infections with resistant bacteria, and emphasize the importance of recognizing ESBL-positive bacteria as increasingly important pathogens that require special precautions and treatment. Our observations suggest that ESBL expressing bacteria in orthopaedic and trauma surgery are not a rare phenomenon any more. PMID- 20544659 TI - Long term preservation of femoral bone following hemiresurfacing. AB - Long term femoral fixation, bone remodeling and neck preservation are demonstrated histologically in three hips treated with hemiresurfacing. They were performed in young patients for Ficat stage III or early IV osteonecrosis as a "time buying procedure". The cases were revised after 13, 16 and 22 years because of cartilage wear which was anticipated. One head was resurfaced using titanium and two with custom alumina ceramic components. Fixation was achieved using early bone cleansing and cementing techniques. Retrieval analysis found remarkable preservation of bone stock and viability without neck narrowing. PMID- 20544660 TI - Surgical debridement with muscle flap transposition and systemic teicoplanin therapy for infected hip arthroplasty. AB - The use of muscle flaps is now accepted as a method for coverage of infected wounds. To obtain complete eradication of infection following hip arthroplasty surgery is combined with antibiotic treatment. Aggressive debridment to remove devitalized tissue followed by vastus lateralis muscle flap transposition may improve the likelihood of success in certain challenging cases. We report two cases of prosthetic joint infection treated by aggressive debridment and vastus lateralis transposition with associated appropriate antibiotic therapy. Complete recovery of functional status was observed. PMID- 20544661 TI - Revision total hip arthroplasty with a modular tapered stem. AB - Femoral stem revision surgery with proximal bone loss may be treated with modular uncemented distal fixation stems. Early results of the ZMR tapered stems with relatively fewer cases were encouraging. In this prospective study, we evaluated the 2 to 10 years survivorship, associated complications and functional outcomes of 84 cases of femoral revision using the ZMR tapered stem. The indications for revision were aseptic loosening (50), periprosthetic fracture (12), infection (17), stem fracture (4) and instability (1). The mean follow-up was 46 months (range, 25-117). The Kaplan-Meier survival with femoral re-revision for any reason as an end-point was 92.7% (95% CI: 87.7%-97.7%). The mean Harris hip score improved from 37 (10-77) points before operation to 72 (41-96) points at last follow-up. The ZMR tapered stem has shown satisfactory results in 2 to 10 years followup in various femoral stem revision conditions. PMID- 20544662 TI - A technique for extracting a buried Kuntscher nail from the femur during total hip arthroplasty. AB - We describe a novel technique that allows safe extraction of a buried Kuntscher nail during total hip arthroplasty in a patient with ipsilateral, symptomatic post-traumatic osteoarthritis of the hip. This method allows the surgeon to visualise the antegrade entry point of the nail allowing safe extraction of the device without compromising the result of the hip arthroplasty. PMID- 20544663 TI - Cyst-like lesion of the acetabular roof - an abnormal finding or an anatomical variant? AB - Cyst-like lesions are frequently found in the area of the acetabulum on MRI scans. However, their presence is not always abnormal. We report four patients with such lesions found on MRI where, during hip arthroscopy, an area resembling a horseshoe-like extension of the cotyloid fossa was found. Clinicians must be aware that not all cystic acetabular lesions are pathological and may simply represent a normal anatomical or developmental variant of the hip joint. They do not always represent an indication for hip arthroscopic surgery. PMID- 20544664 TI - Modified ilioinguinal approach to the acetabulum and pelvis from beneath the inguinal ligament: a subinguinal approach. AB - The ilioinguinal approach is favoured for fractures of the anterior part of the pelvis, but it is associated with some technical difficulties and it is not suitable for some complex fractures. In 2008, a modified ilioinguinal approach was introduced by Farid Yr which afforded visualisation of the inside and outside of the pelvis. The approach involves retroperitoneal access below the inguinal ligament to preserve the integrity of the inguinal canal and allows exposure of anterior and medial wall fractures as well as the anterior hip capsule. Despite the dimensions of the procedure, closure is anatomical because repair of the inguinal canal floor is not required. We report the use of this approach in 17 patients with T-type fractures of the acetabulum, transverse fractures of acetabulum, Tile C1 pelvic fractures, malunion of the pelvis and acetabular dysplasia. The approach is recommended in complex cases of acetabular surgery (including obese or muscular patients) and complicated or old fractures in which a better exposure is required. It is useful in visualisation of the anterior wall and labrum and intra articular structures, and in viewing the internal anatomy of the pelvis and acetabulum. It may be a suitable approach for periacetabular osteotomy. PMID- 20544665 TI - Complications relating to accuracy of reduction of intertrochanteric fractures treated with a compressive hip screw. AB - Intertrochanteric fracture is the most frequent type of fracture in the proximal femur and the compressive hip screw is one of the most popular methods of treatment. The reduction criteria for this type of fracture are ill-defined. The purpose of this study was to validate 3 reduction criteria: displacement, alignment in the anteroposterior and in the lateral plane. We reviewed a cohort of 430 intertrochanteric fractures treated with a compression hip screw. The type of fracture, quality of reduction and technical complications were noted. We observed a relationship between accuracy of reduction and the incidence of complications, even among fractures of the same severity. A displacement bigger than 4mm and failure to accomplish correct alignment (a neck-shaft angle over 125 masculine and less than 20 degrees angulation on the lateral view) was considered a poor reduction and was associated with more complications. PMID- 20544666 TI - The relationship between the presence of metallosis and massive infection in metal-on-metal hip replacements. AB - With the increased use of metal-on-metal as a bearing surface, complications and side effects are being recognised more frequently. We present a small series of a previously unreported complication, which appears specific to metal-on-metal bearing surface arthroplasties: three cases of infection in the presence of local metal debris and histological features of aseptic lymphocytic vasculitis associated lesions (ALVAL). Each case is associated with significant soft tissue loss and bone destruction to such an extent that pelvic discontinuity has occurred. We postulate that the combination of metal debris, ALVAL and tissue necrosis provides a unique environment for peri-prosthetic bacterial growth and rapid spread of infection. PMID- 20544667 TI - Arthroscopic bullet extraction from the hip in the lateral decubitus position. AB - Hip arthroscopy was first described in 1931 by Burman, and in recent years the applications have extended to labral surgery, osteochondroplasty, and a variety of other procedures. Hip arthroscopy may also be employed to extract loose or foreign bodies from the hip, and may be associated with more rapid recovery than an open procedure. We present a case of arthroscopic bullet removal from the hip in a 24-year-old man. PMID- 20544668 TI - Long-term comparison of porous and hydroxyapatite sleeves in femoral revision using the S-ROM modular stem. AB - We prospectively evaluated the results of a single-surgeon series of 28 femoral revision arthroplasties using the S-ROM modular stem with either a porous-coated sleeve (15 hips) or a hydroxyapatite-coated sleeve (13 hips) after a mean of 10 years (range, 8-14 years). Three femoral stems underwent repeat femoral revision for aseptic loosening in association with Paprosky type III bone defects after a mean of 9 years in vivo (range, 8-10 years). One on these 3 had a porous-coated sleeve and the other 2 had a hydroxyapatite-coated sleeve. With repeat revision for any reason as the end point, femoral component survival was 83.8% at 10 years for the entire series, and 93.3% for the porous-coated sleeve group and 76.2% for the hydroxyapatite-coated sleeve group, respectively (log-rank test, P=0.588). No significant difference was detected between the 2 groups regarding postoperative Harris hip scores, bone ingrowth, stress-shielding, osteolysis, or complication rates. At a mean of 10 years postoperatively, hydroxyapatite-coated sleeves offered no clinical benefit over porous-coated sleeves for revision hip replacement using the S-ROM modular stem. Our findings also indicate that hydroxyapatite-coated sleeves did not reduce late mechanical stem failures in cases with a deficient femur. PMID- 20544671 TI - Prevalence of exfoliation syndrome in Estonia. AB - PURPOSE: To estimate the prevalence of exfoliation syndrome (XFS) in Estonia. METHODS: A total of 766 residents, representing the demographics of Tartu, Estonia, were chosen by random sampling from the Estonian Population Database, and invited to participate in this study. Each patient underwent careful slit lamp examination including applanation tonometry before and after pupil dilatation. Presence of XFS was confirmed after mydriasis as typical white-gray fluffy material on the anterior lens surface, and on the pupillary border as well on the corneal endothelium. RESULTS: A total of 424 subjects, 277 female and 147 male, participated in this study. The median age was 70 years (70 years in women and 71 years in men). The overall prevalence of XFS among the study participants in 1 or both eyes was 25.5% (25.2% in men and 25.6% in women). Intraocular pressure measured before and after dilatation was significantly higher in the XFS group. Glaucoma was significantly more frequent in the XFS group than the non-XFS group; 35.7% and 11.3%, respectively. Fifty percent of all patients with glaucoma had exfoliative glaucoma. Cataract was detected in 57.0% of cases in the XFS group compared to 39.5% in the non-XFS group (p=0.002). We found similar prevalence of systemic diseases in both groups for both genders. There was no difference between the 2 groups in visual acuity. CONCLUSIONS: In this population based cross-section study, XFS was found to be a frequent finding in Estonia. Exfoliation syndrome is a risk factor for glaucoma and cataract formation. PMID- 20544672 TI - Alteration of rod and cone function in children with Usher syndrome. AB - PURPOSE: To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. METHODS: Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. RESULTS: Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. CONCLUSIONS: Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood. PMID- 20544673 TI - Efficacy of brimonidine in preventing intraocular pressure spikes following phacoemulsification in glaucoma patients. AB - PURPOSE: To measure intraocular pressure (IOP) elevation 6 and 24 hours after phacoemulsification in patients with glaucoma and to investigate the efficacy of brimonidine tartrate 0.2% in preventing IOP rise on the first postoperative day following cataract surgery. METHODS: In this prospective randomized single-masked study, 86 eyes of 78 patients with well-controlled open-angle glaucoma were scheduled for phacoemulsification surgery. Patients were randomly assigned into 2 groups. Group A received 1 drop of brimonidine tartrate 0.2% and group B, which served as a control group, received 1 drop of artificial tears. Intraocular pressure was measured at baseline, before surgery, and 6 and 24 hours postoperatively. RESULTS: Within each group, we found a statistically significant difference in IOP between baseline and 6 hours postoperatively (p<0.01) and between 6 and 24 hours (p<0.01). There was no statistically significant difference between baseline IOP and 24-hour values. Comparing the 2 groups, there was no statistically significant difference in preoperative and 24-hour postoperative IOP. Six hours after surgery, the mean IOP in the brimonidine group was 18.52+/-4.58 mmHg, compared with 20.86+/-3.79 mmHg in the control group. Treatment with brimonidine tartrate 0.2% significantly reduced postoperative IOP elevation 6 hours following cataract extraction (p=0.009). CONCLUSIONS: Patients with medically well-controlled glaucoma may experience a substantial increase in IOP shortly after phacoemulsification surgery. Instillation of brimonidine tartrate 0.2%, although it significantly reduced IOP elevation following cataract operation, did not completely prevent IOP spikes. PMID- 20544674 TI - Periorbital and orbital cellulitis: a 10-year review of hospitalized children. AB - PURPOSE: Periorbital cellulitis is often difficult to distinguish from orbital cellulitis, which is a potentially lethal infection involving the contents of the orbit. A delay in diagnosis and appropriate treatment may result in serious complications. We studied the predisposing factors, microbiologic data, clinical features, complications, and treatment of periorbital and orbital cellulitis in childhood. METHODS: Eighty-three medical records of patients (mean age 3.7 +/- 3.1 years) admitted to the Department of Pediatrics with a diagnosis of periorbital or orbital cellulitis during the 10-year period January 1997 to December 2007 were retrospectively studied. RESULTS: In this series, periorbital cellulitis occurred more frequently (83%) than orbital cellulitis (17%). Of the children with periorbital cellulitis, 85% were younger than 5 years of age, while 62% of the children with orbital cellulitis were older than 5 years of age. The most common predisposing factors in periorbital cellulitis were upper respiratory infection (68%) and trauma to the eyelids (20%), while sinusitis was more frequently associated with orbital cellulitis (79%). Blood and skin cultures were usually negative. The most common isolated pathogens were Staphylococcus aureus, Streptococcus pneumoniae, and Staphylococcus epidermidis. Forty-five of the 83 children were treated with intravenous ceftriaxone + clindamycin (mean duration 8.6 +/- 5.5 days). Intravenous antibiotics alone was an effective management in most of the patients, but a small proportion (6%) required surgical intervention. CONCLUSIONS: Upper respiratory infection and sinusitis are the most important predisposing factors for periocular infection. Streptococcus species are the predominant causative agents. Both diseases can usually be successfully treated with intravenous antibiotics, but some patients may require surgery to control extensive infection. PMID- 20544675 TI - Investigation of corneal topography after deep lamellar endothelial keratoplasty. AB - PURPOSE: To analyze the 6-month anterior and posterior topographic changes of the cornea after deep lamellar endothelial keratoplasty. METHODS: Orbscan topographies of 22 eyes from 21 patients with corneal decompensation were retrospectively analyzed: 11 eyes received a 9-mm scleral access incision (large incision group) and 11 eyes received a 5-mm scleral access incision (small incision group). All the preoperative and postoperative corneal raw data were imported into custom software which computed the average composite corneal maps and difference maps for both study groups in order to evaluate the corneal response to the surgery. The software delineated 2 concentric zones of the cornea to characterize the regional response following the surgery: the central and peripheral regions. RESULTS: There were no significant differences (analysis of variance, <0.35 D, p>0.05) between 6-month postoperative and preoperative average anterior central corneal topographies in either group. At the end of follow-up, the average posterior curvature tangential map did not significantly differ from before surgery in either group (<0.35 D, p>0.05). However, a significant increase (>0.60 D, p<0.01) in the average posterior central astigmatic power of the cornea was found in both groups. CONCLUSIONS: Deep lamellar endothelial keratoplasty effectively preserves the preoperative keratometric corneal topography, minimizing changes in curvature and astigmatism of the cornea. The great predictability of corneal topography following deep lamellar endothelial keratoplasty is likely to be attributed to the minimal changes that occur in the anterior stroma, the portion of the cornea that appears to be mainly responsible for maintenance of corneal shape. PMID- 20544676 TI - Efficacy and safety of short-duration topical treatment with azithromycin oil based eyedrops in an experimental model of corneal refractive surgery. AB - PURPOSE: To assess the tolerance and side effects of azithromycin eyedrops at the ocular surface after corneal refractive surgery in an experimental animal model. METHODS: The effect of azithromycin eyedrops was evaluated in hen corneas that underwent laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) surgery in 1 eye, using the fellow eye (not manipulated) as a control. Animals were treated bid 3 days prior to surgery and 3 days after surgery with T1225 1.5% azithromycin eyedrops or saline eyedrops (balanced salt solution), or were left untreated as a control. Clinical course and cell biology (apoptosis, proliferation, and differentiation) measurements were assessed. RESULTS: Infections were present in the following proportions of corneas operated on by LASIK: 0% treated with azithromycin, 60% treated with BSS, and 30% untreated. No corneal abscess or keratitis were present in any PRK or unmanipulated corneas. Conjunctival edema and redness were less prevalent in LASIK-operated eyes treated with azithromycin than in BSS-treated or untreated eyes and were not observed in any PRK or unmanipulated corneas. In PRK-operated eyes treated with azithromycin, a decrease was observed in the apoptosis and an increase in the stromal proliferation. There were no differences in these parameters for LASIK and unmanipulated eyes. CONCLUSIONS: Topical administration of T1225 oil-based azithromycin eyedrops was well tolerated in both unmanipulated hen corneas and those treated with corneal refractive surgery (PRK and LASIK). T1225 demonstrated a potent antibiotic effect after LASIK treatment. PMID- 20544677 TI - Correlation between optical coherence tomography results and the Scoring Tool for Assessing Risk (STAR) score in patients with ocular hypertension. AB - PURPOSE: To correlate retinal nerve fiber layer thickness (RNFL) and optic nerve head (ONH) parameters measured with optical coherence tomography (OCT) with the Scoring Tool for Assessing Risk (STAR) threshold in patients with ocular hypertension (OH). METHODS: The study included 92 patients with OH. They were divided into low-risk (n=32), moderate-risk (n=36), and high-risk (n=24) groups according to STAR criteria. RNFL and ONH OCT protocols were used to evaluate all study participants. Major parameters for RNFL analysis were average RNFL thickness, superior quadrant, nasal quadrant, inferior quadrant, temporal quadrant, and segmental thickness per 12 o'clock hour position. ONH parameters were vertical integrated rim area (VIRA), horizontal integrated rim width (HIRW), disc diameter, disc area, cup area, rim area, cup-to-disc (C/D) area ratio, horizontal C/D ratio, and vertical C/D ratio. RESULTS: The highest area under receiver operating characteristics curves for distinguishing the high-risk group from the other groups were vertical C/D ratio (0.88), C/D area (0.88), VIRA (0.87), and HIRW (0.81) for ONH parameters, and inferior (0.82) and 6 o'clock hour position (0.77) for peripapillary RNFL thickness measurements. CONCLUSIONS: Inferior average, 6 o'clock hour position analyses for RNFL measurement, and VIRA, HIRW, C/D area, and vertical C/D ratio for ONH measurement were the best parameters for STAR staging in patients with OH. PMID- 20544678 TI - Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy. AB - PURPOSE: Advanced glycation end products (AGEs) accumulation may result from chronic hyperglycemia promoting generation and onset of microangiopathy. The aim of this study was to investigate the association between diabetic retinopathy (DR) and levels of AGEs, pentosidine, and N-carboxymethyl-lysine (CML) in aqueous humor and serum of human patients and their role in predicting the progression of DR. METHODS: Ninety patients with type 2 diabetes mellitus and 30 nondiabetic patients underwent cataract surgery. The diabetic group was divided into 3 subgroups: 35 patients with mild nonproliferative diabetic retinopathy (mild NPDR), 30 patients with severe nonproliferative diabetic retinopathy (severe NPDR), and 25 patients with proliferative diabetic retinopathy (PDR). In the samples, pentosidine was measured by high-performance liquid chromatography and CML using a competitive enzyme-linked immunosorbent assay. RESULTS: Serum levels of pentosidine and CML were significantly increased in patients with type 2 diabetes compared to nondiabetic controls (p<0.001). In diabetic patients, serum pentosidine and CML levels were significantly higher in patients who had PDR than in those with mild NPDR or severe NPDR (both p<0.001). A significant difference was found between aqueous humor CML levels in diabetic and nondiabetic patients and increased along with progression of DR. Significant correlations existed between serum pentosidine and aqueous CML in severe NPDR and PDR (p<0.001). CONCLUSIONS: In patients with type 2 DM, serum levels of pentosidine and CML are related to severity of retinopathy. In addition, aqueous humor level of CML increased along with progression of DR. Pentosidine and CML can be used as biochemical markers of glycoxidation and related to onset or progression of DR. PMID- 20544679 TI - Visual outcome following intraocular foreign bodies: a retrospective review of 5 year clinical experience. AB - PURPOSE: To determine the main prognostic factors related to final visual acuity (VA) after intraocular ocular foreign body (IOFB) extraction. METHODS: We performed a retrospective chart review of 80 patients (84 eyes) who underwent surgical removal of IOFBs and repair of associated ocular trauma. Data on age, gender, presenting clinical features, characteristics of IOFB, complications, interval between time of injury and IOFB removal, and final VA were recorded and analyzed. RESULTS: Male adults were the major population affected by IOFBs. Improved vision outcome was obtained after the removal of IOFBs and surgical repair of the eyes (p=0.011). Factors showing statistical association with final VA included initial VA (p=0.000), size of IOFB (p=0.010), IOFB location inside the eye (p=0.000), and preoperative retinal detachment (p=0.011). Factors showing no statistical association with final VA included nature of IOFB (p=0.445), entrance wound location, other IOFB-related complications (such as cataract, vitreous hemorrhage, secondary glaucoma, hyphema, endophthalmitis, siderosis, and atrophia bulbi), and interval between injury and IOFB removal. CONCLUSIONS: Prognostic factors for poor final VA related to IOFBs included poor initial VA, large IOFB size, posterior segment location, and preoperative retinal detachment. PMID- 20544680 TI - The frequency of pseudoexfoliation syndrome in the middle Black Sea region of Turkey. AB - PURPOSE: To assess the frequency of pseudoexfoliation syndrome (PEX) and evaluate its association with specific ocular diseases in patients attending the Department of Ophthalmology at Gaziosmanpasa University Hospital. METHODS: A prospective study was conducted at the Gaziosmanpasa University Hospital between December 2007 and December 2008. A total of 831 subjects aged 45 or above attending the general ophthalmic clinics were recruited for this study. Each patient underwent complete ophthalmic assessment, including ocular history, visual acuity testing, slit-lamp examination, applanation tonometry, gonioscopy, and fundus examination. RESULTS: Of the 831 subjects, 12.2% had PEX. Pseudoexfoliation was bilateral in 74.2% of cases, significantly associated with cataract, glaucoma, age-related macular degeneration (AMD), and phacodenesis. Of the patients with PEX, 43.6% had cataract, 6.9% had glaucoma, 7.9% had AMD, and 0.9% had phacodenesis. In addition, 9.8% had cataract + glaucoma, 13.7% had cataract + phacodenesis, and 17.8% had all of them. The prevalence of PEX had a tendency to increase with age but had no sex predilection. CONCLUSIONS: The study findings enhance our knowledge of PEX in Anatolia, particularly in the Middle Black Sea region. PMID- 20544681 TI - Is there any difference in target intraocular pressure for exfoliative glaucoma patients with cardiovascular disease history? AB - PURPOSE: To investigate if patients with exfoliation glaucoma (XFG) with cardiovascular disease (CVD) require different target intraocular pressure (IOP) compared to patients with XFG with no CVD for long-term stability. METHODS: A retrospective, multicenter, observational cohort analysis included consecutive patients with XFG from 9 European academic centers, with a minimum of 5 years follow-up. RESULTS: In 201 patients, there was a statistical difference between progressed and non-progressed patients in mean (p=0.0049) and peak (p=0.015) IOP, variance of IOP (p=0.028), and number of medicine changes/year (p=0.0037). At a mean IOP >=22 mmHg, patients progressed in 84% (32/38), between 14 and 21 mmHg in 54% (81/151), and at <=13 mmHg in 33% (4/12). There was no difference in the rate of progression between groups based on CVD history (p=0.65). However, IOP that allowed <=50% progression rate for patients with mild or no CVD was <=20-21 mmHg and <=18 mmHg for patients with severe disease. Further, at IOP >=20 mmHg, 8% (1/12) of patients with severe CVD remained stable in contrast to 38% (16/42) of patients with mild and 21% (4/19) with no CVD history (p=0.0093). By multivariant regression analysis of the IOP and CVD measures, mean IOP was a risk factor for progression (p=0.0097). CONCLUSIONS: Although IOP is the main determinant of progression in XFG under treatment, history of severe CVD should be further investigated as potential risk factor for glaucomatous progression. PMID- 20544682 TI - Ocular neovascularization following central retinal artery occlusion: prevalence and timing of onset. AB - PURPOSE: Debate exists in the literature on the prevalence and etiology of neovascularization following central retinal artery occlusion (CRAO). The reported prevalence varies from 2.5% to 31.6%. We conducted a retrospective study to determine the prevalence of ocular neovascularization following acute CRAO in our institution. METHODS: A retrospective audit of consecutive patients with nonarteritic/thromboembolic CRAO presenting between 1997 and 2009 in a single tertiary teaching hospital. RESULTS: Thirty-three patients were identified as having nonarteritic CRAO, and of this cohort 6 patients (18.2%) developed ocular neovascularization. Neovascular glaucoma was present in 5 cases (15.2%); 2 of these presented through an emergency department with painful eyes, both at 16 weeks post CRAO. The other cases of neovascularization were detected on scheduled follow-ups. Mean time from retinal occlusive event to observed neovascularization was 8.5 weeks (range 2-16 weeks). One case of neovascularization was associated with hemodynamically significant ipsilateral carotid stenosis; no patient had proliferative diabetic retinopathy or other causes of neovascularization. CONCLUSIONS: The prevalence of neovascularization following acute CRAO in our population was 18.2% at an average of 8.5 weeks post CRAO. There was a temporal relationship between the 2 events and no other causes of neovascularization demonstrable in our cohort of patients. There is no consensus on the follow-up regimen post CRAO to detect ocular neovascularization complications. Our study suggests that neovascularization can occur early and regular follow-up especially in the first 4 months is important post CRAO. PMID- 20544683 TI - Single needle revision of failing filtration blebs: a retrospective comparative case series with 5-fluorouracil and mitomycin C. AB - PURPOSE: To assess the success of needling in failed filtration blebs and the potential benefit of using either 5-fluorouracil (5-FU) or mitomycin C (MMC). METHODS: In this retrospective, comparative observational case series, 107 eyes that underwent needle revision with either 5-FU or MMC between July 2003 and May 2008 at Wills Eye Institute were selected. Exclusion criteria included follow-up less than 1 month and a history of glaucoma drainage device. Intraocular pressure (IOP) and number of glaucoma medications were recorded preoperatively and postoperatively. Success was defined as >20% decrease in IOP if glaucoma medications were resumed or <10% decrease in IOP if medications were not resumed post needling or fewer medications than pre needling. RESULTS: Sixty-five patients received 5-FU and 42 patients received MMC for needling. Mean IOP changed from 23.9 mmHg to 13.8 mmHg in the MMC group and from 23.3 mmHg to 13.02 mmHg in the 5-FU group (both p<0.001). Mean glaucoma medications changed from 1.7 to 0.7 in the MMC group and 2.0 to 0.8 in the 5-FU group (both p<0.001) at the end of follow-up. After a mean follow-up of 14.5 months, overall survival was 49.5%. Mean time to failure was 7.7 months. There was a moderately weak association between survival and the immediate postoperative IOP (r=0.262, p=0.01). In comparing MMC and 5-FU, there was no statistically significant difference in survival rate (p=0.267). CONCLUSIONS: Bleb needling may be a safe and effective means of prolonging bleb survival. The only factor associated with success was the immediate postoperative IOP. There was no apparent difference between the use of 5-FU and MMC in this population. A prospective study may provide further confirmation of this finding. PMID- 20544684 TI - Identification of a novel biomarker signature associated with risk for bone metastasis in patients with renal cell carcinoma. AB - When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1alpha, uPA , and PA I-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions. PMID- 20544685 TI - HIF-1alpha is a prognostic marker in oral squamous cell carcinomas. AB - The critical molecular regulator of hypoxia is the hypoxia-inducible factor 1 alpha (HIF-1alpha). The prognostic impact of this regulator protein in oral squamous cell carcinomas (OSCC) has not been comprehensively investigated. The aim of this study was to analyze the expression of HIF-1alpha in 82 patients with OSCC and to correlate it with their disease-specific survival. Immunohistochemical staining for HIF-1alpha was performed on 82 OSCC specimens using a standard immunoperoxidase technique. The expression of HIF-1alpha was correlated with poor disease-specific survival for OSCC patients. Patients with negatively or weakly HIF-1alpha-expressing tumors had a survival rate of 80%, whereas the survival decreased to only 33.6% in case of moderate or strong expression. In multivariate Cox regression analysis, we found a 3.5-fold increased risk of tumor-related death when HIF-1alpha was strongly expressed (p=0.016) compared to negative or weak expression of HIF-1alpha. We suggest HIF 1alpha is an independent prognostic marker in OSCC. Immunohistochemical detection of HIF-1alpha appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade. PMID- 20544686 TI - Evaluation of serum DNA integrity as a screening and prognostic tool in patients with hepatitis C virus-related hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy in Egypt due to the high frequency of hepatitis C virus (HCV) infection among the general population. Circulating free DNA is a potential molecular marker for the diagnosis and prognosis of malignant tumors. DNA released from apoptotic cells usually consists of short uniform fragments while DNA released from cancer cells is longer. The ratio of long DNA fragments to total DNA (DNA integrity) may be a potential marker for early detection of HCC and its progression in HCV patients. METHODS: Sera from 25 patients with HCV-related HCC, 25 patients with chronic HCV infection, and 15 healthy volunteers were examined for Alu repeats by quantitative real-time PCR (qPCR) using 2 sets of primers of 115 and 247 base pairs. DNA integrity was calculated as the ratio of 247-bp to 115-bp Alu fragments. RESULTS: Compared with healthy volunteers and HCV patients, significantly higher DNA integrity was found in HCC patients. DNA integrity was associated with tumor size, TNM stage, vascular invasion, lymph node involvement, and distant metastasis. DNA integrity had a higher sensitivity and specificity in discriminating HCC from HCV patients than total DNA. Patients with high DNA integrity had a significantly shorter overall survival and high DNA integrity was shown to be an independent prognostic factor for survival in HCV-related HCC. CONCLUSIONS: DNA integrity is a promising molecular biomarker for detecting HCC in patients with chronic HCV infection; it reflects the progression and metastatic potential of the tumor, and high DNA integrity is associated with short overall survival in HCV-related HCC. PMID- 20544687 TI - Evidence that genetic variants of metabolic detoxication and cell cycle control are not related to gallbladder cancer risk in Chilean women. AB - BACKGROUND AND AIMS: High consumption of red chili pepper has been shown to be a risk factor for gallbladder cancer (GBC) in Chilean women. However, genetic factors in addition to this and other environmental factors may also be associated with an increased risk of GBC. We aimed to examine the associations of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumor protein p53 (TP53) polymorphisms with the risk of GBC in Chilean women. METHODS: A hospital-based case-control study of 57 patients with GBC, 119 patients with gallstones, and 70 controls was conducted. The statuses of the polymorphisms CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 were assayed using Custom Taqman SNP Genotyping Assays and TaqMan SNP Genotyping Assay. GSTM1 deletion polymorphism was detected by allele-specific PCR analysis. RESULTS: No significant differences in the genotypic or allelic frequencies in the CYP1A1, GSTM1, and TP53 polymorphisms were found between the three groups. CONCLUSION: These genetic variants were not related to an increased risk of GBC in Chilean women. Other polymorphisms, such as red-chili-pepper-related polymorphisms, may contribute to the development of GBC in Chilean women. PMID- 20544688 TI - Predictive and prognostic role of p53 according to tumor phenotype in breast cancer patients treated with preoperative chemotherapy: a single-institution analysis. AB - INTRODUCTION AND AIMS: The p53 protein is a mediator of the cellular response to DNA damage. The aim of this study was to evaluate the predictive and/or prognostic value of p53 expression in relation to the molecular subtypes of breast cancer in patients treated with preoperative chemotherapy. PATIENTS AND METHODS: Patients with stage II-III breast cancer were included in the study. The expression of p53 was evaluated by immunohistochemistry on the diagnostic core biopsy specimen. Patients received 4-6 courses of preoperative chemotherapy. Pathological complete response (pCR) was defined as complete disappearance of invasive tumor in the breast and axillary lymph nodes. RESULTS: 154 patients were included in the study and the molecular subtypes of their tumors were classified as follows: triple negative 18.2%, hormone receptor positive 60.4%, and HER2 positive 21.4%. p53 was expressed in 43.5% of the patients. A significant association between p53 expression and breast cancer molecular subtypes, tumor differentiation, and proliferation was observed. pCR was achieved in 8 patients (5.2%). p53 expression, molecular subtype, and nuclear grading were significant predictors of pCR (odds ratio for pCR in patients with p53-expressing tumors 10.03, p=0.0077). In univariate analysis, the expression of p53 as well as high proliferation and lymph node involvement after preoperative chemotherapy were predictors of a worse disease-free survival. Patients with p53 positivity also had a worse overall survival. In multivariate analysis, both p53 expression and nodal status after preoperative chemotherapy were significantly associated with disease-free and overall survival: the hazard ratios for relapse and death in patients with p53-expressing versus non-p53-expressing tumors were 2.29 (p=0.015) and 7.74 (p=0.002), respectively. The hazard ratios for relapse and death in node positive versus node-negative patients were 3.63 (p=0.003) and 3.64 (p=0.041), respectively. CONCLUSIONS: In this series of patients, p53 expression was significantly associated with markers of aggressive tumor biology, and with a higher likelihood of attaining pCR. p53 expression was a negative prognostic parameter for disease free and overall survival in univariate and multivariate analysis. PMID- 20544689 TI - The characteristic fragmentation and rearrangement reaction of cationized glucopyranosyloxybenzyl tartrates by tandem mass spectrometry. PMID- 20544690 TI - Formation of cyclic acylphosphoramidates in mass spectra of N monoalkyloxyphosphoryl amino acids using electrospray ionization tandem mass spectrometry. AB - The fragmentation reactions of N-monoalkyloxyphosphoryl amino acids (N-MAP-AAs) were studied by electrospray ionization tandem mass spectrometry (ESI-MS). The sodiated cyclic acylphosphoramidates (CAPAs) were formed through a characteristic pentacoordinate phosphate participated rearrangement reaction in the positive-ion ESI-MS/MS and HR-MS/MS of N-MAP-AAs, in which the fragmentation patterns were clearly different from those observed in the corresponding ESI-MS/MS of N dialkyloxyphosphoryl amino acids/peptides and N-phosphono amino acids. The formation of CAPAs depended on the chemical structures of N-terminal phosphoryl groups, such as alkyloxy group, negative charge and alkali metal ion. A possible integrated rearrangement mechanism for both P-N to P-O phosphoryl group migration and formation of CAPAs was proposed. The fragmentation patterns of CAPAs as novel intermediates in gas phase were also investigated. In addition, it was found that the formation of alpha-amino acid CAPAs was more favorable than beta- or gamma CAPAs in gas phase, which was consistent with previous solution-phase experiments. PMID- 20544691 TI - Tandem mass spectrometry for the analysis of self-sorted pseudorotaxanes: the effects of Coulomb interactions. AB - The increasing complexity of self-assembled supramolecules generates the need for analytical techniques that can accurately elucidate their structures. Here, we explore the ability of tandem mass spectrometry to deliver structural information on a series of self-sorted crown ether/ammonium pseudorotaxanes. Of these intertwined molecules, different charge states are accessible and the effects of Coulomb interactions on the fragmentation pattern can be examined. Three different cases can be distinguished: (1) one or more counterions are present in the complex and compete with the crown for binding to the ammonium ion. This destabilizes the supramolecular bond. (2) In multiply charged complexes, charge repulsion significantly alters the fragmentation behavior as compared with singly charged ions. (3) If guest and host are both charged, the supramolecular bond becomes very weak. The different charge states provide different pieces of information about the supramolecules under study. Although singly charged complexes provide data on the building block connectivity, the doubly charged analogs are more reliable with respect to complex stoichiometry. As there are several factors which may cause differences in the gas phase and solution behavior of supramolecules (the presence and absence of solvation, changes in the strength of non-covalent interactions upon ionization), it is important to establish well understood correlations between the complexes' gas-phase behavior and their solution structures. A more detailed understanding will help to characterize the structures of even more complex supramolecular architectures by mass spectrometry. PMID- 20544692 TI - Determination of primary bond scissions by mass spectrometric analysis of ultrasonic degradation products of poly(ethylene oxide-block-propylene oxide) copolymers. AB - Ultrasonic degradation of poly(ethylene oxide-block-propylene oxide) copolymers consisting of a hydrophilic and a hydrophobic portion was studied with the aim to determine the location of bonds involved in the initial scission of the copolymers. LC-APCI-IT-MS and LC-APCI-orbitrap-MS were used for the detailed structural analysis of degradation products. The results indicated that initial bond scissions occurred principally at the boundary regions between backbones of polyethylene oxide (PEO) and polypropylene oxide (PPO) chains. Further structural analysis revealed the presence of oxygen adducts in the degradation products. Comparison with a thermal degradation carried out in helium atmosphere, one can conclude that the oxygen adducts are formed by radical reaction with water or dissolving oxygen molecules. The study demonstrated that chemical reactions as well as physical bond stress scissions are involved in the ultrasonic degradation of the copolymers. PMID- 20544693 TI - In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines. AB - Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary! PMID- 20544694 TI - Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits. AB - Several teratogenic agents, including ionizing radiation and xenobiotics such as phenytoin, benzo[a]pyrene, thalidomide, and methamphetamine, can initiate the formation of reactive oxygen species (ROS) that oxidatively damage cellular macromolecules including DNA. Oxidative DNA damage, and particularly the most prevalent 8-oxoguanine lesion, may adversely affect development, likely via alterations in gene transcription rather than via a mutational mechanism. Contributions from oxidative DNA damage do not exclude roles for alternative mechanisms of initiation like receptor-mediated processes or the formation of covalent xenobiotic-macromolecular adducts, damage to other macromolecular targets like proteins and lipids, and other effects of ROS like altered signal transduction. Even in the absence of teratogen exposure, endogenous developmental oxidative stress can have embryopathic consequences in the absence of key pathways for detoxifying ROS or repairing DNA damage. Critical proteins in pathways for DNA damage detection/repair signaling, like p53 and ataxia telangiectasia mutated, and DNA repair itself, like oxoguanine glycosylase 1 and Cockayne syndrome B, can often, but not always, protect the embryo from ROS initiating teratogens. Protection may be variably dependent upon such factors as the nature of the teratogen and its concentration within the embryo, the stage of development, the species, strain, gender, target tissue and cell type, among other factors. PMID- 20544695 TI - Predicting developmental toxicity through toxicogenomics. AB - Global analysis of gene expression in target cells or tissues in response to a toxicant holds significant promise for predictive toxicology. Toxicants elicit a characteristic pattern of gene expression that is dependent on mechanism of action. These mechanism-specific transcript profiles can be used as the basis for predictive toxicology. Potential applications include prioritizing chemicals for testing and customizing testing approaches based on the chemical. Results that are useful in this predictive context can be obtained from animal or in vitro models. Gene expression analysis can also be used to elucidate the shape of the dose-response curve at exposure levels below the no observed adverse effect level, an important need in risk assessment. In this review, we will illustrate each of these points using our research on estrogen and an estrogenic mode of action as a model for how to use gene expression data in a predictive way. Although gene expression in response to estrogens is tissue, life stage, and sex specific, it is feasible to identify transcript profiles that are diagnostic of this mode of action. PMID- 20544697 TI - The Hemimelic extra toes mouse mutant: Historical perspective on unraveling mechanisms of dysmorphogenesis. AB - Hemimelic extra toes (Hx) arose spontaneously as a dominant mutation in B10.D2/nSnJ mice in 1967. It specifically affects the appendicular skeleton, causing variable foreshortening of the tibia (radius) and preaxial polydactylism. Early anatomical studies revealed anterior overgrowth of the autopod, with decreased apoptosis and increased mitosis in the anterior apical ectodermal ridge and underlying mesenchyme; overextension of apoptosis in the central zeugopod accounted for hemimelia. The Hx mutant phenotype was coarsely mapped to mouse chromosome (Chr) 5 and closely linked to engrailed-2 (En2) and Sonic hedgehog (Shh). This region is syntenic to human Chr 7q36 that harbors several dominant mutations affecting the hand. High-resolution genome mapping identified the Hx mutation as a G --> A base pair transition within Intron 5 of the murine Lmbr1 locus. The critical effect is on a multifunctional conserved regulatory element that acts as a limb-specific, long-distance cis-acting enhancer of Shh expression. As such, the Hx mutant phenotype results from ectopic Shh signals at the anterior margin of the limb bud that directly or indirectly alter FGF4 signaling from the apical ectodermal ridge. Given significant advances in understanding of embryonic development in general and limb development in particular, this review article reveals how research that once attracted interest of teratologists has advanced across the decades to pinpoint a critical molecular lesion and reveal a potential mechanism of a specific malformation that is found commonly in experimental teratology. PMID- 20544698 TI - In vitro developmental toxicology assays: A review of the state of the science of rodent and zebrafish whole embryo culture and embryonic stem cell assays. AB - In vitro developmental model systems have been an important tool for advancing basic research in the embryology and teratology fields. The rat and zebrafish embryo models have had broad utility in both fields for many decades. Furthermore embryonic stem cells, applied as a basic research tool, have broad applications across the development fields and many other fields including cancer, regeneration and epigenetic research. These models have historically been applied in mechanistic studies but were also considered promising for evaluating teratogenic potential of test substances. In recent years, in vitro teratogenicity assays have become an area of interest for supporting the 3 Rs (reduction, refinement, and replacement of animal use). Generation of such assays also provides a means to facilitate early assessment of test agents at a higher throughput without excessive use of animals. In this review, the three models are described with an emphasis of how they are being developed and/or refined to support teratogenicity assessment as screening tools. An overview of the state of the science and future directions are described. PMID- 20544699 TI - Role of environmental factors in axial skeletal dysmorphogenesis. AB - Approximately 1 in 1000 live births is afflicted with an axial skeletal defect. Although many of the known human teratogens can produce axial skeletal defects, the etiology of over half of the observed defects is unknown. The high morbidity associated with these defects demands that we continue to elucidate the mechanisms of axial skeletal teratogens. Advances in cell and molecular biology with respect to normal development and somitogenesis and the pathogenesis and mechanisms of teratogenesis are occurring at a tremendous rate. This allows teratologists and developmental toxicologists the opportunity to revisit old problems with new tools to elucidate common mechanisms between various environmental insults and discover novel targets that aid in the understanding of normal and pathogenic development of the spine. PMID- 20544700 TI - Stereoselective metabolism of benalaxyl in liver microsomes from rat and rabbit. AB - Benalaxyl (BX), methyl-N-phenylacetyl-N-2,6-xylyl alaninate, is a potent acylanilide fungicide and consist of a pair of enantiomers. The stereoselective metabolism of BX was investigated in rat and rabbit microsomes in vitro. The degradation kinetics and the enantiomer fraction (EF) were determined using normal high-performance liquid chromatography with diode array detection and a cellulose-tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC CSP). The t(1/2) of (-)-R-BX and (+)-S-BX in rat liver microsomes were 22.35 and 10.66 min of rac-BX and 5.42 and 4.03 of BX enantiomers. However, the t(1/2) of ( )-R-BX and (+)-S-BX in rabbit liver microsomes were 11.75 and 15.26 min of rac-BX and 5.66 and 9.63 of BX enantiomers. The consequence was consistent with the stereoselective toxicokinetics of BX in vitro. There was no chiral inversion from the (-)-R-BX to (+)-S-BX or inversion from (+)-S-BX to (-)-R-BX in both rabbit and rat microsomes. These results suggested metabolism of BX enantiomers was stereoselective in rat and rabbit liver microsomes. PMID- 20544701 TI - High performance liquid chromatography enantioseparation of the novel designed mexiletine derivatives and its analogs. AB - A series of novel designed mexiletine derivatives and its analogs were prepared, the structures were confirmed by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Electrospray Ionization-Mass Spectrometry (ESI-MS), and the enantioseparations were performed on polysaccharide-based chiral stationary phase (CSP), Chiralcel OD-H, and Chiralcel OJ-H, under normal-phase mode. The effects of the concentration of isopropanol in the mobile phase were studied, seven of the eight enantiomers got baseline separation on Chiralcel OD-H, and five of the eight enantiomers got successfully separation on Chiralcel OJ-H. The effects of structural features were also discussed. PMID- 20544696 TI - Palate morphogenesis: current understanding and future directions. AB - In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of "pieces of information" in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the "big picture." Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the "pedestrian" qualities of inductivism, while increasingly employing modern data mining technologies. The secondary palate has provided an excellent paradigm that has enabled examination of a wide variety of developmental processes. Examination of cellular signal transduction, as it directs embryogenesis, has proven exceptionally revealing with regard to clarification of the "facts" of palatal ontogeny-at least the facts as we currently understand them. Herein, we review the most basic fundamentals of orofacial embryology and discuss how functioning of TGFbeta, BMP, Shh, and Wnt signal transduction pathways contributes to palatal morphogenesis. Our current understanding of palate medial edge epithelial differentiation is also examined. We conclude with a discussion of how the rapidly expanding field of epigenetics, particularly regulation of gene expression by miRNAs and DNA methylation, is critical to control of cell and tissue differentiation, and how examination of these epigenetic processes has already begun to provide a better understanding of, and greater appreciation for, the complexities of palatal morphogenesis. PMID- 20544702 TI - Value of cytology in the intraoperative assessment of ovarian tumors: a review of 402 cases and comparison with frozen section diagnosis. AB - BACKGROUND: Intraoperative pathological assessment is frequently requested in patients with suspected ovarian neoplasia so that optimal surgical management can be performed. In this study the accuracy of intraoperative cytology has been assessed and the results compared with frozen section diagnosis. METHODS: The study comprised 402 ovarian tumors that were submitted for intraoperative assessment in which both cytology preparations, usually scrape smears, and conventional frozen sections were examined. Each technique was evaluated independently, although the diagnosis transmitted to the surgeon was based upon the combination of the clinical, macroscopic, histological, and cytological information. The results were compared with the final pathological diagnosis in each case and cases with discordant diagnoses were reviewed. RESULTS: There were 226 benign lesions, 35 borderline epithelial neoplasms, and 141 malignant tumors according to the final pathological diagnosis. All benign lesions were accurately categorized using both frozen section and cytology. Thirty (86%) of the borderline tumors and 137 (97%) of the malignant tumors were accurately identified on frozen section, whereas the corresponding results for cytology were 23 (66%) and 131 (93%), respectively. There were no false-positive diagnoses with either technique and the overall accuracy was 97.8%. Cytological evaluation provided better morphologic detail, permitted wider tumor sampling, and directed appropriate ancillary investigations in some cases. CONCLUSIONS: Overall, frozen section was more accurate than smear preparations in this series. However, cytology has a complementary role in the intraoperative assessment of ovarian neoplasia and provides a more specific diagnosis in some cases. PMID- 20544703 TI - Telecytopathology for immediate evaluation of fine-needle aspiration specimens. PMID- 20544704 TI - Lagging HPV vaccination rates dampen outlook in US: cloudy prospects for overcoming multiple barriers. PMID- 20544705 TI - The GIST of a tumor's transformation. PMID- 20544706 TI - UbcH10 expression on thyroid fine-needle aspirates. AB - BACKGROUND: Thyroid fine-needle aspiration (FNA) samples belonging to the follicular neoplasm/suspicious for malignancy classes are controversial. The authors identified UbcH10 as a marker useful in the diagnosis of several neoplasms, including thyroid cancer. Here, analysis of UbcH10 expression by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry was applied to FNAs. METHODS: A series of 84 follicular neoplasm/suspicious for malignancy FNAs with histological follow-up (30 malignant) was prospectively collected. UbcH10 immunostaining was performed on cell blocks and compared with that of the proliferation marker Ki-67. At the mRNA level, UbcH10 was compared with CCND2 and PCSK2 expression, these latter being the best performing components of the previously reported 3-gene assay; to determine the diagnostic accuracy, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for each gene individually and in combination was evaluated. RESULTS: UbcH10 and Ki-67 shared a similar pattern; although UbcH10 expression was higher in malignant than in benign lesions (P < .001), staining was sporadic, and the cutoff value derived by the ROC analysis was too low (1.25%) for routine application. Conversely, UbcH10 expression assessment by quantitative RT-PCR was effective. UbcH10 mRNA levels associated with malignant histology were significantly higher than those associated with benign histology (P = .02). The AUC was 0.74 for UbcH10, 0.81 for CCDN2, 0.62 for PCSK2, and 0.84 for UbcH10 and CCND2 combination. CONCLUSIONS: UbcH10 quantitative RT-PCR analysis, rather than immunohistochemistry, is useful to increase the detection of malignancy in thyroid FNAs. UbcH10 may be added as a panel component in quantitative RT-PCR-based assays. PMID- 20544707 TI - Telecytopathology for immediate evaluation of fine-needle aspiration specimens. AB - BACKGROUND: On-site evaluation of fine-needle aspiration (FNA) specimens by a pathologist is essential to obtain adequate samples and provide a preliminary diagnosis. Distance from the laboratory can make this difficult. The authors present their experience with on-site evaluation using telecytopathology. METHODS: Dynamic images of cytology smears were captured and processed with a Nikon digital camera system for microscopy and transmitted via Ethernet. A pathologist accessed the real-time images on a computer and interpreted them while communicating with on-site operators over the telephone. Sample adequacy and accuracy of preliminary diagnosis were compared with those obtained by regular on-site evaluation. RESULTS: A total of 429 telecytopathology cases and 363 conventional on-site cases were compared. Specimens were mainly from the pancreas, gastrointestinal tract, liver, and lymph nodes. Adequacy rate was 94.0% for telecytopathology and 97.7% for conventional cases. Preliminary diagnoses of unsatisfactory, adequate (defer), negative/benign, atypical, neoplasm, suspicious, and positive for malignancy were 6.3%, 13.5%, 14.9%, 17.9%, 7.2%, 8.6%, and 31.5% for telecytopathology and 3.9%, 30.6%, 21.5%, 9.6%, 5.0%, 5.2%, and 24.2% for conventional cases. Preliminary and final diagnoses were discrepant in 7 (1.8%) of 371 telecytopathology cases, and in 8 (3.1%) of 252 conventional cases. Difficulty was encountered in some cases in distinguishing pancreatic endocrine neoplasm from lymphoid proliferations, and low grade pancreatic tumors from chronic pancreatitis via telecytopathology. CONCLUSIONS: On-site evaluation of FNA specimens via telecytopathology assures sample adequacy and accurate preliminary diagnosis compared with the conventional method. It allows pathologists to use their time more efficiently and makes on-site evaluations at remote locations possible. PMID- 20544708 TI - Classifying B-cell non-Hodgkin lymphoma by using MIB-1 proliferative index in fine-needle aspirates. AB - BACKGROUND: MIB-1 proliferation index (PI) has proven helpful for diagnosis and prognosis in non-Hodgkin lymphomas (NHLs). However, validated cutoff values for use in fine-needle aspiration (FNA) samples are not available. We investigated MIB-1 immunocytochemistry as an ancillary technique for stratifying NHL and attempted to establish PI cutpoints in cytologic samples. METHODS: B-cell NHL FNA cases with available cytospins (CS) MIB-1 immunocytochemistry results were included. Demographic, molecular, immunophenotyping and MIB-1 PI data were collected from cytologic reports. Cases were subtyped according to the current World Health Organization classification and separated into indolent, aggressive, and highly aggressive groups. Statistical analysis was performed with pairwise Wilcoxon rank sum test and linear discriminant analysis to suggest appropriate PI cutpoints. RESULTS: Ninety-one NHL cases were subdivided in 56 (61.5%) indolent, 30 (33%) aggressive, and 5 (5.5%) highly aggressive lymphomas. The 3 groups had significantly different MIB-1 PIs from each other. Cutpoints were established for separating indolent (<38%), aggressive (> or =38% to < or =80.1%) and highly aggressive (>80.1%). The groups were adequately predicted in 76 cases (83.5%) using the cutpoints and 15 cases showed discrepant PIs. CONCLUSIONS: MIB-1 immunohistochemistry on CS can help to stratify B-cell NHL and showed a significant increase in PI with tumor aggressiveness. Six misclassified cases had PIs close to the cutpoints. Discrepant MIB-1 PIs were related to dilution of positive cells by non-neoplastic lymphocytes and to the overlapping continuum of features between diffuse large B-cell lymphoma and Burkitt lymphoma. Validation of our approach in an unrelated, prospective dataset is required. PMID- 20544709 TI - The application of cytogenetics and fluorescence in situ hybridization to fine needle aspiration in the diagnosis and subclassification of renal neoplasms. AB - BACKGROUND: Percutaneous fine-needle aspiration (FNA) cytology is an important diagnostic test for the evaluation and management of selected renal masses. Cytogenetic analysis of cytology specimens can serve as an adjunct for precise classification because certain tumors are associated with specific chromosomal aberrations. This study summarizes our experience with the application of conventional cytogenetics and fluorescence in situ hybridization (FISH) to renal FNA specimens. METHODS: All percutaneous renal FNAs performed during 2005 through 2008 were identified from the electronic pathology database. Results of cytogenetic and FISH analyses were correlated with the final diagnoses of the renal FNAs. RESULTS: A total of 303 renal FNAs were performed. During an onsite assessment, a portion of the cytology specimen was allocated for cytogenetic analysis in 74 cases. Karyotypic analysis or FISH was successful in 44 (59%) of these. Characteristic chromosomal abnormalities were observed in 27 cases. In 17 cases, a karyotype revealed a combination of trisomies/tetrasomies and in another 5 cases, FISH revealed trisomy 7 and 17, both of which are consistent with papillary renal cell carcinoma (RCC). Two cases showed 3p deletions consistent with clear cell RCC. Trisomy 3 was observed in 1 case of clear cell RCC. Monosomy 1 and 17 was observed in a case of papillary RCC comprised oncocytic cells. In 1 case of primary renal synovial sarcoma, FISH revealed a rearrangement at the SYT locus (18q11.2). CONCLUSIONS: Renal FNA specimens are amenable to analysis by cytogenetics and FISH in the diagnosis and subclassification of renal neoplasms. PMID- 20544710 TI - p16(INK4a) is superior to high-risk human papillomavirus testing in cervical cytology for the prediction of underlying high-grade dysplasia. AB - BACKGROUND: The primary goal of this study was to compare the clinical performance of an optimized and rigorously controlled immunocytochemical (ICC) assay for p16(INK4a) to high-risk (HR) human papillomavirus (HPV) detection by polymerase chain reaction (PCR) as diagnostic adjuncts for cytology specimens from colposcopy patients. METHODS: : The study included 403 cervical cytology specimens collected within 3 months of colposcopy. The colposcopic impression and cervical biopsy diagnosis served as the standards for correlation with cytological, p16(INK4a), and HPV data. p16(INK4a) was evaluated using an immunoperoxidase-based assay that was linear over 4 logs for the detection of HeLa-spiked positive control cytology specimens, using a threshold for positive test results that was based on receiver operating characteristic curve analysis. HR-HPV was detected by multiplex PCR using genotype-specific primers. RESULTS: : In all combined diagnostic categories (negative for intraepithelial lesion and malignancy, atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion), the p16(INK4a) ICC and HR-HPV assays, respectively, had sensitivity of 81.7% and 83.3% (P = .81) and specificity of 78.1% and 50.9% (P < .001) for the detection of underlying > or =grade 2 cervical intraepithelial neoplasia (CIN) lesions on biopsy. Furthermore, the positive predictive value of p16(INK4a) ICC was greater than that of HR-HPV for patients with biopsies > or =CIN-2 (41.2% and 24.2%, respectively, P = .001). CONCLUSIONS: : This p16(INK4a) immunocytochemical assay has superior specificity but similar sensitivity to HR-HPV testing to predict underlying high-grade dysplastic lesions in patients who are referred for colposcopy. The determination of the overall performance characteristics of p16(INK4a) immunocytochemistry, as an independent test or in combination with HPV testing in low-risk screening populations, however, will require subsequent large-scale prospective clinical trials. PMID- 20544711 TI - Induction of Foxp3 expression in T cells by cellulose acetate beads in vitro. AB - Gene expression of transforming growth factor-beta (TGF-beta) is needed to induce expression of transcription factor forkhead box P3 (Foxp3), which is required for the development and function of regulatory T (Treg) cells. The number of circulating Treg cells and the level of Foxp3 expression increase during granulocyte and monocyte apheresis (GMA), a useful therapy for ulcerative colitis. However, the mechanism underlying GMA-induced Foxp3 expression is unknown. We found that the level of TGF-beta mRNA in peripheral blood mononuclear cells (PBMCs) was augmented just after treatment of peripheral blood with a GMA carrier, cellulose acetate beads, in vitro and that Foxp3 expression in PBMCs increased after culturing these cells for 5 days after the treatment. The augmentation of TGF-beta expression was observed in CD3(-) PBMCs but not in CD3(+) T cells. Furthermore, the increase in Foxp3 expression in T cells depended on co-culture with CD3(-) PBMCs. We conclude that cellulose acetate beads have an ability to induce Foxp3 expression in peripheral blood T cells via augmentation of TGF-beta expression in CD3(-) PBMCs. PMID- 20544712 TI - Selective depletion of peripheral granulocyte/monocyte enhances the efficacy of scheduled maintenance infliximab in Crohn's disease. AB - BACKGROUND: This is the first report on a case of Crohn's disease (CD), who was successfully maintained with a combination of infliximab (IFX) and selective depletion of granulocytes/monocytes by adsorption (GMA). CASE: A 33-year-old female with CD activity index (CDAI) 294.2 responded to iv IFX (5mg/kg) administered at weeks 0, 2, and 6 in combination with 3000 mg/day oral 5 aminosalicylic acid (5-ASA; CDAI = 118). Then IFX at 8 week intervals was given as maintenance therapy. Two weeks before the 5th scheduled IFX, the patient worsened with an increase in stool frequency and a rise in CDAI. GMA was administered at weeks 5, 6, and 7 after her 6th iv IFX. Her CDAI decreased from 166.2 to 126.3 and 111.9 before 2nd and 3rd GMA sessions. She received her 7th iv IFX while the CDAI was 83.6. GMA course was repeated before 8th and 9th IFX. The patient remained in stable clinical and endoscopic remission without experiencing any serious side effect. After achieving mucosal healing, the patient decided to cease IFX therapy while continuing with GMA. CONCLUSIONS: IFX appears to induce and maintain remission of CD, but it may lose its efficacy after repeated administration. GMA is safe and by selectively depleting elevated/activated leukocytes may be a useful adjunct for IFX efficacy. PMID- 20544713 TI - Optimization of cultivation conditions in spin tubes for Chinese hamster ovary cells producing erythropoietin and the comparison of glycosylation patterns in different cultivation vessels. AB - This article describes the optimization of cultivation factor settings, that is the shaking rate and working volume in 50 mL spin tubes for a Chinese hamster ovary cell line expressing recombinant human alpha-erythropoietin, using a response D-optimal surface method. The main objectives of the research were, firstly, to determine a setting in which the product titer and product quality attributes in spin tubes are equivalent to those in 250 mL shake flasks in a seven day batch and, secondly, to find a setting in which the product titer is maximal. The model for product titer prediction as a function of shaking rate and working volume in the defined design space was successfully applied to the optimization of cultivation conditions in spin tubes for the tested cell line. Subsequently, validation experiments were carried out simultaneously in spin tubes, shake flasks and bench scale bioreactors to compare cell culture performance parameters such as growth, productivity and product quality attributes in the form of isoform profiles and glycan antennarity structures. The results of the experiments showed that similar cell culture performance and product quality could be achieved in spin tubes when compared to shake flasks. Additionally, bioreactor titers could be reproduced in spin tubes at high shaking rates and low working volumes, but with differing product quality. Cultivation at lower shaking rates in spin tubes and shake flasks produced a glycoprotein with a product quality slightly comparable to that from bioreactors, but with titers being only two thirds. PMID- 20544714 TI - Simultaneous myocardial strain and dark-blood perfusion imaging using a displacement-encoded MRI pulse sequence. AB - The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in two to three myocardial slices were repeatedly acquired using a single shot pulse sequence for 3 to 4 min, which covers a bolus infusion of Gadolinium contrast. The magnitudes of the images were T(1) weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n = 9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R(2) = 0.765, Bland-Altman standard deviation = 0.15 mL/min/g). In a group of ST-elevation myocardial infarction patients (n = 11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R(2) = 0.72), and the pixelwise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images. PMID- 20544715 TI - Objective detection of subtle freezing of gait episodes in Parkinson's disease. AB - Freezing of gait (FOG) is a clinically defined phenomenon of Parkinson's disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes. We included 10 PD patients with FOG, 10 PD patients without FOG, and 10 controls. Subjects walked on a motorized treadmill while avoiding unexpectedly appearing obstacles. Treadmill walking was videotaped, and FOG episodes were identified by two independent experts. Gait was also analyzed using detailed kinematics. Knee joint signals were processed using time-frequency analysis with combinations of sliding fast Fourier transform and wavelets transform. Twenty FOG episodes occurred during treadmill walking in 5 patients (all with clinically certified FOG), predominantly in relation to obstacle avoidance. FOG was brief when it occurred just before or after obstacle crossing and was characterized by short, rapid steps. Frequency analysis showed a typical qualitative pattern: before the FOG episode an increase in dominant frequency in the 0 to 3 Hz band (festination), followed by decreased power in 0 to 3 Hz band and an increased power in the 3 to 8 Hz band during the FOG episode. This pattern led to an increased FOG index as a qualitative measure. These approaches detected even very brief FOG with acceptable sensitivity (75-83%) and specificity (>95%). We conclude that time-frequency analysis is an appropriate approach to detect brief and subtle FOG episodes. Future work will need to decide whether this approach can support or even replace expert clinical opinion. PMID- 20544717 TI - Overexpression of Pim-1 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. AB - BACKGROUND AND OBJECTIVES: It is well known that provirus integration site for Moloney murine leukemia virus 1 (Pim-1) plays an essential role in the occurrence and development of tumors. Here, we investigated expression of Pim-1 in esophageal squamous cell carcinoma (ESCC) and assessed the correlation between Pim-1 level and prognosis of the patients with ESCC. METHODS: Expression of Pim-1 was investigated by RT-PCR, immunohistochemistry, and in situ hybridization methods. Kaplan-Meier statistics was used to examine the relationship between levels of Pim-1 and prognosis using log-rank test. RESULTS: The results demonstrated that ESCC tissues appeared strong expression levels of Pim-1 mRNA and protein while the normal esophageal tissues were either negative or showed only weak Pim-1 mRNA and protein levels. In addition, we found that Pim-1 expression was significantly correlated with histology grade, clinical staging, and lymph node metastasis (all P < 0.05), but not related to age and sex (all P > 0.05). Furthermore, the results of survival rates analyzed by Kaplan-Meier curve revealed that patients with high Pim-1 mRNA and protein expressions had a poorer prognosis than those with the low Pim-1 expression (P = 0.010 and 0.001, respectively). CONCLUSION: These findings demonstrate that Pim-1 may be used as molecular marker for predicting the prognosis of patients with ESCC. PMID- 20544716 TI - Abnormal explicit but normal implicit sequence learning in premanifest and early Huntington's disease. AB - Learning may occur with or without awareness, as explicit (intentional) or implicit (incidental) learning. The caudate nucleus and the putamen, which are affected early in Huntington's disease (HD), are thought to be essential for motor sequence learning. However, the results of existing studies are inconsistent concerning presence/absence of deficits in implicit and explicit motor sequence learning in HD. We assessed implicit and explicit motor sequence learning using sequences of equivalent structure in 15 individuals with a positive HD genetic test (7 premanifest; 8 early stage disease) and 11 matched controls. The HD group showed evidence of normal implicit motor sequence learning, whereas explicit motor sequence learning was impaired in manifest and premanifest HD gene carriers, with progressive decline with progressive disease. Explicit sequence learning may be a useful cognitive biomarker for HD progression. PMID- 20544718 TI - Trends in treatment for synchronous colorectal liver metastases: differences in outcome before and after 2000. AB - BACKGROUND: The traditional treatment for stage IV colorectal cancer has changed from palliative chemotherapy toward an aggressive multimodality approach. In the current study outcome in patients who underwent surgery for synchronous colorectal liver metastases (CLM) in a single center was evaluated. METHODS: From January 1991 to May 2008 all consecutive patients with synchronous CLM who underwent curative resection of both primary and metastatic disease were included. Date of resection was divided into two groups: date of hepatic resection before and after the year 2000. RESULTS: Fifty patients (26%) with synchronous CLM were resected before 2000 and 142 patients (74%) underwent resection after 2000. The estimated 5-year disease-free survival before and after 2000 was 9% and 27%, respectively (P = 0.379). More patients who underwent resection after 2000 were treated with local therapy or underwent resection for intra-hepatic recurrence (62% vs. 28%, P = 0.033). The estimated 5-year survival before and after 2000 was 26% and 44%, respectively (P = 0.001). CONCLUSION: Survival rates in patients with synchronous CLM have been increased in the past decade. The introduction of new chemotherapeutic drugs and a more aggressive treatment approach in patients with liver recurrence were probably major factors in this progress. PMID- 20544719 TI - Placental specializations of the mountain spiny lizard Sceloporus jarrovi. AB - The lizard Sceloporus jarrovi (Phrynosomatidae) is one of the most widely studied viviparous reptiles of North America. Past research has assumed that placentation in this species is relatively simple and functions mainly in gas exchange. Our examination of the late stage placenta via transmission electron microscopy reveals that S. jarrovi has a unique combination of placental characteristics, with unusual specializations for secretion and absorption. In the chorioallantoic placenta, chorionic and uterine tissues are directly apposed through eggshell loss, and their epithelia are greatly attenuated, enhancing gas exchange; this placenta shows evidence of both nutrient transfer and endocrine function. Contrary to past inferences, a yolk sac placenta forms from the avascular omphalopleure and persists through the end of gestation. The uterine epithelium is enlarged and secretory, and the fetal omphalopleure shows branching absorptive channels and other specializations for uptake. Elsewhere, the omphalopleure develops elongated folds that protrude into a coagulum of degenerating shell membrane and other organic material. Uterine tissue in this region shows specializations for absorption. Placental features in S. jarrovi have unexpected functional implications, and challenge assumptions that specializations for nutrient transfer are confined to matrotrophic species. PMID- 20544724 TI - Shear-mode contact splitting for a microtextured elastomer film. PMID- 20544725 TI - Competition between SLP76 and LAT for PLCgamma1 binding in resting T cells. AB - The constitutive interaction between the P1 domain (a 67-amino-acid functional domain within the proline-rich region) of SLP76 and the SH3 domain of phospholipase Cgamma1 (PLCgamma1) has been shown. To determine the significance of the interaction between SLP76 and PLCgamma1 in resting T cells, we examined molecules associated with PLCgamma1 in the absence of both SLP76 and, more specifically, the P1 domain of SLP76. Using a mutant Jurkat T-cell line, we showed that PLCgamma1 associated with LAT when the constitutive association with SLP76 was blocked. We also found that the PLCgamma1 association with LAT occurred in the membranes of resting T cells. Further experiments demonstrated that LAT competed with SLP76 for PLCgamma1 binding and that the LAT interaction with PLCgamma1 was mediated by the SH3 domain of PLCgamma1. Collectively, these results suggest that the constitutive association of SLP76 with PLCgamma1 is required to prevent the association with LAT as well as the premature recruitment of PLCgamma1 to the cell membrane. PMID- 20544726 TI - Hierarchical Bayesian modeling of random and residual variance-covariance matrices in bivariate mixed effects models. AB - Bivariate mixed effects models are often used to jointly infer upon covariance matrices for both random effects (u) and residuals (e) between two different phenotypes in order to investigate the architecture of their relationship. However, these (co)variances themselves may additionally depend upon covariates as well as additional sets of exchangeable random effects that facilitate borrowing of strength across a large number of clusters. We propose a hierarchical Bayesian extension of the classical bivariate mixed effects model by embedding additional levels of mixed effects modeling of reparameterizations of u level and e-level (co)variances between two traits. These parameters are based upon a recently popularized square-root-free Cholesky decomposition and are readily interpretable, each conveniently facilitating a generalized linear model characterization. Using Markov Chain Monte Carlo methods, we validate our model based on a simulation study and apply it to a joint analysis of milk yield and calving interval phenotypes in Michigan dairy cows. This analysis indicates that the e-level relationship between the two traits is highly heterogeneous across herds and depends upon systematic herd management factors. PMID- 20544727 TI - Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation. AB - Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance. PMID- 20544729 TI - Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system. AB - NOD mice spontaneously develop insulin-dependent diabetes around 10-40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward beta cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS(-/-) and ICOSL(-/-) NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4(+) and CD8(+) T cells from diseased donors to naive NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS(-/-) NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS(-/-) NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells. PMID- 20544728 TI - Bcl11b represses a mature T-cell gene expression program in immature CD4(+)CD8(+) thymocytes. AB - Bcl11b is a transcription factor that, within the hematopoietic system, is expressed specifically in T cells. Although Bcl11b is required for T-cell differentiation in newborn Bcl11b-null mice, and for positive selection in the adult thymus of mice bearing a T-cell-targeted deletion, the gene network regulated by Bcl11b in T cells is unclear. We report herein that Bcl11b is a bifunctional transcriptional regulator, which is required for the correct expression of approximately 1000 genes in CD4(+)CD8(+)CD3(lo) double-positive (DP) thymocytes. Bcl11b-deficient DP cells displayed a gene expression program associated with mature CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) thymocytes, including upregulation of key transcriptional regulators, such as Zbtb7b and Runx3. Bcl11b interacted with regulatory regions of many dysregulated genes, suggesting a direct role in the transcriptional regulation of these genes. However, inappropriate expression of lineage-associated genes did not result in enhanced differentiation, as deletion of Bcl11b in DP cells prevented development of SP thymocytes, and that of canonical NKT cells. These data establish Bcl11b as a crucial transcriptional regulator in thymocytes, in which Bcl11b functions to prevent the premature expression of genes fundamental to the SP and NKT cell differentiation programs. PMID- 20544730 TI - Plasma and liver proteomic analysis of 3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1-(1 piperidinylmethyl)-1,3-2H-indol-2-one-induced hepatotoxicity in Wistar rats. AB - 3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24), a synthetic anti-angiogenic compound, inhibits the growth and metastasis of certain tumors. Previous works have shown that Z24 induces hepatotoxicity in rodents. We examined the hepatotoxic mechanism of Z24 at the protein level and looked for potential biomarkers. We used 2-DE and MALDI-TOF/TOF MS to analyze alternatively expressed proteins in rat liver and plasma after Z24 administration. We also examined apoptosis in rat liver and measured levels of intramitochondrial ROS and NAD(P)H redox in liver cells. We found that 22 nonredundant proteins in the liver and 11 in the plasma were differentially expressed. These proteins were involved in several important metabolic pathways, including carbohydrate, lipid, amino acid, and energy metabolism, biotransformation, apoptosis, etc. Apoptosis in rat liver was confirmed with the terminal deoxynucleotidyl transferase dUTP-nick end labeling assay. In mitochondria, Z24 increased the ROS and decreased the NAD(P)H levels. Thus, inhibition of carbohydrate aerobic oxidation, fatty acid beta-oxidation, and oxidative phosphorylation is a potential mechanism of Z24-induced hepatotoxicity, resulting in mitochondrial dysfunction and apoptosis-mediated cell death. In addition, fetub protein and argininosuccinate synthase in plasma may be potential biomarkers of Z24-induced hepatotoxicity. PMID- 20544731 TI - A systems biology view of evolutionary genetics: network-driven processes incorporate much more variation than evolutionary genetics can handle. This variation is hard to formalise but allows fast change. PMID- 20544732 TI - Proteolysis approach without chemical modification for a simple and rapid analysis of disulfide bonds using thermostable protease-immobilized microreactors. AB - Disulfide bonds in proteins are important not only for the conformational stability of the protein but also for the regulation of oxidation-reduction in signal transduction. The conventional method for the assignment of disulfide bond by chemical cleavage and/or proteolysis is a time-consuming multi-step procedure. In this study, we report a simple and rapid analysis of disulfide bond from protein digests that were prepared by the thermostable protease-immobilized microreactors. The feasibility and performance of this approach were evaluated by digesting lysozyme and BSA at several temperatures. The proteins which stabilize their conformations by disulfide bonds were thermally denatured during proteolysis and were efficiently digested by the immobilized protease but not by free protease. The digests were directly analyzed by ESI-TOF MS without any purification or concentration step. All four disulfide bonds on lysozyme and 10 of 17 on BSA were assigned from the digests by the trypsin-immobilized microreactor at 50 degrees C. The procedure for proteolysis and the assignment were achieved within 2 h without any reduction and alkylation procedure. From the present results, the proteolysis approach by the thermostable protease immobilized microreactor provides a strategy for the high-throughput analysis of disulfide bond in proteomics. PMID- 20544733 TI - Non-coding RNAs: Meet thy masters. AB - New DNA sequencing technologies have provided novel insights into eukaryotic genomes, epigenomes, and the transcriptome, including the identification of new non-coding RNA (ncRNA) classes such as promoter-associated RNAs and long RNAs. Moreover, it is now clear that up to 90% of eukaryotic genomes are transcribed, generating an extraordinary range of RNAs with no coding capacity. Taken together, these new discoveries are modifying the status quo in genomic science by demonstrating that the eukaryotic gene pool is divided into two distinct categories of transcripts: protein-coding and non-coding. The function of the majority of ncRNAs produced by the transcriptome is largely unknown; however, it is probable that many are associated with epigenetic mechanisms. The purpose of this review is to describe the most recent discoveries in the ncRNA field that implicate these molecules as key players in the epigenome. PMID- 20544734 TI - Rediscovering Waddington in the post-genomic age: Operationalising Waddington's epigenetics reveals new ways to investigate the generation and modulation of phenotypic variation. PMID- 20544735 TI - Why bacteria matter in animal development and evolution. AB - While largely studied because of their harmful effects on human health, there is growing appreciation that bacteria are important partners for invertebrates and vertebrates, including man. Epithelia in metazoans do not only select their microbiota; a coevolved consortium of microbes enables both invertebrates and vertebrates to expand the range of diet supply, to shape the complex immune system and to control pathogenic bacteria. Microbes in zebrafish and mice regulate gut epithelial homeostasis. In a squid, microbes control the development of the symbiotic light organ. These discoveries point to a key role for bacteria in any metazoan existence, and imply that beneficial bacteria-host interactions should be considered an integral part of development and evolution. PMID- 20544736 TI - TRPM1: the endpoint of the mGluR6 signal transduction cascade in retinal ON bipolar cells. AB - For almost 30 years the ion channel that initiates the ON visual pathway in vertebrate vision has remained elusive. Recent findings now indicate that the pathway, which begins with unbinding of glutamate from the metabotropic glutamate receptor 6 (mGluR6), ends with the opening of the transient receptor potential (TRP)M1 cation channel. As a component of the mGluR6 signal transduction pathway, mutations in TRPM1 would be expected to cause congenital stationary night blindness (CSNB), and several such mutations have already been identified in CSNB families. Furthermore, expression of TRPM1 in both the retina and skin raises the possibility that a genetic link exists between certain types of visual and skin disorders. PMID- 20544737 TI - What the European Research Council is looking for in applications. PMID- 20544739 TI - Intracellular antibodies and cancer: new technologies offer therapeutic opportunities. AB - Since the realisation that the antigen-binding regions of antibodies, the variable (V) regions, can be uncoupled from the rest of the molecule to create fragments that recognise and abrogate particular protein functions in cells, the use of antibody fragments inside cells has become an important tool in bioscience. Diverse libraries of antibody fragments plus in vivo screening can be used to isolate single chain variable fragments comprising VH and VL segments or single V-region domains. Some of these are interfering antibody fragments that compete with protein-protein interactions, providing lead molecules for drug interactions that until now have been considered difficult or undruggable. It may be possible to deliver or express antibody fragments in target cells as macrodrugs per se. In future incarnations of intracellular antibodies, however, the structural information of the interaction interface of target and antibody fragment should facilitate development of binding site mimics as small drug-like molecules. This is a new dawn for intracellular antibody fragments both as macrodrugs and as precursors of drugs to treat human diseases and should finally lead to the removal of the epithet of the 'undruggable' protein-protein interactions. PMID- 20544740 TI - An embryonic story: analysis of the gene regulative network controlling Xist expression in mouse embryonic stem cells. AB - In mice, dosage compensation of X-linked gene expression is achieved through the inactivation of one of the two X-chromosomes in XX female cells. The complex epigenetic process leading to X-inactivation is largely controlled by Xist and Tsix, two non-coding genes of opposing function. Xist RNA triggers X-inactivation by coating the inactive X, while Tsix is critical for the designation of the active X-chromosome through cis-repression of Xist RNA accumulation. Recently, a plethora of trans-acting factors and cis-regulating elements have been suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X-linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. PMID- 20544741 TI - RNA as the substrate for epigenome-environment interactions: RNA guidance of epigenetic processes and the expansion of RNA editing in animals underpins development, phenotypic plasticity, learning, and cognition. PMID- 20544743 TI - Excerpt from: World records in chemistry, H.-J. Quadbeck-Seeger (Ed.), Wiley-VCH, 1999. PMID- 20544744 TI - Group 2 promoted hydrogen release from NMe2H.BH3: intermediates and catalysis. AB - Both homo- and heteroleptic alkyl and amide complexes of the Group 2 elements Mg and Ca are shown to be active for the catalytic dehydrocoupling of Me(2)NH.BH(3). Reactions of either magnesium dialkyls or the beta-diketiminate complex [HC{(Me)CN(Dipp)}(2)MgnBu] with four or two equivalents of Me(2)NHBH(3), respectively, produce compounds containing the [H(3)BNMe(2)BH(2)Me(2)N](-) ion, which coordinates to the magnesium centers through Mg-N and Mg...HB interactions in both the solution and solid states. Thermolysis of these compounds at 60 degrees C produces the cyclic product [(H(2)BNMe(2))(2)] and, it is proposed, magnesium hydrido species by an unprecedented delta-hydride elimination process. Calcium-based species, although less reactive than their magnesium-based counterparts, are found to engage in similar dehydrocoupling reactivity and to produce a similar distribution of products under thermally promoted catalytic conditions. A mechanism for these observations is presented that involves initial production and insertion of H(2)B=NMe(2) into polarized M-N bonds as the major B N bond-forming step. The efficacy of this insertion and subsequent beta- or delta hydride elimination steps is proposed to be dependent upon the charge density and polarizing capability of the participating Group 2 center, providing a rationale for the observed differences in reactivity between magnesium and calcium. PMID- 20544745 TI - Cu and Au metal-organic frameworks bridge the gap between homogeneous and heterogeneous catalysts for alkene cyclopropanation reactions. AB - The copper and gold metal-organic frameworks (MOFs) [Cu(3)(BTC)(2)(H(2)O)(3)](n), [Cu(3)(BTC)(2)] (BTC=benzene-1,3,5-tricarboxylate), and IRMOF-3-SI-Au are active and reusable solid catalysts for the cyclopropanation of alkenes with high chemo- and diastereoselectivities. This type of material gives better results than previous solid catalysts while working together with the homogeneous catalysts. These MOFs can help to bridge the gap between homogeneous and heterogeneous catalysis. PMID- 20544746 TI - Simple biosensor with high selectivity and sensitivity: thiol-specific biomolecular probing and intracellular imaging by AIE fluorogen on a TLC plate through a thiol-ene click mechanism. AB - A handy, specific, sensitive bioprobe has been developed. Tetraphenylethene (TPE) was functionalized by a maleimide (MI) group, giving a TPE-MI adduct that was nonemissive in both solution and the solid state. It was readily transformed into a fluorogen showing an aggregation-induced emission (AIE) property by the click addition of thiol to its MI pendant. The click reaction and the AIE effect enabled TPE-MI to function as a thiol-specific bioprobe in the solid state. Thus, the spot of TPE-MI on a TLC plate became emissive when it had been exposed to L cysteine, an amino acid containing a thiol group, but remained nonemissive when exposed to other amino acids that lack free thiol units. The thiol-activated emission was rapid and strong, readily detected by the naked eye at an analyte concentration as low as approximately 1 ppb, thanks to the "lighting up" nature of the bioprobing process. Similarly, the emission of TPE-MI was turned on only by the proteins containing free thiol units, such as glutathione. Clear fluorescence images were taken when living cells were stained by using TPE-MI as a visualization agent, affording a facile fluorescent maker for mapping the distribution of thiol species in cellular systems. PMID- 20544747 TI - Phosphine-alkene ligands as mechanistic probes in the Pauson-Khand reaction. AB - An alkyne tetracarbonyl dicobalt complex with a chelated phosphine-alkene ligand, in which the phosphorus atom and the alkene from the ligand are attached to the same cobalt atom has been prepared, isolated, and characterized by X-ray crystallography. The complex serves as a mechanistic model for an intermediate of the Pauson-Khand (PK) reaction. Although the alkene fragment is located in an equatorial coordination site with an appropriate orientation, and, therefore, should undergo insertion, it failed to give the PK product upon either thermal or N-methylmorpholine N-oxide activation. However, a phosphine-alkene complex that contains a terminal alkene readily provided the corresponding PK product. We attribute this change in reactivity to the different ability of each olefin to undergo 1,2-insertion. These results provide further insights into the factors that govern a crucial step in the PK reaction, the olefin insertion. PMID- 20544748 TI - A general approach to fabricate diverse noble-metal (Au, Pt, Ag, Pt/Au)/Fe2O3 hybrid nanomaterials. AB - A novel, facile, and general one-pot strategy is explored for the synthesis of diverse noble-metal (Au, Pt, Ag, or Pt/Au)/Fe(2)O(3) hybrid nanoparticles with the assistance of lysine (which is a nontoxic, user friendly amino acid that is compatible with organisms) and without using any other functionalization reagents. Control experiments show that lysine, which contains both amino and carboxylic groups, plays dual and crucial roles as both linker and capping agents in attaching noble metals with a small size and uniform distribution onto an Fe(2)O(3) support. Considering the perfect compatibility of lysine with organism, this approach may find potentials in biochemistry and biological applications. Furthermore, this novel route is also an attractive alternative and supplement to the current methods using a silane coupling agent or polyelectrolyte for preparing hybrid nanomaterials. To demonstrate the usage of such hybrid nanomaterials, a chemical gas sensor has been fabricated from the as-synthesized Au/Fe(2)O(3) nanoparticles and investigated for ethanol detection. Results show that the hybrid sensor exhibits significantly improved sensor performances in terms of high sensitivity, low detection limit, better selectivity, and good reproducibility in comparison with pristine Fe(2)O(3). Most importantly, this general approach can be further employed to fabricate other hybrid nanomaterials based on different support materials. PMID- 20544750 TI - Atomistic characterisation of Li+ mobility and conductivity in Li(7-x)PS(6-x)Ix argyrodites from molecular dynamics simulations, solid-state NMR, and impedance spectroscopy. AB - The atomistic mechanisms of Li(+) ion mobility/conductivity in Li(7-x)PS(6-x)I(x) argyrodites are explored from both experimental and theoretical viewpoints. Ionic conductivity in the title compound is associated with a solid-solid phase transition, which was characterised by low-temperature differential scanning calorimetry, (7)Li and (127)I NMR investigations, impedance measurements and molecular dynamics simulations. The NMR signals of both isotopes are dominated by anisotropic interactions at low temperatures. A significant narrowing of the NMR signal indicates a motional averaging of the anisotropic interactions above 177+/ 2 K. The activation energy to ionic conductivity was assessed from both impedance spectroscopy and molecular dynamics simulations. The latter revealed that a series of interstitial sites become accessible to the Li(+) ions, whilst the remaining ions stay at their respective sites in the argyrodite lattice. The interstitial positions each correspond to the centres of tetrahedra of S/I atoms, and differ only in terms of their common corners, edges, or faces with adjacent PS(4) tetrahedra. From connectivity analyses and free-energy rankings, a specific tetrahedron is identified as the key restriction to ionic conductivity, and is clearly differentiated from local mobility, which follows a different mechanism with much lower activation energy. Interpolation of the lattice parameters as derived from X-ray diffraction experiments indicates a homogeneity range for Li(7 x)PS(6-x)I(x) with 0.97 < or = x < or = 1.00. Within this range, molecular dynamics simulations predict Li(+) conductivity at ambient conditions to vary considerably. PMID- 20544749 TI - 3D-2D-0D stepwise deconstruction of a water framework templated by a nanoporous organic-inorganic hybrid host. AB - The supramolecular salt [H(2)pip](3)[Ge(hedp)(2)].14H(2)O (1) [H(2)pip(2+)=piperazine cation C(4)H(12)N(2)(2+); hedp(5-)=deprotonated form of etidronic acid, C(2)H(3)P(2)O(7)(5-)) is reported. This consists of an organic inorganic hybrid hydrogen-bonded nanoporous framework, the internal surface of which acts as a template for the three-dimensional (3D) clustering of water molecules. The structure and molecular dynamics of this material are characterised by single-crystal X-ray diffraction, thermogravimetric analysis, Raman (H/D isotopic substitution) spectroscopy, and (2)H solid-state (wide-line and MAS) NMR spectroscopy. Material 1 is shown to be unusual because 1) few nanoporous materials exhibit a well-organised 3D framework of water molecules, 2) it provides a unique opportunity to follow experimentally and to rationalise the deconstruction of a 3D water framework and 3) despite the fact that the hybrid framework is a supramolecular salt, the structure does not collapse after dehydration and the final material is crystalline. PMID- 20544751 TI - Simple synthesis of ruthenium pi complexes of aromatic amino acids and small peptides. AB - The interaction of [Ru(eta(6)-C(10)H(8))(Cp)](+) (Cp=C(5)H(5)) with aromatic amino acids (L-phenylalanine, L-tyrosine, L-tryptophane, D-phenylglycine, and L threo-3-phenylserine) under visible-light irradiation gives the corresponding [Ru(eta(6)-amino acid)(Cp)](+) complexes in near-quantitative yield. The reaction proceeds in air at room temperature in water and tolerates the presence of non aromatic amino acids (except those which are sulfur containing), monosaccharides, and nucleotides. The complex [Ru(eta(6)-C(10)H(8))(Cp)](+) was also used for selective labeling of Tyr and Phe residues of small peptides, namely, angiotensin I and II derivatives. PMID- 20544752 TI - Near-IR core-substituted naphthalenediimide fluorescent chemosensors for zinc ions: ligand effects on PET and ICT channels. AB - Near-IR (NIR) emission can offer distinct advantages for both in vitro and in vivo biological applications. Two NIR fluorescent turn-on sensors N,N'-di-n-butyl 2-(N-{2-[bis(pyridin-2-ylmethyl)amino]ethyl})-6-(N-piperidinyl)naphthalene 1,4,5,8-tetracarboxylic acid bisimide and N,N'-di- n-butyl-2-[N,N,N'-tri(pyridin 2-ylmethyl)amino]ethyl-6-(N-piperidinyl)naphthalene-1,4,5,8-tetracarboxylic acid bisimide (PND and PNT) for Zn(2+) based on naphthalenediimide fluorophore are reported. Our strategy was to choose core-substituted naphthalenediimide (NDI) as a novel NIR fluorophore and N,N-di(pyridin-2-ylmethyl)ethane-1,2-diamine (DPEA) or N,N,N'-tri(pyridin-2-ylmethyl)ethane-1,2-diamine (TPEA) as the receptor, respectively, so as to improve the selectivity to Zn(2+). In the case of PND, the negligible shift in absorption and emission spectra is strongly suggestive that the secondary nitrogen atom (directly connected to the NDI moiety, N(1)) is little disturbed with Zn(2+). The fluorescence enhancement of PND with Zn(2+) titration is dominated with a typical photoinduced electron-transfer (PET) process. In contrast, the N(1) atom for PNT can participate in the coordination of Zn(2+) ion, diminishing the electron delocalization of the NDI moiety and resulting in intramolecular charge-transfer (ICT) disturbance. For PNT, the distinct blueshift in both absorbance and fluorescence is indicative of a combination of PET and ICT processes, which unexpectedly decreases the sensitivity to Zn(2+). Due to the differential binding mode caused by the ligand effect, PND shows excellent selectivity to Zn(2+) over other metal ions, with a larger fluorescent enhancement centered at 650 nm. Also both PND and PNT were successfully used to image intracellular Zn(2+) ions in the living KB cells. PMID- 20544754 TI - Efficient one-pot synthesis of N-containing heterocycles by multicomponent coupling of silicon-tethered diynes, nitriles, and isocyanides through intramolecular cyclization of iminoacyl-Zr intermediates. AB - An efficient multicomponent synthesis of 5-azaindoles and dihydropyrrolo[3,2 c]azepines was achieved by zirconocene-mediated coupling of silicon-tethered diynes, nitriles, and isocyanides. The synthesis, structures, and intramolecular cyclization of mono- and bis(iminoacyl)--Zr intermediates were investigated to elucidate the reaction process. Upon hydrolysis, the isolated mono(iminoacyl)--Zr intermediates underwent intramolecular cyclization to afford tetrasubstituted 5 azaindoles, whereas intramolecular cyclization of bis(iminoacyl)--Zr intermediates led to the formation of dihydropyrrolo[3,2-c]azepines. The structure of a bis(iminoacyl)--Zr intermediate, formed through insertion of two molecules of CyNC into the Zr--C bond, and structures of two dihydropyrrolo[3,2 c]azepines were characterized by single-crystal X-ray structural analysis. PMID- 20544753 TI - N-sulfinyl amines as a nitrogen source in the asymmetric intramolecular aza Michael reaction: total synthesis of (-)-pinidinol. AB - N-Sulfinyl amines have been successfully employed as nitrogen nucleophiles for the asymmetric intramolecular aza-Michael reaction. The synthetic strategy involves a cross-metathesis reaction followed by the Michael-type cyclization, either in a base-catalyzed two-step procedure or in a tandem fashion. The developed methodology allows access to chiral substituted pyrrolidines and piperidines bearing one or two stereocenters and it has been applied to the synthesis of the piperidine alkaloid (-)-pinidinol. PMID- 20544755 TI - AlCl3 and BDMAEE: a pair of potent reactive regulators of aryl Grignard reagents and highly catalytic asymmetric arylation of aldehydes. PMID- 20544756 TI - Zn-Zn-bonded compounds that contain monoanionic oxygen-donor ligands. PMID- 20544757 TI - Temperature-controlled supramolecular vesicles modulated by p sulfonatocalix[5]arene with pyrene. PMID- 20544758 TI - Colloidal hybrid nanostructures: a new type of functional materials. AB - One key goal of nanocrystal research is the development of experimental methods to selectively control the composition and shape of nanocrystals over a wide range of material combinations. The ability to selectively arrange nanosized domains of metallic, semiconducting, and magnetic materials into a single hybrid nanoparticle offers an intriguing route to engineer nanomaterials with multiple functionalities or the enhanced properties of one domain. In this Review, we focus on recent strategies used to create semiconductor-metal hybrid nanoparticles, present the emergent properties of these multicomponent materials, and discuss their potential applicability in different technologies. PMID- 20544759 TI - Single bifunctional ruthenium catalyst for one-pot cyclization and hydration giving functionalized indoles and benzofurans. PMID- 20544760 TI - Chiral self-recognition and self-discrimination of strapped perylene bisimides by pi-stacking dimerization. PMID- 20544761 TI - Data processing on a unimolecular platform. PMID- 20544762 TI - Autoxidative carbon-carbon bond formation from carbon-hydrogen bonds. PMID- 20544763 TI - An isoreticular series of metal-organic frameworks with dendritic hexacarboxylate ligands and exceptionally high gas-uptake capacity. PMID- 20544764 TI - A structured macroporous silicon/graphene heterojunction for efficient photoconversion. PMID- 20544765 TI - The synthesis of an extra-large-pore zeolite with double three-ring building units and a low framework density. PMID- 20544766 TI - Full chirality transfer in the conversion of secondary alcohols into tertiary boronic esters and alcohols using lithiation-borylation reactions. PMID- 20544767 TI - Aryl trifluoroborates in Suzuki-Miyaura coupling: the roles of endogenous aryl boronic acid and fluoride. PMID- 20544768 TI - Nonhydrolytic synthesis of branched alkoxysiloxane oligomers Si[OSiH(OR)2]4 (R=Me, Et). PMID- 20544769 TI - Highly selective ratiometric emission color change by zinc-assisted self-assembly processes. PMID- 20544772 TI - Modification of substrate specificity resulting in an epoxide hydrolase with shifted enantiopreference for (2,3-epoxypropyl)benzene. AB - Random mutagenesis targeted at hotspots of noncatalytic active-site residues of potato epoxide hydrolase StEH1 combined with an enzyme-activity screen allowed the isolation of enzyme variants displaying altered enantiopreference in the catalyzed hydrolysis of (2,3-epoxypropyl)benzene. The wild-type enzyme favored the S enantiomer with a ratio of 2.5:1, whereas the variant displaying the most radical functional changes showed a 15:1 preference for the R enantiomer. This mutant had accumulated four substitutions distributed over two out of four mutated hotspots: W106L, L109Y, V141K, and I151V. The underlying causes of the enantioselectivity were a decreased catalytic efficiency in the catalyzed hydrolysis of the S enantiomer combined with retained activity with the R enantiomer. The results demonstrate the feasibility of molding the stereoselectivity of this biocatalytically relevant enzyme. PMID- 20544774 TI - Towards dynamic drug design: identification and optimization of beta galactosidase inhibitors from a dynamic hemithioacetal system. AB - A discovery strategy relying on the identification of fragments through resolution of a constitutional dynamic system, coupled to subsequent static ligand design and optimization, is demonstrated. The strategic design and synthesis of the best molecular fragments identified from a dynamic hemithioacetal system into static ligand structures yielded a range of beta galactosidase inhibitors. Two series of structures mimicking the hemithioacetal motif were envisaged: thioglycosides and C-glycosides. Inhibition studies provided important structural information for the two groups, and 1-thiobenzyl beta-D-galactopyranoside demonstrated the best inhibitory effects. PMID- 20544775 TI - Triplexes with 8-Aza-2'-deoxyisoguanosine replacing protonated dC: probing third strand stability with a fluorescent nucleobase targeting duplex DNA. AB - The fluorescent 8-aza-2'-deoxyisoguanosine (4) as well as the parent 2' deoxyisoguanosine (1) were used as protonated dCH(+) surrogates in the third strand of oligonucleotide triplexes. Stable triplexes were formed by Hoogsteen base pairing. In contrast to dC, triplexes containing nucleoside 1 or 4 in place of dCH(+) are already formed under neutral conditions or even at alkaline pH values. Triplex melting can be monitored separately from duplex dissociation in cases in which the third strand contains the fluorescent nucleoside 4. Third strand binding of oligonucleotides with 4, opposite to dG, was selective as demonstrated by hybridisation experiments studying mismatch discrimination. Third strand binding is more efficient when the stability of the DNA duplex is reduced by mismatches, giving third-strand binding more flexibility. PMID- 20544776 TI - Enzymic disruption of N-aroyl-L-homoserine lactone-based quorum sensing. PMID- 20544777 TI - Methylene blue adsorption on a DMPA lipid langmuir monolayer. AB - Adsorption of methylene blue (MB) onto a dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer is studied by molecular dynamics (MD) simulations, UV reflection spectroscopy and surface potential measurements. The free-energy profile associated with MB transfer from water to the lipid monolayer shows two minima of -66 and -60 kJ mol(-1) for its solid and gas phase, respectively, corresponding to a spontaneous thermodynamic process. From the position of the free-energy minima, it is possible to predict the precise location of MB in the interior of the DMPA monolayer. Thus, MB is accommodated in the phosphoryl or carbonyl region of the DMPA Langmuir air/water interface, depending on the isomorphic state (solid or gas phase, respectively). Reorientation of MB, measured from the bulk solution to the interior of the lipid monolayer, passes from a random orientation in bulk solution to an orientation parallel to the surface of the lipid monolayer when MB is absorbed. PMID- 20544778 TI - Local work function differences at line defects in aluminium oxide on NiAl(110). PMID- 20544780 TI - Energy landscapes of clusters bound by short-ranged potentials. PMID- 20544779 TI - Systematic variation of length ratio and the formation of smectic A and smectic C phases. AB - The phase diagrams of four binary mixtures of chemically similar smectogenic mesogens differing only in molecular length are investigated. In these bidisperse systems the length ratio varies systematically. The phase diagrams show the stabilization of the smectic A and the destabilization of the smectic C phase with increasing length ratio as a general trend. Detailed small-angle X-ray diffraction and electro-optic measurements revealed a decrease in smectic translational order and a continuous reduction of the tilt angle with increasing length difference. These surprising results are of general interest for the understanding of the structure and dynamics of smectic phases. The remarkably strong impact of the length difference on the smectic layer structure and the phase behavior is discussed from a mechanistic point of view taking into account sterical interactions. For the observed structural changes in these bidisperse smectics we propose pronounced out-of-layer fluctuations with increasing length difference as driving force, causing neighboring molecules within nearest layer into a smectic A-like packing. PMID- 20544781 TI - Boron atoms as loop accelerator and surface stabilizer in platelet-type carbon nanofibers. PMID- 20544782 TI - Role of low-coordinated surface sites in olefin hydrogenation: a molecular beam study on Pd nanoparticles and Pd(111). PMID- 20544783 TI - Synthesis, 3D-QSAR, and structural modeling of benzolactam derivatives with binding affinity for the D(2) and D(3) receptors. AB - A series of 37 benzolactam derivatives were synthesized, and their respective affinities for the dopamine D(2) and D(3) receptors evaluated. The relationships between structures and binding affinities were investigated using both ligand based (3D-QSAR) and receptor-based methods. The results revealed the importance of diverse structural features in explaining the differences in the observed affinities, such as the location of the benzolactam carbonyl oxygen, or the overall length of the compounds. The optimal values for such ligand properties are slightly different for the D(2) and D(3) receptors, even though the binding sites present a very high degree of homology. We explain these differences by the presence of a hydrogen bond network in the D(2) receptor which is absent in the D(3) receptor and limits the dimensions of the binding pocket, causing residues in helix 7 to become less accessible. The implications of these results for the design of more potent and selective benzolactam derivatives are presented and discussed. PMID- 20544784 TI - A combined high-resolution mass spectrometric and in silico approach for the characterisation of small ligands of beta2-microglobulin. AB - Beta(2)-microglobulin (beta(2)-m) is a protein responsible for a severe complication of long-term hemodialysis, known as dialysis-related amyloidosis, in which initial beta(2)-m misfolding leads to amyloid fibril deposition, mainly in the skeletal tissue. Whereas much attention is paid to understanding the complex mechanism of amyloid formation, the evaluation of small molecules that may bind beta(2)-m and possibly inhibit the aggregation process is still largely unexplored mainly because the protein lacks a specific active site. Based on our previous findings, we selected a pilot set of sulfonated molecules that are known to either bind or not to the protein, including binders that are anti amyloidogenic. We show how a complementary approach, using high-resolution mass spectrometry and in silico studies, can offer rapid and precise information on affinity, as well as insight into the structural requisites that favour or disfavour the inhibitory activity. Overall, this approach can be used for predictive purposes and for a rapid screening of fibrillogenesis inhibitors. PMID- 20544785 TI - Orexin receptor antagonists: a new concept in CNS disorders? PMID- 20544786 TI - Off-target effects related to the phosphorothioate modification of nucleic acids. AB - Phosphorothioate antisense oligonucleotides have been widely used in clinical studies for rational sequence-specific gene silencing. However, several sequence unspecific off-target effects have been recently described for this compound class. In contrast to siRNA-mediated knockdown of the same gene, the bcl-2 targeted oblimersen (Genasense, G3139) downregulates a number of proteins involved in apoptotic resistance and several glycolytic enzymes in 607B human melanoma cells. Regardless of their target, phosphorothioate-modified antisense and siRNA compounds, but not oligonucleotides with a phosphodiester backbone, resulted in a similar impact on the proteome. Unspecifically downregulated proteins include cancer markers involved in apoptotic resistance and endoplasmatic reticulum (ER) stress such as the 78 kDa glucose regulated protein (GRP 78), protein disulfide isomerase A3 (PDIA3, GRP 58), calumenin, and galectin 1, as well as the glycolytic enzymes triose phosphate isomerase, glyceraldehyde phosphodehydrogenase, and phosphoglycerate mutase. The depletion of the glycolytic enzymes is reflected by a decrease in L-lactate production, indicating a partial reversal of the Warburg effect. Compared with other phosphorothioate oligonucleotides, oblimersen generally led to a more pronounced effect both in terms of the number of influenced proteins and the extent of downregulation, suggesting a synergistic effect of Bcl-2 downregulation. PMID- 20544787 TI - Photocatalytic hydrogen evolution by [FeFe] hydrogenase mimics in homogeneous solution. AB - To mimic [FeFe] hydrogenases (H(2)ases) in nature, molecular photocatalysts 1 a, 1 b, and 1 c anchoring rhenium(I) complex S to one of the iron cores of [FeFe] H(2)ases model complex C, have been constructed for H(2) generation by visible light in homogeneous solution. The time-dependence of H(2) evolution and a spectroscopic study demonstrate that the orientation of S and the specific bridge in 1 a, 1 b, and 1 c are important both for the electron-transfer step from the excited S* to the catalytic C, and the formation of unprecedented long-lived charge separation for 1 a (780 micros), 1 b, and 1 c (>2 ms) in [FeFe]-H(2)ases mimics. The fast forward electron-transfer step from the excited S* to the catalytic C but the slow back electron-transfer step of the charge-recombination in the designed photocatalysts 1 a, 1 b, and 1 c are reminiscent of the behavior of [FeFe]-H(2)ases in nature. PMID- 20544788 TI - Benzothiadiazole containing D-pi-A conjugated compounds for dye-sensitized solar cells: synthesis, properties, and photovoltaic performances. AB - Two D-pi-A conjugated molecules, BzTCA and BzTMCA, were developed through facile synthetic approaches for dye-sensitized solar cells. The investigation of the photophysical properties of BzTCA and BzTMCA both in dilute solutions and in thin films indicates that their absorption exhibits a wide coverage of the solar spectrum. The absorption features for BzTCA and BzTMCA commence at about 710 nm in solution, and at about 800 nm in the solid state. The absorption maxima (lambda(max)) for both BzTCA and BzTMCA on TiO(2) film are almost the same as those in dilute solution. Their HOMOs and LUMOs were found to partly overlap at the center of these dyes, which guarantees appreciable interactions between the donors and acceptors. The investigation of the performance of dye-sensitized solar cells fabricated from BzTCA and BzTMCA indicated that the power-conversion efficiencies are 6.04 % and 4.68 %, respectively, which could be comparable with the normal sensitizer N3. BzTMCA showed lower incident photon-to-electron conversion efficiency (IPCE) and J(sc) values relative to BzTCA, which is probably because of the weaker driving force of dye regeneration and electron injection process of BzTMCA. The IPCE responsive area reached nearly 800 nm, which provides great potential for further improvement of the photocurrent density and power-conversion efficiency. Our investigations demonstrate that both dyes BzTCA and BzTMCA could be promising candidates for dye-sensitized solar cells. PMID- 20544789 TI - Ladder-type pi-conjugated 4-hetero-1,4-dihydrophosphinines: a structure-property study. AB - Pi-conjugated six-membered 1,4-dihydrophosphinines containing a heteroatom (Si, P, S) at the 4 position were synthesized and systematically studied. X-ray crystallographic analyses showed that the central six-membered heterocyclic rings are almost planar. The sum of the angles around the phosphorus atom increases by 23 degrees from the trivalent phosphorus to the phosphonium atom in the thiaphosphinine system, which is consistent with the NMR spectroscopic studies. UV/Vis spectroscopy and theoretical calculations revealed that the communication between the phosphorus center and the benzothiophene moiety is enhanced by the incorporation of a sulfur atom into the molecular scaffold. The increased conjugation endows the thiaphosphinines with interesting emission properties. Theoretical calculations supported the postulation that the orbital coupling between the pi system and a sigma* orbital could be enhanced in the thiaphosphinine system, especially through a phosphonium center. Cyclic voltammetry studies revealed that the thiaphosphinine oxide, thiaphosphonium, and cis-diphosphinine oxide exhibit quasi-reversible reduction processes, which demonstrate that simple changes in the bridge heteroatoms help to efficiently tune the redox properties of the ladder-type 4-hetero-1,4-dihydrophosphinines. PMID- 20544790 TI - A spinel oxynitride with visible-light photocatalytic activity. PMID- 20544791 TI - N6-(2-(R)-propargylglycyl)lysine as a clickable pyrrolysine mimic. PMID- 20544792 TI - Thinnest two-dimensional nanomaterial-graphene for solar energy. AB - Graphene is a rapidly rising star in materials science. This two-dimensional material exhibits unique properties, such as low resistance, excellent optical transmittance, and high mechanical and chemical stabilities. These exceptional advantages possess great promise for its potential applications in photovoltaic devices. In this Review, we present the status of graphene research for solar energy with emphasis on solar cells. Firstly, the preparation and properties of graphene are described. Secondly, applications of graphene as transparent conductive electrodes and counter electrodes are presented. Thirdly, graphene based electron- (or hole) accepting materials for solar energy conversion are evaluated. Fourthly, the promoting effect of graphene on photovoltaic devices and the photocatalytic property of graphene-semiconductor composites are discussed. Finally, the challenges to increase the power conversion efficiency of graphene based solar cells are explored. PMID- 20544793 TI - Simultaneous aqueous-phase reforming and KOH carbonation to produce CO(x)-free hydrogen in a single reactor. PMID- 20544794 TI - Unique form of the infrequent extensor carpi radialis accessorius muscle observed bilaterally. PMID- 20544796 TI - alpha4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)-binding protein. AB - Mammalian alpha4 phosphoprotein, the homolog of yeast Tap42, is a component of the mammalian target-of-rapamycin (mTOR) pathway that regulates ribogenesis, the initiation of translation, and cell-cycle progression. alpha4 is known to interact with the catalytic subunit of protein phosphatase 2A (PP2Ac) and to regulate PP2A activity. Using alpha4 as bait in yeast two-hybrid screening of a human K562 erythroleukemia cDNA library, EDD (E3 isolated by differential display) E3 ubiquitin ligase was identified as a new protein partner of alpha4. EDD is the mammalian ortholog of Drosophila hyperplastic discs gene (hyd) that controls cell proliferation during development. The EDD protein contains a PABC domain that is present in poly(A)-binding protein (PABP), suggesting that PABP may also interact with alpha4. PABP recruits translation factors to the poly(A) tails of mRNAs. In the present study, immunoprecipitation/immunoblotting (IP/IB) analyses showed a physical interaction between alpha4 and EDD in rat Nb2 T lymphoma and human MCF-7 breast cancer cell lines. alpha4 also interacted with PABP in Nb2, MCF-7 and the human Jurkat T-leukemic and K562 myeloma cell lines. COS-1 cells, transfected with Flag-tagged-pSG5-EDD, gave a (Flag)-EDD-alpha4 immunocomplex. Furthermore, deletion mutants of alpha4 were constructed to determine the binding site for EDD. IP/IB analysis showed that EDD bound to the C terminal region of alpha4, independent of the alpha4-PP2Ac binding site. Therefore, in addition to PP2Ac, alpha4 interacts with EDD and PABP, suggesting its involvement in multiple steps in the mTOR pathway that leads to translation initiation and cell-cycle progression. PMID- 20544795 TI - Effect of hyperthermia in combination with TRAIL on the JNK-Bim signal transduction pathway and growth of xenograft tumors. AB - Approximately 25% of patients with colorectal cancer develop metastases to the liver, and surgery is currently the best treatment available. But there are several patients who are unresectable, and isolated hepatic perfusion (IHP) offers a different approach in helping to treat these patients. IHP is a method used for isolating the liver and delivering high doses of chemotherapeutic agents. The efficacy of IHP has been improved by combining hyperthermia not only with chemotherapeutics but with other deliverable agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we used human colorectal cancer CX-1 cells and treated them with hyperthermia and TRAIL, causing cytotoxicity. We were able to demonstrate that the numbers of live cells were significantly reduced with hyperthermia and 10 ng/ml of TRAIL combined. We also showed that the effect of hyperthermia on TRAIL in our studies was enhancement of the apoptotic pathway by the promotion of JNK and Bim(EL) activity as well as PARP cleavage. We have also used our CX-1 cells to generate tumors in Balb/c nude mice. With intratumoral injections of TRAIL combined with hyperthermia at 42 degrees C, we were able to show a delayed onset of tumor growth in our xenograft model. PMID- 20544797 TI - Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin-1alpha and beta. AB - Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions. We previously showed that keratinocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1alpha and beta. Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1alpha or beta in presence or absence of TGF-beta1. IL-1 suppressed basal and TGF-beta induced CTGF mRNA and protein expression. IL-1alpha and beta inhibited TGF-beta stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements. Furthermore, IL-1alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition, RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin. PMID- 20544798 TI - Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. AB - BACKGROUND: Low folate and high homocysteine (Hcy) concentrations are associated with pregnancy-related pathologies such as spina bifida. Polymorphisms in folate/Hcy metabolic enzymes may contribute to this potentially pathogenic biochemical phenotype. METHODS: The study comprised 26 Caucasian and 23 African American premenopausal women. Subjects gave fasting blood samples for biochemical phenotyping and genotyping. Total Hcy (tHcy) and both plasma and red blood cell (RBC) folate derivatives (i.e. tetrahydrofolate [THF], 5-methylTHF [5-MTHF], and 5,10-methenylTHF [5,10-MTHF]) were measured using stable isotope dilution liquid chromatography, multiple reaction monitoring, and mass spectrometry. Eleven polymorphisms from nine folate/Hcy pathway genes were genotyped. Tests of association between genetic, lifestyle, and biochemical variables were applied. RESULTS: In African American women, tHcy concentrations were associated (p < 0.05) with total RBC folate, RBC 5-MTHF, B(12), and polymorphisms in methionine synthase (MTR) and thymidylate synthase (TYMS). In Caucasian women, tHcy concentrations were not associated with total folate levels, but were associated (p < 0.05) with RBC THF, ratios of RBC 5-MTHF:THF, and polymorphisms in 5,10 methylenetetrahydrofolate reductase (MTHFR) and MTR. In African Americans, folate derivative levels were associated with smoking, B(12), and polymorphisms in MTR, TYMS, methionine synthase reductase (MTRR), and reduced folate carrier1 (RFC1). In Caucasians, folate derivative levels were associated with vitamin use, B(12), and polymorphisms in MTHFR, TYMS, and RFC1. CONCLUSIONS: Polymorphisms in the folate/Hcy pathway are associated with tHcy and folate derivative levels. In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies. PMID- 20544800 TI - Nanomedicine and ethics: is there anything new or unique? AB - As medicine moves toward being able to predict what you will die from and when, nanomedicine is expected to enhance human capabilities and properties and promises the ability of health care professionals to diagnose, treat, and share medical information nearly instantaneously. It promises to deliver drugs directly to the source of the disease, i.e. tumor. This article examines the literature surrounding ethics associated with nanomedicine, and asks whether these ethical issues are new and unique. While opinions differ, this review concludes that none of the ethical questions surrounding nanomedicine are new or unique, and would hold true for any new medical device or medicine that was being evaluated. The real issue becomes public acceptance of nanomedicine and how much risk society is willing to accept with a new technology before it is proven effective and 'safe'. While ethical foresight can prove effective in forecasting potential problems, in reality, ethics may not be capable of evaluating such a technology that has yet proven effective in all it has promised. PMID- 20544799 TI - The relationship between sonic Hedgehog signaling, cilia, and neural tube defects. AB - The Hedgehog signaling pathway is essential for many aspects of normal embryonic development, including formation and patterning of the neural tube. Absence of the sonic hedgehog (shh) ligand is associated with the midline defect holoprosencephaly, whereas increased Shh signaling is associated with exencephaly and spina bifida. To complicate this apparently simple relationship, mutation of proteins required for function of cilia often leads to impaired Shh signaling and to disruption of neural tube closure. In this article, we review the literature on Shh pathway mutants and discuss the relationship between Shh signaling, cilia, and neural tube defects. PMID- 20544801 TI - Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population. AB - BACKGROUND: Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population. METHODS: We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group. RESULTS: Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR](AG+AAvsGG), 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382 2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025). CONCLUSIONS: Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample. PMID- 20544802 TI - Gender-dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty. PMID- 20544803 TI - Effects of ethanol, formaldehyde, and gentle heat fixation in confocal resonance Raman microscopy of purple nonsulfur bacteria. AB - Resonance Raman microscopy is well suited to examine living bacterial samples without further preparation. Therefore, comparatively little thought has been given to its compatibility with common fixation methods. However, fixation of cell samples is a very important tool in the microbiological sciences, allowing the preservation of samples in a specific condition for further examination, future measurements, transport, or later reference. We examined the effects of three common fixatives-ethanol, formaldehyde solution, and gentle heat--on the resonant Raman spectrum of three generic bacteria species, Rhodobacter sphaeroides DSM 158(T), Rhodopseudomonas palustris DSM 123(T), and Rhodospirillum rubrum DSM 467(T), holding carotenoid- and heme-chromophores in confocal Raman microscopy. In addition, we analyzed the effect of poly-L-lysine coating of microscope slides, widely used for mounting biological and medical samples, on subsequent confocal Raman measurements of native and fixed samples. The results indicate that ethanol is preferable to formaldehyde as fixative if applied for less than 24 h, whereas heat fixation has a strong, detrimental effect on the resonant Raman spectrum of bacteria. Formaldehyde fixation excels at fixation times above 24 h, but causes an overall reduction in signal intensity. Poly-L lysine coating has no discernable effect on the Raman spectra of samples fixed with ethanol or heat, but it further decreases the signal intensity, especially at higher wavenumbers, in the spectra of samples fixed with formaldehyde. PMID- 20544804 TI - Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation. AB - Bioactive glass scaffolds with a microstructure similar to that of dry human trabecular bone but with three different compositions were evaluated for potential applications in bone repair. The preparation of the scaffolds and the effect of the glass composition on the degradation and conversion of the scaffolds to a hydroxyapatite (HA)-type material in a simulated body fluid (SBF) are reported here (Part I). The in vitro response of osteogenic cells to the scaffolds and the in vivo evaluation of the scaffolds in a rat subcutaneous implantation model are described in Part II. Scaffolds (porosity = 78-82%; pore size = 100-500 microm) were prepared using a polymer foam replication technique. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. The conversion rate of the scaffolds to HA in the SBF increased markedly with the B2O3 content of the glass. Concurrently, the pH of the SBF also increased with the B2O3 content of the scaffolds. The compressive strengths of the as-prepared scaffolds (5-11 MPa) were in the upper range of values reported for trabecular bone, but they decreased markedly with immersion time in the SBF and with increasing B2O3 content of the glass. The results show that scaffolds with a wide range of bioactivity and degradation rate can be achieved by replacing varying amounts of SiO(2) in silicate bioactive glass with B2O3. PMID- 20544805 TI - Neuropeptide regulators of the juvenile hormone biosynthesis (in vitro) in the beetle, Tenebrio molitor (Coleoptera, Tenebrionidae). AB - The genome of Tribolium castaneum encodes two allatostatin [AS type B; W(X)(6)Wamide and AS type C; PISCF-OH] and one allatotropin (AT) precursor, but no AS type A (FGLamide) (Tribolium Genome Sequencing Consortium, 2008: Nature 452:949-955). Here we studied the activity (in vitro) of peptides derived from these precursors on the synthesis/release of juvenile hormone (JH) III. The corpora cardiaca-corpora allata (CC-CA) complexes of adult females of another tenebrionid beetle, the mealworm Tenebrio molitor, were used. Incubating the gland complexes in a medium containing Trica-AS B3 peptide, we showed that the peptide has allatostatic function in T. molitor. The activity of the type C AS depended on the age of the test animals and their intrinsic rate of JH III biosynthesis. The Trica-AS C peptide inhibited the JH release from CA of 3-day old females with a high intrinsic rate of JH synthesis, but activated JH release from the CA of 7-day-old females with a lower intrinsic rate of JH production. The allatotropin peptide (Trica-AT) also activated the JH release from the CA of 7-day-old females in a dose-dependent and reversible manner. Unexpectedly, a type A AS derived from the precursor of the American cockroach Periplaneta americana (Peram-AS A2b) inhibited the JH release from the CA of younger and older females in the concentration range of 10(-8) to 10(-4) M, and the effects were fully reversible in the absence of peptide. These data suggest a complex role of allatoactive neuropeptides in the regulation of JH III biosynthesis in beetles. PMID- 20544806 TI - The cynomolgus monkey as a model for developmental toxicity studies: variability of pregnancy losses, statistical power estimates, and group size considerations. AB - BACKGROUND: This work evaluates pregnancy and infant loss in 1,069 vehicle treated cynomolgus monkeys from 78 embryo-fetal development (EFD) studies and 14 pre-postnatal development (PPND) studies accrued during 1981-2007. METHODS: Losses were analysed by survival function and hazard ratio using logistic regression for influence of year, study type (e.g., dose duration), and test item route of administration (ig, im, iv, sc). RESULTS: Neither study type nor route of dosing affected pregnancy outcome. Losses were higher pre-1990 (104 losses/347 pregnancies) compared to 1990 onwards (94 losses/722 pregnancies). Losses were greatest before gestation day 50 and at parturition. Using post-1989 data, Monte Carlo simulations of pregnancy outcomes were created. The power associated with the comparison of vehicle survival curves and simulated adverse survival curves was examined. This showed that EFD studies with initial vehicle group sizes of 16 and 20 have an 80% probability of having 13 and 16 ongoing pregnancies at gestational day 100, respectively. For PPND studies with initial vehicle group sizes of 16, 20, or 28, there is an 80% likelihood of having 9, 11, or 16 infants at day 7 post-partum, respectively. A PPND study initiated with group size 20 could detect a threefold increase of test item-related pregnancy or infant loss. CONCLUSIONS: For designing and managing primate developmental toxicity studies, this type of analysis provides an objective tool to facilitate decisions either by supplementing groups with additional pregnant animals or stopping a group because an adverse effect on offspring survival has already been adequately revealed. PMID- 20544807 TI - Ethyl t-butyl ether: review of reproductive and developmental toxicity. AB - Ethyl t-butyl ether (ETBE) is a motor fuel oxygenate used in reformulated gasoline. Knowledge of developmental and reproductive toxicity potential of ETBE is critical for making informed decisions about acceptance and regulations. This review discusses toxicology studies providing information about effects on reproduction and the conceptus. Seven GLP-compliant studies following widely accepted protocols have focused specifically on developmental and reproductive toxicity (DART) in rats and rabbits exposed to ETBE by gavage with doses up to 1,000 mg/kg body weight/day, the limit specified in standardized test guidelines. Other repeat-dose general toxicology studies have administered ETBE to rodents for up to 180 days, and included reproductive organ weights, histology, or other indications of reproductive system structure or function. DART potential of the main ETBE metabolite t-butyl alcohol and class-related MTBE has also been studied. More GLP-compliant studies exist for evaluating ETBE using well established, currently recommended protocols than are available for many other chemicals used today. The database for determining ETBE DART potential is adequate, although not all study details are currently easily accessible for peer review. ETBE does not appear to be selectively toxic to reproduction or embryofetal development in the absence of other manifestations of general toxicity. Studies using recommended methods for sample preservation and analysis have shown no targeted effect on the reproductive system. No embryofetal effects were observed in rabbits. Early postnatal rat pup deaths show no clear dose response and have largely been attributed to total litter losses with accompanying evidence of maternal neglect or frank maternal morbidity. PMID- 20544808 TI - Longitudinal tracking of gait and balance impairments in cerebellar disease. AB - Cerebellar damage typically results in ataxia and can be caused by stroke, tumor, or one of many forms of degenerative disease. Since few pharmacological options are available, most treatments rely heavily on rehabilitation therapy. Little data exist on methods for tracking the progression of ataxia, which is critical for assessing the efficacy of current and newly developing treatments. Here, we tracked the severity of ataxia, with a particular emphasis on gait and balance dysfunction, in a group of individuals with cerebellar damage using the International Cooperative Ataxia Rating Scale (ICARS) and several instrumented laboratory measures of gait and balance impairments over 1 year. We found that the ICARS was able to distinguish between subjects with static lesions and those with degenerative disorders, was sensitive to increases in ataxia severity occurring over 1 year, and correlated well with specific instrumented measures of gait in persons with cerebellar degeneration. These results suggest the ICARS is a valuable tool for clinicians and investigators to document and track long-term changes in gait and balance performance in individuals with cerebellar degenerative disorders. PMID- 20544809 TI - Standard guidelines for publication of deep brain stimulation studies in Parkinson's disease (Guide4DBS-PD). AB - While the use of deep brain stimulation (DBS) for the treatment of neurological disorders has risen substantially over the last decade, it is often difficult to compare the results from different studies due to the lack of consistent reporting of key study parameters. We present guidelines to standardize the reporting of clinical studies of DBS for Parkinson's disease (PD). These guidelines provide a minimal set of required data elements to facilitate the interpretation and comparison of results across published clinical studies. The guidelines, summarized in the format of a checklist, may also have utility in the planning of clinical studies of DBS for PD as well as other neurological and psychiatric disorders. PMID- 20544810 TI - Rationale for delayed-start study of pramipexole in Parkinson's disease: the PROUD study. AB - Perhaps the most important unmet need in Parkinson's disease (PD) is the ability to slow or prevent progression of the neurodegeneration that underlies the motor and nonmotor features of this disorder. Pramipexole, a dopamine agonist used for the symptomatic treatment of PD, has demonstrated neuroprotective properties in laboratory studies. The PRamipexole On Underlying Disease (PROUD) study is a randomized, double-blind clinical trial evaluating the ability of pramipexole to modify disease progression using a delayed-start design. PD patients (n = 535) with mean age 62.5 years, mean duration since diagnosis of 4.4 months, and mean total Unified Parkinson's disease Rating Scale (UPDRS) score of 24.5 were recruited. In Phase I, patients were randomly assigned to be titrated to 1.5 mg pramipexole or placebo and maintained on study drug for 6-9 months. In Phase II, all patients were titrated to 1.5 mg pramipexole and maintained on study drug until the end of the study at 15 months. No rescue medication was allowed in the protocol. The primary endpoint is the change in total UPDRS score (parts I-III) from baseline to 15 months. A range of secondary endpoints separately assess UPDRS subscales, quality of life, depression, and impulse control disorders. A sub-study examined dopamine transporter uptake scans at baseline and 15 months. The results of PROUD will provide insight into the potential for early versus delayed treatment with pramipexole to modify motor outcome at 15 months in recently diagnosed PD patients. PMID- 20544811 TI - Congenital mirror movements in Parkinson's disease: clinical and neurophysiological observations. PMID- 20544812 TI - Acute onset flaccid quadriparesis in pediatric non-Hodgkin lymphoma: vincristine induced or Guillain-Barre syndrome? AB - Immunological involvement of peripheral nervous system in non-Hodgkin lymphoma (NHL) is very rare and it may be difficult to differentiate it from vincristine induced neuropathy. We report clinical and electrophysiological findings of an 8 year-old male with NHL who developed acute onset fulminant motor sensory autonomic neuropathy during induction chemotherapy which included vincristine. Characteristic clinical picture and nerve conduction studies favored Guillain Barre syndrome. The patient improved rapidly with intravenous immunoglobulin and supportive care. It is possible that an immune mechanism damaged the peripheral nervous system in the patient without ruling out the adverse effects of vinca alkaloids. PMID- 20544813 TI - Transcranial brain sonography in Parkinson's disease with restless legs syndrome. AB - Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD-related RLS (pRLS). Sixty-three PD patients (median age 64.6 +/- 10.6 years), 40 iRLS patients (53.1 +/- 11.7 years), and 40 healthy controls (69.1 +/- 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD-RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD-RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. PMID- 20544814 TI - Benign hereditary chorea: clinical and neuroimaging features in an Italian family. AB - Benign hereditary chorea is an autosomal dominant disorder characterized by early onset nonprogressive chorea, caused by mutations of the thyroid transcription factor-1 (TITF-1) gene. Clinical heterogeneity has been reported and thyroid and respiratory abnormalities may be present. We describe 3 patients of an Italian family carrying the S145X mutation in the TITF-1 gene with mild motor delay, childhood onset dyskinesias, and subtle cognitive impairment. A child in the third generation presented with congenital hypothyroidism and neonatal respiratory distress. Imaging studies in 2 patients showed mild ventricular enlargement and empty sella at magnetic resonance imaging and hypometabolism of basal ganglia and cortex at 18-Fluoro-2-deoxy-glucose positron emission tomography. PMID- 20544815 TI - Characteristic head drops and axial extension in advanced chorea-acanthocytosis. AB - Chorea-acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced chorea-acanthocytosis. PMID- 20544816 TI - The pharmacological treatment for uremic restless legs syndrome: evidence-based review. AB - Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthesis of the evidence is needed in order to evaluate the effectiveness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double-blind trials on treatments for uremic RLS. The outcomes considered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life measured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg movement while asleep in the treatment group. No combined analysis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few therapeutic trials on patients with uremia with RLS have been published, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Therapy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed. PMID- 20544817 TI - Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor. AB - To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty-one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor. PMID- 20544818 TI - Rosai-Dorfman disease presenting in the oropharynx. AB - BACKGROUND: We report a case of Rosai-Dorfman disease (RDD) presenting as an oropharyngeal mass, and we provide a detailed discussion of this rare clinical entity. METHODS: An initial biopsy, described as being consistent with lymphoma, was reviewed at a second outside institution and was thought to be reactive lymphoid hyperplasia. The patient then presented to our institution for a second opinion. Direct laryngoscopy revealed a firm 1- to 2-cm lesion involving the left soft palate and superior tonsillar pillar. RESULTS: The diagnosis of RDD was confirmed with immunohistochemical staining on both cytology and histology. The patient elected conservative management and has remained asymptomatic for over 15 months. CONCLUSION: The diagnosis of RDD may be challenging in cases presenting initially with extranodal disease. Close follow-up and repeat biopsies may be necessary. Identification of Rosai-Dorfman cells with emperipolesis and confirmation with appropriate immunohistochemical staining on both cytology and histology is diagnostic of RDD. Conservative treatment is appropriate in select cases. PMID- 20544819 TI - The impact of miscarriage and parity on patterns of maternal distress in pregnancy. AB - The purpose of the current study was to examine patterns of state anxiety and pregnancy-specific distress across pregnancy in a diverse sample of women with (n = 113) and without (n = 250) prior miscarriage. For both groups, state anxiety and pregnancy-specific distress were highest in the first trimester and decreased significantly over the course of pregnancy. Compared to women without prior miscarriage, women with prior miscarriage experienced greater state anxiety in the second and third trimesters. Having a living child did not buffer state anxiety in women with a prior miscarriage. Attention to patterns of distress can contribute to delivery of appropriate support resources to women experiencing pregnancy after miscarriage and may help reduce risk for stress-related outcomes. PMID- 20544820 TI - Chemical inducers and transcriptional markers of oligodendrocyte differentiation. AB - Oligodendrocytes generate and maintain myelin, which is essential for axonal function and protection of the mammalian central nervous system. To advance our molecular understanding of differentiation by these cells, we screened libraries of pharmacologically active compounds and identified inducers of differentiation of Oli-neu, a stable cell line of mouse oligodendrocyte precursors (OPCs). We identified four broad classes of inducers, namely, forskolin/cAMP (protein kinase A activators), steroids (glucocorticoids and retinoic acid), ErbB2 inhibitors, and nucleoside analogs, and confirmed the activity of these compounds on rat primary oligodendrocyte precursors and mixed cortical cultures. We also analyzed transcriptional responses in the chemically induced mouse and rat OPC differentiation processes and compared these with earlier studies. We confirm the view that ErbB2 is a natural signaling component that is required for OPC proliferation, whereas ErbB2 inhibition or genetic knockdown results in OPC differentiation. PMID- 20544822 TI - Modulation of the spinal excitability by muscle metabosensitive afferent fibers. AB - The aim of this study was to identify the effect of chemical activation of muscle metabosensitive afferent fibers from groups III and IV on Hoffmann (H-) reflex modulation in the vastus medialis muscle. The experiment was conducted in rats and was divided into two experiments. The first experiment consisted of recording the metabosensitive afferent activity from femoral nerve in rats in response to KCl intraarterial injections in nontreated adults and adults treated neonatally with capsaicin. Thus, the dose-response curve was determined. The second experiment consisted of eliciting the H- and M-waves before and after KCl injection in nontreated adult animals and those treated neonatally with capsaicin. Thus, the H(max)/M(max) ratio was measured. Results indicated that, 1) in nontreated animals, afferent fibers peak discharge was found after 10 mM KCl injection; 2) no significant increase in afferent discharge rate was found in capsaicin-treated animal after KCl injections, confirming that capsaicin is an excitotoxic agent that had destroyed the thin metabosensitive nerve fibers; 3) in nontreated animals, H(max)/M(max) ratio was significantly attenuated after a 10 mM KCl injection activating metabosensitive afferent fibers; and 4) in capsaicin treated animals, no significant change in H(max)/M(max) ratio was observed after the KCl injection. These results reinforce the hypothesis that the spinal reflex response was influenced by metabosensitive muscle fibers and provide direct evidence that activation of these fibers could partially explain the reported decrease in H-reflex when metabolites are released in muscle. PMID- 20544821 TI - Altered sensitivity to excitotoxic cell death and glutamate receptor expression between two commonly studied mouse strains. AB - Alterations in glutamatergic synapse function have been implicated in the pathogenesis of many different neurological disorders, including ischemia, epilepsy, Parkinson's disease, Alzheimer's disease, and Huntington's disease. While studying glutamate receptor function in juvenile Batten disease on the C57BL/6J and 129S6/S(v)E(v) mouse backgrounds, we noticed differences unlikely to be due to mutation difference alone. We report here that primary cerebellar granule cell cultures from C57BL/6J mice are more sensitive to N-methyl-D aspartate (NMDA)-mediated cell death. Moreover, sensitivity to AMPA-mediated excitotoxicity is more variable and is dependent on the treatment conditions and age of the cultures. Glutamate receptor surface expression levels examined in vitro by in situ ELISA and in vivo by Western blot in surface cross-linked cerebellar samples indicated that these differences in sensitivity likely are due to strain-dependent differences in cell surface receptor expression levels. We propose that differences in glutamate receptor expression and in excitotoxic vulnerability should be taken into consideration in the context of characterizing disease models on the C57BL/6J and 129S6/S(v)E(v) mouse backgrounds. PMID- 20544823 TI - Deletion of aquaporin-4 renders retinal glial cells more susceptible to osmotic stress. AB - The glial water channel aquaporin-4 (AQP4) is implicated in the control of ion and osmohomeostasis in the sensory retina. Using retinal slices from AQP4 deficient and wild-type mice, we investigated whether AQP4 is involved in the regulation of glial cell volume under altered osmotic conditions. Superfusion of retinal slices with a hypoosmolar solution induced a rapid swelling of glial somata in tissues from AQP4 null mice but not from wild-type mice. The swelling was mediated by oxidative stress, inflammatory lipid mediators, and sodium influx into the cells and was prevented by activation of glutamatergic and purinergic receptors. Distinct inflammatory proteins, including interleukin-1 beta, interleukin-6, and inducible nitric oxide synthase, were up-regulated in the retina of AQP4 null mice compared with control, whereas cyclooxygenase-2 was down regulated. The data suggest that water flux through AQP4 is involved in the rapid volume regulation of retinal glial (Muller) cells in response to osmotic stress and that deletion of AQP4 results in an inflammatory response of the retinal tissue. Possible implications of the data for understanding the pathophysiology of neuromyelitis optica, a human disease that has been suggested to involve serum antibodies to AQP4, are discussed. PMID- 20544824 TI - Hypothyroid state does not protect but delays neuronal death in the hippocampal CA1 region following transient cerebral ischemia: focus on oxidative stress and gliosis. AB - We investigated protective effects of hypothyroidism on delayed neuronal death, gliosis, lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) in the gerbil hippocampal CA1 region (CA1) after 5 min of transient cerebral ischemia. The hypothyroidism was induced by 0.025% methimazole treatment. Free triiodothyronine and thyroxine levels were markedly decreased in the hypothyroid group. Four days after ischemia/reperfusion, only a few NeuN-immunoreactive (+) neurons were detected in the CA1 of euthyroid-ischemia (eu-ischemia) group; however, at this time point, the number of NeuN(+) neurons was significantly higher in the hypothyroid-ischemia (hypo-ischemia) group than in the eu-ischemia group. At 5 days postischemia, NeuN(+) neurons were significantly decreased in the hypo ischemia group: The number of NeuN(+) neurons in this group was similar to that in the eu-ischemia group. Activations of GFAP(+) astrocytes and Iba-1(+) microglia in the CA1 were higher in the eu-ischemia group 3 and 4 days after ischemia/reperfusion. At 5 days postischemia, the activations of both the glial cells in the CA1 were similar between the two groups. 4-Hydroxy-2-nonenal (HNE), a marker for lipid peroxidation, immunoreactivity in the eu-ischemia group was higher than in the hypo-ischemia group; at 5 days postischemia, the immunoreactivity was similar between the two groups. In contrast, SOD1 level was lower in the CA1 of the eu-ischemia group. These results suggest that hypothyroid state does not protect against delayed neuronal death but only delays the neuronal death in the hippocampal CA1 region after transient cerebral ischemia by reducing lipid peroxidation and increasing SOD1. PMID- 20544825 TI - Glial cell line-derived neurotrophic factor-secreting genetically modified human bone marrow-derived mesenchymal stem cells promote recovery in a rat model of Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of nigrostriatal dopaminergic (DA) neurons. The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF), the most potent neurotrophic factor for DA neurons, has been demonstrated in many experimental models of PD. However, chronic delivery of GDNF to DA neurons in the brain remains an unmet challenge. Here, we report the effects of GDNF-releasing Notch-induced human bone marrow-derived mesenchymal stem cells (MSC) grafted into striatum of the 6-hydroxydopamine (6-OHDA) progressively lesioned rat model of PD. Human MSC, obtained from bone marrow aspirates of young, healthy adult volunteers, were transiently transfected with the intracellular domain of the Notch1 gene (NICD) to generate SB623 cells. SB623 cells expressing GDNF and/or humanized Renilla green fluorescent protein (hrGFP) following lentiviral transduction or nontransduced cells were stereotaxically placed into rat striatum 1 week after a unilateral partial 6-OHDA striatal lesion. At 4 weeks, rats that had received GDNF-transduced SB623 cells had significantly decreased amphetamine induced rotation compared with control rats, although this effect was not observed in rats that received GFP-transduced or nontransduced SB623 cells. At 5 weeks, rejuvenated tyrosine hydroxylase-immunoreactive (TH-IR) fibers that appeared to be host DA axons were observed in and around grafts. This effect was more prominent in rats that received GDNF-secreting cells and was not observed in controls. These observations suggest that human bone-marrow derived MSC, genetically modified to secrete GDNF, hold potential as an allogeneic or autologous stem cell therapy for PD. PMID- 20544826 TI - Effects of zona incerta lesions on striatal neurochemistry and behavioral asymmetry in 6-hydroxydopamine-lesioned rats. AB - Analysis of optimal sites for neurosurgical interventions in patients with Parkinson's disease (PD) suggests that significant clinical benefits may be achieved by involvement of the zona incerta (ZI). Unilateral electrolytic ZI lesions were made in intact and ipsilaterally 6-hydroxydopamine (6OHDA)-lesioned rats. Extracellular levels of glutamate, dopamine, and its metabolites in the ipsilateral striatum of awake rats were measured by using microdialysis, and tests of behavioral asymmetry were performed. In intact rats, ZI lesions had no effect on striatal extracellular glutamate or absolute levels of dopamine or metabolites, but dopamine metabolism decreased. After ZI lesions, contralateral forepaw use decreased in the forepaw adjusting steps test, but there was no change in response to vibrissa stimulation or cylinder exploration. There was no development of rotational asymmetry with amphetamine. In 6OHDA-lesioned rats, striatal extracellular glutamate levels were elevated compared with controls. ZI lesions reduced the increased levels of glutamate back to normal values. ZI lesions reduced dopamine and homovanillic acid levels and showed a trend toward a decrease in dopamine metabolism. 6OHDA-lesioned rats demonstrated the expected asymmetry of motor behaviors. After ZI lesions, ipsilateral turns following amphetamine injection were reduced, and there was a trend toward improved symmetry of forepaw use as determined with the forepaw adjusting steps test. There was no change in forepaw use with vibrissa stimulation or cylinder exploration. These data indicate that lesions of the ZI can affect striatal neurochemistry and motor behavioral asymmetry and suggest potential mechanisms by which ZI lesions may improve symptoms in PD. PMID- 20544828 TI - 3R tau expression modifies behavior in transgenic mice. AB - Tauopathy is a group of disorders characterized by the accumulation of hyperphosphorylated tau protein in the brain, resulting in dementia. Here, tau related behavior was evaluated in a mouse model with brain overexpression of the shortest human tau isoform (0N3R). Two groups of animals [tau-transgenic (tau-tg) and control littermates] were tested for learning and memory at 1 and 7 months. In the Morris water maze, all mice learned the task at 1 month of age and did not learn at 7 months. In contrast, at 7 months, the tau-tg animals demonstrated better retention of the passive avoidance response compared with their control littermates, which did not learn. In the open field test, no differences were measured between transgenic and nontransgenic young mice, but significantly higher locomotion was observed in the 7-month-old tau-tg mice compared with controls. Behavior during the elevated plus maze test was the same at 1 month, but at 7 months increased entrance to the different arms was observed in the tau tg group. Tau expression and phosphorylation levels were analyzed at 8 months. In the subcortical brain region associated with passive avoidance behavior, the tau tg mice demonstrated increased brain tau expression coupled with reduced relative phosphorylation. In contrast, increased tau expression and phosphorylation were measured in the cerebral cortex of the tau-tg mice. In conclusion, 7-8-month-old tau-tg mice overexpressing nonmutated 0N3R human tau isoform demonstrated enhanced behavior in the passive avoidance test, paralleled by relative tau hypophosphorylation in the subcortical brain region. PMID- 20544827 TI - Corticotropin-releasing factor-2 activation prevents gentamicin-induced oxidative stress in cells derived from the inner ear. AB - Generation of reactive oxygen species (ROS) is a common denominator in many conditions leading to cell death in the cochlea, yet little is known of the cochlea's endogenous mechanisms involved in preventing oxidative stress and its consequences in the cochlea. We have recently described a corticotropin-releasing factor (CRF) signaling system in the inner ear involved in susceptibility to noise-induced hearing loss. We use biochemical and proteomics assays to define further the role of CRF signaling in the response of cochlear cells to aminoglycoside exposure. We demonstrate that activity via the CRF(2) class of receptors protects against aminoglycoside-induced ROS production and activation of cell death pathways. This study suggests for the first time a role for CRF signaling in protecting the cochlea against oxidative stress, and our proteomics data suggest novel mechanisms beyond induction of free radical scavengers that are involved in its protective mechanisms. PMID- 20544829 TI - Melatonin's protective action against ischemic neuronal damage is associated with up-regulation of the MT2 melatonin receptor. AB - Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. In the present study, we examined the relationship between the neuroprotective effects of melatonin and the activation of MT2 melatonin receptor in the hippocampal CA1 region (CA1) after transient cerebral ischemia. MT2 immunoreactivity and protein levels were increased in the CA1 after ischemic damage. Most of MT2-immunoreactive cells were colocalized with astrocytes, not microglia, in the ischemic CA1. In the melatonin-sham group, MT2 immunoreaction and protein levels were increased compared with the sham group, and MT2 immunoreactivity and its protein levels in the melatonin-ischemia group were similar to those in the melatonin-sham group. In addition, melatonin treatment attenuated the activation of astrocytes and microglia. These results indicate that MT2 are increased and expressed in astrocytes in the ischemic region after an ischemic insult. The activation of MT2 melatonin receptor in the CA1 after melatonin treatment may be involved in the neuroprotective effect associated with melatonin after ischemic injury. PMID- 20544830 TI - Amyloid-beta oligomers impair fear conditioned memory in a calcineurin-dependent fashion in mice. AB - Soluble oligomeric aggregates of the amyloid-beta (A beta) peptide are believed to be the most neurotoxic A beta species affecting the brain in Alzheimer disease (AD), a terminal neurodegenerative disorder involving severe cognitive decline underscored by initial synaptic dysfunction and later extensive neuronal death in the CNS. Recent evidence indicates that A beta oligomers are recruited at the synapse, oppose expression of long-term potentiation (LTP), perturb intracellular calcium balance, disrupt dendritic spines, and induce memory deficits. However, the molecular mechanisms behind these outcomes are only partially understood; achieving such insight is necessary for the comprehension of A beta-mediated neuronal dysfunction. We have investigated the role of the phosphatase calcineurin (CaN) in these pathological processes of AD. CaN is especially abundant in the CNS, where it is involved in synaptic activity, LTP, and memory function. Here, we describe how oligomeric A beta treatment causes memory deficits and depresses LTP expression in a CaN-dependent fashion. Mice given a single intracerebroventricular injection of A beta oligomers exhibited increased CaN activity and decreased pCREB, a transcription factor involved in proper synaptic function, accompanied by decreased memory in a fear conditioning task. These effects were reversed by treatment with the CaN inhibitor FK506. We further found that expression of hippocampal LTP in acutely cultured rodent brain slices was opposed by A beta oligomers and that this effect was also reversed by FK506. Collectively, these results indicate that CaN activation may play a central role in mediating synaptic and memory disruption induced by acute oligomeric A beta treatment in mice. PMID- 20544832 TI - Chronic caloric restriction reduces tissue damage and improves spatial memory in a rat model of traumatic brain injury. AB - Although it has been known for some time that chronic caloric or dietary restriction reduces the risk of neurodegenerative disorders and injury following ischemia, the possible role of chronic restriction in improving outcomes after traumatic brain injury (TBI) has not been previously studied. Therefore, 2-month old male Sprague-Dawley rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric-restriction group (CR) that was provided with 70% of the food intake of AL rats (n = 10/group). After 4 months, a weight-drop device (300 g) was used to produce a 2-mm bilateral medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n = 10) were used as sham-operated controls. The CR diet resulted in body weights that were reduced by 30% compared with AL controls. Not only did CR decrease the size of the cortical lesion after injury, there were marked improvements in spatial memory as measured by Morris water maze that included an increase in the number of animals successfully finding the platform as well as significantly reduced time to finding the hidden platform. Western analysis, used to examine the expression of proteins that play a role in neuronal survival, revealed significant increases in brain-derived neurotrophic factor (BDNF) in the cortical region around the site of injury and in the hippocampus in CR rats after injury. These findings suggest that molecular mechanisms involved in cell survival may play a role in reducing tissue damage and improving cognition after TBI and that these mechanisms can be regulated by dietary interventions. PMID- 20544831 TI - The decade of the dendritic NMDA spike. AB - In the field of cortical cellular physiology, much effort has been invested in understanding thick apical dendrites of pyramidal neurons and the regenerative sodium and calcium spikes that take place in the apical trunk. Here we focus on thin dendrites of pyramidal cells (basal, oblique, and tuft dendrites), and we discuss one relatively novel form of an electrical signal ("NMDA spike") that is specific for these branches. Basal, oblique, and apical tuft dendrites receive a high density of glutamatergic synaptic contacts. Synchronous activation of 10-50 neighboring glutamatergic synapses triggers a local dendritic regenerative potential, NMDA spike/plateau, which is characterized by significant local amplitude (40-50 mV) and an extraordinary duration (up to several hundred milliseconds). The NMDA plateau potential, when it is initiated in an apical tuft dendrite, is able to maintain a good portion of that tuft in a sustained depolarized state. However, if NMDA-dominated plateau potentials originate in proximal segments of basal dendrites, they regularly bring the neuronal cell body into a sustained depolarized state, which resembles a cortical Up state. At each dendritic initiation site (basal, oblique, and tuft) an NMDA spike creates favorable conditions for causal interactions of active synaptic inputs, including the spatial or temporal binding of information, as well as processes of short term and long-term synaptic modifications (e.g., long-term potentiation or long term depression). Because of their strong amplitudes and durations, local dendritic NMDA spikes make up the cellular substrate for multisite independent subunit computations that enrich the computational power and repertoire of cortical pyramidal cells. We propose that NMDA spikes are likely to play significant roles in cortical information processing in awake animals (spatiotemporal binding, working memory) and during slow-wave sleep (neuronal Up states, consolidation of memories). PMID- 20544833 TI - An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats. AB - Hypertension reduces endothelial nitric oxide synthase (eNOS) expression and leads to endothelial dysfunction. However, few studies have demonstrated the influences of hypertension on eNOS function in the cerebral cortex. The present study investigates the influences of hypertension on endothelial function in the cerebral cortex and the protective effects of antihypertensive agents against brain ischemia through the preservation of endothelial function. Five- and ten week-old male Wistar rats and spontaneously hypertensive rats (SHR) were used for experiments. Five-week-old SHR received olmesartan, hydralazine, or vehicle for 5 weeks in drinking water. eNOS activation in the cerebral cortex was evaluated by analyzing levels of total and Ser(1177)-phosphorylated eNOS protein by Western blot. Blood pressure of 10-week-old SHR without treatment was clearly high, and the ratio of phospho-eNOS/total eNOS protein was significantly low. Five-week treatment with olmesartan or hydralazine suppressed the elevation of blood pressure and the reduction of phosphorylated eNOS-Ser(1177) in SHR, and olmesartan was more effective in maintaining phosphorylation of eNOS-Ser(1177) than hydralazine. To assess the contribution of eNOS to maintaining cerebral blood flow (CBF), we monitored CBF by laser-Doppler flowmetry after L-N(5)-(1 iminoethyl)ornithine (L-NIO) infusion. CBF response to L-NIO was preserved in olmesartan-treated SHR but not in hydralazine-treated SHR. Furthermore, infarct volume 48 hr after transient focal brain ischemia in olmesartan-treated SHR was significantly reduced compared with vehicle-treated SHR. These findings indicate that chronic prehypertensive treatment with olmesartan could attenuate brain ischemic injury through the maintenance of endothelial function in the cerebral cortex in SHR. PMID- 20544835 TI - The reliance on unclaimed cadavers for anatomical teaching by medical schools in Africa. AB - The study of gross Anatomy through the use of cadaveric dissections in medical schools is an essential part of the comprehensive learning of human Anatomy, and unsurprisingly, 90% of the surveyed medical schools in Africa used cadaveric dissections. Donated cadavers now make up 80% of the total cadavers in North American medical schools and all the cadavers used for dissection in the United Kingdom are donated. Because the sources of cadavers used in Africa are not clearly known, a questionnaire to gather information on cadavers used at medical schools was designed from the relevant literature and was sent by electronic mail to 123 Anatomy lecturers in 23 African countries (48 medical schools). Fourteen lecturers from 14 medical schools in ten countries responded to the questionnaires. The results indicate that, in most countries, the cadavers are unclaimed bodies from the hospitals and prisons, and the bodies of dead bandits. In South Africa and Zimbabwe, the donations are mostly from the white community, and medical school in the Islamic country of Libya is importing cadavers from India. The lack of knowledge about body donation programes and firmly held cultural and religious burial traditions may explain the lack of bequests from black communities. The use of unclaimed bodies may disproportionally affect people who were homeless and poor, criminals, people with fewer social links, and social outcasts. The Anatomy lecturers felt that there should be broader national awareness programes for body donations, although the benefits of this could take decades to materialize. PMID- 20544834 TI - Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in rats. AB - Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model. PMID- 20544837 TI - Lipid accumulation and metabolism in polychaete spermatogenesis: Role of the large discoidal lipoprotein. AB - In most oviparous animals, lipoprotein-mediated lipid transport plays an important role in the nutrient supply for the oocyte. In male gametes, lipids are used as energy substrates in spermatozoa but nothing is yet known about their origin and metabolism throughout spermatogenesis. The lipid profiles analyzed from different stages of male germ cell development in the marine annelid Nereis virens were found to undergo a dramatic change from primary triacylglycerides at the beginning of germ cell development to cholesterol and phospholipids at the end of development as demonstrated by HPLC with evaporative light scattering detection and mass spectrometry. The uptake of a large discoidal lipoprotein into the developing germ cells could be demonstrated by fluorescence labeling and electron microscopic techniques as well as by the presence of a lipoprotein receptor in the germ cells, thus establishing its role in lipid supply. The incorporated lipoprotein discs were found to be stored as intact complexes indicating that they are not readily degraded upon endocytotic uptake. The change in lipid composition during germ cell development reflects their metabolic activity, especially in spermatogonia. The high concentration of lipids maintained by spermatogonia during the early phase of gametogenesis seems to be required for the later rapid processes of meiosis and spermatocyte differentiation. At times when peak demand of lipids arises for membrane synthesis and increased metabolism, this may be met more efficiently by a rapid on-site mobilization of lipids instead of an external supply. PMID- 20544836 TI - Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population. AB - OBJECTIVE: Quantitative measures are needed to identify diabetic patients at higher risk for CV events. Cell-derived microparticles (MPs) are submicron membrane vesicles released from activated cells that are indicative of cell damage. Progenitor cells (PCs) including proangiogenic cells (PACs), often termed endothelial progenitor cells (EPCs), are mediators of reparative capacity. We examined whether the relationship of MPs to PCs/PACs could be used as an improved and clinically feasible index of vascular pathology. METHODS AND RESULTS: Plasma samples were collected from patients with early-stage (ES, Diagnosis < 1 year) and long-term (LT, Diagnosis > 5 years,) Type 2 diabetes and compared with age related healthy subjects (H). PC and MP subtypes were measured by a combination of flow cytometry and ELISA-based methods. The ratio of procoagulant MPs/CD34(+) PCs proved a valuable index to distinguish between subject groups (P = 0.01). This index of compromised vascular function was highest in the LT group despite intensive statin therapy and was more informative than a range of soluble protein biomarkers. CONCLUSIONS: This is the first report of a relationship between MPs and PCs in Type 2 diabetes. This ratio may provide a quantitative and clinically feasible measurement of vascular dysfunction and cardiovascular risk in patients with diabetes. (c) 2010 International Clinical Cytometry Society. PMID- 20544838 TI - Human papillomavirus status in head and neck cancer: the ethics of disclosure. AB - Human papillomavirus (HPV) is an emerging causative factor for squamous carcinoma of the oropharynx and perhaps other head and neck cancers. There is a great deal of uncertainty regarding the clinical significance and implications of HPV status in this patient population. As a result, there is no established protocol for informing patients of the potential link between viral infection and their cancer. This paper discusses some of the ethical issues involved with informing head and neck cancer patients of their HPV status, recognizing the dilemma posed by unresolved clinical questions and the need to respect the autonomy of patients by disclosing relevant information. PMID- 20544839 TI - Neighborhood socioeconomic status and behavioral pathways to risks of colon and rectal cancer in women. AB - BACKGROUND: Neighborhood amenities and resources plausibly determine individual modifiable risk factors for colon and rectal cancer. Evidence on the associations between neighborhood socioeconomic status (SES) and incident colon and rectal cancer is limited. METHODS: The authors analyzed a prospective cohort of 111,129 women in the Nurses' Health Study with no history of cancer in 1986 followed to 2006. Neighborhood SES was based on Census-derived characteristics of block groups of residence. Cox models were used to estimate the multivariate-adjusted associations between neighborhood SES and incident colon and rectal cancer, and to examine for effect modification. For significant associations, path models were estimated with behavioral risk factors included as potential mediators. RESULTS: Neighborhood SES was unassociated with colon cancer among all women. However, among women with college or greater education, higher neighborhood SES was inversely related to colon cancer (P for trend = .01; P for interaction between neighborhood SES and education = .03). Path analysis suggested mediation by red meat intakes and body mass index (BMI). Higher neighborhood SES was inversely related to rectal cancer among all women (relative risk in highest quintile, 0.64; 95% confidence interval, 0.44-0.93; P for trend = .08). Path analysis was consistent with mediation by multivitamin use and BMI. CONCLUSIONS: These findings suggest that living in a higher-SES neighborhood may protect against rectal cancer in women and colon cancer in higher-educated women, mediated by selected behavioral risk factors. Risk factor differences between colon and rectal cancer may account for discrepancies in estimated neighborhood effects by cancer site. PMID- 20544840 TI - HMGA2 and the p19Arf-TP53-CDKN1A axis: a delicate balance in the growth of uterine leiomyomas. AB - Pathogenetically, uterine leiomyomas (ULs) can be interpreted as the result of a monoclonal abnormal proliferation of myometrial cells. Oncogene-induced senescence (OIS) is a frequent phenomenon in premalignant lesions that leads to a growth arrest mainly by the activation of two potent growth-inhibitory pathways as represented by p16(Ink4a) and p19(Arf). The relevance of OIS for the development of UL has not been addressed, but HMGA2, encoded by a major target gene of recurrent chromosomal abnormalities in UL, has been implicated in the repression of the Ink4a/Arf (CDKN2A) locus. This prompted us to examine if HMGA2 contributes to the growth of leiomyomas by repressing this locus. Contrary to the expectations, we were able to show that generally ULs express significantly higher levels of p19(Arf) mRNA than myometrium and that UL with 12q14 approximately 15 rearrangements showed higher expression levels than UL with other cytogenetic aberrations. Furthermore, the finding of a significant correlation between the expressions of p19(Arf) and CDKN1A shows that p19(Arf) triggers senescence rather than apoptosis in UL. Furthermore, the expression levels of HMGA2, p19(Arf), and CDKN1A were found to be correlated with the size of the tumors, indicating that an enhanced growth potential is counterbalanced by the p19(Arf) pathway. Mechanistically, the UL may thus execute a program already present in their cell of origin, where it is activated to protect the genome, for example, in the case of enhanced proliferation. In summary, the results identify the p19(Arf)-TP53-CDKN1A pathway as a major player in the growth control and genomic stability of uterine fibroids. PMID- 20544841 TI - High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy-neutral loss of heterozygosity and copy number alterations that target single genes. AB - A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy-neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL-associated copy number regions were revealed including losses of 1p32-36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy-neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2-q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high-resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single-gene somatic aberrations in FL tumorigenesis. PMID- 20544842 TI - MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia. AB - Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in mature B-cell neoplasms. Recent findings have also revealed their significant role in B-cell precursor acute lymphoblastic leukemia. As a rule, IGH translocations generate transcriptional activation of the oncogene localized in the proximity of the breakpoint. In this study, we describe a pediatric case of B-cell precursor acute lymphoblastic leukemia showing microRNA 125b-1 (MIR125B1) and BLID gene overexpression, resulting from a novel t(11;14)(q24.1;q32) translocation involving IGH. This is the first report describing the upregulation of a microRNA due to its juxtaposition to protein coding gene regulatory elements and the overexpression of two neighboring genes as a consequence of transcriptional enhancers localized in the vicinity of the IGH gene. PMID- 20544843 TI - ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas. AB - Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons. PMID- 20544844 TI - Genomic profile of endometrial tumors depends on morphological subtype, not on tamoxifen exposure. AB - Tamoxifen has been a very effective treatment for breast cancer for several decades, however, at the same time increases the risk of endometrial cancer, especially after prolonged exposure. In addition, tamoxifen has been associated with a higher proportion of unfavorable uterine tumor subtypes (carcinosarcomas and serous adenocarcinomas) with worse survival. We investigated whether endometrial tumors, which developed after prolonged tamoxifen treatment for breast cancer, are genetically different from endometrial tumors without preceding tamoxifen exposure. Array CGH was used on archival formalin-fixed paraffin embedded endometrial tumors to determine genomic aberrations. We compared the genomic profiles of 52 endometrial tumors from breast cancer patients after long-term (>or=2 years) tamoxifen use (endometrioid adenocarcinomas, n = 26; carcinosarcomas, n = 14; and serous adenocarcinomas, n = 12) with endometrial tumors from unexposed breast cancer patients (n = 45). Genomic profiles were correlated with tamoxifen exposure, tumor subtypes, and histopathological characteristics of the endometrial tumors. The common uterine corpus cancers of the endometrioid subtype show few genomic aberrations. Tumors with many genomic aberrations were in general ER-negative. In contrast, carcinosarcomas and serous adenocarcinomas showed many aberrations; however, they were indistinguishable from each other. Tumors that developed after prolonged tamoxifen use did not show more or different aberrations than unexposed tumors. This was true for all tumor subtypes. Thus, endometrial carcinomas that develop after prolonged tamoxifen use cannot be distinguished from nonusers on basis of their tumor genomic profile. PMID- 20544845 TI - GLO1-A novel amplified gene in human cancer. AB - To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification. PMID- 20544846 TI - Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci. AB - We compared genomic breakpoints at the PML and RARA loci in 23 patients with therapy-related acute promyelocytic leukemia (t-APL) and 25 de novo APL cases.Eighteen of 23 t-APL cases received the topoisomerase II poison mitoxantrone for their primary disorder. DNA breaks were clustered in a previously reported 8 bp "hot spot" region of PML corresponding to a preferred site of mitoxantrone-induced DNA topoisomerase II-mediated cleavage in 39% of t APL occurring in patients exposed to this agent and in none of the cases arising de novo (P = 0.007). As to RARA breakpoints, clustering in a 3' region of intron 2 (region B) was found in 65% of t-APL and 28% of de novo APL patients, respectively. Scan statistics revealed significant clustering of RARA breakpoints in region B in t-APL cases (P = 0.001) as compared to de novo APL (P = 1). Furthermore, approximately 300 bp downstream of RARA region B contained a sequence highly homologous to a topoisomerase II consensus sequence. Biased distribution of DNA breakpoints at both PML and RARA loci suggest the existence of different pathogenetic mechanisms in t-APL as compared with de novo APL. PMID- 20544847 TI - Somatic alterations in the melanoma genome: a high-resolution array-based comparative genomic hybridization study. AB - We performed DNA microarray-based comparative genomic hybridization to identify somatic alterations specific to melanoma genome in 60 human cell lines from metastasized melanoma and from 44 corresponding peripheral blood mononuclear cells. Our data showed gross but nonrandom somatic changes specific to the tumor genome. Although the CDKN2A (78%) and PTEN (70%) loci were the major targets of mono-allelic and bi-allelic deletions, amplifications affected loci with BRAF (53%) and NRAS (12%) as well as EGFR (52%), MITF (40%), NOTCH2 (35%), CCND1 (18%), MDM2 (18%), CCNE1 (10%), and CDK4 (8%). The amplified loci carried additional genes, many of which could potentially play a role in melanoma. Distinct patterns of copy number changes showed that alterations in CDKN2A tended to be more clustered in cell lines with mutations in the BRAF and NRAS genes; the PTEN locus was targeted mainly in conjunction with BRAF mutations. Amplification of CCND1, CDK4, and other loci was significantly increased in cell lines without BRAF-NRAS mutations and so was the loss of chromosome arms 13q and 16q. Our data suggest involvement of distinct genetic pathways that are driven either through oncogenic BRAF and NRAS mutations complemented by aberrations in the CDKN2A and PTEN genes or involve amplification of oncogenic genomic loci and loss of 13q and 16q. It also emerges that each tumor besides being affected by major and most common somatic genetic alterations also acquires additional genetic alterations that could be crucial in determining response to small molecular inhibitors that are being currently pursued. PMID- 20544848 TI - Colorectal cancers show distinct mutation spectra in members of the canonical WNT signaling pathway according to their anatomical location and type of genetic instability. AB - It is unclear whether the mutation spectra in WNT genes vary among distinct types of colorectal tumors. We have analyzed mutations in specific WNT genes in a cohort of 52 colorectal tumors and performed a meta-analysis of previous studies. Notably, significant differences were found among the mutation spectra. We have previously shown that in familial adenomatous polyposis, APC somatic mutations are selected to provide the "just-right" level of WNT signaling for tumor formation. Here, we found that APC mutations encompassing at least two beta catenin down-regulating motifs (20 a.a. repeats) are significantly more frequent in microsatellite unstable (MSI-H) than in microsatellite stable (MSS) tumors where truncations retaining less than two repeats are more frequent (P = 0.0009). Moreover, in cases where both APC hits are detected, selection for mutations retaining a cumulative number of two 20 a.a. repeats became apparent in MSI-H tumors (P = 0.001). This type of mutations were also more frequent in proximal versus distal colonic tumors, regardless of MSI status (P = 0.0008). Among MSI-H tumors, CTNNB1 mutations were significantly more frequent in HNPCC than in sporadic lesions (28% versus 6%, P < 10-6) and were preferentially detected in the proximal colon, independently of MSI status (P = 0.017). In conclusion, the observed spectra of WNT gene mutations in colorectal tumors are likely the result from selection of specific levels of beta-catenin signaling, optimal for tumor formation in the context of specific anatomical locations and forms of genetic instability. We suggest that this may underlie the preferential location of MMR deficient tumors in the proximal colon. PMID- 20544850 TI - Disruption of transient receptor potential canonical channel 1 causes incomplete cytokinesis and slows the growth of human malignant gliomas. AB - Despite decades of research, primary brain tumors, gliomas, lack effective treatment options and present a huge clinical challenge. Particularly, the most malignant subtype, Glioblastoma multiforme, proliferates extensively and cells often undergo incomplete cell divisions, resulting in multinucleated cells. We now present evidence that multinucleated glioma cells result from the functional loss of transient receptor potential canonical 1 (TRPC1) channels, plasma membrane proteins involved in agonist-induced calcium entry and reloading of intracellular Ca(2+) stores. Pharmacological inhibition or shRNA mediated suppression of TRPC1 causes loss of functional channels and store-operated calcium entry in D54MG glioma cells. This is associated with reduced cell proliferation and, frequently, with incomplete cell division. The resulting multinucleated cells are reminiscent of those found in patient biopsies. In a flank tumor model, tumor size was significantly decreased when TRPC1 expression was disrupted using a doxycycline inducible shRNA knockdown approach. These results suggest that TRPC1 channels play an important role in glioma cell division most likely by regulating calcium signaling during cytokinesis. PMID- 20544851 TI - In the hypoxic central nervous system, endothelial cell proliferation is followed by astrocyte activation, proliferation, and increased expression of the alpha 6 beta 4 integrin and dystroglycan. AB - Cerebral hypoxia induces a profound angiogenic response in the central nervous system (CNS). Using a mouse model of chronic cerebral hypoxia, we previously demonstrated that angiogenic vessels in the hypoxic CNS show marked upregulation of the extracellular matrix (ECM) protein fibronectin, along with increased expression of its major receptor, alpha 5 beta 1 integrin on brain endothelial cells (BEC). As cerebral hypoxia also leads to glial activation, the aim of the current study was to define the temporal relationship between BEC responses and glial cell activation in this model of cerebral hypoxia. This revealed that BEC fibronectin/alpha 5 beta 1 integrin expression and proliferation both reached maximal level after 4-day hypoxia. Interestingly, up to 4-day hypoxia, all dividing cells were BEC, but at later time-points proliferating astrocytes were also observed. GFAP staining revealed that hypoxia induced marked astrocyte activation that reached maximal level between 7- and 14-day hypoxia. As newly formed cerebral capillaries require ensheathment by astrocyte end-feet to acquire mature brain endothelium characteristics, we next examined how expression of astrocyte end-feet adhesion molecules is regulated by hypoxia. This showed that the astrocyte adhesion receptors alpha 6 beta 4 integrin and dystroglycan were both markedly upregulated, with a time-course that closely resembled astrocyte activation. Taken together, this evidence shows that cerebral hypoxia promotes first an endothelial response, in which fibronectin promotes BEC proliferation. This is then followed by an astrocyte response, involving astrocyte activation, proliferation, and reorganization of astrocyte end-feet, which correlates with increased expression of astrocyte end-feet adhesion molecules. PMID- 20544852 TI - Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons. AB - Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDH alpha). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorylated PDH alpha. Dephosphorylation of astrocytic PDH alpha restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed. PMID- 20544853 TI - Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. AB - Vascular/parenchymal crosstalk is increasingly recognized as important in the development and maintenance of healthy vascularized tissues. The retina is an excellent model in which to study the role of cell type-specific contributions to the process of blood vessel and neuronal growth. During retinal vascular development, glial cells such as astrocytes provide the template over which endothelial cells migrate to form the retinal vascular network, and hypoxia regulated vascular endothelial growth factor (VEGF) has been demonstrated to play a critical role in this process as well as pathological neovascularization. To investigate the nature of cell-specific contributions to this process, we deleted VEGF and its upstream regulators, the hypoxia-inducible transcription factors HIF 1 alpha and HIF-2 alpha, and the negative regulator of HIF alpha, von Hippel Lindau protein (VHL), in astrocytes. We found that loss of hypoxic response and VEGF production in astrocytes does not impair normal development of retinal vasculature, indicating that astrocyte-derived VEGF is not essential for this process. In contrast, using a model of oxygen-induced ischemic retinopathy, we show that astrocyte-derived VEGF is essential for hypoxia-induced neovascularization. Thus, we demonstrate that astrocytes in the retina have highly divergent roles during developmental, physiological angiogenesis, and ischemia-driven, pathological neovascularization. PMID- 20544854 TI - Metallothionein-3 regulates lysosomal function in cultured astrocytes under both normal and oxidative conditions. AB - Cellular zinc plays a key role in lysosomal change and cell death in neurons and astrocytes under oxidative stress. Here, using astrocytes lacking metallothionein 3 (MT3), a potential source of labile zinc in the brain, we studied the role of MT3 in oxidative stress responses. H(2)O(2) induced a large increase in labile zinc in wild-type (WT) astrocytes, but stimulated only a modest rise in MT3-null astrocytes. In addition, H(2)O(2)-induced lysosomal membrane permeabilization (LMP) and cell death were comparably attenuated in MT3-null astrocytes. Expression and glycosylation of Lamp1 (lysosome-associated membrane protein 1) and Lamp2 were increased in MT3-null astrocytes, and the activities of several lysosomal enzymes were significantly reduced, indicating an effect of MT3 on lysosomal components. Consistent with lysosomal dysfunction in MT3-null cells, the level of LC3-II (microtubule-associated protein 1 light chain 3), a marker of early autophagy, was increased by oxidative stress in WT astrocytes, but not in MT3-null cells. Similar changes in Lamp1, LC3, and cathepsin-D were induced by the lysosomal inhibitors bafilomycin A1, chloroquine, and monensin, indicating that lysosomal dysfunction may lie upstream of changes observed in MT3-null astrocytes. Consistent with this idea, lysosomal accumulation of cholesterol and lipofuscin were augmented in MT3-null astrocytes. Similar to the results seen in MT3-null cells, MT3 knockdown by siRNA inhibited oxidative stress-induced increases in zinc and LMP. These results indicate that MT3 may play a key role in normal lysosomal function in cultured astrocytes. PMID- 20544855 TI - Glycosphingolipid synthesis in cerebellar Purkinje neurons: roles in myelin formation and axonal homeostasis. AB - Glycosphingolipids (GSLs) occur in all mammalian plasma membranes. They are most abundant in neuronal cells and have essential roles in brain development. Glucosylceramide (GlcCer) synthase, which is encoded by the Ugcg gene, is the key enzyme driving the synthesis of most neuronal GSLs. Experiments using conditional Nestin-Cre Ugcg knockout mice have shown that GSL synthesis in vivo is essential, especially for brain maturation. However, the roles of GSL synthesis in mature neurons remain elusive, since Nestin-Cre is expressed in neural precursors as well as in postmitotic neurons. To address this problem, we generated Purkinje cell-specific Ugcg knockout mice using mice that express Cre under the control of the L7 promoter. In these mice, Purkinje cells survived for at least 10-18 weeks after Ugcg deletion. We observed apparent axonal degeneration characterized by the accumulation of axonal transport cargos and aberrant membrane structures. Dendrites, however, were not affected. In addition, loss of GSLs disrupted myelin sheaths, which were characterized by detached paranodal loops. Notably, we observed doubly myelinated axons enveloped by an additional concentric myelin sheath around the original sheath. Our data show that axonal GlcCer-based GSLs are essential for axonal homeostasis and correct myelin sheath formation. PMID- 20544856 TI - Intermediate filaments attenuate stimulation-dependent mobility of endosomes/lysosomes in astrocytes. AB - Intermediate filament (IF) proteins upregulation is a hallmark of astrocyte activation and reactive gliosis, but its pathophysiological implications remain incompletely understood. A recently reported association between IFs and directional mobility of peptidergic vesicles allows us to hypothesize that IFs affect vesicle dynamics and exocytosis-mediated astrocyte communication with neighboring cells. Here, we ask whether the trafficking of recycling vesicles (i.e., those fused to and then retrieved from the plasma membrane) and endosomes/lysosomes depends on IFs. Recycling vesicles were labeled by antibodies against vesicle glutamate transporter 1 (VGLUT1) and atrial natriuretic peptide (ANP), respectively, and by lysotracker, which labels endosomes/lysosomes. Quantitative fluorescence microscopy was used to monitor the mobility of labeled vesicles in astrocytes, derived from either wild-type (WT) mice or mice deficient in glial fibrillary acidic protein and vimentin (GFAP(-/-)Vim(-/-)), the latter lacking astrocyte IFs. Stimulation with ionomycin or ATP enhanced the mobility of VGLUT1-positive vesicles and reduced the mobility of ANP-positive vesicles in WT astrocytes. In GFAP(-/-)Vim(-/-) astrocytes, both vesicle types responded to stimulation, but the relative increase in mobility of VGLUT1-positive vesicles was more prominent compared with nonstimulated cells, whereas the stimulation dependent attenuation of ANP-positive vesicles mobility was reduced compared with nonstimulated cells. The mobility of endosomes/lysosomes decreased following stimulation in WT astrocytes. However, in GFAP(-/-)Vim(-/-) astrocytes, a small increase in the mobility of endosomes/lysosomes was observed. These findings show that astrocyte IFs differentially affect the stimulation-dependent mobility of vesicles. We propose that upregulation of IFs in pathologic states may alter the function of astrocytes by deregulating vesicle trafficking. PMID- 20544857 TI - In vivo expression of neuroglobin in reactive astrocytes during neuropathology in murine models of traumatic brain injury, cerebral malaria, and autoimmune encephalitis. AB - Neuroglobin (Ngb) is proposed to be a neuron-specific, hypoxia-responsive, neuroprotective protein. However, results are conflicting concerning both Ngb's physiological and pathological significance. This study was designed to investigate the in vivo localization and regulation of Ngb in different neuropathological models representing traumatic injury, infectious, autoimmune, and excitotoxic pathogeneses. We profiled Ngb immunohistochemistry in murine models of traumatic brain injury, cerebral malaria, experimental autoimmune encephalitis, and kainic acid (KA)-mediated epileptic seizures that, to our knowledge, have not been studied in the context of Ngb. In control mice Ngb was expressed exclusively in neurons. In all pathological models except KA, in addition to neurons Ngb was present in reactive astrocytes. Ngb positive astrocytes were found within regions associated with most severe pathology and the astroglial scar. This is the first report of Ngb present in reactive astroglia and in scar-forming astrocytes in response to different pathological conditions relevant to human disease. In light of previously reported cyto protective properties of Ngb, further insight may result in therapeutic ramifications. PMID- 20544858 TI - Alteration of glial-neuronal metabolic interactions in a mouse model of Alexander disease. AB - Alexander disease is a rare and usually fatal neurological disorder characterized by the abundant presence of protein aggregates in astrocytes. Most cases result from dominant missense de novo mutations in the gene encoding glial fibrillary acidic protein (GFAP), but how these mutations lead to aggregate formation and compromise function is not known. A transgenic mouse line (Tg73.7) over expressing human GFAP produces astrocytic aggregates indistinguishable from those seen in the human disease, making them a model of this disorder. To investigate possible metabolic changes associated with Alexander disease Tg73.7 mice and controls were injected simultaneously with [1-(13)C]glucose to analyze neuronal metabolism and [1,2-(13)C]acetate to monitor astrocytic metabolism. Brain extracts were analyzed by (1)H magnetic resonance spectroscopy (MRS) to quantify amounts of several key metabolites, and by (13)C MRS to analyze amino acid neurotransmitter metabolism. In the cerebral cortex, reduced utilization of [1,2 (13)C]acetate was observed for synthesis of glutamine, glutamate, and GABA, and the concentration of the marker for neuronal mitochondrial metabolism, N acetylaspartate (NAA) was decreased. This indicates impaired astrocytic and neuronal metabolism and decreased transfer of glutamine from astrocytes to neurons compared with control mice. In the cerebellum, glutamine and GABA content and labeling from [1-(13)C]glucose were increased. Evidence for brain edema was found in the increased amount of water and of the osmoregulators myo-inositol and taurine. It can be concluded that astrocyte-neuronal interactions were altered differently in distinct regions. PMID- 20544859 TI - Astrocytic A beta 1-42 uptake is determined by A beta-aggregation state and the presence of amyloid-associated proteins. AB - Intracerebral accumulation of amyloid-beta (A beta) leading to A beta plaque formation, is the main hallmark of Alzheimer's disease and might be caused by defective A beta-clearance. We previously found primary human astrocytes and microglia able to bind and ingest A beta 1-42 in vitro, which appeared to be limited by A beta 1-42 fibril formation. We now confirm that astrocytic A beta uptake depends on size and/or composition of A beta-aggregates as astrocytes preferably take up oligomeric A beta over fibrillar A beta. Upon exposure to either fluorescence-labelled A beta 1-42 oligomers (A beta(oligo)) or fibrils (A beta(fib)), a larger (3.7 times more) proportion of astrocytes ingested oligomers compared to fibrils, as determined by flow cytometry. A beta-internalization was verified using confocal microscopy and live-cell imaging. Neither uptake of A beta(oligo) nor A beta(fib), triggered proinflammatory activation of the astrocytes, as judged by quantification of interleukin-6 and monocyte chemoattractant protein-1 release. Amyloid-associated proteins, including alpha1 antichymotrypsin (ACT), serum amyloid P component (SAP), C1q and apolipoproteins E (ApoE) and J (ApoJ) were earlier found to influence A beta-aggregation. Here, astrocytic uptake of A beta(fib) increased when added to the cells in combination with SAP and C1q (SAP/C1q), but was unchanged in the presence of ApoE, ApoJ and ACT. Interestingly, ApoJ and ApoE dramatically reduced the number of A beta(oligo)-positive astrocytes, whereas SAP/C1q slightly reduced A beta(oligo) uptake. Thus, amyloid-associated proteins, especially ApoJ and ApoE, can alter A beta-uptake in vitro and hence may influence A beta clearance and plaque formation in vivo. PMID- 20544860 TI - Foxp3 is a novel repressor of microglia activation. AB - Forkhead transcription factor 3 (Foxp3) is critical for generating CD4(+)CD25(+) regulatory T cells. However, its role in microglia has not been identified. Here, we show that Foxp3 is expressed in microglia and is upregulated upon activation. In Foxp3 mutant mice (Foxp3(sf)), microglia release higher levels of inflammatory cytokines and mediators such as NO, MCP-1, CXCL10, and ROS upon liposaccharide treatment than the wild type, while TNF-alpha and IL-1 beta were not significantly different between wild and mutant microglial cells. In addition, Foxp3 silencing enhances inflammatory responses, suggesting that the major role of Foxp3 in microglia is that of a repressor of activation. Similarly, Foxp3 overexpression reduces inflammatory responses in microglia. We also demonstrate that Foxp3 interacts directly with NF-kappaB and modulates its transcriptional activities. These findings point to the importance of Foxp3 in NF-kappaB mediated inflammatory responses in microglia. PMID- 20544861 TI - Microglia express functional 11 beta-hydroxysteroid dehydrogenase type 1. AB - Glucocorticoids are potent regulators of inflammation exerting permissive, stimulatory, and suppressive effects. Glucocorticoid access to intracellular receptors is regulated by the activity of two distinct enzymes known as 11 beta hydroxysteroid dehydrogenase (11 beta HSD) Type 1 and Type 2, which catalyze the activation or deactivation of glucocorticoids. Although expression of these enzymes in major organ systems and their roles in the metabolic effects of glucocorticoids have been described, their role in the inflammatory response has only recently started to be addressed. In this report, we have studied the expression and activity of 11 beta HSD Type 1 and Type 2 in microglia cells. Microglia, the brain's resident macrophages, initiate and orchestrate CNS inflammatory responses. Importantly, activated microglia are implicated in most neurodegenerative conditions, making them key subjects of study. We found that microglia expressed 11 beta HSD-1, but not 11 beta HSD-2, both in ex vivo FACS sorted adult cells and in vitro primary cultures. 11 beta HSD-1 expression was increased in LPS-activated microglia. Moreover, 11 beta HSD-1 catalyzed the metabolic conversion of 11-dehydro-corticosterone into corticosterone (CORT), which potently reduced cytokine production in activated microglia. We propose that 11 beta HSD-1 may provide microglia with an intrinsic mechanism to autoregulate and inhibit proinflammatory mediator production through CORT formation. PMID- 20544862 TI - The impact of Roux-en-Y gastric bypass surgery for morbid obesity on second trimester obstetric ultrasound completion rates. AB - PURPOSE: Weight loss after bariatric surgery occurs by preferential loss of visceral and central body fat. We hypothesized that 2nd trimester sonographic completion rates would be higher among women with prior gastric bypass compared with women of similar body mass index without a prior gastric bypass. METHODS: Women with gastric bypass undergoing 2(nd) trimester sonographic examination were matched 1:1 with controls for body mass index and prior cesarean section. The primary outcome was completion of the fetal anatomic evaluation according to American Institute of Ultrasound in Medicine guidelines. RESULTS: Initial sonogram completion rates for cases, 28/40 (70%), and controls (30/40, 75%) were similar (p = 0.62). Completion rates for women returning for follow-up were 100% in both groups. Overall completing rates were identical for cases (37/40, 92.5%) and controls (37/40, 92.5%). CONCLUSION: Previous gastric bypass surgery does not affect 2nd trimester sonographic completion rates. PMID- 20544863 TI - Observer variability in the sonographic evaluation of thyroid nodules. AB - OBJECTIVE: Inter- and intraobserver variabilities in the description and diagnostic categorization of sonographic (US) features of thyroid nodules were evaluated. METHODS: The current study was conducted on 72 malignant nodules and 61 benign nodules. The US findings for each thyroid nodule were analyzed twice at a 6-week interval by five radiologists. The analyses were in accordance with the guidelines proposed by the Thyroid Study Group of the Korean Society of Neuroradiology and Head and Neck Radiology (TSGKSNRHNR). Inter- and intraobserver variabilities were calculated using Cohen's kappa statistics. The sensitivity, specificity, positive-predictive value, and negative-predictive value in the assessment of the diagnostic accuracy using these guidelines were calculated. RESULT: The interobserver agreement was fair to substantial for US features and categorization. Of the US features of the thyroid nodules, internal content (solid versus cystic) showed substantial agreement (k = 0.64). There was moderate agreement with regard to shape, echogenicity, calcification, and diagnostic categories (k = 0.42, 0.57, 0.55, and 0.55, respectively). There was fair agreement for margin, echotexture, and capsule invasion (k = 0.34, 0.26, and 0.32, respectively). With regard to intraobserver agreement, there was moderate to substantial agreement for all US features except for echotexture and capsule invasion, which showed fair agreement. In particular, there was moderate to almost perfect agreement for the diagnostic category. The sensitivity, specificity, positive-predictive value, and negative-predictive value were 65.3% 81.9%, 60.7%-68.9%, 69.7%-73.8%, and 66.6%-75.5%, respectively. CONCLUSION: There were high degrees of inter- and intraobserver agreement using the "Guidelines for diagnostic thyroid ultrasonography," of the TSGKSNRHNR in the description and categorization of thyroid nodules. PMID- 20544864 TI - Sonographic diagnosis of parotid gland lesions: correlation with the results of sonographically guided fine-needle aspiration biopsy. AB - PURPOSE: The aim was to assess the value of ultrasound (US) in differentiating benign from malignant parotid gland lesions. METHODS: During a 3-year period, US guided fine-needle aspiration biopsy was performed on 89 parotid lesions with a size > or = 5 mm in 68 patients. In 80 (90%) lesions, specimens were adequate for cytologic analysis. We recorded the seven following US parameters: size, number, echogenicity, echotexture, margins' clarity, distal acoustic enhancement, and regional lymph node enlargement. RESULTS: Fine-needle aspiration biopsy revealed 18 (22%) malignant tumors, 30 (38%) benign tumors, and 32 (40%) nonneoplastic lesions. The mean size of the malignant tumors was 25 +/- 17 mm versus 27 +/- 17 mm for benign tumors versus 21 +/- 12 mm for nonneoplastic lesions (p > 0.05). Among 33 solitary tumors, 9 were malignant tumors and 24 were benign tumors. The majority of the parotid lesions were hypoechoic. The US feature that was most often associated with a benign lesion was distal acoustic enhancement. The US features that suggested malignancy were a heterogeneous echotexture, indistinct margins, and regional lymph node enlargement. CONCLUSION: US can aid in the differentiation of parotid gland tumors, although benign and malignant parotid tumors often have a similar sonographic appearance. PMID- 20544865 TI - Sonography of the normal greater occipital nerve and obliquus capitis inferior muscle. AB - BACKGROUND: To use sonography to measure the cross-sectional area (CSA) of the greater occipital nerve (GON) and the adjacent obliquus capitis inferior muscle (OCI) in normal subjects. METHODS: Data from 30 asymptomatic subjects between the ages of 22 and 35 were collected. CSA and circumference of the GON and CSA of OCI were measured using sonography. Interexaminer reliability analysis was performed using the intraclass correlation coefficient. RESULTS: The CSA of the GON and OCI were 2 mm2 +/- 1 mm2 and 1.86 cm2 +/- 0.51 cm2, respectively. The average circumference of the GON was 4.8 mm +/- 1.3 mm. The interexaminer reliability of the measurements was excellent with intraclass correlation coefficient coefficients of 0.91, 0.84, and 0.73 for the GON CSA, GON circumference, and OCI CSA, respectively. CONCLUSION: We report the normal values of the CSA of the GON and OCI. Knowledge of these normal values may facilitate the diagnosis of GON entrapment and provide outcome measures in therapeutic interventions. PMID- 20544866 TI - Preoperative localization of cystic lesions in the knee using ultrasound-guided injection of indigo carmine. AB - PURPOSE: To evaluate the feasibility and effectiveness of preoperative localization of cystic lesions in the knee using ultrasound-guided indigo carmine injection. METHOD: Twenty-three cysts in the knee in 23 patients (M:F = 15:8, mean age, 42 years) were localized preoperatively by ultrasound-guided indigo carmine injection. These included 12 meniscal cysts, 7 popliteal cysts, and 4 ganglion cysts. To stain the lesions, 0.2-3 mL of indigo carmine was injected into the cyst using a 22-gauge spinal needle. After localization, the patient was immediately transferred to the operating room and surgery was performed. Intraoperative findings and arthroscopic images were reviewed. RESULT: All 23 cysts were stained successfully. Twenty cases were confirmed during arthroscopy and 3 cases were confirmed during excisional surgery. There was no significant bleeding/hematoma or anaphylactic reaction. Four patients felt pain during aspiration before indigo carmine injection. The lesions were stained blue and could be clearly identified by the surgeon and were removed arthroscopically or by open surgery. CONCLUSION: Preoperative localization of cystic lesions in the knee joint region using ultrasound-guided indigo carmine injection is a feasible technique and can be easily and safely be performed. PMID- 20544867 TI - Testicular microlithiasis: analysis of prevalence and associated testicular cancer in Taiwanese men. AB - PURPOSE: To determine the incidence of testicular microlithiasis (TM) in Taiwanese males who were referred for scrotal sonography (US) and to evaluate the association between TM and cancer, with state-of-the-art equipment. METHODS: This retrospective study included 513 males who underwent scrotal US in a period of 7 months. The US images and charts of each patient were reviewed to determine the presence of TM and note relevant clinical information. RESULTS: The data for all 513 patients were analyzed. Their age was 0-91 years (mean, 54.3 years). The overall incidence of TM was 14.4% (74/513); 6.2% (32/513) had classic TM, and 8.2% had limited TM. The incidence of testicular cancer in this population was 1.6% (8/513). Six of eight (75%) patients who had testicular cancer at presentation had classic TM or limited TM. There was a significant difference (P < 0.01) between the rate of malignancy in subjects with TM (6/74) and that in subjects without TM (2/439). CONCLUSION: The incidence of TM in Taiwanese people may be higher than previously reported, which may be due to the difference in methodology and increased awareness of the US findings. Although there was a significant difference in the rate of malignancy in males with TM compared with those without TM, the question remains whether TM independently increases the risk of testicular malignancy. PMID- 20544868 TI - Contrast-enhanced ultrasound features of primary splenic lymphoma. AB - We report a case of primary splenic lymphoma incidentally detected on abdominal ultrasound as a well-defined homogenous hypoechoic splenic mass. Further characterization with contrast-enhanced ultrasound showed the mass to enhance homogenously during the arterial phase to a degree similar to that of the normal splenic parenchyma followed by rapid washout becoming hypoenhanced on delayed phase. PMID- 20544869 TI - Sonographic diagnosis and successful medical management of an intramural ectopic pregnancy. AB - We report a case of posterior wall intramural pregnancy in a 36-year-old primigravida at 6 weeks gestation. Sonographic examination showed a viable intramural pregnancy distorting the contour of the uterus. The pregnancy was terminated by intrafetal injection of potassium chloride followed by intra amniotic methotrexate injection. PMID- 20544870 TI - An unusual growth of ovarian cystic teratoma with multiple floating balls during pregnancy: a case report. AB - We report a case of ovarian cystic teratoma with an important growth during pregnancy and the sonographic appearance of intracystic multiple, mobile, polygonal structures called intracystic "fat balls." Due to the rapid growth of the lesion, which exceeded 15 cm in diameter, a right oophorectomy was performed. Histopathologic diagnosis confirmed the mature cystic teratoma. The presence of floating balls composed of keratin and fat is rarely seen but is pathognomonic of mature cystic teratomas. Growth of a teratoma during pregnancy is a rare condition. PMID- 20544871 TI - Fetal bowel calcifications: a sign of anal atresia with rectourethral fistula. AB - Fetal bowel calcifications were observed at 24 weeks of gestation in a male fetus, suggesting an anorectal malformation (ARM) with rectourethral fistula. At birth, the newborn presented with complex ARM including anal atresia, rectourethral fistula, and esophageal atresia. The prenatal sonographic visualization of calcifications within distended bowel should raise the suspicion of ARM including anal atresia and rectourethral fistula, the presence of such calcification depending on the timing of onset of fistula formation. PMID- 20544872 TI - Sonographic appearance of a metastasis to the breast from a cerebellar medulloblastoma. AB - We present the case of a 29-year-old woman with a medulloblastoma of the cerebellum who developed a breast mass during the course of her disease. Core biopsy of the breast lesion revealed a metastatic medulloblastoma. Development of metastasis to the breast from medulloblastoma is very rare and the prognosis for such patients is poor. It is important to distinguish primary breast cancer from metastasis to the breast, because the therapeutic options as well as the prognosis are very different. PMID- 20544873 TI - Comparative sperm ultrastructure in Nemertea. AB - Although the monophyly of Nemertea is strongly supported by unique morphological characters and results of molecular phylogenetic studies, their ingroup relationships are largely unresolved. To contribute solving this problem we studied sperm ultrastructure of 12 nemertean species that belong to different subtaxa representing the commonly recognized major monophyletic groups. The study yielded a set of 26 characters with an unexpected variation among species of the same genus (Tubulanus and Procephalothrix species), whereas other species varied in metric values or only one character state (Ramphogordius). In some species, the sperm nucleus has grooves (Zygonemertes virescens, Amphiporus imparispinosus) that may be twisted and give a spiral shape to the sperm head (Paranemertes peregrina, Emplectonema gracile). To make the characters from sperm ultrastructure accessible for further phylogenetic analyses, they were coded in a character matrix. Published data for eight species turned out to be sufficiently detailed to be included. Comparative evaluation of available information on the sperm ultrastructure suggests that subtaxa of Heteronemertea and Hoplonemertea are supported as monophyletic by sperm morphology. However, the data do not provide information on the existing contradictions regarding the internal relationships of "Palaeonemertea." Nevertheless, our study provides evidence that sperm ultrastructure yields numerous potentially informative characters that will be included in upcoming phylogenetic analyses. PMID- 20544874 TI - A comparative study of incisor procumbency and mandibular morphology in vampire bats. AB - The three species of vampire bats (Phyllostomidae: Desmodontinae), Desmodus rotundus, Diaemus youngi, and Diphylla ecaudata, are the only mammals that obtain all nutrition from vertebrate blood (sanguinivory). Because of the unique challenges of this dietary niche, vampire bats possess a suite of behavioral, physiological, and morphological specializations. Morphological specializations include a dentition characterized by small, bladelike, non-occlusive cheek teeth, large canines, and extremely large, procumbent, sickle-shaped upper central incisors. The tips of these incisors rest in cuplike pits in the mandible behind the lower incisors (mandibular pits). Here, we use microCT scanning and high resolution radiography to describe the morphology of the mandible and anterior dentition in vampire bats, focusing on the relationship between symphyseal fusion, mandibular pit size, incisor size, and procumbency. In Desmodus and Diaemus, highly procumbent upper incisors are associated with relatively small mandibular pits, an unfused mandibular symphysis with substantial bony interdigitations linking the dentaries, and a diastema between the lower central incisors that helps to facilitate the lapping of blood from a wound. In Diphylla, less procumbent upper incisors are associated with relatively large mandibular pits, a completely fused mandibular symphysis, and a continuous lower toothrow lacking a central diastema. We hypothesize that symphyseal morphology and the presence or absence of the diastema are associated with the angle of upper incisor procumbency and mandibular pit development, and that spatial constraints influence the morphology of the symphysis. Finally, this morphological variation suggests that Diphylla utilizes a different feeding strategy as compared to Desmodus and Diaemus, possibly resulting from the functional demands of specialization on avian, rather than mammalian, blood. PMID- 20544875 TI - Postembryonic development of Antygomonas incomitata (Kinorhyncha: Cyclorhagida). AB - Postembryonic development in the kinorhynch species Antygomonas incomitata was examined using scanning electron microscopy. The morphology of the six juvenile stages, J-1 to J-6, varies at numerous details, but they can also be distinguished by a few key characters. Juvenile stage 1 by its composition of only nine trunk segments; J-2 by the combination of possessing 10 trunk segments, but no cuspidate spines on segment 9; J-3 by the presence of cuspidate spines on segment 9, but only one pair of cuspidate spines on segment 8; J-4 by the combination of 10 trunk segments only, but having two pairs of cuspidate spines on segment 8; J-5 by possessing 11 trunk segments and same spine compositions as adults but is still maintaining postmarginal spiculae; J-6 specimens closely resemble adults and are most easily identified by their reduced trunk lengths. New segments are formed in a growth zone in the anterior part of the terminal segment. The complete number of segments is reached in J-5. Development of cuticular head and trunk structures are described through all postembryonic stages and following developmental patterns could be outlined: the mouth cone possesses outer oral styles from J-1, but in J-1 to J-3, the styles alternate in size. Scalids of the introvert are added after each molt, and scalids appear earliest in the anterior rings, whereas scalids in more posterior rings are added in older postembryonic stages. The early J-1 stage is poor in spines and sensory spots and both structures increase in number after each molt. The complete spine composition is reached in J-4, whereas new sensory spots appear after all molts, inclusive the final one from J-6 to adult. Sensory spots in the paraventral positions often appear as Type 3 sensory spots but are through development transformed to Type 2. This transformation happens earliest on the anterior segments. PMID- 20544876 TI - Shape of articular surface of crocodilian (Archosauria) elbow joints and its relevance to sauropsids. AB - The determination of area and shape of articular surfaces on the limb bones of extinct archosaurs is difficult because of postmortem decomposition of the fibrous tissue and articular cartilages that provide the complex three dimensional joint surfaces in vivo. This study aims at describing the shape of the articular cartilages in the elbow joints of six crocodilian specimens; comparing its structure with that of four birds, three testudines, and five squamates; and comparing the shapes of the surfaces of the calcified and the articular cartilages in the elbow joints of an Alligator specimen. The shapes of the articular cartilages of crocodilian elbow joint are shown to resemble those of birds. The humerus possesses an olecranon fossa positioned approximately at the midportion of the distal epiphysis and bordering the margin of the extensor side of the articular surface. The ulna possesses a prominent intercotylar process at approximately the middle of its articular surface, and splits the surface into the radial and ulnar cotylae. This divides the articular cartilage into an articular surface on the flexor portion, and the olecranon on the extensor portion. The intercotylar process fits into the olecranon fossa to restrict elbow joint extension. Dinosaurs and pterosaurs, phylogenetically bracketed by Crocodylia and Aves (birds), may have possessed a similar olecranon fossa and intercotylar process on their articular cartilages. Although these shapes are rarely recognizable on the bones, their impressions on the surfaces of the calcified cartilages provide an important indication of the extensor margin of the articular surfaces. This, in turn, helps to determine the maximum angle of extension of the elbow joint in archosaurs. PMID- 20544877 TI - The mitochondrial genome: dynamics, mechanisms of repair, and a target in disease and therapy. PMID- 20544878 TI - The mitochondrial proteome: a dynamic functional program in tissues and disease states. AB - The nuclear DNA transcriptional programming of the mitochondria proteome varies dramatically between tissues depending on its functional requirements. This programming generally regulates all of the proteins associated with a metabolic or biosynthetic pathway associated with a given function, essentially regulating the maximum rate of the pathway while keeping the enzymes at the same molar ratio. This may permit the same regulatory mechanisms to function at low- and high-flux capacity situations. This alteration in total protein content results in rather dramatic changes in the mitochondria proteome between tissues. A tissues mitochondria proteome also changes with disease state, in Type 1 diabetes the liver mitochondrial proteome shifts to support ATP production, urea synthesis, and fatty acid oxidation. Acute flux regulation is modulated by numerous posttranslational events that also are highly variable between tissues. The most studied posttranslational modification is protein phosphorylation, which is found all of the complexes of oxidative phosphorylation and most of the major metabolic pathways. The functional significance of these modifications is currently a major area of research along with the kinase and phosphatase regulatory network. This near ubiquitous presence of protein phosphorylations, and other posttranslational events, in the matrix suggest that not all posttranslational events have functional significance. Screening methods are being introduced to detect the active or dynamic posttranslational sites to focus attention on sites that might provide insight into regulatory mechanisms. PMID- 20544881 TI - Mitochondrial dysfunction in neurodegenerative diseases and cancer. AB - Mitochondria are important integrators of cellular function and therefore affect the homeostatic balance of the cell. Besides their important role in producing adenosine triphosphate through oxidative phosphorylation, mitochondria are involved in the control of cytosolic calcium concentration, metabolism of key cellular intermediates, and Fe/S cluster biogenesis and contributed to programmed cell death. Mitochondria are also one of the major cellular producers of reactive oxygen species (ROS). Several human pathologies, including neurodegenerative diseases and cancer, are associated with mitochondrial dysfunction and increased ROS damage. This article reviews how dysfunctional mitochondria contribute to Alzheimer's disease, Parkinson's disease, Huntington's disease, and several human cancers. PMID- 20544880 TI - Reactive species and mitochondrial dysfunction: mechanistic significance of 4 hydroxynonenal. AB - Mitochondrial dysfunction is a global term used in the context of "unhealthy" mitochondria. In practical terms, mitochondria are extremely complex and highly adaptive in structure, chemical and enzymatic composition, subcellular distribution and functional interaction with other components of cells. Consequently, altered mitochondrial properties that are used in experimental studies as measures of mitochondrial dysfunction often provide little or no distinction between adaptive and maladaptive changes. This is especially a problem in terms of generation of oxidant species by mitochondria, wherein increased generation of superoxide anion radical (O(2*)(-)) or hydrogen peroxide (H(2)O(2)) is often considered synonymously with mitochondrial dysfunction. However, these oxidative species are signaling molecules in normal physiology so that a change in production or abundance is not a good criterion for mitochondrial dysfunction. In this review, we consider generation of reactive electrophiles and consequent modification of mitochondrial proteins as a means to define mitochondrial dysfunction. Accumulated evidence indicates that 4 hydroxynonenal (HNE) modification of proteins reflects mitochondrial dysfunction and provides an operational criterion for experimental definition of mitochondrial dysfunction. Improved means to detect and quantify mitochondrial HNE-protein adduct formation could allow its use for environmental healthrisk assessment. Furthermore, application of improved mass spectrometry-based proteomic methods will lead to further understanding of the critical targets contributing to disease risk. PMID- 20544882 TI - DNA repair in mammalian mitochondria: Much more than we thought? AB - For many years, the repair of most damage in mitochondrial DNA (mtDNA) was thought limited to short-patch base excision repair (SP-BER), which replaces a single nucleotide by the sequential action of DNA glycosylases, an apurinic/apyrimidinic (AP) endonuclease, the mitochondrial DNA polymerase gamma, an abasic lyase activity, and mitochondrial DNA ligase. However, the likely array of lesions inflicted on mtDNA by oxygen radicals and the possibility of replication errors and disruptions indicated that such a restricted repair repertoire would be inadequate. Recent studies have considerably expanded our knowledge of mtDNA repair to include long-patch base excision repair (LP-BER), mismatch repair, and homologous recombination and nonhomologous end-joining. In addition, elimination of mutagenic 8-oxodeoxyguanosine triphosphate (8-oxodGTP) helps prevent cell death due to the accumulation of this oxidation product in mtDNA. Although it was suspected for many years that irreparably damaged mtDNA might be targeted for degradation, only recently was clear evidence provided for this hypothesis. Therefore, multiple DNA repair pathways and controlled degradation of mtDNA function together to maintain the integrity of mitochondrial genome. PMID- 20544879 TI - A compendium of human mitochondrial gene expression machinery with links to disease. AB - Mammalian mitochondrial DNA encodes 37 essential genes required for ATP production via oxidative phosphorylation, instability or misregulation of which is associated with human diseases and aging. Other than the mtDNA-encoded RNA species (13 mRNAs, 12S and 16S rRNAs, and 22 tRNAs), the remaining factors needed for mitochondrial gene expression (i.e., transcription, RNA processing/modification, and translation), including a dedicated set of mitochondrial ribosomal proteins, are products of nuclear genes that are imported into the mitochondrial matrix. Herein, we inventory the human mitochondrial gene expression machinery, and, while doing so, we highlight specific associations of these regulatory factors with human disease. Major new breakthroughs have been made recently in this burgeoning area that set the stage for exciting future studies on the key outstanding issue of how mitochondrial gene expression is regulated differentially in vivo. This should promote a greater understanding of why mtDNA mutations and dysfunction cause the complex and tissue-specific pathology characteristic of mitochondrial disease states and how mitochondrial dysfunction contributes to more common human pathology and aging. PMID- 20544883 TI - Generation, function, and prognostic utility of somatic mitochondrial DNA mutations in cancer. AB - Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline important caveats for interpreting the detected mutations--particularly differentiating causality from association--and suggest how new mutational assays may help resolve fundamental controversies in the field and delineate the origin and expansion of neoplastic cell lineages. Finally, we discuss the potential clinical utility of mtDNA mutations for improving the sensitivity of early cancer diagnosis, rapidly detecting cancer recurrence, and predicting the disease outcome. PMID- 20544884 TI - Mitochondrial DNA mutations in disease and aging. AB - The human mitochondrial genome involves over 1,000 genes, dispersed across the maternally inherited mitochondrial DNA (mtDNA) and the biparentally inherited nuclear DNA (nDNA). The mtDNA encodes 13 core proteins that determine the efficiency of the mitochondrial energy-generating system, oxidative phosphorylation (OXPHOS), plus the RNA genes for their translation within the mitochondrion. The mtDNA has a very high mutation rate, which results in three classes of clinically relevant mtDNA mutations: recently deleterious germline line mutations resulting in mitochondrial disease; ancient regional variants, a subset of which permitted humans to adapt to differences in their energetic environments; and somatic mutations that accumulate with age eroding mitochondrial energy production and providing the aging clock. Mutations in nDNA encoded OXPHOS structural genes can also cause mitochondrial disease, and alterations in nDNA mitochondrial biogenesis genes can destabilize the mtDNA and lead to clinical phenotypes. Finally, when combined, nonpathogenic nDNA and mtDNA protein variants can be functionally incompatible and cause disease. The essential functions of the conserved mtDNA proteins and their high mutation rate raise the question as to why the cumulative mtDNA genetic load does not result in species extinction. Studies of mice harboring deleterious mtDNA mutations have shown that the mammalian ovary selectively eliminates the most deleterious mtDNA mutations. However, milder mtDNA mutations are transmitted through the ovary and the female germline and introduced into the general population. This unique genetic system provides a flexible method for generating genetic variation in cellular and organismal energetics that permits species to adapt to alterations in their regional energetic environment. PMID- 20544886 TI - Chemical vapor deposition of conformal, functional, and responsive polymer films. AB - Chemical vapor deposition (CVD) polymerization utilizes the delivery of vapor phase monomers to form chemically well-defined polymeric films directly on the surface of a substrate. CVD polymers are desirable as conformal surface modification layers exhibiting strong retention of organic functional groups, and, in some cases, are responsive to external stimuli. Traditional wet-chemical chain- and step-growth mechanisms guide the development of new heterogeneous CVD polymerization techniques. Commonality with inorganic CVD methods facilitates the fabrication of hybrid devices. CVD polymers bridge microfabrication technology with chemical, biological, and nanoparticle systems and assembly. Robust interfaces can be achieved through covalent grafting enabling high-resolution (60 nm) patterning, even on flexible substrates. Utilizing only low-energy input to drive selective chemistry, modest vacuum, and room-temperature substrates, CVD polymerization is compatible with thermally sensitive substrates, such as paper, textiles, and plastics. CVD methods are particularly valuable for insoluble and infusible films, including fluoropolymers, electrically conductive polymers, and controllably crosslinked networks and for the potential to reduce environmental, health, and safety impacts associated with solvents. Quantitative models aid the development of large-area and roll-to-roll CVD polymer reactors. Relevant background, fundamental principles, and selected applications are reviewed. PMID- 20544885 TI - The approaches for manipulating mitochondrial proteome. AB - Over the past decade a large volume of research data has accumulated which has established a fundamental role for mitochondria in normal cellular functioning, as well as in various pathologies. Mitochondria play a pivotal role in metabolism and energy production, and are one of the key players involved in programmed cell death. On the other hand, mitochondrial dysfunction is implicated, directly or indirectly in numerous pathological conditions including inherited mitochondrial disorders, diabetes, cardiovascular and neurodegenerative diseases, and a variety of malignancies. The ability to modulate mitochondrial function by altering the diverse protein component of this organelle may be of great value for developing future therapeutic interventions. This review will discuss approaches used to introduce proteins into mitochondria. One group of methods utilizes strategies aimed at expressing proteins from genes in the nucleus. These include overexpression of nuclear-encoded mitochondrial proteins, allotopic expression, which is the re-coding and relocation of mitochondrial genes to the nucleus for expression and subsequent delivery of their gene products to mitochondria, and xenotopic expression, which is the nuclear expression of genes coding electron transport chain components from distant species, for delivery of their products to mammalian mitochondria. Additionally, antigenomic and progenomic strategies which focus on expression of mitochondrially targeted nuclear proteins involved in the maintenance of mtDNA will be discussed. The second group of methods considered will focus on attempts to use purified proteins for mitochondrial delivery. Special consideration has been given to the complexities involved in targeting exogenous proteins to mitochondria. PMID- 20544887 TI - Highly ordered nanoporous alumina on conducting substrates with adhesion enhanced by surface modification: universal templates for ultrahigh-density arrays of nanorods. PMID- 20544888 TI - Multilevel atomic-scale transistors based on metallic quantum point contacts. PMID- 20544889 TI - Oxidized gold thin films: an effective material for high-performance flexible organic optoelectronics. PMID- 20544890 TI - Microcrimped collagen fiber-elastin composites. PMID- 20544891 TI - Ambipolar memory devices based on reduced graphene oxide and nanoparticles. PMID- 20544892 TI - Structural characterization of multi-quantum wells in electroabsorption-modulated lasers by using synchrotron radiation micrometer-beams. PMID- 20544893 TI - B4C-nanowires/carbon-microfiber hybrid structures and composites from cotton T shirts. PMID- 20544894 TI - Chemosensors for viruses based on artificial immunoglobulin copies. PMID- 20544895 TI - Bio-inspired synthesis and mechanical properties of calcite-polymer particle composites. PMID- 20544896 TI - Efficient blue-light-emitting polymer heterostructure devices: the fabrication of multilayer structures from orthogonal solvents. PMID- 20544898 TI - Alteration of the alpha-synuclein folding landscape by a mutation related to Parkinson's disease. PMID- 20544900 TI - Cerium vanadate nanorod arrays from ionic chelator-mediated self-assembly. PMID- 20544899 TI - Bright three-photon luminescence from gold/silver alloyed nanostructures for bioimaging with negligible photothermal toxicity. PMID- 20544901 TI - Metallacyclic pyridylidene structures from reactions of terminal pyridylidenes with alkenes and acetylene. PMID- 20544902 TI - Asymmetric, protecting-group-free total synthesis of (-)-englerin A. PMID- 20544903 TI - Enantioselective synthesis of (-)-englerins A and B. PMID- 20544904 TI - Synthesis of azaspirocycles and their evaluation in drug discovery. PMID- 20544905 TI - Optical stability of axially chiral push-pull-substituted buta-1,3-dienes: effect of a single methyl group on the C60 surface. PMID- 20544906 TI - Synthesis, crystal structure, and reactivity of the strong methylating agent Me2B12Cl12. PMID- 20544908 TI - Steadiness in plantar flexor muscles and its relation to postural sway in young and elderly adults. AB - To investigate the functional significance of force fluctuations during voluntary contraction with a select muscle group, we examined the association between force fluctuations during voluntary contraction with plantar flexor muscles and postural sway during quiet standing in 20 young and 20 elderly adults. Young and elderly subjects maintained a quiet standing position on a force platform. They also performed a force-matching task with unilateral isometric plantar flexion. A positive correlation was found in young and elderly adults between the coefficient of variation (CV) of center of pressure during quiet standing and the CV of force during plantar flexion only at contraction intensities of < or =5% maximum voluntary contraction that corresponded to muscle activity during quiet standing. The electromyogram power in the medial gastrocnemius was greater in the elderly than in young adults by approximately 10 Hz during quiet standing and at low contraction intensities during plantar flexion. Fluctuations in motor output during low-intensity plantar flexion were associated with postural sway during quiet standing in both young and elderly adults. PMID- 20544909 TI - FYN-dependent muscle-immune interaction after sciatic nerve injury. AB - Denervation of skeletal muscles results in loss of muscle mass and contractile force. Recent evidence suggests that local immune system activation plays a key role in these processes, but the mechanisms underlying muscle-immune system cross talk are not understood. The purpose of this study was to address the mechanisms by which muscle responds to denervation and to elucidate the specific role played by FYN in local immune system activation. We studied initial events taking place in the gastrocnemius of wild-type and Fyn(-/-) mice following sciatic nerve transection. Discontinuous sucrose gradient centrifugation was used to prepare lipid rafts at different time-points (1, 7, and 14 days) after surgery. Activation of FYN, cytokine expression (IL-1beta and TNF-alpha), and T-cell activation (CD3 and IL-15) were followed by in vitro kinase assays, enzyme-linked immunoassay (ELISA), Western blotting, and immunoprecipitation. Sciatic nerve injury resulted in increased SRC kinase activity in gastrocnemius lipid rafts. Production of both IL-1beta and TNF-alpha was increased, peaking after 1 day, followed after 7 and 14 days by upregulation of IL-15 and CD3 expression and the development of caveolin-3 and CD3 complexes. The integrity of lipid rafts and the upregulation of SRC kinase activity, cytokine expression, and T-cell activation and cross-talk with muscle cells following denervation were abolished in Fyn(-/-) mice. The integrity of FYN-dependent lipid rafts is required for local immune system activation within denervated muscle, and lipid rafts are implicated in orchestrating muscle-immune-cell cross-talk. These results are likely to provide new insights into the therapy of neuromuscular injury. PMID- 20544910 TI - Transgenic overexpression of laminin alpha1 chain in laminin alpha2 chain deficient mice rescues the disease throughout the lifespan. AB - Several approaches to treat laminin alpha2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha2 chain-deficient mice with transgenic overexpression of laminin alpha1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha2-chain-deficient animals that overexpress laminin alpha1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future. PMID- 20544911 TI - Profiling of innervations of mimetic muscles in fresh human cadavers using a modified Sihler's technique. AB - The nerve map of the human face, although important in guiding facial surgery, has not been well defined. In this study we applied a modified Sihler's technique to profile intramuscular innervation of human mimetic muscles. Six fresh cadaveric heads were used. The intramuscular distribution of the facial nerve in human mimetic muscles was visualized using a modified Sihler's technique. Modified Sihler's staining revealed a three-dimensional picture of the clearly purple-black intramuscular facial and sensory nerves. The nerve branching patterns of both facial halves were asymmetrical. None of the fine nerve branches crossed over the midline. The facial nerve branches divided into secondary rami and formed a mesh-like plexus before entering the target muscles at a right angle. The modified Sihler's technique can profile intramuscular innervation of human mimetic muscles. Our nerve map of the face offers valuable guidance for facial reanimation surgery, facial cosmetic surgery, and parotid surgery. PMID- 20544912 TI - Plasma biomarkers associated with ALS and their relationship to iron homeostasis. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis with variable presentation and disease progression. There is a critical need for a panel of biomarkers to provide clinicians and researchers with additional information. In this study, multiplex immunoassays were used to screen a number of cytokines, growth factors, and iron-related proteins. ALS patients had significantly higher plasma levels of L-ferritin and lower concentrations of transferrin when compared to healthy controls and together classified a test group of subjects with 82% accuracy. Duration of ALS symptoms correlated positively with levels of monocyte chemoattractant protein 1 (MCP-1) and negatively with levels of granulocyte-macrophage colony stimulating factor (GM-CSF). The biomarker profile suggests iron homeostasis is disrupted in ALS patients, and changes in ferritin and transferrin (Tf) appear to be indicators of ongoing inflammatory processes. The data demonstrate a plasma biomarker profile in ALS patients that may differ from published reports of cerebrospinal fluid biomarkers. PMID- 20544913 TI - Quantification of sudomotor innervation: a comparison of three methods. AB - Peripheral sudomotor dysfunction is present in many peripheral neuropathies, but structural assessments of sudomotor fibers rarely occur. We evaluated 36 diabetic and 72 healthy control subjects who underwent detailed neurologic examinations and punch skin biopsies. Physical exam findings were quantified by neuropathy impairment score in the lower limb. Skin biopsies quantified intraepidermal nerve fiber density (IENFD) and sweat gland nerve fiber density (SGNFD) by a manual, automated, and semiquantitative method. The automated and manual SGNFD correlated with the IENFD at the same site (r = 0.62, P < 0.05 automated method, r = 0.67, P < 0.05 manual method). As neuropathy worsened, the SGNFD at the distal leg declined (automated counting r = -0.81, P < 0.001; manual counting r = -0.88, P < 0.001). The semiquantitative method displayed poor inter- and intrareviewer reliability and correlated poorly with standard neuropathy evaluation scores. Our results suggest that sudomotor fibers can be rapidly and reproducibly quantified, and results correlate well with physical exam findings. PMID- 20544914 TI - Localization of frequency-dependent conduction block in carpal tunnel syndrome. AB - Frequency-dependent conduction block (FDB) has been demonstrated in subjects with carpal tunnel syndrome (CTS) when the median nerve was stimulated at 30-Hz frequency proximal to the carpal tunnel (CT). However, it was still questionable whether FDB occurred within the region of the CT or more distally. High-frequency nerve stimulation (HFNS) was performed in controls and in CTS subjects while stimulating the median nerve proximal and distal to the carpal tunnel. The degree of FDB was measured by comparing the 20th thenar CMAP with the 1st following a train of 20 stimuli at 30-Hz. FDB occurred across the CT in 11/12 studies (91.7%) and across the distal portion of the palmar aponeurosis-distal terminal motor branches in 5 of the 11 studies (41.7%). These results suggest that the safety margin for impulse transmission can be impaired distal to the presumed site of injury in CTS. PMID- 20544916 TI - Polyneuropathy caused by cobalt-chromium metallosis after total hip replacement. AB - Although metal intoxication after arthroplasty causes various symptoms, polyneuropathy has never been the focus of clinical investigation. We report the case of a 56-year-old woman with metal neuropathy. She had metallosis after hip arthroplasty with a cobalt-chromium alloy prosthesis. She developed progressive sensory disturbance, hearing loss, and hypothyroidism. Sural nerve biopsy indicated axonopathy. After exchange arthroplasty, blood levels of cobalt and chromium decreased, and her symptoms improved. Cobalt or chromium can cause axonopathy. PMID- 20544915 TI - Neuromuscular junction morphology, fiber-type proportions, and satellite-cell proliferation rates are altered in MyoD(-/-) mice. AB - Gene compensation by members of the myogenic regulatory factor (MRF) family has been proposed to explain the apparent normal adult phenotype of MyoD(-/-) mice. Nerve and field stimulation were used to investigate contraction properties of muscle from MyoD(-/-) mice, and molecular approaches were used to investigate satellite-cell behavior. We demonstrate that MyoD deletion results in major alterations in the organization of the neuromuscular junction, which have a dramatic influence on the physiological contractile properties of skeletal muscle. Second, we show that the lineage progression of satellite cells (especially initial proliferation) in the absence of MyoD is abnormal and linked to perturbations in the nuclear localization of beta-catenin, a key readout of canonical Wnt signaling. These results show that MyoD has unique functions in both developing and adult skeletal muscle that are not carried out by other members of the MRF family. PMID- 20544917 TI - Direct immunofluoresence in vasculitic neuropathy: specificity of vascular immune deposits. AB - In suspected vasculitic neuropathy, vasculitis is demonstrated in only 30% of superficial peroneal nerve (SPN)/peroneus brevis muscle (PBM) specimens. Pathologic predictors of vasculitis are thus needed for non-diagnostic cases. Immune deposits in epineurial vessels have an established sensitivity but unknown specificity. In this study we assessed specificity using direct immunofluorescence (DIF) in SPN/PBM biopsies for suspected vasculitic neuropathy. Biopsies from 13 patients with vasculitis, 13 without vasculitis, and 6 with diabetic radiculoplexus neuropathy (DRPN) were stained for immunoglobulin G (IgG), IgM, and complement 3 (C3), and analyzed in a blinded manner. Vascular immunoglobulin or C3 deposits occurred in 12 of 13 nerve or muscle biopsies (11 of 13 nerves, 5 of 13 muscles) in vasculitis vs. 1 of 13 (1 of 13 nerves, 0 of 13 muscles) in controls (P = 0.00003). Specificity was 92%. For DRPN, vascular immune deposits occurred in 5 of 6 nerves or muscles (4 of 6 nerves, 1 of 5 muscles), similar to vasculitis but significantly different from controls. Epineurial/perimysial vascular deposits of immunoglobulin/C3 by DIF are a specific marker of vasculitic neuropathy. PMID- 20544918 TI - Electrophysiological characteristics of motor units and muscle fibers in trained and untrained young male subjects. AB - We hypothesized that the amplitudes of compound muscle action potentials (CMAPs) and interference pattern analysis (IPA) would be larger in trained subjects compared with untrained subjects, possibly due to hypertrophy of muscle fibers and/or increased central drive. Moreover, we hypothesized that the untrained muscle is less excitable compared with the trained muscle. An electromyographic (EMG) needle electrode was used to record the IPA at maximal voluntary effort. The CMAP was obtained by stimulating the musculocutaneous nerve and recording the brachial biceps muscle using surface electrodes. CMAPs were obtained by direct muscle stimulation (DMS) with two stainless-steel subdermal electrodes placed subcutaneously in the distal third of the muscle. Amplitudes of CMAP and IPA were significantly larger in trained subjects compared with untrained subjects. We found no differences between trained and untrained subjects in IPA power spectrum and turns per second or amplitude of the CMAPs obtained by DMS. Muscle fiber hypertrophy and/or altered central drive may account for our results, but there was no indication of changes in muscle fiber excitability. PMID- 20544919 TI - Pre- and postsynaptic neuromuscular junction abnormalities in musk myasthenia. AB - Autoantibodies to muscle-specific kinase (MuSK) can cause myasthenia gravis (MG). The pathophysiological mechanism remains unknown. We report in vitro electrophysiological and histological studies of the neuromuscular junction in a MuSK MG patient. Low levels of presynaptic acetylcholine release and small miniature endplate potentials were found. This combination of pre- and postsynaptic abnormalities was supported by histology, revealing partially denervated postsynaptic areas, and some degeneration of postsynaptic folds. Results suggest that anti-MuSK antibodies reduce the stability of muscle-nerve contact. PMID- 20544920 TI - Charcot-Marie-Tooth disease with intermediate conduction velocities caused by a novel mutation in the MPZ gene. AB - Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensory and motor neuropathies. Mutations in the gene that encodes for myelin protein zero (MPZ) can produce different phenotypes: CMT1 (with low conduction velocities), CMT2 (less frequent and with unaffected conduction velocities), and CMTID (with intermediate conduction velocities). We report a study of seven patients from a four-generation family. All the affected members of the family had a typical CMT phenotype, but three of them had calf hypertrophy. The nerve conduction velocities (NCV) in all of them were between 35 and 43 m/s. Molecular study revealed the novel mutation Lys214Met in the MPZ gene. Molecular study of the MPZ gene would be useful in cases of CMT in families with intermediate NCV, especially if no mutations in the GJB-1 gene are found or there is male-to-male transmission. PMID- 20544921 TI - Diaphragm displays early and progressive functional deficits in dysferlin deficient mice. AB - Mouse lines with dysferlin deficiency are accepted animal models for limb girdle muscular dystrophy 2B and Miyoshi myopathy, yet slow progression of pathology prevents rapid screening of potential therapies for this disease. Our goal was to define a functional signature for skeletal muscles that lack dysferlin. Force generation and susceptibility to eccentric contractile injury measurements were performed in isolated limb muscles and the diaphragm from 10- and 36-week-old A/J and age-matched control mice. Limb muscles had normal specific force at both 10 and 36 weeks, whereas the diaphragm had significant deficits in both specific force and susceptibility to eccentric contractile injury. Membrane ruptures in the diaphragm during eccentric contractions occurred predominantly in myosin heavy chain 2A-expressing fibers. Dysferlin content did not vary significantly between wildtype muscles, suggesting that there was no correlation between disease severity and normal endogenous levels of the protein. These studies show that, unlike limb muscles, the diaphragm from the A/J mouse displays early deficits in function that may lower the age needed for evaluating potential therapies for dysferlinopathies. PMID- 20544922 TI - Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barre syndrome. AB - We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement. PMID- 20544923 TI - Exercise intolerance due to cytochrome b mutation. AB - Cytochrome b mutations are rare causes of exercise intolerance. We report an 18 year-old man with exercise intolerance since childhood, resting lactic acidosis, cytochrome c oxidase (COX)-positive ragged-red fibers, and isolated muscle complex III deficiency due to a heteroplasmic m.14849T>C mutation in cytochrome b. We review previously described patients carrying mutations in the same gene. COX-positive ragged-red fibers together with exercise intolerance and lactic acidemia provide a clue for the diagnosis of this rare mitochondrial disorder. PMID- 20544925 TI - Vascular pathology in dermatomyositis and anatomic relations to myopathology. AB - The causes of perifascicular myofiber atrophy and capillary pathology in dermatomyositis are incompletely understood. We studied 11 dermatomyositis muscles by histochemistry, immunohistochemistry, and ultrastructure. We found that endomysial capillaries within regions of perifascicular atrophy are not entirely lost, but they have reduced size, endothelial loss, C5b9 complement deposits, and relatively preserved connective tissue molecules and pericytes. In all muscles, the perimysium varies regionally. Some areas contain intermediate sized vessels. Others are avascular. In dermatomyositis, vascular perimysium contains abnormal vessel fragments, perivascular inflammation, and increased PECAM-1. Perifascicular myofiber atrophy and capillary pathology are concentrated near the avascular perimysium. We conclude that both perimysial intermediate sized vessels and endomysial capillaries within regions of perifascicular myofiber atrophy are abnormal in dermatomyositis. Capillary damage and myofiber atrophy are concentrated in regions distant from intermediate-sized perimysial vessels. Chronic immune vascular damage and insufficiency in dermatomyositis may cause ischemia, myofiber atrophy, and capillary damage in "watershed" regions of muscle near the avascular perimysium. PMID- 20544924 TI - Novel diagnostic features of dysferlinopathies. AB - Reports of dysferlinopathy have suggested a clinically heterogeneous group of patients. We identified specific novel molecular and phenotypic features that help distinguish dysferlinopathies from other forms of limb-girdle muscular dystrophy (LGMD). A detailed history, physical exam, and protein and mutation analysis of genomic DNA was done for all subjects. Five of 21 confirmed DYSF gene mutations were not previously reported. A distinct "bulge" of the deltoid muscle in combination with other findings was a striking feature in all patients. Six subjects had atypical calf enlargement, and 3 of these exhibited a paradoxical pattern of dysferlin expression: severely reduced by direct immunofluorescence with overexpression on Western blots. Six patients showed amyloid deposits in muscle that extended these findings to new domains of the dysferlin gene, including the C2G domain. Correlative studies showed colocalization of amyloid with deposition of dysferlin. The present data further serve to guide clinicians facing the expensive task of molecular characterization of patients with an LGMD phenotype. PMID- 20544926 TI - Topographical distribution of motor fascicles in the sciatic-tibial nerve of the rat. AB - Knowledge of the intraneural topography of peripheral nerves may help to improve nerve repair after injuries and the selectivity of neural interfaces. We studied the fascicular pattern of motor fibers of the rat sciatic-tibial nerve. We carried out an anatomical dissection of the muscular tributaries of the tibial nerve in the leg. Immunohistochemistry against choline acetyltransferase was used to identify motor axons. Retrograde tracing allowed localization of the muscular fascicles at proximal levels of the sciatic trunk. The distribution of motor fibers in transverse section of the tibial nerve is not homogeneous; two clusters were identified, each one containing fibers of functionally related muscles. Retrograde tracing allowed for the identification of motor fascicles, each one well localized along the sciatic nerve. In the rat there is a somatotopic organization of the sciatic nerve, with muscular fascicles maintaining the same relative position along the entire nerve. PMID- 20544927 TI - Localization of motor nerve branches of the human psoas muscle. AB - Endplate-targeted botulinum toxin injections can achieve optimal neuromuscular blockade. The goal of this study was to identify the motor endplate (MEP) zone in the human psoas muscle through dissection. In 24 human cadaver psoas muscles the nerve branches and their intramuscular course were followed by stereoscopic microscopic dissection as far as their terminal ramifications. From the lumbar plexus, an average of 3.7 (range 2-7) nerve branches enter the psoas muscle. The proximal and distal limit of the MEP-zone are situated at about 30% and 70%, respectively, of the distance between the twelfth thoracic vertebra (Th12) and the passing of the psoas under the inguinal ligament. In reference to the sacral promontory (P), these limits are respectively from 50% of the Th12-P distance to 20% of the P-pubis distance. This study of the MEP zone of the human psoas muscle can allow the clinician to inject BTX-A close to its site of action. PMID- 20544929 TI - Effect of motor imagery and voluntary muscle contraction on the F wave. AB - We tested the validity of instructing patients to minimally contract the muscle to facilitate F-wave recording in clinical practice. In 12 healthy subjects, F waves were recorded from the first dorsal interosseous muscle at rest, during motor imagery, and at up to 30% of the maximal voluntary contraction (MVC). F wave persistence increased significantly from 32.5 +/- 11.9% (mean +/- SD) at rest to 58.3 +/- 15.2% during motor imagery and 90.0 +/- 8.7% during 3% MVC. It then remained the same during stepwise changes to and from 30% MVC before decreasing significantly from 80.8 +/- 18.5% during 3% MVC to 48.7 +/- 23.8% during motor imagery and 27.0 +/- 16.0% at rest. The trial average of F-wave amplitude showed a similar pattern of facilitation. Motor imagery enhances F-wave persistence and amplitude, which further increase with a slight muscle contraction and show no additional change with a stronger effort. PMID- 20544928 TI - Fus gene mutations in familial and sporadic amyotrophic lateral sclerosis. AB - Mutations in the fused in sarcoma (FUS) gene have recently been found to cause familial amyotrophic lateral sclerosis (FALS). We screened FUS in a cohort of 200 ALS patients [32 FALS and 168 sporadic ALS (SALS)]. In one FALS proband, we identified a mutation (p.R521C) that was also present in her affected daughter. Their clinical phenotype was remarkably similar and atypical of classic ALS, with symmetric proximal pelvic and pectoral weakness. Distal weakness and upper motor neuron features only developed late. Neuropathological examination demonstrated FUS-immunoreactive neuronal and glial inclusions in the spinal cord and many extramotor regions, but no TDP-43 pathology. We also identified a novel mutation (p.G187S) in one SALS patient. Overall, FUS mutations accounted for 3% of our non SOD1, non-TARDBP FALS cases and 0.6% of SALS. This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS cases. Our findings suggest there are specific clinicogenetic correlations and provide the first detailed neuropathological description. PMID- 20544931 TI - Safety of influenza vaccination: Risk-benefit evaluation. PMID- 20544930 TI - A standardized clinical evaluation of patients affected by facioscapulohumeral muscular dystrophy: The FSHD clinical score. AB - To define numerically the clinical severity of facioscapulohumeral muscular dystrophy (FSHD), we developed a protocol that quantifies muscle weakness by combining the functional evaluation of six muscle groups affected in this disease. To validate reproducibility of the protocol, 69 patients were recruited. Each patient was evaluated by at least five neurologists, and an FSHD severity score was given by each examiner. The degree of agreement among clinicians' evaluations was measured by kappa-statistics. Nineteen subjects received a score between 0 and 1, 9 had a score between 2 and 4, 20 received a score between 5 and 10, and 8 had a score between 11 and 15. Of the 13 subjects with D4Z4 alleles within the normal range (ranging from 10 to 150 repeats), 12 obtained a score of 0 and only 1 had a score of 1. Kappa-statistics showed a very high concordance for all muscle groups. We developed a simple, reliable, easily used tool to define the clinical expression of FSHD. Longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use. PMID- 20544932 TI - Cognition in patients with myasthenia gravis. PMID- 20544933 TI - Quadriceps low-frequency fatigue and muscle pain are contraction-type-dependent. AB - Eccentric contractions are thought to induce greater low-frequency fatigue (LFF) and delayed-onset muscle soreness (DOMS) than concentric contractions. In this study we induced a similar amount of eccentric quadriceps muscle fatigue during either a concentric or eccentric fatigue task to compare LFF and DOMS. Subjects (n = 22) performed concentric or eccentric fatigue tasks using 75% of the pre fatigue maximal voluntary contraction (MVC) torque, and both tasks ended when the MVC eccentric torque decreased by 25% pre-fatigue. When subjects reached the failure criterion during the eccentric and concentric tasks, the concentric MVC was 78 +/- 9.8% and 64 +/- 8.4% of initial, respectively. LFF was greater after the concentric than the eccentric protocols (22 +/- 12.4% and 15 +/- 7.6% increase, respectively; P < 0.01). DOMS was over 100% greater for the eccentric protocol. These results indicate that DOMS is not dependent on the events that contribute to LFF. PMID- 20544934 TI - Monitoring disease progression using high-density motor unit number estimation in amyotrophic lateral sclerosis. AB - In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high-density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible. PMID- 20544935 TI - Crimson carrier, a long-acting contrast agent for in vivo near-infrared imaging of injured and diseased muscle. AB - The near-infrared wavelengths (700-900 nm) are the most suitable optical window for light penetration and deep tissue imaging in small animals. Herein we report a near-infrared fluorescent contrast agent, crimson carrier, which acts as a blood pool contrast agent to detect and quantify injury and disease in live animals. After determining the excitation-emission spectra and pharmacokinetics, crimson carrier was injected into myoinjured mice to monitor their recovery. Crimson carrier was also used to image transgenic mice with spontaneous tumors. Crimson carrier has maximal excitation and emission wavelengths of 745 nm and 820 nm, respectively. Elimination occurs predominantly via urinary excretion. We demonstrate the utility of this contrast agent for serial imaging of traumatized muscle as well as muscle tumors. The unique long-acting pharmacokinetics and urinary excretion route characteristics make crimson carrier a contrast agent of choice for the visualization of tumors and injured muscle or other tissues in live animal studies. PMID- 20544936 TI - Restless legs syndrome in chronic inflammatory demyelinating polyneuropathy. AB - The prevalence of restless legs syndrome (RLS) is unknown in chronic inflammatory demyelinating polyneuropathy (CIDP). We prospectively studied 28 patients with CIDP. Prevalence of RLS in CIDP was ascertained by face-to-face interview using validated criteria and compared with that in 28 age- and gender-matched controls. Eleven (39.3%) CIDP patients were diagnosed with RLS, compared with 2 (7.1%) controls (P < 0.01). A significant correlation was ascertained between presence of RLS and lower limb weakness, functional disability, and summated compound muscle action potential (CMAP). The prevalence of RLS in CIDP was significantly higher than in controls in our study population, approaching 40%. Screening for RLS in CIDP patients may be appropriate, particularly in those with weakness, disability, and motor axonal loss in the lower limbs. Our findings may otherwise suggest the existence of peripheral components to the pathophysiology of RLS in patients with CIDP. PMID- 20544937 TI - Randomized trial of botulinum toxin to prevent pes cavus progression in pediatric Charcot-Marie-Tooth disease type 1A. AB - Pes cavus in Charcot-Marie-Tooth disease type 1A (CMT1A) is thought to be due to muscle imbalance of the lower leg. Botulinum toxin type A (BoNT-A) can modify foot deformity in other conditions of muscle imbalance. We tested the safety and effectiveness of BoNT-A on pes cavus progression in pediatric CMT1A. A 24-month, randomized, single-blind trial of BoNT-A was undertaken in 10 affected children (20 legs), aged 3-14 years. The treated leg received intramuscular BoNT-A injections at 6-month intervals in the tibialis posterior and peroneus longus. The control leg received no injections. Primary outcome was radiographic alignment at 24 months. Secondary outcomes were foot posture, ankle flexibility, and strength, assessed every 6 months. Radiographically, BoNT-A produced a small non-significant reduction in cavus progression. There was no effect of BoNT-A on secondary outcomes. There were no serious adverse events. At 24 months, the intramuscular BoNT-A injections proved safe and well-tolerated but did not affect the progression of pes cavus in CMT1A. PMID- 20544938 TI - Endurance exercise training in myostatin null mice. AB - The growth factor myostatin (Mstn) is a negative regulator of skeletal muscle mass. Mstn(-/-) muscles are hypertrophied, stronger, and more glycolytic than Mstn(+/+) muscles, suggesting that they might not perform endurance exercise as well as Mstn(+/+) mice. Indeed, it has previously been shown that treadmill exercise training reduces triceps weight in Mstn(-/-) mice. To analyze the response of Mstn(-/-) muscle to endurance exercise in detail, we carried out endurance training over 4 weeks to examine muscle mass, histology, and oxidative enzyme activity. We found that muscle mass was reduced with training in several muscles from both genotypes, with no evidence of muscle damage. Citrate synthase activity was increased with training in control and mutant mice. Non-trained Mstn(-/-) mice did, however, have lower maximal exercise capacity compared with Mstn(+/+) mice. These results show that Mstn(-/-) muscle retains the metabolic plasticity necessary to adapt normally to endurance training. PMID- 20544939 TI - Hypoglossal nerve conduction findings in obstructive sleep apnea. AB - Denervation of oropharyngeal muscles in obstructive sleep apnea (OSA) has been suggested by needle electromyography (EMG) and muscle biopsy, but little is known about oropharyngeal nerve conduction abnormalities in OSA. We sought to compare hypoglossal nerve conduction studies in patients with and without OSA. Unilateral hypoglossal nerve conduction studies were performed on 20 subjects with OSA and 20 age-matched controls using standard techniques. Median age was 48 years in OSA subjects and 47 years in controls. Hypoglossal compound muscle action potential (CMAP) amplitudes were significantly reduced (P = 0.01, Wilcoxon signed-rank test), but prolongation of latencies in OSA subjects did not reach significance in comparison to those of controls. Among a subgroup of subjects without polyneuropathy (15 pairs), reduced amplitudes in OSA subjects retained borderline significance (P = 0.05). Hypoglossal nerve conduction abnormalities may distinguish patients with OSA from controls. These abnormalities could potentially contribute to, or arise from, OSA. PMID- 20544940 TI - Characterization of skeletal muscle effects associated with daptomycin in rats. AB - Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram-positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (